Systemic lupus erythematosusFrom Wikipedia, the free encyclopediaFor other uses, see lupus (disambiguation).

Systemic lupus erythematosusClassification and external resources

A drawing of the typical "butterfly rash"ICD-10 L 93. , M 32. ICD-9 710.0OMIM 152700DiseasesDB 12782MedlinePlus 000435eMedicine med/2228 emerg/564MeSH D008180

Systemic lupus erythematosus ( i / s ɨ ̍ s t ɛ m ɪ k ̍ l uː p ə s ̩ ɛr ɨ θ iː m ə ̍ t oʊ s ə s / ), often abbreviated to SLE or lupus, is a systemic autoimmune disease (or autoimmune connective tissue disease) that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage.[1] It is a Type III hypersensitivity reaction caused by antibody-immune complex formation.

SLE most often harms the heart, joints, skin, lungs, blood vessels, liver, kidneys, and nervous system. The course of the disease is unpredictable, with periods of illness (called flares) alternating with remissions. The disease occurs nine times more often in women than in men, especially in women in child-bearing years ages 15 to 35, and is also more common in those of non-European descent.[2][3][4]

SLE is treatable using immunosuppression, mainly with cyclophosphamide, corticosteroids and other immunosuppressants; there is currently no cure. SLE can be fatal, although with recent

medical advances, fatalities are becoming increasingly rare. Survival for people with SLE in the United States, Canada, and Europe has risen to approximately 95% at five years, 90% at 10 years, and 78% at 20 years,[4] and now approaches that of matched controls without lupus.

Contents

[hide]

1 Signs and symptoms 2 Causes

o 2.1 Genetics o 2.2 Environmental triggers o 2.3 Drug reactions o 2.4 Non-SLE forms of lupus

3 Pathophysiology o 3.1 Transmission o 3.2 Abnormalities in apoptosis o 3.3 Clearance deficiency o 3.4 Accumulation in germinal centres o 3.5 Anti-nRNP autoimmunity o 3.6 Others

4 Diagnosis o 4.1 Laboratory tests o 4.2 Diagnostic criteria

5 Prevention 6 Treatment

o 6.1 Medications o 6.2 Lifestyle changes o 6.3 Renal transplantation o 6.4 Hughes syndrome o 6.5 Management of pregnancy

7 Prognosis 8 Epidemiology 9 History and culture

o 9.1 Etymology o 9.2 History

10 Notable cases 11 Research 12 See also 13 References 14 External links

[edit] Signs and symptoms

Common symptoms of SLE.[5]

SLE is one of several diseases known as "the great imitators" because it often mimics or is mistaken for other illnesses.[6] SLE is a classical item in differential diagnosis,[2] because SLE symptoms vary widely and come and go unpredictably. Diagnosis can thus be elusive, with some people suffering unexplained symptoms of untreated SLE for years.

Common initial and chronic complaints include fever, malaise, joint pains, myalgias, fatigue, and temporary loss of cognitive abilities. Because they are so often seen with other diseases, these signs and symptoms are not part of the diagnostic criteria for SLE. When occurring in conjunction with other signs and symptoms (see below), however, they are considered suggestive.[7]

Dermatological manifestations

As many as 30% of sufferers have some dermatological symptoms (and 65% suffer such symptoms at some point), with 30% to 50% suffering from the classic malar rash (or butterfly rash) associated with the disease. Some may exhibit thick, red scaly patches on the skin (referred to as discoid lupus). Alopecia; mouth, nasal, urinary tract and vaginal ulcers, and lesions on the skin are also possible manifestations. Tiny tears in delicate tissue around the eyes can occur after even minimal rubbing.

Musculoskeletal

The most commonly sought medical attention is for joint pain, with the small joints of the hand and wrist usually affected, although all joints are at risk. The Lupus Foundation of America estimates more than 90 percent of those affected will experience joint and/or muscle pain at some time during the course of their illness.[8] Unlike rheumatoid arthritis, lupus arthritis is less disabling and usually does not cause severe destruction of the joints. Fewer than ten percent of

people with lupus arthritis will develop deformities of the hands and feet.[8] SLE patients are at particular risk of developing osteoarticular tuberculosis.[9]

A possible association between rheumatoid arthritis and SLE has been suggested,[10] and SLE may be associated with an increased risk of bone fractures in relatively young women.[11]

Hematological

Anemia may develop in up to 50% of cases. Low platelet and white blood cell counts may be due to the disease or a side effect of pharmacological treatment. People with SLE may have an association with antiphospholipid antibody syndrome [12] (a thrombotic disorder), wherein autoantibodies to phospholipids are present in their serum. Abnormalities associated with antiphospholipid antibody syndrome include a paradoxical prolonged partial thromboplastin time (which usually occurs in hemorrhagic disorders) and a positive test for antiphospholipid antibodies; the combination of such findings have earned the term "lupus anticoagulant-positive". Another autoantibody finding in SLE is the anticardiolipin antibody, which can cause a false positive test for syphilis.[citation needed]

Cardiac

A person with SLE may have inflammation of various parts of the heart, such as pericarditis, myocarditis, and endocarditis. The endocarditis of SLE is characteristically noninfective (Libman-Sacks endocarditis), and involves either the mitral valve or the tricuspid valve. Atherosclerosis also tends to occur more often and advances more rapidly than in the general population.[13][14][15]

Pulmonary

Lung and pleura inflammation can cause pleuritis, pleural effusion, lupus pneumonitis, chronic diffuse interstitial lung disease, pulmonary hypertension, pulmonary emboli, pulmonary hemorrhage, and shrinking lung syndrome.

Renal

Painless hematuria or proteinuria may often be the only presenting renal symptom. Acute or chronic renal impairment may develop with lupus nephritis, leading to acute or end-stage renal failure. Because of early recognition and management of SLE, end-stage renal failure occurs in less than 5% of cases.

A histological hallmark of SLE is membranous glomerulonephritis with "wire loop" abnormalities.[16] This finding is due to immune complex deposition along the glomerular basement membrane, leading to a typical granular appearance in immunofluorescence testing.

Neuropsychiatric

Neuropsychiatric syndromes can result when SLE affects the central or peripheral nervous systems. The American College of Rheumatology defines 19 neuropsychiatric syndromes in systemic lupus erythematosus.[17] The diagnosis of neuropsychiatric syndromes concurrent with SLE is one of the most difficult challenges in medicine, because it can involve so many different patterns of symptoms, some of which may be mistaken for signs of infectious disease or stroke.[18]

The most common neuropsychiatric disorder people with SLE have is headache,[19] although the existence of a specific lupus headache and the optimal approach to headache in SLE cases remains controversial.[20] Other common neuropsychiatric manifestation of SLE include cognitive dysfunction, mood disorder, cerebrovascular disease,[19] seizures, polyneuropathy,[19] anxiety disorder, and psychosis. It can rarely present with intracranial hypertension syndrome, characterized by an elevated intracranial pressure, papilledema, and headache with occasional abducens nerve paresis, absence of a space-occupying lesion or ventricular enlargement, and normal cerebrospinal fluid chemical and hematological constituents.[21]

More rare manifestations are acute confusional state, Guillain-Barré syndrome, aseptic meningitis, autonomic disorder, demyelinating syndrome, mononeuropathy (which might manifest as mononeuritis multiplex), movement disorder (more specifically, chorea), myasthenia gravis, myelopathy, cranial neuropathy and plexopathy.

Neurological

Neural symptoms contribute to a significant percentage of morbidity and mortality in patients with lupus.[22] As a result, the neural side of lupus is being studied in hopes of reducing morbidity and mortality rates.[17] The neural manifestation of lupus is known as neuropsychiatric systematic lupus erythematosus (NPSLE). One aspect of this disease is severe damage to the epithelial cells of the blood-brain barrier.

Lupus has a wide range of symptoms which span the body. The neurological symptoms include headaches,[19] depression, seizures, cognitive dysfunction, mood disorder, cerebrovascular disease,[19] polyneuropathy,[19] anxiety disorder, psychosis, and in some extreme cases, personality disorders.[23] In certain regions, depression reportedly affects up to 60% of women suffering from SLE.[24]

ReproductiveFurther information: Systemic lupus erythematosus and pregnancy

SLE causes an increased rate of fetal death in utero and spontaneous abortion (miscarriage). The overall live-birth rate in SLE patient has been estimated to be 72%.[25] Pregnancy outcome appears to be worse in SLE patients whose disease flares up during pregnancy.[26]

Neonatal lupus is the occurrence of SLE symptoms in an infant born from a mother with SLE, most commonly presenting with a rash resembling discoid lupus erythematosus, and sometimes with systemic abnormalities such as heart block or hepatosplenomegaly.[27] Neonatal lupus is usually benign and self-limited.[27]

Systemic

Fatigue in SLE is probably multifactorial and has been related to not only disease activity or complications such as anemia or hypothyroidism, but also to pain, depression, poor sleep quality, poor physical fitness and perceived lack of social support.[28][29]

[edit] Causes

There is no one specific cause of SLE. There are, however, a number of environmental triggers and a number of genetic susceptibilities.[30][31]

[edit] Genetics

The first mechanism may arise genetically. Research indicates SLE may have a genetic link. SLE does run in families, but no single causal gene has been identified. Instead, multiple genes appear to influence a person's chance of developing lupus when triggered by environmental factors. The most important genes are located in the HLA region on chromosome 6, where mutations may occur randomly (de novo) or may be inherited. HLA class I, class II, and class III are associated with SLE, but only classes I and II contribute independently to increased risk of SLE.[32] Other genes which contain risk variants for SLE are IRF5, PTPN22, STAT4,[33] CDKN1A,[34] ITGAM, BLK,[33] TNFSF4 and BANK1.[35] Some of the susceptibility genes may be population specific.[33]

[edit] Environmental triggers

The second mechanism may be due to environmental factors. These factors may not only exacerbate existing SLE conditions, but also trigger the initial onset.

Researchers have sought to find a connection between certain infectious agents (viruses and bacteria), but no pathogen can be consistently linked to the disease. Some researchers have found that women with silicone gel-filled breast implants have produced antibodies to their own collagen, but it is not known how often these antibodies occur in the general population, and there are no data that show these antibodies cause connective tissue diseases such as SLE. There is also a small but growing body of evidence linking SLE to lipstick usage.[36][37][38]

[edit] Drug reactions

Drug-induced lupus erythematosus is a (generally) reversible condition that usually occurs in people being treated for a long-term illness. Drug-induced lupus mimics SLE. However, symptoms of drug-induced lupus generally disappear once the medication that triggered the episode is stopped. More than 38 medications can cause this condition, the most common of which are procainamide, hydralazine, quinidine, and phenytoin.[2]

[edit] Non-SLE forms of lupus

Discoid (cutaneous) lupus is limited to skin symptoms and is diagnosed by biopsy of rash on the face, neck, scalp or arms.

[edit] Pathophysiology

One manifestation of SLE is abnormalities in apoptosis, a type of programmed cell death in which aging or damaged cells are neatly disposed of as a part of normal growth or functioning.

[edit] Transmission

In SLE, the body's immune system produces antibodies against itself, particularly against proteins in the cell nucleus. SLE is triggered by environmental factors that are unknown.

"All the key components of the immune system are involved in the underlying mechanisms [of SLE]" according to Rahman, and SLE is the prototypical autoimmune disease. The immune system must have a balance (homeostasis) between being sensitive enough to protect against infection, and being too sensitive and attacking the body's own proteins (autoimmunity). From an evolutionary perspective, according to Crow, the population must have enough genetic diversity to protect itself against a wide range of possible infection; some genetic combinations result in autoimmunity. The likely environmental triggers include ultraviolet light, drugs, and viruses. These stimuli cause the destruction of cells and expose their DNA, histones, and other proteins, particularly parts of the cell nucleus. Because of genetic variations in different components of the immune system, in some people the immune system attacks these nuclear-related proteins and produces antibodies against them. In the end, these antibody complexes damage blood vessels in critical areas of the body, such as the glomeruli of the kidney; these antibody attacks are the cause of SLE. Researchers are now identifying the individual genes, the proteins they produce, and their role in the immune system. Each protein is a link on the autoimmune chain, and researchers are trying to find drugs to break each of those links.[2][39][40]

SLE is a chronic inflammatory disease believed to be a type III hypersensitivity response with potential type II involvement.[41] Reticulate and stellate acral pigmentation should be considered a possible manifestation of SLE and high titers of anticardiolipin antibodies, or a consequence of therapy.[42]

[edit] Abnormalities in apoptosis

Apoptosis is increased in monocytes and keratinocytes Expression of Fas by B cells and T cells is increased There are correlations between the apoptotic rates of lymphocytes and disease activity.

Tingible body macrophages (TBMs) – large phagocytic cells in the germinal centers of secondary lymph nodes – express CD68 protein. These cells normally engulf B cells that have undergone apoptosis after somatic hypermutation. In some people with SLE, significantly fewer TBMs can be found, and these cells rarely contain material from apoptotic B cells. Also, uningested apoptotic nuclei can be found outside of TBMs. This material may present a threat to the tolerization of B cells and T cells. Dendritic cells in the germinal center may endocytose such

antigenic material and present it to T cells, activating them. Also, apoptotic chromatin and nuclei may attach to the surfaces of follicular dendritic cells and make this material available for activating other B cells that may have randomly acquired self-specificity through somatic hypermutation.[43]

[edit] Clearance deficiency

Clearance deficiency

The exact mechanisms for the development of SLE are still unclear, since the pathogenesis is a multifactorial event. Beside discussed causations, impaired clearance of dying cells is a potential pathway for the development of this systemic autoimmune disease. This includes deficient phagocytic activity and scant serum components in addition to increased apoptosis.

Monocytes isolated from whole blood of SLE sufferers show reduced expression of CD44 surface molecules involved in the uptake of apoptotic cells. Most of the monocytes and tingible body macrophages (TBMs), which are found in the germinal centres of lymph nodes, even show a definitely different morphology; they are smaller or scarce and die earlier. Serum components like complement factors, CRP, and some glycoproteins are, furthermore, decisively important for an efficiently operating phagocytosis. With SLE, these components are often missing, diminished, or inefficient.

Recent research has found an association between certain lupus patients (especially those with lupus nephritis) and an impairment in degrading neutrophil extracellular traps (NETs). These were due to DNAse1 inhibiting factors, or NET protecting factors in patient serum, rather than abnormalities in the DNAse1 itself.[44] DNAse1 mutations in lupus have so far only been found in some Japanese cohorts.[45]

The clearance of early apoptotic cells is an important function in multicellular organisms. It leads to a progression of the apoptosis process and finally to secondary necrosis of the cells if this ability is disturbed. Necrotic cells release nuclear fragments as potential autoantigens, as well as internal danger signals, inducing maturation of dendritic cells (DCs), since they have lost their membranes' integrity. Increased appearance of apoptotic cells also simulates inefficient clearance. That leads to maturation of DCs and also to the presentation of intracellular antigens

of late apoptotic or secondary necrotic cells, via MHC molecules. Autoimmunity possibly results by the extended exposure to nuclear and intracellular autoantigens derived from late apoptotic and secondary necrotic cells. B and T cell tolerance for apoptotic cells is abrogated, and the lymphocytes get activated by these autoantigens; inflammation and the production of autoantibodies by plasma cells is initiated. A clearance deficiency in the skin for apoptotic cells has also been observed in people with cutaneous lupus erythematosus (CLE).[46]

Germinal centres

[edit] Accumulation in germinal centres

In healthy conditions, apoptotic lymphocytes are removed in germinal centres by specialized phagocytes, the tingible body macrophages (TBM), which is why no free apoptotic and potential autoantigenic material can be seen. In some people with SLE, accumulation of apoptotic debris can be observed in GC because of an ineffective clearance of apoptotic cells. In close proximity to TBM, follicular dendritic cells (FDC) are localised in GC, which attach antigen material to their surface and, in contrast to bone marrow-derived DC, neither take it up nor present it via MHC molecules.

Autoreactive B cells can accidentally emerge during somatic hypermutation and migrate into the GC light zone. Autoreactive B cells, maturated coincidentally, normally do not receive survival signals by antigen planted on follicular dendritic cells, and perish by apoptosis. In the case of clearance deficiency, apoptotic nuclear debris accumulates in the light zone of GC and gets attached to FDC. This serves as a germinal centre survival signal for autoreactive B-cells. After migration into the mantle zone, autoreactive B cells require further survival signals from autoreactive helper T cells, which promote the maturation of autoantibody-producing plasma

cells and B memory cells. In the presence of autoreactive T cells, a chronic autoimmune disease may be the consequence.

[edit] Anti-nRNP autoimmunity

Autoantibodies to nRNP A and nRNP C initially targeted restricted, proline-rich motifs. Antibody binding subsequently spread to other epitopes. The similarity and cross-reactivity between the initial targets of nRNP and Sm autoantibodies identifies a likely commonality in cause and a focal point for intermolecular epitope spreading.[47]

[edit] Others

Elevated expression of HMGB1 was found in the sera of patients and mice with systemic lupus erythematosus, high mobility group box 1 (HMGB1) is a nuclear protein participating in chromatin architecture and transcriptional regulation. Recently, there is increasing evidence HMGB1 contributes to the pathogenesis of chronic inflammatory and autoimmune diseases due to its proinflammatory and immunostimulatory properties.[48]

[edit] Diagnosis

Microphotograph of a histological section of human skin prepared for direct immunofluorescence using an anti-IgG antibody. The skin is from a person with systemic lupus erythematosus and shows IgG deposits at two different places: The first is a bandlike deposit along the epidermal basement membrane ("lupus band test" is positive); the second is within the nuclei of the epidermal cells (antinuclear antibodies are present).

[edit] Laboratory tests

Antinuclear antibody (ANA) testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologic testing for SLE. Several techniques are used to detect ANAs. Clinically the most widely used method is indirect immunofluorescence. The pattern of fluorescence suggests the type of antibody present in the patient's serum.

ANA screening yields positive results in many connective tissue disorders and other autoimmune diseases, and may occur in normal individuals. Subtypes of antinuclear antibodies include anti-Smith and anti-double stranded DNA (dsDNA) antibodies (which are linked to SLE) and anti-

histone antibodies (which are linked to drug-induced lupus). Anti-dsDNA antibodies are highly specific for SLE; they are present in 70% of cases, whereas they appear in only 0.5% of people without SLE.[2] The anti-dsDNA antibody titers also tend to reflect disease activity, although not in all cases.[2] Other ANA that may occur in SLE sufferers are anti-U1 RNP (which also appears in systemic sclerosis), SS-A (or anti-Ro) and SS-B (or anti-La; both of which are more common in Sjögren's syndrome). SS-A and SS-B confer a specific risk for heart conduction block in neonatal lupus.[49]

Other tests routinely performed in suspected SLE are complement system levels (low levels suggest consumption by the immune system), electrolytes and renal function (disturbed if the kidney is involved), liver enzymes, and complete blood count.

The lupus erythematosus (LE) cell test was commonly used for diagnosis, but it is no longer used because the LE cells are only found in 50–75% of SLE cases, and they are also found in some people with rheumatoid arthritis, scleroderma, and drug sensitivities. Because of this, the LE cell test is now performed only rarely and is mostly of historical significance.[50]

[edit] Diagnostic criteria

Some physicians make a diagnosis on the basis of the American College of Rheumatology (ACR) classification criteria. The criteria, however, were established mainly for use in scientific research including use in randomized controlled trials which require higher confidence levels, so some people with SLE may not pass the full criteria.

[edit] Criteria

The American College of Rheumatology established eleven criteria in 1982,[51] which were revised in 1997[52] as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individuals and do not do well in that capacity. For the purpose of identifying patients for clinical studies, a person has SLE if any 4 out of 11 symptoms are present simultaneously or serially on two separate occasions.

