SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

Dr. Angelo Smith M.DWHPL

Autoimmune disease that affects multisystems

1.5 million cases of lupus Prevalence of 17 to 48 per

100,000 population Women > Men - 9:1 ratio 90% cases are women African Americans > Whites Onset usually between ages of

15 and 45 years, but Can occur in childhood or later

in life

Clinical Manifestations

Ranges from a relatively mild disorder to rapidly progressing, affecting many body systems.

Chronic with relapsing and remitting course.

Most commonly affects the skin / muscles, lining of lungs, heart, nervous tissue, and kidneys

Etiology

Etiology is unknown Most probable causes

Genetic influence Hormones Environmental factors Certain medications

Pathogenesis of SLE

Pathophysiology

Autoimmune reactions directed against constituents of cell nucleus, DNA

Antibody response related to B and T cell hyperactivity

General symptoms

The most common symptoms listed as initial complaints are fatigue, fever, and weight loss.

Fever: fever secondary to active disease was recorded from 50% to 86%. No fever curve or pattern is characteristic. It can be difficult, but very important to distinguish the fever of SLE from that caused by complicating infections.

Clinical Manifestations

Infection Increased susceptibility to infections

Fever should be considered serious

Infections such as pneumonia are a common cause of death

Fatigue is common in patients with SLE, especially during periods of disease activity. It is also often the only symptom that remains after treatment of acute flares.

Low grade fever, anemia, or any source of inflammation can result in fatigue.

Clinical Manifestations

Dermatologic Cutaneous vascular lesions Photosensitivity Butterfly rash (Malar Rash) Oral/nasopharyngeal ulcers Alopecia

Malar Rash

Discoid Rash

Maculopapular eruption

Oral Ulcers

Raynaud’s phenomenon is commonly found in lupus. It lack specificity.

(a triphasic reaction of distal digits to cold or emotion, in which the skin colour changes from white to blue to red)

Vasculitic skin lesion

Clinical Manifestations

Musculoskeletal (jaccoud arthropathy) Polyarthralgia with morning stiffness A vascular necrosis Arthritis bilateral – hands / wrists /

kneesSwan neck fingersUlnar deviationSubluxation with hyperlaxity of joints

Avacular necrosis of bone

Clinical Manifestations

Cardiopulmonary Tachypnea Pleurisy Dysrhythmias Accelerated CAD Pericarditis

Pulmonary manifestations Pleurisy it is the most common

manifestation of pulmonary involvement of SLE. The volume of pleural effusions usually is small to moderate and maybe unilateral or bilateral. Large pleural effusion are uncommon. It usually exudative in character.

Pleural effusions may also occur in SLE patients with nephrotic syndrome, infection, cardiac failure.

Lung 1) acute lupus pneumonitis:

fever, dyspnea, cough with scanty sputum, hemoptysis, tachypnea and pleuritic chest pain.

2) pulmonary hemorrhage 3) chronic diffuse interstitial

lung disease. the diagnosis should not be made

until infectious processes such as viral pneumonia, tuberculosis, and other bacterial, fungal and pneumocystis carinii infection have been completely excluded.

Cardiovascular manifestations

Pericarditis is the most common cardiac manifestation of SLE.

Myocarditis (the clinical features of lupus myocarditis resembles that of viral myocarditis)

Libman-Sacks endocarditis and valvular disease

Hypertension, cardiac failure

SLE can be associated with endocarditis.

Shown here is Libman-Sacks endocarditis in which there are many flat, reddish-tan vegetations spreading over the mitral valve and chordae.

Clinical Manifestations

Renal Lupus nephritisRanging from mild proteinuria to glomerulonephritis

Primary goal in treatment is slowing the progression

Haematuria Proteinure (>0.5g protein/d or

3+ ) Cast

Lupus nephritis

Class I Minimal mesangial Normal light microscopy; abnormal electron microscopy

Class II Mesangial proliferative

Hypercellular on light microscopy

Class III Focal proliferative <50% glomeruli involved

Class IV Diffuse proliferative >50% glomeruli involved; segmental/global

Class V Membranous Predominantly nephrotic disease

Class VI Advanced sclerosing Chronic lesions and sclerosis

Clinical Manifestations

Nervous system Generalized/focal seizures Peripheral neuropathy Cognitive dysfunction

DisorientationMemory and reasoning deficitsPsychiatric symptoms – severe depression / psychosis

Clinical Manifestations

Red blood cells a normochromic, normocytic

anemia is frequently found in SLE. They appears to be related to chronic inflammation, drug-related haemorrhage.

haemolytic anemia as detected by the Coombs’ test is the feature of SLE.

on rare occasion, a serum antibody may be produced which impairs red cell production.

Platelets thrombocytopenia (<100*109/L)

appears to be mediated by anti-platelet antibodies or/and anti-phospholipid antibodies.

White blood cell leucopenia (<4.0*109/L), its cause

is probably a combination of destruction of white cells by autoantibodies, decreased marrow production, increased or marginal splenic pooling, and complement activation.

it should also noted that the immunosuppressive drugs used in the treatment of SLE may cause a marked leucopenia.

