POLYMYALGIA RHEUMATICA AND GIANT CELL ARTERITIS

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are two closely related inflammatory syndromes.

Occur in the same patient population, suggesting common risk factors and pathogenic pathways.

Both syndromes share laboratory abnormalities that reflect a vigorous acute-phase response and are critical for diagnosing and monitoring affected patients.

GIANT CELL ARTERITIS

EPIDEMIOLOGY Incidence of GCA varies widely in different

populations, from less than 0.1 per 100,000 to 33 per 100,000 persons aged 50 years and older.

Highest incidence figures found in Scandinavians and in Americans of Scandinavian descent.

The lowest incidence of GCA is reported in Japanese, northern Indians, and African Americans.

Women are affected about twice as often as men.

Age is the greatest risk factor for developing either condition.

The incidence of GCA rises from 1.54 cases per 100,000 people in the sixth decade to 20.7 per 100,000 in the eighth decade.

Experimental evidence supports a T-cell–mediated immunopathology of GCA.

B cells are not found within the arterial wall; no pathognomic antibodies have been identifi ed; and hypergammaglobulinemia is absent.

Panarteritis of medium and large arteries is combined with an intense systemic inflammatory syndrome.

Vasculitic lesions cause luminal occlusion and tissue ischemia or aortic aneurysm.

Preferentially targeted vascular beds include the branches of the external carotid, subclavian, common carotid, and vertebral arteries and aorta.

(1) MONONUCLEAR CELLS ENTER THE ADVENTITIA VIA THE VASA VASORUM, WHERE T CELLS RECOGNIZE ANTIGENS AND PRODUCEIFN-GAMMA. (2) THE INFI TRATE ADVANCES TO THE MEDIA, WHERE MACROPHAGES AND GIANT CELLS UNDERGO DIFFERENTIATION AND EXERT TISSUE-INJURIOUS EFFECTOR FUNCTIONS. (3) THE ARTERY RESPONDS WITH NEOANGIOGENESIS AND INTIMAL HYPERPLASIA.

PATHOGENESIS OF GIANT CELL ARTERITIS.

SYMPTOMS AND SIGNS GIANT CELL ARTERITIS AMERICAN COLLEGE OF RHEUMATOLOGY 1990

CRITERIA FOR THE CLASSIFICATION OF GIANT CELL ARTERITIS

1. Age at disease onset ≥ 50 years2. Headache of new onset or new type3. Tenderness or decreased pulsation of

temporal artery4. Elevated erythrocyte sedimentation rate

(≥50 mm/hr)5. Histologic changes of arteritis (either

granulomatous lesions, usually with multinucleated giant cells, or diffuse mononuclear cell infiltration)

CLASSIC PRESENTING MANIFESTATIONS OF GIANT CELL ARTERITIS

Symptoms Percentage of Cases

Headache 70

Jaw claudication 50

Constitutional symptoms 50

Polymyalgia rheumatica 40

Visual loss 20

Abnormal temporal artery 50

Anemia 80

Erythrocyte sedimentation rate >50 mm/h

90

Arthritis 15

ATYPICAL MANIFESTATIONS OF GCA ( PRESENT IN 40% OF CASES)Fever of unknown origin

Respiratory tract symptoms

Neurologic symptoms

Large artery involvement

Tumor like lesions

SIADH

GCA causes 2% of all cases of fever of unknown origin

 Dry cough  Mononeuritis multiplex

Claudication in arms or legs

Especially of the breasts and ovaries

accounts for 16% of all cases of fuo in patients over the age of 65.

Throat pain Stroke Unequal arm blood pressures

white blood cell count is almost always normal

Tongue pain

Transient ischemic attack

Thoracic aortic aneurysm

presenting complaint in 1 of 25.

Dementia

Hallucinations

Giant cell arteritis presents with two major symptomatic complexes,

A. Signs of vascular insufficiency resulting from impaired blood flow .

B. Signs of systemic inflammation. Symptoms can wax and wane and resolve

temporarily, even in the absence of treatment.

Cranial Vasculature Arteritis

Extracranial Arteritis

Systemic Inflammatory Syndrome

Headaches Aortic Arch Syndrome

WastingSyndrome

Ischemia of the Eye, Brain

Fever of Unknown Origin

Ischemia of the Cranial nerves

Malaise

CRANIAL ARTERITIS

SYMPTOMS1. Headaches 2. Scalp tenderness3. Jaw claudication4. Tongue claudication5. Visual loss6. Transient ischemic attacks7. Strokes

Headache : Diffuse or Localized, usually in the temporal, occipital, or periorbital areas.

severe, refractory to standard analgesics, and interfere with sleep.

Scalp tenderness : Localized over the temporal and occipital arteries or diffuse

OCULAR COMPLICATIONS

15% of patients experience ophthalmic complications.

Ischemia in the territory of the ophthalmic artery is the leading cause of ocular problems.

Visual loss is1. Pain free2. Partial or complete3. Unilateral or Bilateral4. Irreversible.