1. Malar rash (rash on cheeks); sensitivity = 57%; specificity = 96%.[53]

2. Discoid rash (red, scaly patches on skin that cause scarring); sensitivity = 18%; specificity = 99%.[53]

3. Serositis: Pleurisy (inflammation of the membrane around the lungs) or pericarditis (inflammation of the membrane around the heart); sensitivity = 56%; specificity = 86% (pleural is more sensitive; cardiac is more specific).[53]

4. Oral ulcers (includes oral or nasopharyngeal ulcers); sensitivity = 27%; specificity = 96%.[53]

5. Arthritis : nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion; sensitivity = 86%; specificity = 37%.[53]

6. Photosensitivity (exposure to ultraviolet light causes rash, or other symptoms of SLE flareups); sensitivity = 43%; specificity = 96%.[53]

7. Blood—hematologic disorder—hemolytic anemia (low red blood cell count) or leukopenia (white blood cell count<4000/µl), lymphopenia (<1500/µl) or

thrombocytopenia (<100000/µl) in the absence of offending drug; sensitivity = 59%; specificity = 89%.[53] Hypocomplementemia is also seen, due to either consumption of C3 and C4 by immune complex-induced inflammation or to congenitally complement deficiency, which may predispose to SLE.

8. Renal disorder: More than 0.5 g per day protein in urine or cellular casts seen in urine under a microscope; sensitivity = 51%; specificity = 94%.[53]

9. Antinuclear antibody test positive; sensitivity = 99%; specificity = 49%.[53]

10. Immunologic disorder: Positive anti-Smith, anti-ds DNA, antiphospholipid antibody, and/or false positive serological test for syphilis; sensitivity = 85%; specificity = 93%.[53] Presence of anti-ss DNA in 70% of cases (though also positive with rheumatic disease and healthy persons).[54]

11. Neurologic disorder: Seizures or psychosis; sensitivity = 20%; specificity = 98%.[53]

[edit] Criteria for individual diagnosis

Some people, especially those with antiphospholipid syndrome, may have SLE without four of the above criteria, and also SLE may present with features other than those listed in the criteria.[55][56][57]

Recursive partitioning has been used to identify more parsimonious criteria.[53] This analysis presented two diagnostic classification trees:

1. Simplest classification tree: SLE is diagnosed if a person has an immunologic disorder (anti-DNA antibody, anti-Smith antibody, false positive syphilis test, or LE cells) or malar rash. It has sensitivity = 92% and specificity = 92%.

2. Full classification tree: Uses 6 criteria. It has sensitivity = 97% and specificity = 95%.

Other alternative criteria have been suggested, e.g. the St. Thomas' Hospital "alternative" criteria in 1998.[58]

[edit] Prevention

SLE is not understood well enough to be prevented, but, when the disease develops, quality of life can be improved through flare prevention. The warning signs of an impending flare include increased fatigue, pain, rash, fever, abdominal discomfort, headache, and dizziness. Early recognition of warning signs and good communication with a doctor can help individuals remain active, experience less pain, and reduce medical visits.[59]

As longevity of people with SLE increases, the likelihood of complications also increases in four areas: cardiovascular disease, infections, osteoporosis, and cancer. Standard preventive measures, screening for related diseases may be necessary to deal with the increased risks due to the side effects of medications. Extra vigilance is considered warranted in particular for cancers affecting the immune system.[60]

[edit] Treatment

The treatment of SLE involves preventing flares and reducing their severity and duration when they occur.

Treatment can include corticosteroids and anti-malarial drugs. Certain types of lupus nephritis such as diffuse proliferative glomerulonephritis require bouts of cytotoxic drugs. These drugs include cyclophosphamide and mycophenolate.

Hydroxychloroquine (HCQ) was the last medication approved by the FDA for lupus in 1955.[61] Some drugs approved for other diseases are used for SLE 'off-label'. In November 2010, an FDA advisory panel recommended approving Benlysta (belimumab) as a treatment for the pain and flare-ups common in lupus. The drug was approved by the FDA in March 2011.[62]

[edit] Medications

Due to the variety of symptoms and organ system involvement with SLE, its severity in an individual must be assessed in order to successfully treat SLE. Mild or remittant disease may, sometimes, be safely left untreated. If required, nonsteroidal anti-inflammatory drugs and antimalarials may be used. Medications such as Prednisone, Cellcept and Prograf have been used in the past. A number of potential treatments are in clinical trials.[63]

[edit] Disease-modifying antirheumatic drugs

Disease-modifying antirheumatic drugs (DMARDs) are used preventively to reduce the incidence of flares, the process of the disease, and lower the need for steroid use; when flares occur, they are treated with corticosteroids. DMARDs commonly in use are antimalarials such as plaquenil and immunosuppressants (e.g. methotrexate and azathioprine). Hydroxychloroquine is an FDA-approved antimalarial used for constitutional, cutaneous, and articular manifestations. Hydroxychloroquine has relatively few side effects, and there is evidence that it improves survival among people who have SLE.[61] Cyclophosphamide is used for severe glomerulonephritis or other organ-damaging complications. Mycophenolic acid is also used for treatment of lupus nephritis, but it is not FDA-approved for this indication, and FDA is investigating reports that it may be associated with birth defects when used by pregnant women.[64]

[edit] Immunosuppressive drugs

In more severe cases, medications that modulate the immune system (primarily corticosteroids and immunosuppressants) are used to control the disease and prevent recurrence of symptoms (known as flares). Depending on the dosage, people who require steroids may develop Cushing's syndrome, side-effects of which may include obesity, puffy round face, diabetes mellitus, large appetite, difficulty sleeping and osteoporosis. Those side-effects can subside if and when the large initial dosage is reduced, but long-term use of even low doses can cause elevated blood pressure and cataracts.

Numerous new immunosuppressive drugs are being actively tested for SLE. Rather than suppressing the immune system nonspecifically, as corticosteroids do, they target the responses

of individual [types of] immune cells. Some of these drugs are already FDA-approved for treatment of rheumatoid arthritis.[61] See also Belimumab and Atacicept. Lupuzor has given encouraging results in a phase IIb trial[65]

[edit] Analgesia

Since a large percentage of people with SLE suffer from varying amounts of chronic pain, stronger prescription analgesics (pain killers) may be used if over-the-counter drugs (mainly nonsteroidal anti-inflammatory drugs) do not provide effective relief. Potent NSAIDs such as indomethacin and diclofenac are relatively contraindicated for patients with SLE because they increase the risk of kidney failure and heart failure.[61]

Moderate pain is typically treated with mild prescription opiates such as dextropropoxyphene and co-codamol. Moderate to severe chronic pain is treated with stronger opioids, such as hydrocodone or longer-acting continuous-release opioids, such as oxycodone, MS Contin, or methadone. The fentanyl duragesic transdermal patch is also a widely-used treatment option for the chronic pain caused by complications because of its long-acting timed release and ease of use. When opioids are used for prolonged periods, drug tolerance, chemical dependency, and addiction may occur. Opiate addiction is not typically a concern, since the condition is not likely to ever completely disappear. Thus, lifelong treatment with opioids is fairly common for chronic pain symptoms, accompanied by periodic titration that is typical of any long-term opioid regimen.

[edit] Intravenous Immunoglobulins (IVIGs)

Intravenous immunoglobulins may be used to control SLE with organ involvement, or vasculitis. It is believed that they reduce antibody production or promote the clearance of immune complexes from the body, even though their mechanism of action is not well-understood.[66] Unlike immunosuppressives and corticosteroids, IVIGs do not suppress the immune system, so there is less risk of serious infections with these drugs.[67]

[edit] Lifestyle changes

Avoiding sunlight is the primary change to the lifestyle of SLE sufferers, as sunlight is known to exacerbate the disease, as is the debilitating effect of intense fatigue. These two problems can lead to patients becoming housebound for long periods of time. Drugs unrelated to SLE should be prescribed only when known not to exacerbate the disease. Occupational exposure to silica, pesticides and mercury can also make the disease worsen.[30]

[edit] Renal transplantation

Renal transplants are the treatment of choice for end-stage renal disease, which is one of the complications of lupus nephritis, but the recurrence of the full disease is common in up to 30% of patients.[68]

[edit] Hughes syndrome

Hughes syndrome, also known as the antiphospholipid syndrome or sticky blood syndrome, is also related to the onset of neural lupus symptoms in the brain. In this form of the disease the cause is very different from lupus: thromboses (blood clots or "sticky blood") form in blood vessels, which prove to be fatal if they move within the blood stream.[55] If the thromboses migrate to the brain, they can potentially cause a stroke by blocking the blood supply to the brain.

If this disorder is suspected in patients, brain scans are usually required for early detection. These scans can show localized areas of the brain where blood supply has not been adequate. The treatment plan for these patients requires thinning of the blood. Often, aspirin is prescribed for this purpose, although in more severe cases anticoagulants such as warfarin are used.[69]

[edit] Management of pregnancy

Further information: Systemic lupus erythematosus and pregnancy

While most infants born to mothers who have SLE are healthy, pregnant mothers with SLE should remain under medical care until delivery. Neonatal lupus is rare, but identification of mothers at highest risk for complications allows for prompt treatment before or after birth. In addition, SLE can flare up during pregnancy, and proper treatment can maintain the health of the mother longer. Women pregnant and known to have anti-Ro (SSA) or anti-La antibodies (SSB) often have echocardiograms during the 16th and 30th weeks of pregnancy to monitor the health of the heart and surrounding vasculature.[59]

Contraception and other reliable forms of pregnancy prevention is routinely advised for women with SLE, since getting pregnant during active disease was found to be harmful. Lupus nephritis was the most common manifestation.

[edit] Prognosis

SLE is considered incurable, but highly treatable.

In the 1950s, most people diagnosed with SLE lived fewer than five years. Advances in diagnosis and treatment have improved survival to the point where over 90% now survive for more than ten years, and many can live relatively asymptomatically. (It is important to note that "ten years" in this statistic does not indicate an average survival rate, but is merely the length of the referenced study. According to the Lupus Foundation of America, "the majority of people with lupus today can expect to live a normal lifespan."[70])

Prognosis is normally worse for men and children than for women; however, if symptoms are present after age 60, the disease tends to run a more benign course. Early mortality, within 5 years, is due to organ failure or overwhelming infections, both of which can be modified by early diagnosis and treatment. The mortality risk is fivefold when compared to the normal population in the late stages, which can be attributed to cardiovascular diseases acquired from corticosteroid therapy, the leading cause of death for people with SLE.[61]

To reduce potential for cardiovascular issues, high blood pressure and high cholesterol should be prevented or treated aggressively. Steroids should be used at the lowest dose for the shortest possible period, and other drugs that can reduce symptoms should be used whenever possible.[61] High serum creatinine, hypertension, nephrotic syndrome, anemia and hypoalbuminemia are poor prognostic factors.[71]

The ANA is the most sensitive screening test for evaluation, whereas anti-Sm (anti-Smith) is the most specific. The dsDNA (double-stranded DNA) antibody is also fairly specific and often fluctuates with disease activity; as such, the dsDNA titre is sometimes useful to monitor disease flares or response to treatment.[72]

[edit] Epidemiology

The rate of SLE varies considerably between countries, ethnicity, gender, and changes over time.[73] In the United States the prevalence of SLE is estimated to be about 53 per 100,000, translating to about 159,000 out of 300 million people in the US being affected.[73][74] In Northern Europe the rate is about 40 per 100,000 people.[75] SLE occurs more frequently and with greater severity among those of non-European descent.[74] That rate has been found to be as high as 159 per 100,000 among those of Afro-Caribbean descent.[73]

SLE, like many autoimmune diseases, affects females more frequently than males, at a rate of almost 9 to 1.[73]

The incidence of SLE in the United States increased from 1.0 in 1955 to 7.6 in 1974. Whether the increase is due to better diagnosis or to increasing frequency of the disease is unknown.[73]

[edit] History and culture

[edit] Etymology

There are several explanations ventured for the term lupus erythematosus. Lupus is Latin for wolf,[76] and "erythro" is derived from ερυθρός, Greek for "red." All explanations originate with the reddish, butterfly-shaped malar rash that the disease classically exhibits across the nose and cheeks.

1. In various accounts, some doctors thought the rash resembled the pattern of fur on a wolf's face.

2. In other accounts, doctors thought that the rash, which was often more severe in earlier centuries, created lesions that resembled wolf bites or scratches.

3. Another account claims that the term "lupus" did not come from Latin directly, but from the term for a French style of mask that women reportedly wore to conceal the rash on their faces. The mask is called a "loup," French for "wolf."

[edit] History

The history of SLE can be divided into three periods: classical, neoclassical, and modern. The classical period began when the disease was first recognized in the Middle Ages and saw the description of the dermatological manifestation of the disorder. The term lupus is attributed to 12th-century physician Rogerius, who used it to describe the classic malar rash. The neoclassical period was heralded by Móric Kaposi's recognition in 1872 of the systemic manifestations of the disease. The modern period began in 1948 with the discovery of the LE cell (the lupus erythematosus cell—a misnomer, as it occurs with other diseases as well) and is characterised by advances in our knowledge of the pathophysiology and clinical-laboratory features of the disease, as well as advances in treatment.[77]

Medical historians have theorized that people with porphyria (a disease that shares many symptoms with SLE) generated folklore stories of vampires and werewolves, due to the photosensitivity, scarring, hair growth, and porphyrin brownish-red stained teeth in severe recessive forms of porphyria (or combinations of the disorder, known as dual, homozygous, or compound heterozygous porphyrias).[77]

Useful medication for the disease was first found in 1894, when quinine was first reported as an effective therapy. Four years later, the use of salicylates in conjunction with quinine was noted to be of still greater benefit. This was the best available treatment until the middle of the twentieth century, when Hench discovered the efficacy of corticosteroids in the treatment of SLE.[77]

[edit] Notable cases

Michael Jackson suffered from both SLE and vitiligo.[78] Diagnosed in 1986, and confirmed by his dermatologist, Dr. Arnold Klein, who presented legal documents during court depositions.

Lady Gaga has been tested borderline positive for SLE, however she claims not to be affected by the symptoms yet. The revelations caused considerable dismay amongst her fans, leading to Gaga herself addressing the matter in an interview with Larry King,[79] saying she hopes to avoid symptoms by maintaining a healthy lifestyle.[80]

Louisa May Alcott , American author best known for her novel Little Women, has been suggested to have had SLE.[81]

Inday Ba (also known as N'Deaye Ba), a Swedish-born actress who died from SLE complications at age 32.[82]

Donald Byrne , American chess player who died from SLE complications in 1976.[83]

Caroline Dorough-Cochran, sister of Howie D. of the Backstreet Boys, died of SLE complications. He founded the Dorough Lupus Foundation in her memory.

J Dilla (also known as Jay Dee), a hip-hop producer and beat maker who died of SLE complications in 2006.[84]

Lauren Shuler Donner , American movie producer.[85]

Hugh Gaitskell , British politician who died of SLE complications in 1963 aged 56.[86]

Seal , British musician (discoid lupus) Sophie Howard , British glamour model[87]

Teddi King , American singer, died of SLE complications in 1977.[88]

Charles Kuralt , former anchor of CBS Sunday Morning, died of SLE complications in 1997.[89]

Ferdinand Marcos , former Philippine president, died of SLE complications in 1989.[90]

Mary Elizabeth McDonough , American actress; blames her SLE on leaky silicone breast implants.[91]

Flannery O'Connor , American fiction writer who died of SLE complications in 1964.[92]

Elaine Paige , British actress and singer[93]

Tim Raines , former major league baseball player[94]

Mercedes Scelba-Shorte , America's Next Top Model Season Two runner-up and model.[95]

Ray Walston , character actor who died of SLE complications in 2001 after a six-year battle with the disease.[96]

Michael Wayne , Hollywood director, and producer, part owner of Batjac Productions, son of legendary actor John Wayne, died of heart failure resulting from SLE complications in 2003.[97]

Kéllé Bryan , member of 90s British pop group Eternal, became ill with lupus in 1999.[98]

Toni Braxton , American R&B singer, songwriter and actress.[99]

[edit] Research

Since lupus is considered to be currently incurable, current research is being geared towards finding a possible cause, a cure, and more effective treatment plans to extend and increase the quality of life for lupus patients.

Several papers discuss the importance of the presence of antibodies in the brain that are only produced in patients with lupus. One such paper highlights the inhibition of astrocyte proliferation in brain tissue from lupus patient serum.[100] Astrocytes are glial cells in the brain that participate in the support of cells that form the blood brain barrier. They are extremely useful in that they provide a nutritional balance between ions in the brain, keeping it at a normal level.[101] In this study, researchers used immunofluorescence to track the antibodies near the corpus callosum to determine whether anticardiolipin antibodies have an inhibitory effect on brain cells and whether they elicit thrombus formation in brain vessels, which plays a part in neuropsychiatric lupus.

However, the majority of the recent papers focus on the effect of lupus on blood-brain barrier integrity. It was found that 20–70% of lupus patients with neurological symptoms have some form of a central nervous system involvement.[102] This can be determined using various imaging methods as well as lumbar puncture (spinal tap) to assess cerebrospinal fluid.

In a study conducted in London, researchers measured the albumin content in the brain using imaging and spinal fluid. The images were used to illustrate blood brain barrier damage while the spinal tap was used to measure the protein content in the brain. Albumin is a protein that can be carried into the brain through the blood brain barrier by other transport proteins. If the ratio of albumin outside the barrier to inside the barrier is high, this means that either the barrier is damaged, or the transport proteins are not functioning well. This blood brain barrier damage can impact lupus patients by increasing their discomfort and increasing the intensity of the disease.[103]

A study called BLISS-76 tested the drug, Belimumab (HGS1006, LymphoStat-B ), a fully human monoclonal anti-BLyS antibody. BLyS stimulates and extends the life of B lymphocytes, which produce antibodies against foreign and self cells.[104] The drug, branded Benlysta, was approved by the FDA in March 2011. Notwithstanding the approval, the FDA emphasized that the drug will not work in all cases, and that more research and advanced therapies are called for.[62]

At Stanford School of Medicine Institute for Immunity Transplantation and Infection, trials are underway for use of DHEA as a therapeutic agent for the treatment of mild to moderate SLE.[105]

[106]

Systemic Lupus ErythematosusSystemic lupus erythematosus (SLE) can cause various symptoms, the most common being joint pains, skin rashes and tiredness. Problems with kidneys and other organs can occur in severe cases. Treatment includes anti-inflammatory painkillers to ease joint pains. Steroids and/or other medication is sometimes also needed.

What is systemic lupus erythematosus?

Systemic lupus erythematosus is a chronic (persistent) disease that causes inflammation in various parts of the body. It is commonly just called SLE or 'lupus'. The severity of SLE ranges from mild to severe. There are two main forms of lupus. Discoid lupus only affects only the skin and is not discussed in this leaflet. The other form is systemic lupus erythematosus which involves the skin and joints and may involve internal organs such as the heart or kidney as well.

Who gets SLE?

SLE affects about 3 in 10,000 people in the UK. It is ten times more common in women than men. It most typically develops in women aged between 20 and 40. However, anyone at any age can be affected. It is more common in people from Afro-Caribbean, Asian, or Chinese origin. Although SLE can run in families, only 3 in 100 of children of patients with SLE will actually develop the disease.

What causes SLE?

SLE is an auto-immune disease. This means that the immune system (which normally protects the body from infections) mistakenly attacks itself. This can cause symptoms and may damage the affected parts of the body. Other autoimmune diseases include diabetes, rheumatoid arthritis and thyroid disorders.

It is not known why SLE occurs. Some factor may trigger the immune system to attack itself. Possible triggers of SLE include infections, drugs (for examples minocycline or hydralazine) or

sunlight. Hormone changes may play a role in SLE which could explain why it is much more common in women.

What are the symptoms of SLE?

The symptoms and severity of SLE vary tremendously between people. Many people have fatigue (tiredness), weight loss and a mild fever. In addition, one or more of the following may develop:

Joint and muscle pains

Most people with SLE develop some joint and muscle pains. Sometimes only a few joints are affected whereas other people have many joints affected. The small joints of the hands and feet tend to be the ones affected most. The pains may 'flit' from joint to joint. Joint stiffness is common and is usually worse first thing in the morning. Mild joint swelling may occur but severe arthritis with joint damage is unusual.

Skin, mouth and hair

A red rash which develops over the cheeks and nose is common (the 'butterfly rash'). Other areas of skin exposed to sunlight (hands, wrists, etc) may also develop a rash. About 6 in 10 people with SLE find that their skin is very sensitive to sunlight. Various other rashes may develop. The blood vessels just under the skin may also be affected and cause poor circulation to the fingers and toes (Raynaud's phenomenon). Mouth ulcers are more common in people with SLE. Some hair may fall out (alopecia). Any hair loss tends to be minor and cause hair 'thinning' rather than bald patches. However, quite serious hair loss sometimes develops, although the hair often grows back when SLE is less active.

