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 CELLSRECOGNIZE ANTIGENS AND PRODUCEIFN-GAMMA.(2) THE INFI TRATE ADVANCES TO THE MEDIA, WHERE MACROPHAGES AND GIANT CELLSUNDERGO DIFFERENTIATION AND EXERT TISSUE-INJURIOUS EFFECTOR FUNCTIONS. (3) THE ARTERY RESPONDS WITH NEOANGIOGENESIS AND INTIMAL HYPERPLASIA.
SYMPTOMS AND SIGNSGIANT CELL ARTERITIS AMERICAN COLLEGE OF RHEUMATOLOGY 1990 CRITERIA FOR THE CLASSIFICATION OF GIANT CELL ARTERITIS1. 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)
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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 Extracranial Arteritis SystemicArteritis Inflammatory SyndromeHeadaches Aortic Arch Syndrome Wasting SyndromeIschemia of the Eye, Fever of UnknownBrain OriginIschemia of the MalaiseCranial nerves
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
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 WITHARTERITIS1. Fever. 15% of cases, fever of unknown origin is the initial presentation2. 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 SHOWINGIRREGULARITY OF THE RIGHT SUBCLAVIAN ARTERY WITHOCCLUSION AT THE AXILLARY-BRACHIAL JUNCTION AND FORMATION OF COLLATERALVESSELS
MAGNETIC RESONANCE ANGIOGRAM OF THE GREAT VESSELSSHOWS NARROWING OF THE SUBCLAVIAN ARTERY DISTAL TO THE ORIGIN OFTHE VERTEBRAL ARTERY.
CONTRAST-ENHANCED CT IMAGE OF THE CHEST SHOWS PRONOUNCED ECTASIA OFTHEASCENDING AORTA, MINIMAL THICKENING, AND IRREGULARITY OF THE WALL.
MAKING A DIAGNOSIS The diagnosis of GCA is suggested by the1. Clinical picture2. 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, orC. Conventional angiography showing long, smooth arterial taperings uncharacteristic of atherosclerosis
TEMPORAL ARTER BIOPSY SPECIMEN IS SHOWN.CHARACTERISTIC CHANGES INCLUDE A PANMURAL MONONUCLEAR INFI LTRATE, DESTRUCTIONOF 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 CRITERIAChuang et al, 1982 Healey, 19841) Age at onset = 50 years or 1) Age at onset = 50 years or older older2) Erythrocyte sedimentation rate 2) Erythrocyte sedimentation rate > 40 mm/hr > 40 mm/hr3) Bilateral aching and stiffness 3) Pain persisting for ≥ 1 month for ≥ 1 month and involving two and involving two of the of the following areas: following areas: neck, Neck or Torso shoulders, and pelvic girdle Shoulders or Proximal regions 4) Absence of other diseases of the arms capable of causing the musculoskeletal symptoms Hips or Proximal aspects of the thighs 5) Morning stiffness lasting more than 1 hour4) Exclusion of all other diagnoses causing polymyalgia 6) Rapid response to prednisone rheumatica–like symptoms (≤20 mg/day)
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 WITHPOLYMYALGIAS1) 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.