Most common cause is anterior ischemic optic neuropathy resulting from occlusion of the posterior ciliary arteries supplying the optic nerve.

Ophthalmologic examination:pale disc edema resulting from ischemic damage to the optic nerve head

LARGE-VESSEL ARTERITIS AND AORTITIS

Stenotic lesions occur in1) Distal subclavian arteries 2) Axillary arteries3) Brachial arteries

AORTITIS

Aortic arch syndrome: Ischemia of the upper extremities Pulseless disease.

Ischemic pain during :Activities involving the arms, such as brushing teeth, working overhead.

Blood pressure readings are asymmetric, bilaterally diminished, or absent.

Raynaud’s phenomenon–like symptoms with paleness, bluish discoloration, and dysesthesias

Tissue gangrene, affecting the fingertips Bilateral, or unilateral involvement or asymmetric

patterning

SYSTEMIC INFLAMMATORY SYNDROME WITH ARTERITIS

1. Fever. 15% of cases, fever of unknown origin is the initial presentation

2. Malaise.3. Fatigue.4. Weakness. 5. Anorexia, Weight loss.6. Depression.

CLINICAL SPECTRUM OF THE GIANT CELL ARTERITIS/POLYMYALGIA RHEUMATICA SYNDROME.

LABORATORY FINDINGS

The ESR averages about 100 mm/h in GCA. An ESR >30 mm/h is present in 96% of

patients with GCA, and an ESR of >50 mm/h is seen in 87% of patients with GCA.

The Creactive protein is also usually elevated and may be more sensitive than the ESR in detecting flares.

The anemia, typically normochromic and normocytic, is usually mild with a hematocrit often in the 32–35 range.

The platelet count, often elevated nonspecifically by inflammatory disorders, is frequently increased in GCA.

Magnetic resonance angiography or computed tomography angiography can provide noninvasive assessment of larger artery disease.

Positron emission tomography scanning can demonstrate occult large-vessel inflammation.

IMAGING STUDIES

Blood vessel imaging has gained importance as a method for assessing the extent of vasculitis or even for making a GCA diagnosis.

In patients with the subclavian, axillary, vertebral, carotid artery involvement, imaging can establish the diagnosis.

Detecting and monitoring aortic arch involvement depend heavily on imaging procedures.

Conventional radiographic angiography remains superior for detailed assessment of vessel anatomy and luminal status and is an absolute requirement for preoperative evaluation.

FDG-PET reportedly indicates inflammatory activity in the vessel wall in GCA and PMR.

Increased uptake of labeled glucose by inflammatory cells provides the underlying mechanisms of detection, but no properly designed studies have been conducted to assess this procedure’s specificity and sensitivity.

Specifically, it is unknown whether subtle inflammation in atherosclerotic lesions can be distinguished from active arteritis in a patient population expected to have widespread atherosclerosis.

OCCLUSION OF THE AXILLARY-BRACHIAL JUNCTION. ANGIOGRAM SHOWING IRREGULARITY OF THE RIGHT SUBCLAVIAN ARTERY WITHOCCLUSION AT THE AXILLARY-BRACHIAL JUNCTION AND FORMATION OF COLLATERAL VESSELS

DIGITAL SUBTRACTION IMAGE.

MAGNETIC RESONANCE ANGIOGRAM OF THE GREAT VESSELSSHOWS NARROWING OF THE SUBCLAVIAN ARTERY DISTAL TO THE ORIGIN OF THE VERTEBRAL ARTERY.

CONTRAST-ENHANCED CT IMAGE OF THE CHEST SHOWS PRONOUNCED ECTASIA OF THEASCENDING AORTA, MINIMAL THICKENING, AND IRREGULARITY OF THE WALL.

MAKING A DIAGNOSIS

The diagnosis of GCA is suggested by the 1. Clinical picture 2. Elevated ESR3. Proven by a positive temporal artery biopsy. Patients with large artery involvement

Subclavian disease, are diagnosed byA. Magnetic resonance imaging,B. Computed tomography angiography, or C. Conventional angiography showing long,

smooth arterial taperings uncharacteristic of atherosclerosis

TEMPORAL ARTER BIOPSY SPECIMEN IS SHOWN. CHARACTERISTIC CHANGES INCLUDE A PANMURAL MONONUCLEAR INFI LTRATE, DESTRUCTION OF THE INTERNAL AND EXTERNAL ELASTIC LAMINAE, AND CONCENTRIC INTIMAL HYPERPLASIA.

TREATMENT

Corticosteroids Corticosteroids are highly effective in GCA

treatment. Initial doses of 60 mg prednisone or

equivalent have been recommended. Initial doses should be maintained until

reversible manifestations of the disease have responded and the systemic inflammatory syndrome is suppressed.

Under close monitoring for clinical signs of disease reactivation, the dose of prednisone generally can be tapered by 10% every 1 to 2 weeks.