Blood and lymph

A mild anaemia is common. Other blood problems such as reduced numbers of white blood cells or platelets (the cells that help the blood to clot) are less common. A tendency to form blood clots is an uncommon complication. Some lymph glands may swell.

Heart and lungs

The tissues that cover the heart and lung (the pleura and pericardium) may become inflamed. This can cause pleurisy (pains in the side of the chest) or pericarditis (central chest pains). The actual heart or lung tissue is less commonly affected.

Kidneys

Around 1 in 3 people with SLE may develop inflammation of the kidneys which can lead to the kidneys leaking protein and blood into the urine. This does not usually cause problems unless the disease is very severe. Kidney failure is an uncommon complication.

Brain and nervous system

Mental health problems in SLE are fairly common and include depression and anxiety. Although mild depression can be part of the disease itself, it can also be due to your reaction to having a serious illness. It is not uncommon for people to have difficulties in coping with having SLE. It is important to share any feelings you have have with your doctor as treatment can be really beneficial. Occasionally, inflammation of the brain can lead to epilepsy, headaches, migraines and other conditions.

How does SLE progress?

In some cases the symptoms develop quite slowly. At first they may be confused with other problems as there are many possible causes of joint pains and tiredness. Sometimes several symptoms occur together. Symptoms range from mild to severe. For example:

Mild SLE. Many people with SLE just have joint and/or skin symptoms with tiredness. These are unpleasant but are not serious or life threatening.

Moderate SLE. This includes some inflammation of other parts of the body apart from joints and skin. This may include pleurisy, pericarditis or mild kidney inflammation.

Severe SLE. In some cases, severe inflammation develops which can cause damage to organs such as the heart, lung, brain or kidneys. This can even be life-threatening.

Typically, there are times when the disease flares up (relapses) and symptoms become worse for a few weeks, sometimes longer. These relapses tend to alternate with times when symptoms settle down (remission). The reason why symptoms flare-up or settle down is not yet fully understood.

How is SLE diagnosed?

If your symptoms suggest SLE then your doctor will usually do some blood tests. Most people with SLE have an antibody called antinuclear antibody in their blood. (Antibodies are small proteins that are part of the immune system.) Another antibody called anti-doubled stranded DNA (dsDNA) is a often present in people with SLE. Various other antibodies are also associated with SLE. However, they can also occur in perfectly well people who do not have SLE. However, typical symptoms combined with high levels of certain antibodies usually indicate that you have developed SLE.

Once SLE is diagnosed, you will normally be advised to have regular checks and tests. For example, regular blood tests to check for anaemia and urine tests to check for kidney problems. A blood test to measure a blood chemical called 'complement' (another part of the immune system) can assess the activity of the disease. The level of this chemical reflects how 'active' the disease is.

Other tests including scans and X-rays may be advised to check on the function of the heart, kidneys and other organs if the disease is thought to be affecting these areas of the body.

What are the treatments for SLE?

Although there is no cure for SLE, this condition can usually be controlled and symptoms eased. Most people with SLE are seen regularly by a specialist who advises on treatment. The treatments may vary from time to time, depending on the severity of the disease or flare-up of symptoms and also which parts of the body are affected. You may even not need any treatment if you have very mild symptoms.

Treatment options include the following:

Non-steroidal anti-inflammatory drugs (NSAIDs)

These are often called anti-inflammatory painkillers and are commonly prescribed to ease joint or muscle pains. Examples of these are ibuprofen, naproxen and diclofenac. The main possible side-effects from these drugs are stomach and gut problems such as pain or bleeding in the stomach. If necessary, other medication can be prescribed to protect the stomach from these possible side-effects.

Hydroxychloroquine

Hydroxychloroquine is often effective at improving skin problems, tiredness and joint pains that are not well controlled by non-steroidal anti-inflammatory drugs. It is not clear how this drug works in SLE. It may take 6-12 weeks for it to become fully effective. The dose is often reduced to a lower 'maintenance' dose once symptoms have eased. Many people with SLE take this drug long-term to keep symptoms away. Side-effects are uncommon. The most serious is damage to the eye which is unusual. Your doctor is likely to check your vision before you start it and then every year. If you are taking this drug and notice any changes in your vision, you should inform your doctor promptly.

Steroids

Steroid tablets are usually advised if you develop more severe symptoms. Steroids reduce inflammation and the dose is usually given as low as possible in order to reduce any side effects from the steroids. Steroids may cause side-effects if taken for long periods. These include thinning of the bones (osteoporosis), thinning of the skin, weight gain, muscle wasting, high blood pressure and other problems.

Immunosuppressants

Drugs such as azathioprine, ciclosporin, cyclophosphamide, methotrexate and mycophenolate may be advised if you have severe SLE. These drugs are called immunosuppressive drugs because they work by suppressing the immune system. One side effect of these drugs is that you will be more prone to developing infections. If you take one of these you need to have regular blood and urine tests to look out for possible side-effects.

What is the prognosis (outlook) for people with SLE?

Most people with SLE lead active, normal lives. The outlook for people with SLE is much better than it was in the past. Modern treatments are more effective. For many people with SLE, symptoms are mild or moderate with little risk to life. The joint and skin symptoms may persist, but can usually be eased with treatment. For most people with SLE, the pattern of their disease becomes established within ten years; so if serious problems have not developed in this time then they are unlikely to do so.

For a few people, SLE is severe and can be life-threatening. Severe inflammation of the kidneys leading to kidney failure can rarely occur. Severe brain involvement is also rare but can be very serious. However, modern immunosuppressive treatments have improved the outlook even for people with severe disease. Some people find that symptoms settle in their middle age and they can come off all treatment.

Some other points about SLE

Avoid the sun. Strong sunlight can aggravate symptoms of SLE. Long sleeved clothing and wide brimmed hats are best in sunny weather. On hot sunny days you should wear a sunblock on exposed skin with a protection factor of 25 or above that protects against UVA and UVB.

Try to avoid infections. If you have SLE you are more prone to infection, particularly if you take steroids or immunosuppressant medication. Avoid contact with people who have infections.

Pregnancy. Although fertility is not usually affected in people SLE, some women with SLE have a higher chance of miscarriage. Women who have badly inflamed kidneys due to SLE may have high blood pressure in pregnancy. However, most women with mild or well controlled SLE at the start of pregnancy are likely to go through pregnancy with few problems.

Some contraceptive pills may not be advised depending on disease severity. A doctor or nurse will advise on the best method of contraception.

Other auto-immune diseases such as Sjögren's syndrome and thyroid problems are more common than average if you have SLE. These are sometimes tested for in people with SLE.

Further help

This leaflet is only an introduction to a disease that can be confusing. Further help, support and information can be obtained from:

Lupus UK

1 Eastern Road, Romford, Essex, RM1 3NHTel: 01708 731251 Web: www.lupusuk.com

Arthritis Research UK

Copeman House, St Mary's Court, St Mary's Gate, Chesterfield, Derbyshire, S41 7TDTel: 01246 558033 Web: www.arthritisresearchuk.org

References

D'Cruz DP ; Systemic lupus erythematosus. BMJ. 2006 Apr 15;332(7546):890-4. Kozora E, Ellison MC, West S ; Depression, fatigue, and pain in systemic lupus

erythematosus (SLE): relationship to the American College of Rheumatology SLE neuropsychological battery. Arthritis Rheum. 2006 Aug 15;55(4):628-35. [abstract]

Ocular Toxicity and Hydroxychloroquine: Guidelines for Screening , British Association of Dermatologists (2004)

CASE 3: SYSTEMIC LUPUS

Patient Presentation:A twenty nine year old female presented with a ten year history of severe fatigue, joint pains, skin problems, and immune dysregulation. She had been diagnosed with Systemic Lupus Erythematosis, and undergone years of corticosteroid usage including prednisone and methotrexate. She described her situation as "desperate" and was on the verge of suicide. Her husband, a medical physician, tried to dissuade her from consulting with us since there was "nothing of any usefulness for her condition outside of the drugs that she was already taking".

The patient appeared weak, pale, and had very poor muscle tone. She was despondent over her condition and had been convinced by her medical physicians over the years that her condition was permanent and would get worse with time. This had become a self-fullfilling prophecy. It took some time to convince the patient that her attitude needed to become more optimistic, that any recovery would be slow and difficult, but that due to her age, we were very hopeful that with hard work she could improve her health and vitality.

Laboratory Studies: The patient was anemic, had extremely low amino acid levels and abnormal bowel flora. The diet consisted of refined carbohydrates, coffee, and fast foods. She had numerous food and inhalant allergies. A glucose tolerance test revealed dysinsulinism. Hair analysis revealed elevated aluminum, mercury, and cadmium.

Program of Care: Major dietetic reform was initiated with elimination of allergens and refined carbohydrates. The patient was advised to avoid future dental silver/mercury amalgams and consider replacements with composite fillings. An amino acid blend was constructed based on her laboratory study. In addition to a whole foods diet, specific supplements were given to improve functioning of the body as a whole and the immune system specifically. Accupressure was employed. The patient began training in meditation and relaxation disciplines.

Outcome: The first several weeks were rough. The patient missed the stimulation of her coffee and junk food and suffered withdrawal symptoms as she avoided her food allergens. Within two months she began to notice improved energy and a decrease in muscle and joint pain. Her skin began to improve and her color became more healthy. Encouraged by the improvements, the patient increased her efforts and continued to reap health rewards. She ceased taking the steroids and

LectureINFINITE VARIETY: An Introduction To Biochemical IndividualityPart IPart II  CASE STUDIESPart III

methotrexate. Four years later the patient is pursuing a nursing career and enjoys good health. She has only occasional joint discomforts which she describes as "minor in nature."

Systemic Lupus Erythematosus

Marilee G. Bomar, RN, MSN

Overview

This case describes a clinical presentation of a young woman with systemic lupus erythematosus (SLE) as well as medical treatment and self-management skills for persons to live successfully with SLE. Included are specifics about chronic illness, self-management skills, learning self-management skills and potential benefits of using self-management skills.

This case is designed for health professionals and students in physical therapy, occupational therapy, physicians, nurses, psychologists, nutritionists, social workers, and other related fields of study.

Objectives

Define systemic lupus erythematosus (SLE). Describe how SLE is diagnosed. Describe the main categories of medications used in the treatment of SLE. List other medical treatments that may be needed for people with SLE. Define self-management. Discuss evidence that supports self-management. Identify resources for further information about SLE. Patient Presents

Sondra Lee Evan is a 30-year-old female who presented for an obstetrics follow-up 6 weeks post-miscarriage. She was 10 weeks pregnant at the time of her miscarriage.

She has been off work since the miscarriage and complains of arthralgia and extreme fatigue as well as feeling "blah." She is not on any medications. She does take a multivitamin. Her other complaints include decreased appetite, joint swelling and stiffness, and difficulty sleeping.

Patient History

Mrs. Evan has been married for six years and has one 5-year-old son. She attended two years of college and works full time as an accounting assistant for a large manufacturing firm. She has been active in her community and church. She also volunteers with her son's daycare and participates in his swimming and sporting activities.

Mrs. Evan is of African American/American Indian descent. Her parents are alive and in good health. Her mother has type 2 diabetes mellitus that is controlled with lifestyle

changes and oral medications. Her father has hypertension that is controlled by lifestyle changes (dietary changes, exercise, and weight loss) and medication. Both sets of grandparents have died from a motor vehicle accident, or from complications from diabetes mellitus or heart disease.

Mrs. Evan reports having the "normal" childhood illnesses of chickenpox and mumps. She denies any complications or prolonged illnesses or injuries. She denies any known family history of lupus, rheumatoid arthritis or other rheumatic conditions.

She reports that her current level of fatigue is challenging to her as she was always active and energetic prior to her miscarriage. She describes needing to rest after her morning routine of showering, dressing and fixing breakfast. She reports that she is only able to complete one or two other tasks such as vacuuming, laundry or dusting before she needs to rest again.

Mrs. Evan describes her sleeping pattern as follows: difficulty falling asleep, waking after 2 to 3 hours followed by difficulty returning to sleep for 1 or more hours after waking, then feeling like her sleep was not restful when she gets out of bed in the morning. She notes that her lack of sleep interferes with her memory and coping abilities. She states, "I always prided myself on remembering names, dates, and appointments. Now, if I don't write it down immediately, I forget it. I also find myself irritated at little things that normally would not bother me."

Mrs. Evan describes pain, swelling and stiffness in her joints as progressing over the past 3 months. She first noted stiffness in her fingers in the morning and after activity such as typing on the computer. About 2 months ago she noticed swelling in her fingers and wrists. Initially she thought this was due to her pregnancy and the hot July weather. In the past 2 to 3 weeks she has noticed swelling in her knee along with difficulty rising from a seated position. She describes the pain as intermittent, most notable in the morning and after activity involving her hands and knees. Her pain is relieved by rest and by Tylenol or ibuprofen.

Mrs. Evan explains that her appetite remained decreased after her morning sickness subsided 2½ months ago. She denies any type of rash after sun exposure, but reports that her arms and tops of her feet itch after she is in the sun without sunscreen.

Physical Exam

Height: 64" Weight: 108 lbs Temperature: 99.6°F HR: 82 bpm Resp: 20/min. BP: 112/70

Mrs. Evan exhibits the following signs: joint stiffness and swelling especially noted in her hands and wrists bilaterally. Her right knee is also noted to have some swelling along with decreased range of motion (ROM). It is also noted that her weight had decreased by 10 pounds since her miscarriage.

On exam, Dr. Smith did not find an abdominal mass and there was no tenderness on palpation of the abdomen. No heart murmur or irregularity is noted in Mrs. Evan's heart

rate on auscultation. Dr. Smith orders lab tests including complete blood count (CBC), chemistry profile, thyroid panel, erythrocyte sedimentation rate (ESR), and a urinalysis. X-rays of Mrs. Evan's hands and knees bilaterally and an abdominal ultrasound are ordered.

Dr. Smith explains to Mrs. Evan that she suspects a rheumatic condition, but must also rule out the possibility of a more acute problem such as an infection or thyroid disorder. Dr. Smith explains that joint stiffness and swelling along with the decreased ROM, the fatigue, and low-grade fever suggest the presence of a rheumatic condition.

In addition to the physical exam and diagnostic tests, Dr. Smith takes a detailed history and requests that Mrs. Evan keep a daily log of her temperature. At the conclusion of her visit, Mrs. Evan is given the schedule for her tests and is told she can expect a phone call with the results in approximately 48 hours.

Follow-up Phone Conference

Two days later, Dr. Smith contacts Mrs. Evan, summarizes the test results, and reports that an acute infection has been ruled out. Dr. Smith asks Mrs. Evan if she has had any change in her symptoms and if she has ever been seen by a rheumatologist.

Dr. Smith explains that given the symptoms, history, physical exam, and diagnostic test results, she feels Mrs. Evan has a rheumatic condition that needs further investigation by a rheumatologist. She provides Mrs. Evan with the names of three local rheumatologists and will provide referral information along with a complete set of records to the one Mrs. Evan chooses. In addition, Dr. Smith checks to see that Mrs. Evan has no drug allergies and prescribes Vioxx® [since 2004 removed from the US market].

Complete blood count (CBC)

ComponentMrs. Evan's

ResultsNormal Range *

Red blood cells (RBC) 4.0 million/mm3 Female 4.2 - 5.4 million/mm3 Male 4.7 - 6.1 million/mm3

White blood cells (WBC) 3,950/mm3 5,000 - 10,000/mm3

Hemoglobin (Hgb) 11 g/dl Female 12 - 16 g/dl Male 14 - 18 g/dl

Hematocrit (Hct) 36% Female 37 - 47% Male 42 - 52%

Platelet count 148,700/mm3 150,000 - 400,000/mm3

Mean corpuscular volume (MCV) 86 µm 80-95 µm

Mean corpuscular hemoglobin (MCH) 28 pg 27-31 pg

Mean corpuscular hemoglobin concentration (MCHC)

33 g/dl 32 - 36 g/dl

Neutrophils 62% 55 - 70%

Lymphocytes 28% 20 - 40%

Monocytes 7% 2 - 8%

Eosinophils 2% 1 - 4%

Basophils 1% 0.5 - 1.0%

* Normal ranges may vary among different references. These normal ranges given are for adults.

Chemistry profile

Component Mrs. Evan's Results Normal Range *

Alkaline phosphatase 25 U/ml 13 - 39 U/ml

Asparate amino transferase (AST) 28 U/ml 5 - 40 U/ml

Alanine amino transferase (ALT) 22 U/ml Female 5 - 35 U/ml

Blood urea nitrogen (BUN) 25.5 mg/dl 8.0 - 25.0 mg/dl

Creatinine 1.8 mg/dl 0.7 - 1.5 mg/dl

Sodium (Na) 138 mEq/L 137 - 147 mEq/L

Chloride (Cl) 104 mEq/L 100 - 106 mEq/L

Potassium (K) 4.2 mEq/L 3.5 - 5 mEq/L

Carbon dioxide (CO2) 25 mEq/L 24 - 29 mEq/L

Calcium (Ca) 8.7 mg/dl 8.5 - 10.3 mg/dl

Phosphate 3.9 mg/dl 3 - 4.5 mg/dl

Uric acid 3.1 mg/dl 2.6 - 7.2 mg/dl

pH 7.42 7.35 - 7.45

* Normal ranges may vary among different references. These normal ranges given are for adults.

Thyroid panel

Component Mrs. Evan's Results Normal Range *

Triiodothyronine (T3) 167 ng/dl 110 - 230 ng/dl

Thyroxine (T4) 6 µg/dl 4 - 11 µg/dl

Thyroid stimulating hormone (TSH) 8 µU/ml 2 - 10 µU/ml

* Normal ranges may vary among different references. These normal ranges given are for adults.

Erythrocyte sedimentation rate (ESR) measures in millimeters how fast red blood cells

cling together, fall and settle in the bottom of the glass tube over one hour. This test is nonspecific and is used to detect inflammatory, neoplastic, infectious, and necrotic

processes. For inflammation, the higher the rate, the greater the amount of inflammation. The normal range for ESR:

Male: up to 15 mm/hr. Female: up to 20 mm/hr. Mrs. Evan's results: 240 mm/hr.

Urinalysis (UA)

Component Mrs. Evan's Results Normal Range *

Color Amber Yellow - amber

Turbidity Clear Clear to slightly hazy

Specific gravity 1.018 1.010 - 1.025

pH 5.0 4.6 - 4.8

Glucose Negative Negative

Ketones Negative Negative

Blood Negative Negative

Protein Trace Negative

Bilirubin Negative Negative

Urobilinogen 0.5 0.1 - 1.0

Nitrate for bacteria Negative Negative

Leukocyte esterase Negative Negative

Casts Occasional hyaline casts Negative to occasional hyaline casts

RBCs Occasional Negative or rare

Crystals Negative Negative

WBCs Rare Negative or rare

Epithelial cells Few Few

* Normal ranges may vary among different references. These normal ranges given are for adults.

X-rays: Hands, wrists and knees showed soft tissue swelling and no joint space narrowing or bone damage.

Interpretation of Lab Values, History and Physical Exam At this point, given her symptoms of arthralgia, extreme fatigue, decreased appetite, joint

swelling and stiffness, and difficulty sleeping, the test results suggest a rheumatic disease. The physical findings of joint stiffness and swelling in her hands and wrists, and swelling and decreased ROM in her right knee also support this conclusion. In addition, the high ESR and slightly high kidney function indicated by the BUN, creatinine and trace of protein in the urine also suggest the possibility of a rheumatic disease. Given these results, it is likely the rheumatologist will order further tests.

Rheumatology Referral

Mrs. Evan sees Dr. Blue, a rheumatologist, the following month. Dr. Blue reviews the records from Dr. Smith as well as the temperature log Mrs. Evan has been keeping. The temperature log shows daily temperatures ranging from 99.0°F to 99.8°F. Mrs. Evan's symptoms remain unchanged since her visit with Dr. Smith. She has noted some relief from pain and the swelling in her hands and knee is somewhat less than it was before she started the medication. Her physical exam remains unchanged from her visit with Dr. Smith.