Gastrointestinal and hepatic manifestation

Esophagitis, dysphagia, nausea, vomiting: (drug related in most cases)

Chronic intestinal pseudo-obstruction, mesenteric vasculitis, protein-losing enteropathy

Pancreatitis Lupus hepatitis

Diagnostic Studies

No specific test SLE is diagnosed primarily

on criteria relating to patient history, physical examination, and laboratory findings

On examination Constitutional – lymphadenopathy,

hepatosplenomegaly Musculoskeletal – Jaccoud

arthropathy Dermatologic - capillaroscopy Renal Neuropsychiatric Cardiopulmonary – friction rubs,

pulmonary embolism, Libman-Sacks endocarditis

GIT – peritonitis, pancreatitis, mesenteric vasculitis

Diagnostic Studies

Antinuclear antibodies ANA and other antibodies indicate

autoimmune disease Anti-DNA and anti-Smith antibody

tests most specific for SLE LE prep can be positive with other

rheumatoid diseases ESR & CRP are indicative of

inflammatory activity

Radiological studies

Joint x-rays: no erosions, periarticular osteopenia + soft tissue swelling

CXR/CT chest: interstitial lung disease, pneumonitis, pulmonary emboli, alveolar hemorrhage

CTBrain or Brain MRI ± angiography: lupus white matter changes, vasculitis or stroke

Echo: pericardial effusion, pulmonary hypertension or Libman-Sacks endocarditis

Additional work-up

- Serum cr. and albumin- CBC w/ diff- U/A- ESR- Complement levels- Renal profile if warranted

Invasive procedures

LP – nonspecific ↑cells + protein, ↓ glucose

Renal biopsy – prognosis and Rx

Skin biopsy

Diagnostic criteria

American College of Rheumatology

4/11 criteria (sens 85%, specif 95%)

“SOAP BRAIN MD” Serositis – heart, lung,

peritoneum Oral ulcers – painless esp

palate Arthritis – non-erosive Photosensitivity

Diagnostic criteria Blood disorders - ↓RBC (Coombs +),

PLT, WCC, Lymphocytes Renal involvement – proteinuria /±

casts ANA – titer > 1:160 Immunologic phenomena – LE cells,

anti-dsDNA Ab, anti-Sm Ab, antiphospholipid Ab, false WR +

Neurological disorders – seizures/ psychosis

Malar rash – cheeks + nasal bridge Discoid rash – rimmed with scaling,

follicular plugging

Treatment Treatment plans are based on patient age,

sex, health, symptoms, and lifestyle and on disease severity Fever, skin, musculoskeletal and serositis =

milder disease CNS and renal involvement – aggressive Rx

Goals of treatment are to: -prevent flares -treat flares when they occur -minimize organ damage and

complications

Collaborative Care

Drug therapy NSAIDs Antimalarial drugs Steroid-sparing drugs Corticosteroids Immunosuppressive drugs

Conservative management

For those w/out major organ involvement. NSAIDs: to control pain, swelling, and

fever Caution w/ NSAIDS though. SLE pts are at

increased risk for aseptic meningitis Antimalarials: Generally to treat fatigue

joint pain, skin rashes, and inflammation of the lungs

Commonly used: Hydroxycholorquine Used alone or in combination with other

drugs

Corticosteroids (Mainstay of SLE treatment)

To rapidly suppress inflammation Usually start with high-dose IV

pulse and convert to PO steroids with goal of tapering and converting to something else.

Commonly used: prednisone, hydrocortisone, methylprednisolone, and dexamethasone

Immunosuppressives Primarily for CNS/renal involvement Mycophenolate mofetil (cellcept) Azathioprine (imuran): requires several

months to be effective, effective in smaller percentage of patients

MTX: for treatment of dermatitis and arthritis, not life-threatening disease

Cyclosporine: used in steroid-resistant SLE, risk of nephrotoxicity

Cyclophosphamide (cytoxan) Almost all trials performed on patients with nephritis

Differential diagnosis

Drug induced lupus erythematosis

Vasculitis Leukemia HIV Multiple sclerosis Parvovirus or other viral

infections

Prognosis

Benign to rapidly progressive Better for isolated skin + musculoskeletal

disease vs renal and CNS Death rate 3X age-comparable general

population

Mortality

Nephritis (most within 5 yrs of symptoms) Infectious (active SLE + Rx – most common) CVS disease (50X more MI than other woman) Malignancy (chronic inflammation + Rx)

SLE disease activity index (SLEDAI)Clinical feature score

seizure , psychosis , organ brain syndrome 8

visual disturbance, cranial nerve disorder 8

lupus headache, cerebrovascular accidents, 8

vasculitis 8

arthritis 4

myositis 4

urinary casts, hematuria, proteinure, pyuria 4

rash, alopecia, mucosal ulcers, 2

pleurisy, pericarditis 2

low complement, increased DNA binding 2

fever 1

thrombocytopenia, leucopenia 1

Other therapy

Plasma exchange Intravenous Immunoglobulin Stem cell transplantation Immune therapy ( anti-IL10,

anti-CD20, and immune tolerance therapy)