Aspirin is an important adjunctive treatment for GCA patients without contraindications.

ADJUVANT THERAPY

While on chronic corticosteroids, patients should be monitored for bone mineral density, hypertension, and diabetes mellitus.

Measures to prevent osteoporosis include calcium and vitamin D supplements, bone protective therapy.

PROGNOSIS

If diagnosed and treated promptly, progression of the downstream effects of arterial wall inflammation, in particular lumen occlusion with tissue ischemia, can be prevented.

In the majority of patients, GCA does not enter remissions that are sustained indefi nitely after discontinuation of glucocorticoids

POLYMYALGIA RHEUMATICA

Polymyalgia rheumatica is a syndrome of pain and stiffness, typically affecting proximal muscles of the shoulder and pelvic girdle.

PMR is frequently encountered in patients with GCA in whom it may precede, follow, or accompany manifestations of vasculitis.

A small proportion (10%-20%) of patients with PMR and no clinical evidence of vasculitis have frank vascular inflammation on biopsy.

POLYMYALGIA RHEUMATICA: DIAGNOSTIC CRITERIA

1) Age at onset = 50 years or older

2) Erythrocyte sedimentation rate > 40 mm/hr

3) Bilateral aching and stiffness for ≥ 1 month and involving two of the following areas:

Neck or Torso Shoulders or Proximal regions

of the arms Hips or Proximal aspects of

the thighs4) Exclusion of all other

diagnoses causing polymyalgia rheumatica–like symptoms

1) Age at onset = 50 years or older

2) Erythrocyte sedimentation rate > 40 mm/hr

3) Pain persisting for ≥ 1 month and involving two of the following areas: neck, shoulders, and pelvic girdle

4) Absence of other diseases capable of causing the musculoskeletal symptoms

5) Morning stiffness lasting more than 1 hour

6) Rapid response to prednisone (≤20 mg/day)

Chuang et al, 1982 Healey, 1984

PMR affects the same patient population as GCA, but occurs approximately two to three times more frequently.

Women are affected more often than men, and the diagnosis is extremely unlikely in individuals younger than 50 years of age.

High-risk populations: Scandinavians and other peoples of Northern European descent.

Annual incidence rates have been estimated at 20 to 53 per 100,000 persons over the age of 50 years.

In low-risk populations, such as Italians, the annual incidence rates for individuals aged 50 years and older are only 10 cases per 100,000.

CLINICAL FEATURES

Onset is abrupt Aching and pain in the muscles of the neck,

shoulders, lower back, hips, thighs, and occasionally the trunk.

Myalgias are Symmetrical. Nocturnal pain. Weight loss, anorexia, malaise, and

depression are common.

Patients with PMR must be carefully evaluated for possible GCA.

A negative temporal artery biopsy does not exclude the possibility of large vessel vasculitis targeting primarily the subclavian and axillary arteries and the aorta.

Signs of vascular insufficiency, including claudication in the extremities, bruits over arteries, and discrepant blood pressure readings should alert the physician to the possibility of GCA .

MRA can be helpful in confirming the concomitant diagnosis of large vessel vasculitis.

Biceps tendonitis and glenohumeral synovitis may also be present.

Ultrasonography reveals fluid accumulation in the bursae; T2-weighted MRI shows thickening and edema.

DIFFERENTIAL DIAGNOSIS1) Arthropathies2) Shoulder disorders3) Inflammatory myopathies4) Hypothyroidism5) Parkinson’sdisease6) Malignancies7) Infections. 8) Lack of the typical and impressive improvement

upon initiation of therapy can provide a clue towards reevaluating the diagnosis of PMR

DISEASE ENTITIES WITH POLYMYALGIAS1) Rheumatoid arthritis2) Rotator cuff syndrome3) Osteoarthritis of shoulder and hip joints4) Fibromyalgia5) Polymyositis/dermatomyositis6) Spondyloarthritis7) Systemic lupus erythematosus8) Vasculitides9) Paraneoplastic myalgias10) Infection-associated myalgias11) Statin therapy12) RS3PE (remitting seronegative symmetric synovitis and

pitting edema)13) Parkinson’s disease14) Hypothyroidism

TREATMENT

Polymyalgia rheumatica is dramatically responsive to glucocorticoid therapy.

Two thirds of patients can be expected to respond with remission of pain and stiffness when started on 20 mg/day or less prednisone.

Some patients will need doses as high as 40 mg/day for complete clinical control.

Patients initially controlled on 20 mg/day of prednisone can usually taper the dose by 2.5 mg every 10 to 14 days.

In many patients, PMR can go into long-term remission, and prednisone can be discontinued.

PROGNOSIS

The prognosis of patients with PMR is good. In the majority of patients, the condition is

self-limited. A proportion of patients will eventually

present with typical symmetrical polyarthritis, fulfilling the criteria for the diagnosis of seronegative rheumatoid arthritis.

Such patients may require disease-modifying antirheumatic drug (DMARD) therapy.