Dr. Blue agrees that the signs and symptoms point to a rheumatic disease. Dr. Blue states that further diagnostic tests are needed to determine the specific disease and that she suspects systemic lupus erythematosus. A blood test for antinuclear antibodies has been ordered as well as repeat CBC, chemistry profile and UA.

Systemic Lupus Erythematosus (SLE) SLE or lupus, is one of three types of lupus. The second type is discoid lupus which is

limited to the skin. The third type is drug-induced lupus. Drug-induced lupus often occurs when certain prescribed medications bring about the signs and symptoms of lupus.

SLE is a systemic, chronic inflammatory auto-immune disease that can affect the skin, joints, blood, kidneys, and cardiovascular system. SLE can range from mild disease only affecting a few organs to severe, even life-threatening problems. It is estimated that 1.5 million people have some form of lupus in the United States. Lupus affects women 10 to 15 times more frequently than men, and African American, American Indian, and Asian ethnic origins are affected more often than Caucasian. Each case of SLE is unique as the symptoms and progression will vary. As SLE progresses there will be periods when very few symptoms are noted (remissions) and other times when the disease is very active (flares).

The cause of SLE is unknown. Scientists currently believe that there is a genetic predisposition to the disease with environmental factors playing a triggering role in the symptoms being expressed. Some environmental factors that have been studied include antibiotics, infections, ultraviolet light, extreme stress, and hormones. There are ongoing studies about the relationship of hormones in women from puberty to menopause and the incidence of SLE.

Referral Results

Mrs. Evan's ANA is positive and the pattern interpreted is most suggestive of that seen with SLE.

The results of Mrs. Evan's CBC, chemistry profile and UA remain unchanged from the initial information received from Dr. Smith. Dr. Blue diagnoses SLE based on the signs and symptoms noted in the medical records and mentioned in the interpretation earlier along with the findings of the diagnostic tests. Dr. Blue uses the American College of Rheumatology's classification criteria.

Medical Treatment

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

SLE is a chronic inflammatory disease. The NSAIDs (see also FDA warnings about NSAIDS and CV and GI risks) relieve fever, pain muscle aches, malaise, inflammation, and serositis. Over 20 NSAIDS are available by prescription or over-the-counter. Vioxx® was prescribed by Dr. Smith. Vioxx®, one of the newer NSAIDs but later withdrawn by the manufacturer, is classified as a cyclooxygenase - 2 (COX-2) inhibitor. The COX-2s act with basically the same inflammation-fighting properties as traditional NSAIDs, but the COX-2s do not influence natural protective mechanisms of the stomach and are less likely to cause gastrointestinal distress and stomach ulcers.

Disease-Modifying Antirheumatic Drugs (DMARDs)

The DMARDs are used to alter the course of the destructive inflammatory process. We describe three categories of DMARDs for treating lupus: antimalarials, glucocorticoids, and immunosuppressives.

1. Antimalarials. Their value in rheumatic diseases was originally discovered following anecdotal reports from soldiers who took Atabrine during the war in the 1940s to prevent malaria. In addition to preventing malaria, Atabrine improved their rashes and joint symptoms. Atabrine was discontinued and has since been replaced with hydroxychloroquine (Plaquenil®).

Antimalarials work by blocking ultraviolet light from damaging skin, lowering cholesterol levels, blocking cytokines that promote inflammation, and altering the acid-base balance of cells, thus limiting their ability to process antigens and lessening antibodies. Another important feature is that antimalarials do not lower blood counts or make patients more susceptible to infection. The onset of action is two to three months with benefits noted by patients in four to six months. Antimalarials are not used in the management of organ-threatening lupus.

Report any medication side effects. Those most commonly noted include diarrhea, loss of appetite, nausea, rash and black spots in visual field. Eye exams are recommended before starting therapy and every year after.

2. Glucocorticoids. These hormones, which come in many forms, regulate many of the body's physiologic functions. When used for pharmacologic activities, they mainly stabilize the cells, making them less likely to engage in the inflammatory process. They also block numerous chemical pathways and decrease the number of circulating lymphocytes.

The most commonly-prescribed glucocorticoid used in the treatment of lupus is prednisone. Prednisone is generally used for treating active, organ - threatening lupus. Patients with involvement of the heart, lungs, kidneys, liver, or blood are begun on higher doses than patients with severe flare-ups of non-organ threatening lupus or patients with chronic, mild, non-organ-threatening lupus. The last group of patients are on the lowest daily doses.

Patients should take this medication as directed. When ordered once daily, it should be

taken at breakfast with food. It may be ordered up to four times per day during acute inflammation as it is more quickly metabolized. Patients should not stop taking this medication abruptly as the adrenal gland has not been producing glucocorticoids and cannot respond to an abrupt removal of prednisone. The dosage of this medication is designed to be reduced gradually (tapered).

Prednisone requires careful monitoring and can cause serious complications. In the beginning, side effects may include heartburn, palpitations, agitation, and difficulty sleeping. Additional side effects may occur over time. These include thin skin, bruises, hair loss (upper head and temples), increased facial hair, impaired wound healing, muscle weakness, loss of calcium in bones, cataracts, glaucoma, hypertension, increased appetite, elevated blood sugar, menstrual irregularity, weight gain (centrally - noted at the belly and buttocks), confusion, difficulty concentrating, fluid retention with bloating and puffiness (noted especially in face and ankles), decreased potassium levels, heartburn which can lead to ulcers, and a much greater risk of infection. Not all patients experience these side effects, but it is important to recognize the possibility and monitor for them carefully.

One group of these side effects are known as Cushing's syndrome. Cushing's includes weight gain, moon-face appearance, thin skin, muscle weakness and brittle bones. If steroids are used, every effort is generally explored to reduce the dosage to its lowest possible effective level.

3. Immunosuppressives. Immunosuppressives are classified into chemotherapy agents and anti-rejection medications for transplant patients. They are also referred to as cytotoxic or "steroid sparing" medicines.

These medications fall into different categories according to the actions they perform. In lupus, the most common chemotherapy agents include cyclophosphamide) and methotrexate (Rheumatrex®). Each one has specific uses in the treatment of lupus and side effects can be problematic. Azathioprine is an anti-rejection medication.

Patient's Medication

Mrs. Evan was placed on prednisone as she has beginning signs of kidney involvement based on her lab results and UA. She was given information about lupus and about her medications, and about community resources and how to contact the clinic. This information was reviewed with her. She was encouraged to call with questions and to report any possible side effects of the medication. She was given an appointment to follow-up in one month and lab work was ordered prior to that appointment.

Self-Management Skills in Chronic Illness

Most people are capable of pulling their resources and energy together to deal with acute health problems such as a cold or pneumonia. Acute health problems begin with a sudden onset, are easily diagnosed, are relatively short lived, and the treatment results in cure of the acute illness.

On the other hand, chronic illness has a gradual onset, can be difficult to diagnose, lasts for and indefinite amount of time, has a rocky course, and there is rarely a cure.

Chronic illness affects all aspects of a person's life and may require ongoing treatment and lifestyle changes for the person to continue functioning at a desirable level. One example to consider is pain. Pain acts as a warning signal to our body indicating a problem. In acute pain, once the cause is treated then the pain goes away. Chronic pain such as that experienced by someone with arthritis or lupus is different. Often a pain cycle may develop. Once the cycle begins it is difficult to stop. Medical treatment and self-management are important ways to intervene and stop the pain cycle.

The pain cycle visually represents what may occur in a person with a chronic illness such as lupus. The end points (pain, fatigue, withdrawal, depression) may differ from one individual to the next. It is the continuous cycle that poses a problem as it can keep a person from pursuing his/her interests and vocation. It is helpful and possible to prevent this cycle from occurring. It is necessary to find interventions that stop the cycle and help the person live successfully with his/her chronic illness. Medical treatment, alternative health measures, and self-management are examples of interventions aimed at stopping the continuous cycle.

Self-management skills refer to all the daily decisions a person makes to attain the greatest possible physical functioning and mental outlook to positively manage his/her chronic illness:

communication, coping strategies and stress reduction,

physical activity and exercise, managing medications, nutrition, and decisions about medical and alternative health care options.

We will discuss each of these.

Communication

Communication includes all the different people and situations an individual may encounter on a daily basis. For a person with a chronic illness such as lupus a typical day may include family, friends, employer and health care team. Some simple tips may help Mrs. Evan in her daily encounters.

Effective communication involves more than one person. Be clear and concise. Use "I" messages. "I feel..." Acknowledge the other person and his/her message. If clarification is needed, ask the person to rephrase what was said or rephrase what the

person said. Non-verbal communication sends an important message. Humor is sometimes useful when a conversation goes in the wrong direction. Knowing

when to use humor is important.

A patient should learn to communicate effectively with members of the health care team. The patient needs to get his/her message across to the health care professional in the limited time available. The patient can practice this by using a Communication Action Plan.

This plan should be something the patient wants to do and it should answer important points he/she want to make during the appointment with the health care professional.

Example Communication Action Plan

Where (location): At my next appointment with my physician.

When (time of day): Next Tuesday at 1:30 p.m.

How often (days of week):

One day each week I will summarize how I feel and concerns I need to communicate at my next appointment.

What (message do I want to communicate):

To narrow my information to give to the doctor to my three most important issues to be addressed during my appointment.

Fall back plan (what to do if ...):

If I am unable to complete my list on Friday each week, I will jot a reminder on my appointment calendar for the following Monday morning.

How sure (0 - 10 see scale below*):

8

* This rating scale helps you determine how certain you are that you can accomplish your plan. 0 = I cannot do this plan and 10 = I am sure I can do this plan.

"On a scale of 0 to 10, with 0 being totally uncertain and 10 being totally certain, how sure am I that I can accomplish this plan?" If your score is below 7, ask yourself how you can change the plan to make it achievable. If your score is 7 or above, this represents a realistic plan.

A form of this plan can be used for any area of self-management in which a person has a desire to improve his/her skills.

Coping Strategies and Stress Reduction

One coping theme is finding more information about the person's own chronic illness(es). The patient should know what resources are available. Educate the patient and his/her family about the chronic illness. Family and friends provide ongoing support important to success in managing a chronic illness. This support may be emotional, physical, spiritual, financial, and so on.

Another coping theme is the use of stress management [scroll down] techniques such as meditation. There are many ways to manage stress, but a person must be willing to learn the selected technique well enough to use regularly. Other stress reduction techniques include muscle relaxation, guided imagery, distraction, writing a journal, and biofeedback.

Biofeedback involves equipment that measures heart rate and muscle tension. Some insurance plans will pay for biofeedback equipment when it is ordered by a physician. Other stress management techniques involve talking with a trusted friend, joining a support group or self-help course, or talking with a professional such as a social worker, psychologist, or counselor.

Physical Activity

Physical activity and exercise are important in the self-management of chronic illness. Generally, there are two main reasons to exercise. The first is physical activity to improve general health, and the second is exercise for physical fitness. We will address only physical activity to improve general health.

In 2010 the Surgeon General issued a vision for a healthy and fit nation, including suggestions for physical activity. In summary, the guidelines for improving health include participating in physical activity four or more days a week, the activity should be of moderate intensity measured by achieving maximal heart rate (220 minus age in years), and the amount of exercise can be accumulated to reach total 30 minutes during the day. Physical activity helps keep you healthy, and suggestions for exercise are available for people of any age to get started.

Anyone with a chronic illness should check with his/her doctor before beginning a new exercise program. Lupus is a good example where the accumulation of 30 minutes is important since fatigue can be an issue. It is also important not to put too much strain on the joints. One type of physical activity that has been found especially helpful is aquatics. A warm water pool is the key

to aquatics for anyone with arthritis. The Arthritis Foundation recommends the water temperature be 83°--88°F.

Managing Medications

Managing medications is an important self-management skill. Some tips for patients to manage them sensibly include:

Know about the medication(s) you are taking: name of the drug, reason for taking it, what it is supposed to do, dosage, time(s) of day to take it, how to take it (with food or on an empty stomach), any interactions with food or other medications, possible side effects, and any special tests needed to monitor the use of the medication.

Ways to remember to take your medication: set it next to a reminder like your toothbrush or coffee cup, use a medication chart, use a medication organizer, set an alarm on your watch, or have a family member ask if you have taken your medication.

Do not let your medications run out. Get your refill a few days before you take your last dose.

If you take any over-the-counter medication(s), check the safety of taking them with prescribed medication.

Check the expiration date on all medications and discard any unused portion. When a new medication is prescribed, ask the pharmacist to check for any possible drug

interactions.

Medications can be harmful when used incorrectly. Patients should ask their pharmacist, physician or nurse if they are unclear about any aspect of taking their medication(s) or if they have questions about effectiveness or side effects.

Nutrition

It is especially important for a person with a chronic illness like lupus to eat a balanced diet. Consider the patient's food allergies and the current literature.

Patients should be well-informed shoppers by reading labels and comparing the nutritional value of the food they eat.

Alternative Health Care

Alternative health care, also called alternative therapy, complementary therapy, or integrative health care, has become big business over the past decade. These different terms comprise a vast array of therapies including exercise, biofeedback, diet, acupuncture, massage, and herbs. Fully research any alternative health care option and consider the potential impact it may have on a prescribed treatment. Many health care providers have become open to discussing this issue with patients as the number of people using these therapies has increased as well as some of the documented dangers ( Horstman, 1999; Sierpina, 2001).

The information on self-management skills discussed in this case is only a small portion of what is available from the literature, from a self-help course, or from the internet.

Benefits and Evidence for Self-Management in Chronic Illness

What are the benefits and evidence to support the use of self-management skills?

The person feels more in control of his/her situation ( Braden, 1991; Ferrell, 1998; Lorig et al., 2000).

The person feels valued as an active participant in his/her health care. Particular types of self-management skills have been examined for the benefits received:

Physical activity has been found to promote general health, decrease pain and stiffness, and decreased feelings of depression as well as improved mood and sleep. Exercise improves daily energy level ( Gecht, et al., 1996; Minor & Lane, 1996; Wallace, 2000).

Aquatics in a warm water pool have been found to promote flexibility and movement ( Ferrell, 1998; Minor & Lane, 1996).

Participating in a self-help or self-management course demonstrated decreased reports of pain, increased functional abilities and a reduced number of hospitalizations and physician visits ( Braden, 1991; Lorig, et al., 2000).

Patient's Perspective

Deb O'Neal was diagnosed with lupus six years ago. She noted her first symptoms 30 years ago. Deb remains active and educated herself about every aspect of lupus. She states, "Once I received the diagnosis I went to the library to find out everything I could about lupus." One resource she mentioned is The Lupus Book.

Deb states that over the years she has carefully weighed the benefits and risks (short- and long-term) of any type of treatment suggested by her health care team or that she feels may benefit her. She does gentle exercise, keeps up with any new research, attends a support group, goes for regular appointments with her health care team, and regularly asks questions. She uses alternative health options including massage and acupuncture.

Review

Systemic lupus erythematous (SLE or lupus) is a complex form of arthritis that is an auto-immune disease. The signs and symptoms can be vague and are suggestive of other forms of

arthritis as well as other disease processes. In this case, we have presented information to help distinguish lupus as well as provide treatment information. Since lupus is a chronic illness, we also presented self-management skills because of their importance in the overall treatment plan.

Topic Overview

What is systemic lupus erythematosus, or lupus?

Lupus is an autoimmune disease, which means that the body's natural defense system (immune system) attacks its own tissues instead of attacking foreign substances like bacteria and viruses. This causes inflammation. Inflammation causes swelling, pain, and tissue damage throughout the body. If you develop severe lupus, you may have problems with your kidneys, heart, lungs, nervous system, or blood cells. Lupus is the common name for systemic lupus erythematosus, also called SLE.

Although some people with lupus have only mild symptoms, the disease is lifelong and can become severe. But most people can control their symptoms and prevent severe damage to their organs. They do this by seeing their doctors often for checkups, getting enough rest and exercise, and taking medicines.

This topic focuses on systemic lupus erythematosus (SLE), the most common and most serious type of lupus. But there are four other types of lupus: discoid or cutaneous lupus, drug-induced systemic lupus, neonatal lupus, and subacute cutaneous lupus.

What causes lupus?

The exact cause of lupus is not known. Experts believe that some people are born with certain genes that affect how the immune system works and that they are more likely to get lupus. Then a number of other factors can trigger lupus attacks. These include viral infections, including the virus that causes mononucleosis, and sunlight.

Although these things can trigger lupus, they may affect one person but not another person.

What are the symptoms?

Lupus symptoms vary widely, and they come and go. The times when symptoms get worse are called relapses, or flares. The times when symptoms are under control are called remissions.

Common symptoms include feeling very tired and having joint pain or swelling (arthritis), a fever, and a skin rash . The rash often happens after you have been in the sun. Mouth sores and hair loss may occur. Over time, some people with lupus have problems with the heart, lungs, kidneys, blood cells, or nervous system.

How is lupus diagnosed?

There is no single test for lupus. Because lupus affects different people in different ways, it can be hard to diagnose.

Your doctor will check for lupus by examining you, asking you questions about your medical history and common symptoms, and doing some urine and blood tests. It is easier for your doctor to diagnose lupus if you have the most common symptoms and your blood has certain proteins. These proteins are called antinuclear antibodies, or ANAs. But other problems can cause your body to make ANAs, so doctors will use blood tests and other tests to find out if you have lupus.

How is it treated?

Lupus is treated by:

Applying corticosteroid cream for rashes. Taking nonsteroidal anti-inflammatory drugs (NSAIDs) for mild joint or muscle pain and

fever. Taking antimalarial medicines to treat fatigue, joint pain, and skin rashes. Taking corticosteroids if other medicines are not controlling your symptoms.

Because corticosteroids are powerful medicines and can cause serious side effects, the doctor will recommend the lowest dose that will give the most benefit.

The doctor may also recommend other medicines that slow down the immune system.

How can you manage lupus?

One of the goals of controlling mild to moderate lupus symptoms is to prevent flares, the times when your symptoms are worse. Some of the other things you can do include:

Rest to reduce stress. Avoid the sun. Wear sunscreen and protective clothing when you are outside. Exercise regularly to prevent fatigue and joint stiffness. Stop smoking. Learn the warning signs of a symptoms flare, such as fatigue, pain, and rash, and take

steps to control them.

With good self-care, most people with lupus can keep doing their regular daily activities.

It is important to learn about lupus so that you can understand how it might affect your life and how you can best cope with it. Also, help your family and friends understand your limitations and needs when your symptoms flare. Develop a support system of family, friends, and health professionals.

Lupus

Online version updated August 2011

Handout on Health: Systemic Lupus Erythematosus

This booklet is for people who have systemic lupus erythematosus, commonly called SLE or lupus, as well as for their families and friends and others who want to better understand the disease. The booklet describes the disease and its symptoms and contains information about diagnosis and treatment, as well as current research efforts supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and other components of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH). It also discusses issues such as health care, pregnancy, and quality of life for people with lupus. If you have further questions after reading this booklet, you may wish to discuss them with your doctor.

Defining Lupus Understanding What Causes Lupus Symptoms of Lupus Diagnosing Lupus Treating Lupus Lupus and Quality of Life Pregnancy and Contraception for Women With Lupus Current Research Hope for the Future For More Information

Information Boxes

Common Symptoms of Lupus Diagnostic Tools for Lupus Warning Signs of a Flare Preventing a Flare Tips for Working With Your Doctor

Defining Lupus

Lupus is one of many disorders of the immune system known as autoimmune diseases. In autoimmune diseases, the immune system turns against parts of the body it is designed to protect. This leads to inflammation and damage to various body tissues. Lupus can affect many parts of the body, including the joints, skin, kidneys, heart, lungs, blood vessels, and brain. Although people with the disease may have many different symptoms, some of the most common ones include extreme fatigue, painful or swollen joints (arthritis), unexplained fever, skin rashes, and kidney problems.

At present, there is no cure for lupus. However, lupus can be effectively treated with drugs, and most people with the disease can lead active, healthy lives. Lupus is characterized by periods of illness, called flares, and periods of wellness, or remission. Understanding how to prevent flares and how to treat them when they do occur helps people with lupus maintain better health. Intense research is underway, and scientists funded by NIH are continuing to make great strides in understanding the disease, which may ultimately lead to a cure.

Two of the major questions researchers are studying are who gets lupus and why. We know that many more women than men have lupus. Lupus is two to three times more common in African American women than in Caucasian women and is also more common in women of Hispanic, Asian, and Native American descent. African American and Hispanic women are also more likely to have active disease and serious organ system involvement. In addition, lupus can run in families, but the risk that a child or a brother or sister of a patient will also have lupus is still quite low. It is difficult to estimate how many people in the United States have the disease, because its symptoms vary widely and its onset is often hard to pinpoint.

There are several kinds of lupus:

Systemic lupus erythematosus (SLE) is the form of the disease that most people are referring to when they say “lupus.” The word “systemic” means the disease can affect many parts of the body. The symptoms of SLE may be mild or serious. Although SLE usually first affects people between the ages of 15 and 45 years, it can occur in childhood or later in life as well. This booklet focuses on SLE.

Discoid lupus erythematosus is a chronic skin disorder in which a red, raised rash appears on the face, scalp, or elsewhere. The raised areas may become thick and scaly and may cause scarring. The rash may last for days or years and may recur. A small percentage of people with discoid lupus have or develop SLE later.

Subacute cutaneous lupus erythematosus refers to skin lesions that appear on parts of the body exposed to sun. The lesions do not cause scarring.

Drug-induced lupus is a form of lupus caused by medications. Many different drugs can cause drug-induced lupus. They include some antiseizure medications, high blood pressure medications, antibiotics and antifungals, thyroid medications, and oral contraceptive pills. Symptoms are similar to those of SLE (arthritis, rash, fever, and chest pain), and they typically go away completely when the drug is stopped. The kidneys and brain are rarely involved.

Neonatal lupus is a rare disease that can occur in newborn babies of women with SLE, Sjögren’s syndrome, or no disease at all. Scientists suspect that neonatal lupus is caused in part by autoantibodies in the mother’s blood called anti-Ro (SSA) and anti-La (SSB). Autoantibodies (“auto” means self) are blood proteins that act against the body’s own parts. At birth, the babies have a skin rash, liver problems, and low blood counts. These symptoms gradually go away over several months. In rare instances, babies with neonatal lupus may have congenital heart block, a serious heart problem in which the formation of fibrous tissue in the baby’s heart interferes with the electrical impulses that affect heart rhythm. Neonatal lupus is rare, and most infants of mothers with SLE are entirely healthy. All women who are pregnant and known to have anti-Ro (SSA) or anti-La (SSB) antibodies should be monitored by echocardiograms (a test that monitors the heart and surrounding blood vessels) during the 16th and 30th weeks of pregnancy. It is important for women with SLE or other related autoimmune disorders to be under a doctor’s care during pregnancy. Doctors can now identify mothers at highest risk for complications, allowing for prompt treatment of the infant at or before birth. SLE can also flare during pregnancy, and prompt treatment can keep the mother healthier longer.

Understanding What Causes Lupus

Lupus is a complex disease, and its cause is unknown. Scientists are making progress in understanding lupus, as described here and in the “Current Research” section of this booklet.

In studies of identical twins—who are born with the exact same genes—when one twin has lupus, the other twin has a 24-percent chance of developing it. This and other research suggests that genetics plays an important role, but it also shows that genes alone do not determine who gets lupus, and that other factors play a role. Some of the factors scientists are studying include sunlight, stress, hormones, cigarette smoke, certain drugs, and infectious agents such as viruses. Recent research has confirmed that one virus, Epstein-Barr virus (EBV), which causes mononucleosis, is a cause of lupus in genetically susceptible people.

Scientists believe there is no single gene that predisposes people to lupus. Rather, studies suggest that a number of different genes may be involved in determining a person’s likelihood of developing the disease, which tissues and organs are affected, and the severity of disease. Researchers have begun to make headway in identifying some of those genes, which could eventually lead to better ways to treat and perhaps even prevent lupus.

In lupus, the body’s immune system does not work as it should. A healthy immune system produces proteins called antibodies and specific cells called lymphocytes that help fight and destroy viruses, bacteria, and other foreign substances that invade the body. In lupus, the immune system produces antibodies against the body’s healthy cells and tissues. These antibodies, called autoantibodies, contribute to the inflammation of various parts of the body and can cause damage to organs and tissues. The most common type of autoantibody that develops in people with lupus is called an antinuclear antibody (ANA) because it reacts with parts of the cell’s nucleus (command center). Doctors and scientists do not yet understand all of the factors that cause inflammation and tissue damage in lupus, and researchers are actively exploring them.

Common Symptoms of Lupus

Painful or swollen joints and muscle pain Unexplained fever Red rashes, most commonly on the face Chest pain upon deep breathing Unusual loss of hair Pale or purple fingers or toes from cold or stress (Raynaud's phenomenon) Sensitivity to the sun Swelling (edema) in legs or around eyes Mouth ulcers Swollen glands Extreme fatigue

Symptoms of Lupus

Each person with lupus has slightly different symptoms that can range from mild to severe and may come and go over time. However, some of the most common symptoms of lupus include painful or swollen joints (arthritis), unexplained fever, and extreme fatigue. A characteristic red skin rash—the so-called butterfly or malar rash—may appear across the nose and cheeks. Rashes may also occur on the face and ears, upper arms, shoulders, chest, and hands and other areas exposed to the sun. Because many people with lupus are sensitive to sunlight (called photosensitivity), skin rashes often first develop or worsen after sun exposure.

Other symptoms of lupus include chest pain, hair loss, anemia (a decrease in red blood cells), mouth ulcers, and pale or purple fingers and toes from cold and stress. Some people also experience headaches, dizziness, depression, confusion, or seizures. New symptoms may continue to appear years after the initial diagnosis, and different symptoms can occur at different times. In some people with lupus, only one system of the body, such as the skin or joints, is affected. Other people experience symptoms in many parts of their body. Just how seriously a body system is affected varies from person to person. The following systems in the body also can be affected by lupus.

Kidneys: Inflammation of the kidneys (nephritis) can impair their ability to get rid of waste products and other toxins from the body effectively. There is usually no pain associated with kidney involvement, although some patients may notice dark urine and swelling around their eyes, legs, ankles, or fingers. Most often, the only indication of kidney disease is an abnormal urine or blood test. Because the kidneys are so important to overall health, lupus affecting the kidneys generally requires intensive drug treatment to prevent permanent damage.

Lungs: Some people with lupus develop pleuritis, an inflammation of the lining of the chest cavity that causes chest pain, particularly with breathing. Patients with lupus also may get pneumonia.

Central nervous system: In some patients, lupus affects the brain or central nervous system. This can cause headaches, dizziness, depression, memory disturbances, vision problems, seizures, stroke, or changes in behavior.

Blood vessels: Blood vessels may become inflamed (vasculitis), affecting the way blood circulates through the body. The inflammation may be mild and may not require treatment or may be severe and require immediate attention. People with lupus are also at increased risk for atherosclerosis (hardening of the arteries).

Blood: People with lupus may develop anemia, leukopenia (a decreased number of white blood cells), or thrombocytopenia (a decrease in the number of platelets in the blood, which assist in clotting). People with lupus who have a type of autoantibody called antiphospholipid antibodies have an increased risk of blood clots.

Heart: In some people with lupus, inflammation can occur in the heart itself (myocarditis and endocarditis) or the membrane that surrounds it (pericarditis), causing chest pains or other symptoms. Endocarditis can damage the heart valves, causing the valve surface to thicken and develop growths, which can cause heart murmurs. However, this usually doesn’t affect the valves’ function.

Diagnosing Lupus

Diagnosing lupus can be difficult. It may take months or even years for doctors to piece together the symptoms to diagnose this complex disease accurately. Making a correct diagnosis of lupus requires knowledge and awareness on the part of the doctor and good communication on the part of the patient. Giving the doctor a complete, accurate medical history (for example, what health problems you have had and for how long) is critical to the process of diagnosis. This information, along with a physical examination and the results of laboratory tests, helps the doctor consider other diseases that may mimic lupus, or determine if you truly have the disease. Reaching a diagnosis may take time as new symptoms appear.

No single test can determine whether a person has lupus, but several laboratory tests may help the doctor to confirm a diagnosis of lupus or rule out other causes for a person’s symptoms. The most useful tests identify certain autoantibodies often present in the blood of people with lupus. For example, the antinuclear antibody (ANA) test is commonly used to look for autoantibodies that react against components of the nucleus, or “command center,” of the body’s cells. Most people with lupus test positive for ANA; however, there are a number of other causes of a positive ANA besides lupus, including infections and other autoimmune diseases, and occasionally it is found in healthy people. The ANA test simply provides another clue for the doctor to consider in making a diagnosis. In addition, there are blood tests for individual types of autoantibodies that are more specific to people with lupus, although not all people with lupus test positive for these and not all people with these antibodies have lupus. These antibodies include anti-DNA, anti-Sm, anti-RNP, anti-Ro (SSA), and anti-La (SSB). The doctor may use these antibody tests to help make a diagnosis of lupus.

Some tests are used less frequently but may be helpful if the cause of a person’s symptoms remains unclear. The doctor may order a biopsy of the skin or kidneys if those body systems are affected. Some doctors may order a test for anticardiolipin (or antiphospholipid) antibody. The presence of this antibody may indicate increased risk for blood clotting and increased risk for miscarriage in pregnant women with lupus. Again, all these tests merely serve as tools to give the doctor clues and information in making a diagnosis. The doctor will look at the entire picture—medical history, symptoms, and test results—to determine if a person has lupus.

Diagnostic Tools for Lupus

Medical history Complete physical examination Laboratory tests:

o Complete blood count (CBC)o Erythrocyte sedimentation rate (ESR)o Urinalysiso Blood chemistrieso Complement levelso Antinuclear antibody test (ANA)o Other autoantibody tests (anti-DNA, anti-Sm, anti-RNP, anti-Ro [SSA], anti-La [SSB])o Anticardiolipin antibody test

Skin biopsy Kidney biopsy

Other laboratory tests are used to monitor the progress of the disease once it has been diagnosed. A complete blood count, urinalysis, blood chemistries, and the erythrocyte sedimentation rate test (a test to measure inflammation) can provide valuable information. Another common test measures the blood level of a group of substances called complement, which help antibodies fight invaders. A low level of complement could mean the substance is being used up because of an immune response in the body, such as that which occurs during a flare of lupus.

X rays and other imaging tests can help doctors see the organs affected by SLE.

Treating Lupus

Diagnosing and treating lupus often require a team effort between the patient and several types of health care professionals. A person with lupus can go to his or her family doctor or internist, or can visit a rheumatologist. A rheumatologist is a doctor who specializes in rheumatic diseases (arthritis and other inflammatory disorders, often involving the immune system). Clinical immunologists (doctors specializing in immune system disorders) may also treat people with lupus. As treatment progresses, other professionals often help. These may include nurses, psychologists, social workers, nephrologists (doctors who treat kidney disease), cardiologists (doctors specializing in the heart and blood vessels), hematologists (doctors specializing in blood disorders), enodocrinologists (doctors specializing in problems related to the glands and hormones), dermatologists (doctors who treat skin disease), and neurologists (doctors specializing in disorders of the nervous system).

The range and effectiveness of treatments for lupus have increased dramatically in recent decades, giving doctors more choices in how to manage the disease. It is important for the patient to work closely with the doctor and take an active role in managing the disease. Once lupus has been diagnosed, the doctor will develop a treatment plan based on the patient’s age, sex, health, symptoms, and lifestyle. Treatment plans are tailored to the individual’s needs and may change over time. In developing a treatment plan, the doctor has several goals: to prevent flares, to treat them when they do occur, and to minimize organ damage and complications. The doctor and patient should reevaluate the plan regularly to ensure it is as effective as possible.

NSAIDs: For people with joint or chest pain or fever, drugs that decrease inflammation, called nonsteroidal anti-inflammatory drugs (NSAIDs), are often used. Although some NSAIDs, such as ibuprofen and naproxen, are available over the counter, a doctor’s prescription is necessary for others. NSAIDs may be used alone or in combination with other types of drugs to control pain, swelling, and fever. Even though some NSAIDs may be purchased without a prescription, it is important that they be taken under a doctor’s direction. Common side effects of NSAIDs can include stomach upset, heartburn, diarrhea, and fluid retention. Some people with lupus also develop liver, kidney, or even neurological complications, making it especially important to stay in close contact with the doctor while taking these medications.

Antimalarials: Antimalarials are another type of drug commonly used to treat lupus. These drugs were originally used to treat malaria, but doctors have found that they also are useful for lupus. A common antimalarial used to treat lupus is hydroxychloroquine (Plaquenil1). It may be used alone or in combination with other drugs and generally is used to treat fatigue, joint pain, skin rashes, and inflammation of the lungs. Clinical studies have found that continuous treatment with antimalarials may prevent flares from recurring. Side effects of antimalarials can include stomach upset and, extremely rarely, damage to the retina of the eye.

1Brand names included in this publication are provided as examples only, and their inclusion does not mean that these products are endorsed by the National Institutes of Health or any other Government agency. Also, if a particular brand name is not mentioned, this does not mean or imply that the product is unsatisfactory.

Corticosteroids: The mainstay of lupus treatment involves the use of corticosteroid hormones, such as prednisone (Deltasone), hydrocortisone, methylprednisolone (Medrol), and

dexamethasone (Decadron, Hexadrol). Corticosteroids are related to cortisol, which is a natural anti-inflammatory hormone. They work by rapidly suppressing inflammation. Corticosteroids can be given by mouth, in creams applied to the skin, by injection or by intravenous (IV) infusion (dripping the drug into the vein through a small tube). Because they are potent drugs, the doctor will seek the lowest dose with the greatest benefit. Short-term side effects of corticosteroids include swelling, increased appetite, and weight gain. These side effects generally stop when the drug is stopped. It is dangerous to stop taking corticosteroids suddenly, so it is very important that the doctor and patient work together in changing the corticosteroid dose. Sometimes doctors give very large amounts of corticosteroid by IV infusion over a brief period of time (days) (“bolus” or “pulse” therapy). With this treatment, the typical side effects are less likely and slow withdrawal is unnecessary.

Long-term side effects of corticosteroids can include stretch marks on the skin, weakened or damaged bones (osteoporosis and osteonecrosis), high blood pressure, damage to the arteries, high blood sugar (diabetes), infections, and cataracts. Typically, the higher the dose and the longer they are taken, the greater the risk and severity of side effects. Researchers are working to develop ways to limit or offset the use of corticosteroids. For example, corticosteroids may be used in combination with other, less potent drugs, or the doctor may try to slowly decrease the dose once the disease is under control. People with lupus who are using corticosteroids should talk to their doctors about taking supplemental calcium and vitamin D or other drugs to reduce the risk of osteoporosis (weakened, fragile bones).

Immunosuppressives: For some patients whose kidneys or central nervous systems are affected by lupus, a type of drug called an immunosuppressive may be used. Immunosuppressives, such as cyclophosphamide (Cytoxan) and mycophenolate mofetil (CellCept), restrain the overactive immune system by blocking the production of immune cells. These drugs may be given by mouth or by IV infusion. Side effects may include nausea, vomiting, hair loss, bladder problems, decreased fertility, and increased risk of cancer and infection. The risk for side effects increases with the length of treatment. As with other treatments for lupus, there is a risk of relapse after the immunosuppressives have been stopped.

BLyS-specific inhibitors: Belimumab (Benlysta®), a B-lymphocyte stimulator (BLyS) protein inhibitor, was approved by the U.S. Food and Drug Administration (FDA) in March 2011 for patients with lupus who are receiving other standard therapies, including those listed above. Given by IV infusion, it may reduce the number of abnormal B cells thought to be a problem in lupus. The most common side effects include nausea, diarrhea, and fever. Patients may also experience reactions at the infusion site, for which antihistamines can be given in advance. Less commonly, serious infections may result.

In studies conducted so far, African American patients and patients of African heritage did not appear to respond to belimumab. An additional study of this patient population will be conducted to further evaluate belimumab in this subgroup of lupus patients. However, this difference in response to a treatment may be another indicator of the various ways that the disease affects different patients.

Other therapies: In some patients, methotrexate (Folex, Mexate, Rheumatrex), a disease-modifying antirheumatic drug, may be used to help control the disease. Other treatments may include hormonal therapies such as dehydroepiandrosterone (DHEA) and intravenous immunoglobulin (proteins derived from human blood), which may be useful for controlling lupus when other treatments haven’t worked.

Working closely with the doctor helps ensure that treatments for lupus are as successful as possible. Because some treatments may cause harmful side effects, it is important to report any new symptoms to the doctor promptly. It is also important not to stop or change treatments without talking to the doctor first. In addition to medications for lupus itself, in many cases it may be necessary to take additional medications to treat problems related to lupus such as high cholesterol, high blood pressure, or infection.

Alternative and complementary therapies: Because of the nature and cost of the medications used to treat lupus and the potential for serious side effects, many patients seek other ways of treating the disease. Some alternative approaches people have tried include special diets, nutritional supplements, fish oils, ointments and creams, chiropractic treatment, and homeopathy. Although these methods may not be harmful in and of themselves and may be associated with symptomatic or psychosocial benefit, no research to date shows that they affect the disease process or prevent organ damage. Some alternative or complementary approaches may help the patient cope or reduce some of the stress associated with living with a chronic illness. If the doctor feels the approach has value and will not be harmful, it can be incorporated into the patient’s treatment plan. However, it is important not to neglect regular health care or treatment of serious symptoms. An open dialogue between the patient and doctor about the relative values of complementary and alternative therapies allows the patient to make an informed choice about treatment options.

Lupus and Quality of Life

A diagnosis of lupus can have a significant impact on quality of life, including the ability to work. Recent research on work loss associated with lupus, funded in part by NIAMS, estimated that almost three-quarters of the study’s 982 participants would stop working before the usual age of retirement, and that half of those who had jobs when they were diagnosed (during their mid-thirties, on average) would no longer be working by the age of 50. The researchers determined that demographics and work characteristics (the physical and psychological demands of jobs and the degree of control over assignments and work environment) had the most impact on work loss.

Despite the symptoms of lupus and the potential side effects of treatment, people with lupus can maintain a high quality of life overall. One key to managing lupus is to understand the disease and its impact. Learning to recognize the warning signs of a flare can help the patient take steps to ward it off or reduce its intensity. Many people with lupus experience increased fatigue, pain, a rash, fever, abdominal discomfort, headache, or dizziness just before a flare. Developing strategies to prevent flares can also be helpful, such as learning to recognize your warning signals and maintaining good communication with your doctor.

It is also important for people with lupus to receive regular health care, instead of seeking help only when symptoms worsen. Results from a medical exam and laboratory work on a regular basis allows the doctor to note any changes and to identify and treat flares early. The treatment plan, which is tailored to the individual’s specific needs and circumstances, can be adjusted accordingly. If new symptoms are identified early, treatments may be more effective. Other concerns also can be addressed at regular checkups. The doctor can provide guidance about such issues as the use of sunscreens, stress reduction, and the importance of structured exercise and rest, as well as birth control and family planning. Because people with lupus can be more susceptible to infections, the doctor may recommend yearly influenza vaccinations or pneumococcal vaccinations for some patients.

Women with lupus should receive regular preventive health care, such as gynecological and breast examinations. Men with lupus should have the prostate-specific antigen (PSA) test. Both men and women need to have their blood pressure and cholesterol checked on a regular basis. If a person is taking corticosteroids or antimalarial medications, an eye exam should be done at least yearly to screen for and treat eye problems.

People with lupus should also be aware of their increased risk of premature cardiovascular disease. This makes healthy lifestyle choices such as eating well, exercising regularly, and not smoking particularly important for people with lupus.

Warning Signs of a Flare

Increased fatigue Pain Rash Fever Abdominal discomfort Headache Dizziness

Preventing a Flare

Learn to recognize your warning signals. Maintain good communication with your doctor.

Staying healthy requires extra effort and care for people with lupus, so it becomes especially important to develop strategies for maintaining wellness. Wellness involves close attention to the body, mind, and spirit. One of the primary goals of wellness for people with lupus is coping with the stress of having a chronic disorder. Effective stress management varies from person to person. Some approaches that may help include exercise, relaxation techniques such as meditation, and setting priorities for spending time and energy.

Developing and maintaining a good support system is also important. A support system may include family, friends, medical professionals, community organizations, and support groups. Participating in a support group can provide emotional help, boost self-esteem and morale, and help develop or improve coping skills. (For more information on support groups, see the “For More Information” section at the end of this booklet.)

Tips for Working With Your Doctor

Seek a health care provider who is familiar with SLE and who will listen to and address your concerns. Provide complete, accurate medical information. Make a list of your questions and concerns in advance. Be honest and share your point of view with the health care provider. Ask for clarification or further explanation if you need it. Talk to other members of the health care team, such as nurses, therapists, or pharmacists. Do not hesitate to discuss sensitive subjects (for example, birth control, intimacy) with your doctor. Discuss any treatment changes with your doctor before making them.

Learning more about lupus may also help. Studies have shown that patients who are well-informed and participate actively in their own care experience less pain, make fewer visits to the doctor, build self-confidence, and remain more active.

Pregnancy and Contraception for Women With Lupus

Although pregnancy in women with lupus is considered high risk, most women with lupus carry their babies safely to the end of their pregnancy. Women with lupus in general have a higher rate of miscarriage and premature births compared with the general population. In addition, women who have antiphospholipid antibodies are at a greater risk of miscarriage in the second trimester because of their increased risk of blood clotting in the placenta. Lupus patients with a history of kidney disease have a higher risk of preeclampsia (hypertension with a buildup of excess watery fluid in cells or tissues of the body). Pregnancy counseling and planning before pregnancy are important. Ideally, a woman should have no signs or symptoms of lupus and be taking no medications for at least 6 months before she becomes pregnant.

Some women may experience a mild to moderate flare during or after their pregnancy; others do not. Pregnant women with lupus, especially those taking corticosteroids, also are more likely to develop high blood pressure, diabetes, hyperglycemia (high blood sugar), and kidney complications, so regular care and good nutrition during pregnancy are essential. It is also advisable to have access to a neonatal (newborn) intensive care unit at the time of delivery in case the baby requires special medical attention.

For women with lupus who do not wish to become pregnant or who are taking drugs that could be harmful to an unborn baby, reliable birth control is important. Previously, oral contraceptives (birth control pills) were not an option for women with lupus because doctors feared the hormones in the pill would cause a flare of the disease. However, a large NIH-supported study called Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) found that severe flares were no more common among women with lupus taking oral contraceptives than those taking a placebo (inactive pill). As a result of this study, published in 2005, doctors are increasingly prescribing oral contraceptives to women with inactive or stable disease.

Current Research

Lupus is the focus of intense research as scientists try to determine what causes the disease and how it can best be treated. Some of the questions they are working to answer include: Why are women more likely than men to have the disease? Why are there more cases of lupus in some

racial and ethnic groups, and why are cases in these groups often more severe? What goes wrong in the immune system and why? How can we correct the way the immune system functions once something goes wrong? What treatment approaches will work best to lessen lupus symptoms? How do we cure lupus?

To help answer these questions, scientists are developing new and better ways to study the disease. They are doing laboratory studies that compare various aspects of the immune systems of people with lupus with those of other people both with and without lupus. They also use mice with disorders resembling lupus to better understand the abnormalities of the immune system that occur in lupus and to identify possible new therapies.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a component of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH), has a major focus on lupus research in its on-campus program in Bethesda, Maryland. By evaluating patients with lupus and their relatives, researchers at NIH are learning more about how lupus develops and changes over time.

NIAMS also funds many lupus researchers across the United States. To help scientists gain new knowledge, NIAMS also has established a Specialized Center of Research at the University of Virginia School of Medicine in Charlottesville devoted specifically to lupus research. In addition, NIAMS is funding a Lupus Registry and Repository that gathers medical information, as well as blood and tissue samples from patients and their relatives. This gives researchers across the country access to information and materials they can use to help identify genes that determine susceptibility to the disease.

Another NIAMS-funded registry is collecting information and blood samples from children affected by neonatal lupus and their mothers. Information from the registry forms the basis of family counseling and tracks important data such as recurrence rates in subsequent pregnancies. The hope is that the registry will facilitate improved methods of diagnosis, as well as prevention and treatment for this rare condition.

In 2003, NIH established the Lupus Federal Working Group (LFWG), a collaboration among the NIH Institutes, other Federal agencies, voluntary and professional organizations, and industries with an interest in lupus. The Working Group is led by NIAMS and includes representatives from all relevant U.S. Department of Health and Human Services (HHS) agencies and other Federal departments having an interest in lupus.

Here are some recent major advances in different areas of lupus research:

GeneticsIdentifying genes that play a role in the development of lupus or lupus severity is an active area of research.

NIAMS intramural and extramural investigators have established that a variant in a gene called STAT4, which is associated with lupus susceptibility, is more specifically associated with disease characterized by severe symptoms such as disorders of the kidney. This finding may

allow doctors to determine which patients are at risk of more severe disease and may lead to the development of new treatment for patients at greatest risk of complications.

Scientists have also found a gene that may confer susceptibility to lupus. They have shown that having an alternative form of the gene Ly108 may impair the body’s ability to keep self-destructive B cells in check. This gene is part of a gene family (SLAM) that has been linked to lupus-like disease in mice.

BiomarkersBiomarkers are another significant area of lupus research. Biomarkers are defined as molecules that reflect a specific biological or pathological process, consequence of a process, or a response to a therapeutic intervention. Simply put, they can let the doctor know what is happening in the body—or predict what is going to happen—based on something reliably measurable in tissues, cells, or fluids. NIAMS-supported researchers have identified anti-double-stranded DNA antibodies and complement C3a—both of which can be found in blood tests—as biomarkers for flares, meaning they can predict that a flare will occur. They also showed that moderate doses of prednisone can prevent flares in people having these biomarkers.

In separate research, NIAMS-supported investigators identified a list of proteins in the urine of people with renal disease caused by lupus. These biomarkers can be used to indicate the type and severity of renal disease in these patients, as well as the extent of damage to the kidney. Such biomarkers could form the basis of clinical tests to help doctors establish an effective treatment plan for these patients without putting them through repeated kidney biopsies. Further studies are needed to determine whether urine protein analysis could replace the use of biopsies to assess kidney damage in lupus.

The Disease ProcessOne recent NIAMS-supported study found that the disease process of lupus—including the development of certain autoantibodies and some symptoms of the disease—begin before the disease is diagnosed. Because lupus is different in different people and is characterized by autoimmunity in various systems of the body, the initial presentation can be unpredictable. Many symptoms wax and wane over time, often delaying diagnosis and the start of therapy.

Seeking to identify patterns among early clinical events in lupus, as well as to assess whether the presence of lupus-associated autoantibodies precedes clinical manifestations, investigators looked back at the charts of 130 lupus patients, analyzing 633 serum samples taken at different times and noting when the criteria for a lupus diagnosis were fulfilled. To be classified as having lupus, a person needs to meet at least 4 of 11 criteria. They found that in 80 percent of the patients, at least one clinical criterion for SLE appeared before SLE was diagnosed. Eighty-four percent developed antinuclear antibodies (ANAs). Discoid rashes and seizures were the earliest observed symptoms, with a mean onset of 1.74 years and 1.70 years prior to diagnosis, respectively. Oral ulcers tended to appear only after diagnosis, making this a less useful diagnostic tool. Among SLE patients with renal disease, anti-double-stranded DNA antibodies appeared before or at the same time as American College of Rheumatology (ACR)-defined renal disorder in the majority of patients who had both the autoantibodies and the renal disorder.

Researchers are also making strides in understanding how the disease process affects different organs. One NIAMS investigator reported that a subset of antibodies to DNA can be found in the blood and the brain of lupus patients with cognitive problems. These anti-DNA antibodies bind to specific receptors (NMDA [N-methyl-D-aspartate] receptors) on nerve cells in the brain. In the culture dish, binding of these anti-DNA antibodies to nerve cells results in the death of the cells. In subsequent studies involving mice, the researchers found that these antibodies affect the nervous system only when the blood-brain barrier was broken, allowing the antibodies access to the brain. Where the blood-brain barrier was broken, antibodies bound to the neurons in a specific area of the brain that helps regulate emotion and memory. Tests for cell death in that area of the brain were positive. Behavioral tests on the mice also revealed impaired cognitive function and memory. Perhaps more important was the finding that the nerve cell binding and its damage could be prevented with a drug that inhibits the NMDA receptor. Researchers say the findings suggest that such drugs may eventually be a useful therapy for people with lupus.

TreatmentUnderstandably, identifying and developing better treatments for lupus—and ensuring that patients receive the best treatments—are among the primary goals of lupus research. A 2005 study of 17 adults with lupus that was clinically active despite treatment, found that just one injection of the cancer drug rituximab (Rituxan) eased symptoms for up to a year or more. Several participants were able to reduce or completely stop their regular lupus medications. Rituximab works by lowering the number of B cells—white blood cells that produce antibodies—in the body. It is approved by the U.S. Food and Drug Administration (FDA) for a type of cancer called lymphoma, as well as for rheumatoid arthritis. Further research is needed to better understand its effectiveness and safety and to better determine its role in lupus treatment.

Other research is examining barriers that keep certain populations from complying with their prescribed medical treatment, which could contribute to worse disease outcomes, including disability and death in those populations. One NIAMS-supported study of economically disadvantaged and ethnically diverse people with rheumatoid arthritis or lupus identified fear of side effects, including long-term damage, as a major reason people failed to take prescribed medications for their disease. Other factors identified included belief that medicines are not working, problems with health system such as navigating Medicaid requirements and a lack of continuity with the same doctor, and medication cost.

Hope for the Future

With research advances and a better understanding of lupus, the prognosis for people with lupus today is far brighter than it was in the past. It is possible to have lupus and remain active and involved with life, family, and work. As current research efforts unfold, there is continued hope for new treatments, improvements in quality of life, and, ultimately, a way to prevent or cure the disease. The research efforts of today may yield the answers of tomorrow, as scientists continue to unravel the mysteries of lupus.

For More Information

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information ClearinghouseNational Institutes of Health

1 AMS CircleBethesda,  MD 20892-3675Phone: 301-495-4484Toll Free: 877-22-NIAMS (877-226-4267)TTY: 301-565-2966Fax: 301-718-6366Email: NIAMSinfo@mail.nih.govWebsite: http://www.niams.nih.gov

NIAMS, a component of the National Institutes of Health (NIH) within the U.S. Department of Health and Human Services, conducts and supports medical research on the causes, treatment, and prevention of diseases of bones, joints, muscles, and skin; trains scientists to carry out this research; and disseminates information on research progress to improve public health.

American College of Rheumatology (ACR)

2200 Lake Boulevard NEAtlanta,  GA 30319Phone: 404-633-3777Fax: 404-633-1870Website: http://www.rheumatology.org

The American College of Rheumatology (ACR) is an organization of doctors and associated health professionals who specialize in arthritis and related diseases of the bones, joints, and muscles. The Association of Rheumatology Health Professionals, a division of ACR, aims to enhance the knowledge and skills of rheumatology health professionals and to promote their involvement in rheumatology research, education, and quality patient care. The association also works to advance and promote basic and continuing education in rheumatology for health professionals who provide care to people with rheumatic diseases.

Alliance for Lupus Research, Inc.

28 West 44th Street, Suite 501New York,  NY 10036Phone: 212-218-2840Toll Free: (800) 867-1743Website: http://www.lupusresearch.org

The Alliance for Lupus Research, Inc. (ALR), is a nonprofit organization devoted exclusively to the support of promising research for the prevention, treatment, and cure of lupus. Through accelerated, focused, goal-oriented research programs, the ALR aims to

promote basic and clinical sciences to achieve major advances leading to a better understanding of the causes of lupus.

American Autoimmune-Related Diseases Association, Inc. (AARDA)

22100 Gratiot Ave.East Detroit,  MI 48021Phone: 586-776-3900Toll Free: 800-598-4668Fax: 586-776-3903Email: aarda@aarda.orgWebsite: http://www.aarda.org

The American Autoimmune-Related Diseases Association (AARDA) is a nonprofit voluntary health agency dedicated to bringing a national focus and collaborative effort to the more than 100 known autoimmune diseases through education, awareness, research, and patient services. By collaborating with the National Coalition of Autoimmune Patient Groups (NCAPG), AARDA supports legislative advocacy for autoimmune disease patients. AARDA provides free patient education information, physician and agency referrals, forums and symposia, and a quarterly newsletter.

Arthritis Foundation

P.O. Box 7669Atlanta,  GA 30357-0669Phone: 404-872-7100 Toll Free: 800-283-7800Website: http://www.arthritis.org

The Arthritis Foundation is devoted to supporting arthritis research and providing educational and other services to individuals with arthritis. The foundation publishes a free pamphlet on rheumatoid arthritis and a magazine for members on all types of arthritis. It also provides up-to-date information on research and treatment, nutrition, alternative therapies, and self-management strategies. Chapters nationwide offer exercise programs, classes, support groups, physician referral services, and free literature. The foundation also has free information about lupus, scleroderma, and other autoimmune and rheumatic conditions on its Web site.

Lupus Clinical Trials Consortium, Inc. (LCTC)

142 West 57th Street, Suite 15ANew York,  NY 10019Phone: 212-593-7227Fax: 212-593-3133Email: info@lupus-consortium.orgWebsite: http://www.lupusclinicaltrials.org

The LCTC is a nonprofit organization that encourages the identification and testing of promising new therapies for lupus. It provides infrastructure support grants to certain academic institutions to support their clinical research activities; encourages lupus clinical researchers from those institutions to share their expertise; supports and conducts educational efforts to show the need for lupus clinical research; and disseminates scientific insights to advance the discovery of new lupus therapies.

Lupus Foundation of America (LFA)

2000 L Street, N.W., Suite 410 Washington,  DC 20036Phone: 202-349-1155Toll Free: 800-558-0121Fax: 202-349-1156Website: http://www.lupus.org

The Lupus Foundation of America is a national nonprofit voluntary health organization dedicated to finding the causes of and cure for lupus; and to providing support, services and hope to all people with this condition. The LFA and its network of nearly 300 chapters and support groups conduct programs of research, education, and advocacy.

Lupus Research Institute

330 Seventh Ave, Suite 1701New York,  NY 10001Phone: 212-812-9881Fax: 212-545-1843Email: Lupus@LupusNY.orgWebsite: www.lupusresearchinstitute.org

The Lupus Research Institute provides funds for promising new ideas for curing, preventing, and treating lupus.

Rheuminations, Inc.

142 West 57th Street, Suite 15ANew York,  NY 10019Phone: 212-593-5180Fax: 212-803-0059Website: http://www.dxlupus.org

Rheuminations is a private, nonprofit foundation committed to funding excellence in medical research, which will foster a better understanding of the causes of lupus and bring new treatments to market; educate and empower those who live with lupus and those who care for them; and establish a higher level of public awareness about the disease.

SLE Lupus Foundation

330 Seventh Avenue, Suite 1701New York,  NY 10001Phone: 212-685-4118Toll Free: 800-74-LUPUS (745-8787)Fax: 212-545-1843Email: lupus@lupusny.orgWebsite: http://www.lupusny.org

The SLE Foundation supports and encourages medical research to find the cause and cure of lupus, and improve its diagnosis and treatment. It also provides a wide variety of services to help people with lupus and their families. In addition, this voluntary organization conducts a broad-based public education program to raise awareness of lupus, and increase understanding of this serious chronic autoimmune disease.

Acknowledgments

NIAMS gratefully acknowledges the assistance of Jill P. Buyon, M.D., Hospital for Joint Diseases, New York, New York; Patricia A. Fraser, M.D., Brigham and Women’s Hospital, Boston, Massachusetts; John H. Klippel, M.D., The Arthritis Foundation, Atlanta; Michael D. Lockshin, M.D., Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery, New York, New York; Rosalind Ramsey-Goldman, M.D., Dr.P.H., Northwestern University Medical School, Chicago, Illinois; George Tsokos, M.D., Uniformed Services University of the Health Sciences, Bethesda, Maryland; and Elizabeth Gretz, Ph.D., Barbara Mittleman, M.D., Susana Serrate-Sztein, M.D., and Peter E. Lipsky, M.D., NIAMS, NIH, in the preparation and review of this and earlier versions of this publication. Special thanks also go to the many patients who reviewed this publication and provided valuable input. An earlier version of this booklet was written by Debbie Novak of Johnson, Bassin, and Shaw, Inc.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. The National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse is a public service sponsored by NIAMS that provides health information and information sources. Additional information can be found on the NIAMS Web site at www.niams.nih.gov.

For Your Information

This booklet contains information about medications used to treat the health condition discussed here. When this booklet was printed, we included the most up-to-date (accurate) information available. Occasionally, new information on medication is released.

For updates and for any questions about any medications you are taking, please contact

U.S. Food and Drug Administration

Toll Free: 888–INFO–FDA (888–463–6332)Website: http://www.fda.gov/

For updates and questions about statistics, please contact

Centers for Disease Control and Prevention's National Center for Health Statistics

3311 Toledo Rd.Hyattsville,  MD 20782Toll Free: 800-232-4636Website: http://www.cdc.gov/nchs

Immune: Systemic lupus erythematosus

by Paul Bergner

Medical Herbalism 9(4): 1, 3-13

This article is based on a review of the medical literature, both alternative and conventional,  and on the histories of five cases treated by the author from 1996-1998.  

Systemic lupus erythematosus (SLE) is one of the most serious autoimmune diseases. Unlike other autoimmune conditions, SLE attacks a wide variety of tissues, and lupus-induced kidney damage can cause death. See Table 1 at the end of this article, for a list of the symptomatic manifestations of lupus, which may arise as the immune system attacks various tissues. Exacerbations and remissions of symptoms are typical. Conventional medicine lists lupus as a disease of unknown etiology, although a likely genetic component has been identified. If the disease were entirely due to genetics, however, we would expect to find equal rates among primitive people and those living in the developed countries. Incidence is much higher in the developed countries, and systemic lupus and other autoimmune diseases are rare in primitive societies following traditional lifestyle and dietary habits, although they begin to appear in those societies when Western diet and stresses are introduced (Trowell and Burkitt). Thus, natural therapies involving diet and lifestyle may be effective at modifying or removing the cause of SLE. Conventional treatment is symptomatic only, and in clinical practice drug side effects commonly complicate the symptom picture and make natural treatments more difficult. In emergency conditions or SLE complicated with myocarditis, ascites, uremia, or cerebral edema, conventional treatment should be initiated without delay.

Natural treatment

Natural and herbal treatment of SLE is controversial from a scientific point of view, usually based on empirical approaches, traditional Asian herbalism, or on emerging concepts of pathology which have not been definitively proven in the literature.

TCM syndromes

The underlying syndromes for systemic lupus in traditional Chinese medicine involve Deficiency patterns and Heat syndromes (especially Deficiency Heat or False Fire). The most important Chinese organ system for therapy is the Kidney, which in Western terms most closely fits the hypothalamic-pituitary-adrenal axis. The therapeutic challenge with herbal medicines (regardless of the medical  paradigm) is how to tonify to increase strength in SLE patients without simultaneously increasing heat and inflammation. A window into the therapeutic balance necessary for treating lupus might be seen in the commercial formula Lithospermum 15, produced by the Institute for Traditional Medicine in Portland, OR. Table 1 shows the herbs in Lithospermum 15, and the rationale for their inclusion. Tonics in the formula are mild, and potentially  overstimulating tonics such as deer antler or Asian ginseng (Panax ginseng) are avoided. About 20% of the volume of the formula is composed of cooling, heat-clearing herbs. Whatever paradigm of herbalism is used to treat SLE, the principle of using mild tonic herbs combined with cooling herbs is applicable.

Heat-clearing herbs

The application of traditional Asian terms such as “heating” and “cooling” to Western herbs is in its infancy, and thus classification may be imprecise or subject to debate.  In general, bitter herbs are viewed as “cooling,” and mild bitters may be useful in lupus. During remissions, gentle bitters such as dandelion (taraxacum off.), burdock (Arctium lappa), or agrimony (A. eupatoria, A. pilosa) might be included in formulas. During exacerbations, the stronger artemisia species might be used following the same “heat-clearing” strategy that conventional medicine applies with antimalarial drugs. Sweet Annie (Artemisia annua) is used in China as an antimalarial, and also used for exacerbations of SLE. A dose of 12-24 grams of the dry herb, decocted in a quart of water, and drunk in three doses throughout the day, may be appropriate. American ginseng (Panax quinquefolius) also has cooling properties, as do the leaves of Asian ginseng  (Panax ginseng). Asian ginseng leaf costs only a few dollars a pound, whereas American ginseng root may cost several hundred dollars.

Immunomodulating herbs

Contemporary American herbalists classify a group of herbs, including  reishi mushroom (Ganoderma lucidum), shiitake mushroom (Lentinus edodes),  maitake mushrooms (xxx), and astragalus root (Astragalus membranaceus) as “immunomodulating.” The term is common is the journal articles of Asian scientists researching traditional Asian herbs and medicinal mushrooms (Chang; He J et al; He Y et al, 1992; Wang and Lin; Yoshida et al.) These herbs have complex actions on the immune system when measured in in-vitro and in-vivo trials. Among herbalists the term is used to indicate herbs that have traditionally been used to restore balance to the immune system rather than to stimulate it. The herbs tend to have a neutral “temperature” or mild action in traditional usage, and are traditionally taken for long periods of time in food quantities, especially as soups or decoctions.  The herbs might be administered in a “tonic soup” which the patient can

prepare in large quantities every few days. An example might be reishi mushroom, shiitake mushroom, astragalus, and peony root (Paeonia lactiflora), decocted in a nourishing soup with vegetables, grains as tolerated, meat, or meat broth. Peony root is a cooling tonic which can offset the tendency of astragalus to aggravate inflammation.

The use of echinacea in lupus is controversial, with differences of opinion among practicing herbalists around the world. One of the five patients in this study reported that taking echinacea would make her lupus symptoms worse.  She had tried it several times with rechallenge before stopping its use.

Gut-healing herbs

The article on the “leaky gut” syndrome [see “Gastrointestinal: Leaky gut, molecular mimicry, microchimerism, and autoimmunity” in this volume] explains the possible connection between loss of efficiency of the gut barrier and autoimmune conditions. Restoration of the integrity of the barrier may be the most important herbal therapy for autoimmune diseases, to modify their course or severity. A gut-healing strategy might include demulcent, antiinflammatory, and carminative herbs. One possible basic formula might include equal parts of chamomile (Matricaria recutita, M. chamomila), peppermint (Mentha piperita), fennel (Foeniculum vulgare), and licorice (Glycyrrhiza glabra). The herbs may be given in decoction or powdered. If powdered, they should be given in warm water. Amounts might be modified and other herbs added to the formula, depending on the presenting picture. Demulcents might best be given separately in order to provide more of the herb than would be available in  dose. Slippery elm powder (Ulmus fulva) can be given with applesauce or added to oatmeal. Marshmallow (Althea off), can be given as a simple.

A possible complication of “leaky gut” is an overload  of gut pathogens on the liver. Nutrients and herbs that support liver detoxification may be appropriate as addition either to a leaky gut formula or to tonic soups. The gentler cleansing herbs, such as dandelion, burdock, or agrimony might be preferred, along with the hepatoprotectant milk thistle seed (Silybum marianum). Nutrients such as magnesium and vitamin B6, essential to the process of liver detoxification, may be helpful, and may also reduce elevated estrogen levels which promote hyperactivity of the immune system.

Diet/Supplements/Exercise

Food allergies may be either a cause or a consequence of the leaky gut syndrome. The chief offenders appear to be dairy, wheat, and soy.[see “Gastrointestinal: Leaky gut, molecular mimicry, microchimerism, and autoimmunity” in this volume, for a full discussion of possible mechanisms]. All five SLE patients in this demonstrated severe allergies to dairy and/or wheat, confirmed by removal from the diet and rechallenge. Two of the patients could trigger full-blown lupus flareups with joint pain and/or kidney involvement by eating a single cookie made of wheat, with the outbreak following by 12-36 hours.  Fasting and reintroduction of  suspected foods may dramatically demonstrate to both practitioner and patient the importance of food allergies to the presenting symptom picture.

Abandonment of the modern diet in favor of a whole foods diet is essential in the treatment of lupus. The foods most likely implicated in the Western diseases (see introduction) are sugar, refined flour, and refined oils, and margarine. Refined omega-six oils and margarine combined with a relative deficiency of omega-3 oils, such as appear in fish and wild game, can lead to prostaglandin imbalances that favor the inflammatory response. It is the author’s  experience that flax oil and other omega-3 oils from vegetable sources are usually ineffective in treating inflammatory conditions, despite their popularity among customers of health foods stores. Wild salmon (not farmed) and/or sardines added to the diet on a regular basis can produce dramatic clinical results with reduced inflammation.  

Nutrition supplements administered must be selected for easy assimilation, because impaired digestion or intestinal absorption may otherwise render supplementation useless. An easily assimilable form of magnesium is essential. An ionic liquid mineral supplement high in magnesium is available from Trace Minerals Research in Utah. The author has seen dramatic changes in energy-level and/or inflammation in each of the patients above given this supplement.

Homeopathy, flower essences

A history of suppression of symptoms with pharmaceutical drugs is the rule in lupus patients, even if they are currently refusing recommended steroids or chemotherapy agents. Underlying emotional complexes either predating the illness or in response to it are also common. These two conditions argue for the value of homeopathic remedies or flower essences, traditionally used to treat deep seated emotional conditions or the ill effects of suppression of symptoms with drugs.

Stress management

Each of the lupus patients in this review has suffered from mild to severe post-traumatic stress disorder, following major childhood traumas, sexual or physical abuse, or war, according to DSM IV criteria. Each also had unusual stress in their current situation, such as professional lives characterized by deadline pressures or pressure to overwork, abusive marital situations, or poverty. Chronic stress may lead to exhaustion of cortisol secretion by the adrenal glands (which might be measured by a simple salivary cortisol test). The loss of the antiinflammatory effects of the cortisol can exacerbate the autoimmunity. Dihydroepiandrosterone (DHEA) production by the adrenal glands may also be depleted, further contributing to immune imbalances and reduced tissue repair. TCM treatment of the Kidney organ system (see discussion above) is consistent with restoring proper adrenal function. Reducing stress is no simple matter clinically, and the full array of possibilities might be explored, including psychotherapy, group support, prayer, meditation, spa therapy, extended vacations, etc. DHEA supplementation may be helpful in severe cases of lupus, especially with kidney involvement, or to break the cycle of stress and adrenal depletion. In the author’s opinion, DHEA supplementation should be given only in conjunction with treatments that address the cause, and not relied on to “cure” the illness. Dosages of up to 100 mg of DHEA have been reported in the alternative treatment of lupus (Pizzorno), but therapeutic doses should normally be limited to 10-20 mg per day. DHEA

does not address the cause of the disease, and will not heal the  leaky gut or remove food allergens.

Two-phase strategy

A dual strategy, with separate treatments for outbreaks and remissions, may be useful. Fasting on water and lemon juice and resting during fever or severe inflammation can reduce the antigenic load on the gut and promote elimination of immune complexes. Mild heat-clearing herbs might also be appropriate, while all tonics should be discontinued during such a period. For milder outbreaks, a light diet or modified fast, especially from potentially allergenic foods, might be useful.

Removal of medications

The drugs commonly used to treat lupus, including NSAID and steroids, may themselves cause leaky gut syndrome. While they may have their place in treatment, healing is unlikely without their removal. Birth control pills may also induce leaky gut syndrome.

Case 1: Early Stage Lupus

 Patient: 25 y.o. female, 5’5"  120 lbs.

Overall health self-assessment: 7 of 10

Chief complaint:

Lupus-like autoimmune outbreaks. The patient was told she had “pre-lupus” by her physician.  Raynauds phenomenon. Painful swelling of all the lymph glands in the body during attacks. Joint inflammation. Possible kidney pain. Low grade fever. About four outbreaks a year, spaced at regular three-month intervals. “Could set the calendar by them” Mild hair loss. Most recent outbreak three weeks prior.

Daily meds: 1000 mg Vitamin C. Discontinued all conventional meds eight months prior.

Lifestyle:

6-8 beers per week, in two sittings.

2-3 cups coffee per week

Exercise (walk, jog, bike, etc) 60 minutes per day seven days a week.

Sleeps 6-9 hours per night.

Meditates regularly, especially past 3-6 months.

High stress job. Ending long-term relationship.

Diet: Diet diary revealed possible dairy allergy, with dairy binges. Drinks 2-3 quarts water a day.

Family History:

Father: Stomach ulcer, liver damage secondary to alcoholism. Deceased

Paternal grandfather: allergy; heart disease

Paternal grandmother: enlarged heart; allergies

Great aunts and uncles: heart disease, allergy

Great grandparents: Emphysema, arthritis

Mother: symptoms of lupus without clear diagnosis; hair loss, Raynauds; easy bruising. Minor symptoms. One positive “anti-DNA antibody” test.

Maternal grandfather: stomach ulcer, goiter, M.I., bone cancer, esophageal cancer.

Maternal grandmother: allergy; headaches; arthritis; angina;  osteoporosis.

Great aunts and uncles: enlarged thyroid; hypothyroid; stomach “upsets”

Great grandparents: arthritis; prostate cancer; hypertension; osteoporosis; thyroid problems in extended family.

Client History

Fungal infection on bottom shortly after birth. Treated with “mycolog cream” — combination of nyastatin and corticosteroid.

Breast fed for two weeks, but then put on soy formula.

2 months: first DPT shot, oral polio vaccine. Fungal infection cleared. No obvious adverse reactions to any immunizations. Introduced solid baby food.

3 months (Feb 8) Put on cow’s milk. Doctor says “may eat anything”. Second DPT shot

4 months (March 8) 3rd DPT shot, 2nd oral polio vaccine.  (March 29) fungus on 3 fingers of each hand — index,  middle, thumb — in symmetrical pattern. Tongue  developed “raw spots” Unspecified medication.

6 months, Fungus infection still present

9 months (August 6). Eczema on scalp, head cold, diaper rash. Sulfur-salicylic acid shampoo prescribed for eczema. Meds for cold.

13 months. Corticosteroid cream for scalp eczema. Tegopen (cloxacillin) for recurrence of infection on finger.

Age 6-12 Recurrent strep throat infections. Treated with repeated antibiotics.

Age 12: Tonsillectomy for recurrent strep

Teens: sulfa allergy; developed seasonal allergies to grasses; Mother says developed Raynauds phenomenon in teens.

Age 13: Menarche. ovarian cysts. “bad” periods. Put on bc pills. Continuous until Norplant at age 23

Age 12-17: Repeated urinary tract infections; repeated antibiotics, with yeast infections as side effect. Received multiple prescriptions and antibiotics with simultaneous antifungals. Hospitalized with pyelonephritis. Eventual surgery to “stretch tubes” Doctor says ureters were congenitally too narrow — i.e. incomplete and slow draining of bladder.

Age 22: January. Client says first Raynauds symptoms (See mother’s comments above).

Age 22: March: Norplant. Menstruation stopped for next 2 ½ years

Age 22: July: first lupus outbreak. Doctors thought it was mononucleosis.

Age 24: September. Discontinued Norplant.

Current outbreaks

Swollen glands, tender to touch. All glands in body. Worse in breasts “don’t want them there.” Breast pain makes her cry. Can’t fully extend elbows. Can’t sleep on side. Can’t wear bra or tight clothes. Low grade fever: 100 degrees. Morning-evening fever pattern. Fatigue. Brain “shuts off”, confused, forgetful. Aggravation, frustration. Hair loss is getting worse with latest outbreak (started 2-3 months ago) . Lasts 1-2 weeks. Main trigger is stress. Two outbreaks ago, preceded by flu. Prodromal insomnia. Better with hot bath, better with warm blankets, better with hot tea.

Systems

Urogenital: repeated uti and kidney infection in teens. Surgery to “stretch” the tubes, which doctor said was too narrow, promoting urinary retention.

Female

BC pills since age thirteen after ovarian cysts and ‘bad" periods. Norplant at age 22-25. Suppressed periods completely. Removed nine months ago. Periods now normal, no cramps, every four weeks, 5-6 days. Not “a lot” of blood, no clots. “nice” deep red color. “happy to have it back.”

Digestive: Upper GI pain after meals. Bloating. Cramping in small intestine. Constant gas.

Emotional: expressed these verbally but does not show strong emotions: sadness, anger, stress.

Assessment:

*Congenital immune weakness and tendency to allergy

*Probable dairy allergy.

*Severe antibiotic suppression.

*Possible “leaky gut” syndrome.

*Suppression of fertility and feminine psychological development

*Stress and adrenal exhaustion.

*Post-traumatic stress disorder (events confidential)

Treatments:

Intensive education about the issues involved: food allergy, stress, and leaky gut.

Diet:

Increase fruits and vegetables.

Eliminate dairy

Increase vitamin C to 2-4 grams/day and add equal parts bioflavonoids.

Stress:

Reduce heavy exercise to a moderate level.

Stress management around work.

Rest in natural setting as often as possible.

Chinese immunodulating soup

Red reishi mushroom (Ganoderma lucidum), shiitake mushroom (Lentinus edodes), astragalus (Astragalus membranaceus), poria (Poria cocos), licorice (Glycyrrhiza glabra).

Equal parts. Place three handfuls in a 2 quart pot and simmer for two hours. Take three cups per day. If too “heating” add equal part of peony root (Paeonia lactiflora) and reduce astragalus by one-half part. (The tea was not heating and was well-tolerated by the patient.)

Digestive tea.

Peppermint (Mentha piperita), chamomile (Matricaria recutita), fennel (Foeniculum vulgare), licorice, (Glycyrrhiza glabra), marshmallow (Althea officinalis).

Equal parts. Decoct 1 ounce per pint of tea for 20-30  minutes. Let come to room temperature. Strain and store in refrigerator.  3 cups per day, rewarmed to taste, on empty stomach.

Castor oil packs, 3 days a week. (Client was reluctant to comply, and did not)

Diet for outbreaks (Client had no further outbreaks)

Diluted citrus juice fast for duration of fever. No dairy whatsoever. Complete rest. Consider short stay at nearby spa.

Flower essences

Salvia — extreme stress

Dill — releasing power to others, victimization

Celery — immune support during stress

Psycho-spiritual

To local Wise Woman practitioner for a “blood rites” ceremony to celebrate the psychospiritual passage that had been suppressed at menarche.

Results

The visits included a two-hour intake, with a one-hour educational follow-up. The patient received a dose of the flower essence at the end of second visit, and the formula above to be taken t.i.d. Over the next few weeks, a healing crisis ensued around abuse issues, with a

happy resolution involving forgiveness. Hair loss stopped. During this period she eliminated dairy completely, and reported better overall energy and improved digestive symptoms.

Three month follow-up.

Her lupus outbreaks had previously happened “like clockwork” every three months. At the anticipated three-month point, she ‘felt bad’ for a day and a half, but had no further symptoms. Referred to MD-homeopath for constitutional homeopathy and ongoing monitoring of immune status. Compliance with herbal treatments and elimination of dairy was good.

Five-month follow-up.

Patient called and said she had borderline diastolic hypertension, and asked if the herbs could cause this. I suggested she remove the licorice from all formulas. No further follow-ups.

Case 2: Advanced Systemic Lupus with severe drug side effects

Patient: 45 y.o. female

Diagnosed with SLE at age 40. Drug-induced (methotrexate) cervical cancer at age 43. Chronic constipation since childhood: BM (dry) once in 5-7 days. Chronic gas, bloating, indigestion. Chronic lifelong PMS: bloating, weight-gain, breast tenderness, irritability, mild depression.

History

Almost died at age 2-3 from unidentified illness. Bleeding and convulsions.

Measles, mumps, chicken pox during childhood.

Age eight: Adverse reaction to multiple immunizations for travel: nausea, dizziness, and swelling of arm lasted two weeks.

Chronic fatigue in teenage years.

 Blackout spells as teenager. Ran car into tree.

No medical treatments

Menses at 14 y.o..

History of physical and sexual abuse.

Major PMS in teens and all adult life.

20 y.o. Severe PMS. Arthritic pains during PMS. Prednisone 10 mg for two years. Followed by strep throat in twenties on three occasions, emergency room treatment for one incident. Bladder infections. Treated with short-term antibiotics.

Chronic fatigue in twenties.

Diagnosed as hypoglycemic in thirties.

Married at 35 to chronic addict-alcoholic

Extreme fatigue. Worse after marriage.

Four miscarriages.

Lupus onset was after last miscarriage, which coincided with family financial crisis.

38 y.o. Onset symptoms: Major itching all over body for one month; deep pain in both arms.

One month later: joint pain throughout body. Right little finger ballooned. Could not move neck. Severe headaches. Crying with pain. Physically immobilized. Chills. Peripheral neurological symptoms.

First diagnosis: “transient arthritis” Prednisone 60 mg plus NSAID, oral gold, and Darvocet for sleep.

Moved to rental home after losing house. Collapsed with stress and slept for most of a week.

Second diagnosis: rheumatoid arthritis. Cortisone 60 mg plus gold shots. Adverse (rash) reaction to gold. Gradually tapered cortisone to 5 mg. Rash. Methotrexate 7.5 mg/week. Hands crippled. Methotrexate 10 mg/wk.  

40 y.o. major regression:  low back pain, memory loss, discoid rash. Bronchitis (treated with antibiotics). Blurry vision. Temporary paralysis of right arm. Pain in eyes.

Third diagnosis: “Mixed connective tissue arthritis.” Plaquenil (hydroxychroloquine) 200 mg day and methotrexate 12.5 weekly dose and cortisone (10-12 mg) and NSAID. Ocular side effects to Plaquenil.

Fourth diagnosis: SLE. Prednisone 10 mg; methotrexate 10 mg/wk; NSAID; folic acid 1 mg; Plaquenil 200 mg.

41 y.o. CNS involvement with seizures. NSAID-induced ulcers. Weight loss in spite of prednisone. Plaquenil-induced photosensitivity. Had to wear sunglasses in house. Multiple infections. Excessive bleeding (clotting disorder).

Proteinuria — upped cortisone to 30-50 mg.

42 y.o. Diagnosis: SLE and fibromyalgia. Methotrexate 12.5 mg/wk, prednisone 10 mg; Plaquenil 200 mg. Mixed NSAID. Cortisone injection in wrists.

43 y.o. Bitten by dog and had tetanus shot. Caused lupus flareup.

Severe squamous cell cervical dysplasia and cervical carcinoma in-situ with endocervical gland involvement. Hysterectomy recommended. Patient was told she would die of cancer unless she stopped taking the drugs, or of kidney failure if she stopped taking them.

Treatments

 faced with a likely fatal diagnosis, the patient began to pray and study herbalism and natural healing. Over six months she started taking herbs and weaned herself from all drugs. Was drug-free by September 1995.

Chinese tonic soup. The exact components have varied somewhat but include such items as: Shiitake and reishi mushrooms, astragalus, poria, coix, burdock, watercress, vegetables, brown rice, and millet.

Major juice fast (three months). September 1995. Green juice and carrot.  No joint pain. Energy good. “Never felt better.” Major juice fast (three months). Healing crisis with acne, boils, and mucous discharge. December 1995. Reintroduced foods, and identified dairy, meat, and wheat allergies.

Diet

Sardines four times a week. Salmon (contain antiinflammatory essential fatty acids). Organic vegetables. Organic grains, fresh-ground in vita-mix. Juice in AM: carrot, parsley, fresh ground flax, sesame and sunflower seeds, blackstrap molasses; ½ clove garlic. Soy protein.

Other herbal treatments

Chinese Artemisia (A. argyi) as “Plaquenil substitute” (antimalarial) 19 grams in three cups of water boil ten minutes. Reduces heat and joint pain.

Deglycyrrhizinated licorice (DGL) for NSAID-induced ulcers.

Bupleurum as a simple for PMS

Supplements

Bromelain 1800 mcu tid; Curcumin 500 tid (Patient says turmeric powder is more effective than the extracted curcumin for antiinflammatory effects); Vitamin C 5-6 grams; Pantothenic acid 500 mg bid; Multivitamin; Vitamin E (mixed toc.) 800 iu;

B complex bid

Results

Patient had normal pap in Fall 1995 and has had four more normal paps since.

Possible lupus flareups during herbal treatment:

Hives: treated by Chinese practitioner, cleared in one week.

Pleurisy: Treated successfully with Asclepias tuberosa

Proteinuria: Treated successfully with ground flax seeds and flax seed oil.

Treatment

She approached the author for herbal advice in Summer 1996.  Reduced astragalus and increased burdock in tonic soup to reduce heating effects.

Chamomile for sleep (patient could not tolerate valerian) and antiinflammatory effects.

Leaky gut formula: Equal parts of peppermint, chamomile, fennel, licorice, slippery elm, and marshmallow. Patient removed the licorice because of increased bloating.

Flower essences

Broccoli — balance of personal power

Celery — immune support during stress

Comfrey — higher vibrational damage or injury

Salvia — extreme stress

Dill — Victimization

(Take several drops three times a day or as desired)

Within a week, the flower essences appeared to provoke a strong healing crisis. First symptoms were the emergence of suppressed emotions around her marriage. Then bleeding from rectum, shortness of breath, gums bleeding, cheeks puffed up. Self medicated with raspberry, white oak bark, witch hazel, and slippery elm. Lasted four days. Afterwards could manage lupus symptoms with one-fourth the previous dose of tonic herbs and artemisia.

Fall 1996-Winter 1997

Patient discontinued most of herbal treatments, except for leaky gut formula. Feels generally worse, but is functional. One outbreak of hives (treated by Chinese herbalist). In February 1997 normal bowel movements (1x/day) began for first time in her life. Reintroduce the tonic soup and artemisia.

Patient was under unusual stress during this time, and was counseled on stress-management strategies.

Common elements in both cases

Diagnosis: Patient 1 was told she probably had lupus but did not fit all the diagnostic criteria for it. Patient 2 received multiple misdiagnoses before finally being diagnosed with SLE. This illustrates the vague nature of the diagnosis of SLE.

Etiology:

Both patients had experienced stress in childhood also were experiencing it in their current situations.

Both had been sexually abused or raped, and suffered post-traumatic symptoms from the events.  

Both had extreme digestive symptoms Both had food allergies to dairy and/or wheat, proven by elimination and rechallenge.

The foods provoked exacerbations of lupus symptoms with rechallenge. o Both had a history of severe and repeated suppression of symptoms with

antibiotics and/or steroids.

Successful treatment:

o Both patients had a large degree of self-empowerment and self-direction. o Both stopped all pharmaceutical medications. o Both eliminated food allergens o Both experienced relief of both digestive symptoms and experienced improved

overall health in response to a gut-healing formula o Both complied with treatments in making and regularly consuming a soup of

Chinese immunomodulating herbs o In both cases, a flower essence remedy during later stage of treatment produced

healing crisis

Table 1:  Systemic Lupus Erythematosus

Definition and prevalence

Tissues and cells damaged by deposition of pathogenic auto-antibodies and immune complexes. Specific symptom manifestation is highly variable, and depends on which tissues are involved in the autoimmune response. Exacerbations and remissions are typical.  90% of cases are in women, usually of child-bearing age. More common in Blacks and Hispanics than in whites.

Pathogenesis

Production of pathogenic auto-antibodies and immune complexes coupled with failure to suppress them. Antigen-antibody complexes may be deposited in tissues, initiating inflammation. Usually phagocytosed, but clearance is poor in this and related diseases. Size of complexes may be an important factor C larger cause more tissue damage. Antigen or antibody excesses tend to smaller complexes. Antigen-antibody equivalence or mild antigen excess tend to larger complexes.

Etiology

Genetic factors: Abnormal humoral and cell-mediated immune responses. Genetic defects in aptosis (natural death) of B and/or T-cells.

Pharmaceutical Drugs: SLE may be triggered or aggravated by procainamide, hydralazine, anticonvulsants, penicillins, sulfa drugs, immunizations, and oral contraceptives.

Digestive: Phospholipids in cell walls of enteric bacteria may activate B-cells or antibodies and elicit cross-reactivity to ribose-phosphate backbone in DNA. Suggests important role for ALeaky Gut@ syndrome and molecular mimicry. See accompanying article ALeaky gut, molecular mimicry, and microchimerism@

Hormonal: Estrogen enhances and testosterone reduces antibody responses. May explain higher incidence in women, and triggering effect of oral contraceptives. Suggests importance of avoiding xeno-estrogens, and maximizing hepatic clearance of estrogens.

Immune: B-cell hyperactivity. T-4 and T-cytotoxic cell deficiency during attacks. Elevated anti-nuclear and/or anti-DNA antibody titer and decreased serum complement (C3 and C4) during attacks. Interleukin secretion is diminished. Slow clearance of immune complexes due to inherited or acquired deficiencies in complement system. Overall pattern is one of elevated antibody activity with overall immune deficiency.

Infection: Streptococcal or viral infections may trigger or aggravate.

Stress: Physical or mental stress may trigger or aggravate.

Reproductive: Fertility is normal, but miscarriage is high (30-50%). First trimester of pregnancy and first six weeks post-partum may trigger lupus (See accompanying article ALeaky gut, molecular mimicry, and microchimerism@)

Clinical manifestations

 (only those occurring in a majority of patients are listed, others being possible.)

Systemic (95%): Fatigue, malaise, fever, anorexia, nausea, weight loss

Musculoskeletal (95%): Most common are arthralgias/myalagias and polyarthritis (60%)

Cutaneous (80%): Most common are rashes, oral ulcers, and alopecia. Butterfly rash across nose and cheeks occurs in less than 50%.

Hematologic (85%): Anemia and leukopenia are most common. Clotting and bleeding disorders may also develop.

Neurologic (60%): Possible manifestations are organic brain syndromes, seizures, and peripheral neuropathies. Mild mental dysfunction is most common manifestation.

Cardiopulmonary (60%): Pleurisy, pleural effusions, and pericarditis are most common.

Renal (50%): Proteinuria and cellular casts are most common. Nephrotic syndrome (25%) and renal failure (5-10%) may occur. Most common cause of death in lupus patients.

Gastrointestinal (45%): Nonspecific (anorexia, mild pain, diarrhea) and ascites are most common.

Diagnosis

Symptoms overlap with those of related connective tissue autoimmune disease. The American Rheumatism Association has issued a list of criteria for diagnosis of SLE as follows. Four or more of the signs must be present at some time during the course of the disease.

Malar or discoid rash

Photosensitivity

Oral or nasopharyngeal ulcerations

Nonerosive arthritis of two or more

peripheral joints

Pleuritis or pericarditis

Profuse proteinuria, exceeding 0.5 g./day, or

excessive cellular casts in the urine

Seizures or psychoses

Hemolytic anemia, leukopenia,

lymphopenia, or  thrombocytopenia

Positive lupus erythematosus cell,

anti-DNA, or anti-Sm test or chronic

false-positive serologic test for syphilis

Abnormal titer of antinuclear antibody.

Prognosis

Death may occur in 10-15% of cases due to kidney failure or autoimmune damage to the heart. Serious damage to central  nervous system is also possible.

Conventional treatments

Non-steroidal antiinflammatory drugs (NSAID). Gastrointestinal side effects common. Nephrotoxicity is possible.

Corticosteroids. Full range of side effects common: adrenal disorders, weight gain, infections, hypertension, osteoporosis, bone necrosis, cataracts, glaucoma, diabetes mellitus, myopathy, irregular menses, irritability, insomnia, and psychosis.

Antimalarials. Ocular side effects common.

Sources: Braunwald; Cahill

References

Braunwald, E.  Harrison’s Principles of Internal Medicine, Eleventh Edition. New York: McGraw-Hill, 1987

Cahill, M. Professional Guide to Diseases. Springhouse, Pennsylvania: Springhouse Corporation, 1998

Chang R Functional properties of edible mushrooms. Nutr Rev 1996 Nov;54(11 Pt 2):S91-S93

Dharmananda S. A Bag of Pearls. Portland, Oregon: Institute for Traditional Medicine, 1990

He J, Li Y, Wei S, Guo M, Fu W. Effects of mixture of Astragalus membranaceus, Fructus Ligustri lucidi and Eclipta prostrata on immune function in mice Hua Hsi I Ko Ta Hsueh Hsueh Pao 1992 Sep;23(4):408-411

He Y, Li R, Chen Q, Lin Z, Xia D, Ma L Chemical studies on immunologically active polysaccharides of Ganoderma lucidum(Leyss. ex Fr.) Karst  Chung Kuo Chung Yao Tsa Chih 1992 Apr;17(4):226-228

Pizzorno, J. Total Wellness. Rocklin, California: Prima Publishing, 1996

Trowell, H.C. and Burkitt, D.P. Western Diseases, their Emergence and Prevention.  Cambridge, Massachusetts: Harvard University Press, 1981

Wang GL, Lin ZB The immunomodulatory effect of lentinan. Yao Hsueh Hsueh Pao 1996;31(2):86-90

Yoshida Y, Wang MQ, Liu JN, Shan BE, Yamashita U. Immunomodulating activity of Chinese medicinal herbs and Oldenlandia diffusa in particular Int J Immunopharmacol 1997 Jul;19(7):359-370.

Inflammatory Joint Diseases and rheumatic disorders and Nursing Intervention Lecture

February 15th, 2011 Admin 797 Views

Inflammatory Joint DiseasesRheumatic Disorders- More than 100 different disorders that affect muscles, bones, ligaments, tendons and joints.Rheumatoid arthritis – it is a systemic inflammatory disorder of the connective tissue/joints characterized by chronicity, remissions and exacerbations.

Systemic Lupus Erythematosus (SLE) – A diffuse connective tissue disease affecting multiple body systems – skin, joints, kidney, serous membrane of heart, lungs, lymph nodes and GI tract.Scleroderma– is a chronic autoimmune disease characterized by fibrosis or progressive hardening of skin in patches or diffusely with rigidity of underlying tissues. The cause is unknown ,so there is no direct cure for scleroderma.- Polymyalgia rheumatica (PMR)– is an inflammatory condition of the muscles, which causes pain or stiffness, usually in the neck, shoulders, and hips. The pain can be very sudden, or can occur gradually over a period of time. PMR usually goes away within a year or two after treatment. PMR is usually treated with long courses of oral steroid

Osteoarthritis – is a group of diseases and mechanical abnormalities involving degradation of joints. Clinical manifestations of OA may include joint pain, tenderness, stiffness, creaking, locking of joints. Treatment of OA consists of exercise, manual therapy, lifestyle modification, medication and other interventions to alleviate pain

Ankylosing spondylitis – chronic connective tissue disorder of spine and surrounding cartilaginous joints such as sacroiliac joints and soft tissues around vetebrae. No cure is known for AS, although treatments and medications are available to reduce symptoms and painReiter’s syndrome – is an autoimmune condition that develops in response to an infection in another part of the body. Coming into contact with bacteria and developing an infection can trigger reactive arthritis. The main goal of treatment is to identify the underlying infectious source with the appropriate antibiotics if still present.

Psoriatic arthritis – a skin disease characterized by reddish marinated patches with profuse silvery scaling on extensor surfaces like knees and elbows. Affects around 10-30% of people suffering from the chronic skin condition psoriasis.Gout – is a medical condition that usually presents with recurrent attacks of acute inflammatory arthritis (red, tender, hot, swollen joint) affects the feet, elbows, ankles and knees. It is caused by elevated levels of uric acid in the blood.Systemic Lupus Erythematosus SLE- Increased autoantibody production resulting from abnormal suppressor T-cell function.- Caused by combination of genetic, hormonal and environmental factors.- Onset often in childbearing years and may be insidious or acute.Signs and symptoms:- Arthritis, joint swelling, tenderness and pain.- Skin lesions and butterfly shaped rash on nose and cheeks.- Pericarditis and pleural effusions.- Inflammation of arterioles causing lesions and necrosis.- Lymphadenopathy: swollen/enlarged lymph nodes- Behavioral and cognitive changes- Depression and psychosis- Fever, fatigue, weight loss

SLE Management

- Can be life threatening- Control acute exacerbations that may damage organs- NSAIDS and corticosteroids- Antimalarial medications- Immunosuppressive agents.Nursing Diagnosis of SLE:- Fatigue.- Impaired skin integrity- Body image disturbanceRheumatoid Arthritis- Autoimmune disease- Result of immune response- The arthritis of joints known as synovitis, is inflammation of the synovial membrane that lines joints and tendon sheaths. Joints become swollen, tender and warm, and stiffness limits their movement- Degenerative changes – loss of articular surfaces and joint motion.- Inflammation involves other areas as well as joints, blood vessels, lungs, heart, kidneys.

Assessment Of Rheumatic Arthritis- Functional assessment – gait, posture.- Family History – hereditary componentSigns and symptoms:- Acute onset of bilateral and symmetric pain, joint swelling, warmth, erythema, loss of function.- Begins in small joints of hands, wrists, feet.- Progresses to knees, shoulders, hips, elbows, spine.- Deformity in hands and feet is common, caused by swelling and joint destruction.- Rheumatoid nodules (nontender, movable in subcutaneous tissue over bony prominences).- Raynaud’s phenomenon (cold and stress induced vasospasm in fingers and toes causing cyanosis).Systemic effectsFever, weight loss, fatigue, anemia, lymph node enlargement, arteritis, neuropathy, pericarditis, splenomegaly, dry eyes and mucous membranes.Rheumatic Arthritis Tests- Arthrocenteseis (needle aspiration of synovial fluid – cloudy with increased inflammatory cells)- X-ray shows cartilage abnormality, joint erosion, narrowing of joint space.- Blood tests- Rheumatoid factor,- Increased ESR,- Decreased RBCManagement of Rheumatic Arthritis- Early education, balance of rest and exercise- Salicylates, NSAIDS (anti-inflammatory and analgesic)- Antirheumatic agents- Antimalarials, methotrexate.- Corticosteroids- Antidepressant (amitriptylline) for sleep disturbance

- Reconstructive surgery when pain unrelieved.- Immunosuppressive agents (methotrexate, cyclophosphamide) for advanced diseaseincreased – toxicity, bone marrow suppression, anemia, GI disturbance.Osteoarthritis - Degenerative joint disease- Inflammation and degeneration of cartilage and bone- Many types, some hereditary, related top obesity, joint trauma, heavy physical activity.

Symptoms of Osteoarthritis- Pain, stiffness in morning relieved with movement- Functional impairment- Occurs most often in weight bearing joints (hips, knee, spine) but dinger joints often involved- Bony nodules (painless)- Tender and enlarged joints.- X-ray: loss of joint cartilage, spurs.- Blood studies not usefulManagement- Preventive measures can slow progress- Weight reduction, prevent injuries- Apply heat, rest the joint- Splints and braces to support inflamed joints- Acetaminophen, NSAIDS- Intraarticular injection of corticosteroidsSurgery when pain not manageable or function loss (arthroplasty).Gout- Defect in purine metabolism resulting in hyperuricemia- Oversecretion of uric acid or decreased excretion, or combination- Urate crystals precipitate within the joint causing inflammatory response- Repeated attacks cause accumulations of sodium urate crystals (Tophi) to be deposited in greater toe, hands, ear.- Urate deposits in kidneys cause kidney stones- Causes : severe diet, starvation, excessive intake of high purine foods (shellfish, organ meats) heredity, leukemia, multiple myeloma, altered renal function (caused by diuretics, ASA, ethanol).Signs and symptoms of Gout- Acute gouty arthritis (recurrent, severe attacks of inflammation) triggered by trauma, alcohol ingestion, dieting, medications, stress, illness.- Abrupt onset at night of severe pain, redness, swelling and warmth.- Tophi is a deposit of monosodium urate crystals in people with longstanding high levels of uric acid in the blood- Renal impairment and kidney stones.Management  Of Gout- Colchicine lowers deposits of uric acid- NSAIDS to decrease inflammation- Uricosuric agents (probenecid) to correct hyperuricemia and dissolve deposited urate.

- Allopurinol prevents uric acid formation (side effects of bone marrow suppression, vomiting, abdominal pain).

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Nursing Diagnosis Fatigue

Posted by d.nurisna at Friday, June 18, 2010 . Friday, June 18, 2010 Labels: NURSING DIAGNOSIS Nursing Definition for Nursing Diagnosis Fatigue An overwhelming, sustained sense of exhaustion and decreased capacity for physical and mental work at usual level

Characteristics: Inability to restore energy even after sleep; lack of energy or inability to maintain usual level of physical activity; increase in rest requirements; tired; inability to maintain usual routines; verbalization of an unremitting and overwhelming lack of energy; lethargic or listless; perceived need for additional energy to accomplish routine tasks; increase in physical complaints; compromised concentration; disinterest in surroundings, introspection; decreased performance; compromised libido; drowsy; feelings of guilt for not keeping up with responsibilities

Related Factors: Boring lifestyle; stress; anxiety; depression Humidity; lights; noise; temperature Negative life events; occupation Sleep deprivation; pregnancy; poor physical condition; disease states (cancer, HIV, multiple sclerosis); increased physical exertion; malnutrition; anemia

NOC Outcomes (Nursing Outcomes Classification)• Endurance • Concentration • Energy Conservation • Nutritional Status: Energy

Client Outcomes

Verbalizes increased energy and improved well-being Explains energy conservation plan to offset fatigue 

NIC Interventions (Nursing Interventions Classification)Energy Management

Nursing Interventions

Assess severity of fatigue on a scale of 0 to 10; assess frequency of fatigue, activities associated with increased fatigue, ability to perform activities of daily living (ADLs), times of increased energy, ability to concentrate, mood, and usual pattern of activity.

Evaluate adequacy of nutrition and sleep. Encourage the client to get adequate rest. Refer to Imbalanced Nutrition: less than body requirements or Disturbed Sleep pattern if appropriate.

Determine with help from the primary care practitioner whether there is a physiological or psychological cause of fatigue that could be treated, such as anemia, electrolyte imbalance, hypothyroidism, depression, or medication effect.

Work with the physician to determine if the client has chronic fatigue syndrome. Encourage client to express feelings about fatigue; use active listening techniques and

help identify sources of hope. Encourage client to keep a journal of activities, symptoms of fatigue, and feelings. Assist client with ADLs as necessary; encourage independence without causing

exhaustion. Help client set small, easily achieved short-term goals such as writing two sentences in a

journal daily or walking to the end of the hallway twice daily. With physician's approval, refer to physical therapy for carefully monitored aerobic

exercise program. Refer client to diagnosis-appropriate support groups such as National Chronic Fatigue

Syndrome Association or Multiple Sclerosis Association. Help client identify essential and nonessential tasks and determine what can be delegated. Give client permission to limit social and role demands if needed (e.g., switch to part-

time employment, hire cleaning service). Refer client to occupational therapy to learn new energy-conserving ways to perform

tasks. If client is very weak, refer to physical therapy for prescription and use of a mobility aid

such as a walker. Identify recent losses; monitor for depression as a possible contributing factor to fatigue. Review medications for side effects. Certain medications (e.g., beta-blockers,

antihistamines, pain medications) may cause fatigue in the elderly. 

Home Care Interventions

Assess client's history and current patterns of fatigue as they relate to the home environment. Fatigue may be more pronounced in specific settings for physical or psychological reason.

Assess home for environmental and behavioral triggers of increased fatigue When assisting client with adapting to home and daily patterns, avoid activities of high

energy output. Refer to occupational therapy to accomplish this if necessary. Assist client with identifying or creating a safe, restful place within the home that can be

used routinely (e.g., a room with familiar, nonthreatening, or nonfrightening belongings).

Client/Family Teaching

Share information about fatigue and how to live with it, including need for positive self-talk.

Teach strategies for energy conservation Teach client to carry a pocket calendar, make lists of required activities, and post

reminders around the house. Teach the importance of following a healthy lifestyle with adequate nutrition and rest,

pain relief, and appropriate exercise to decrease fatigue. Teach stress-reduction techniques such as controlled breathing, imagery, and use of

music. See Anxiety care plan if appropriate; anxiety is correlated with increased fatigue.