Biopsies reveal mild inflammation of the synovium and periarticular structures, with the infiltrate made up of macrophages and T cells (especially CD4⁺ helper cells), resembling the infiltrate of GCA. Biopsy of the temporal artery is negative, and interferon-γ levels are not elevated.

Clinically, the onset is gradual, with the condition developing over weeks or months. Bilateral pain and stiffness of periarticular structures in the neck and shoulders are the presentations in two thirds of cases, with hip and thigh involvement accounting for the other one third. Symptoms may begin unilaterally, but eventually, they become bilateral. Many patients experience
both shoulder-girdle and thigh discomfort. Diffuse swelling of the hands and feet occurs in some patients, with pitting edema of the dorsal surfaces being characteristic. Morning stiffness and pain with movement are highly characteristic. Synovitis has been documented histologically, and rotator cuff bursitis and synovitis can be demonstrated by magnetic resonance imaging (MRI). Muscle biopsy specimens are usually normal or show minor inflammatory infiltrates; muscle strength is unimpaired. Low-grade fever, weight loss, and fatigue may accompany the musculoskeletal symptoms and are believed to represent the systemic effects of cytokines produced as part of the inflammatory process. The erythrocyte sedimentation rate (ESR) is characteristically greater than 50 mm/h, but an occasional patient with characteristic clinical features of PMR may have an ESR of less than 40 mm/h and a milder form of the disease. The ESR correlates with disease activity, as do levels of other acute-phase reactants such as interleukin-6 and C-reactive protein.

PMR tends to be a self-limited illness with a duration of 1 to 2 years. Three subsets of patients have been described: One responds promptly to initial steroid therapy and has no flares after taper; the required course of steroids is relatively short. A second also responds satisfactorily but has repeated flares and requires a longer course of steroids. A third does not respond to the initial doses of steroids, so that higher initial amounts are necessary; in addition, more flares occur, and a prolonged course of steroids is required. The risk for progression to temporal arthritis appears to be low in the first group and possibly increased in the last two. The pretreatment ESR and the response of the interleukin-6 level to treatment help to identify these subsets.

As noted, PMR shares many of the immunologic features of GCA, which suggests that PMR may be a forme fruste of the later condition. The risk of developing full-blown vasculitic disease averages 10% to 15%. Why some persons progress to vasculitis whereas others experience only a mild periarticular disease is unknown.

Pathologic manifestations include histiocytic, lymphocytic, and characteristic multinucleated giant cell infiltrations of the walls of medium-sized and large arteries originating from the aortic arch. The aortic arch and any one of these vessels can be involved, but those of the head are most often affected. The reason for this distribution is unknown. The inflammatory process tends to be segmental, producing a patchy distribution with “skip” areas. The internal elastic lamina is fragmented, and intimal proliferation develops as part of the attempted repair process, narrowing the vascular lumen and accounting for the ischemia that ensues. There is no evidence of thrombosis. The aorta does not occlude, but vasculitic involvement does subject it to aneurysmal dilation and intramural hemorrhage.

Several clinicopathologic subtypes have been identified:

The presentation may be gradual or abrupt. Early symptoms may include headache, low-grade temperature, and the aching and stiffness of PMR. Headache is reported in about 70% of cases and is the initial symptom in about 35%. The pain can be piercing or throbbing, often localized to the arteries of the scalp and unlike that of any previous headache. Polymyalgia symptoms may be the presenting manifestation in more than 50% of cases. Constitutional symptoms of fatigue, malaise, anorexia, and weight loss occur in the majority of patients. In about one fifth of patients, the presentation may be atypical, with fever of unknown origin being a classic atypical presentation of GCA (accounting for about 15% of cases of FUO in patients older than the age of 65 years).

As the condition progresses, cranial artery tenderness and enlargement may be noted. The temporal artery is most commonly affected, but any cranial artery may become involved, as may the carotids. Ischemic symptoms such as masseter or jaw claudication (jaw pain with chewing) occur in one third to one half of patients. Visual manifestations are the consequence of vasculitis of the ophthalmic or posterior ciliary arteries. Blindness, the most dreaded manifestation, has an abrupt onset and irreversible course unless it is treated very aggressively and very early (seelater discussion). Vision loss is sometimes preceded by transient visual symptoms, such as amaurosis fugax, flashing lights, diplopia, or field defects. In untreated patients, visual loss occurs in up to 50% of cases; loss in one eye increases the risk of loss in the other to 50%. Acute hearing loss and vertigo have also been reported, as has painful dysphagia. Carotid involvement may present as localized tenderness in the neck accompanied by neurologic deficits.

An aortic arch syndrome may occur if the arch or a major branch vessel is involved. The risk for aortic aneurysm and dissection is increased nearly 20-fold in such persons; most often, the thoracic aorta is involved, but occasionally, just the abdominal aorta is affected, leading to gastrointestinal complaints. Granulomatous inflammation of the aortic wall is found. Subclavian occlusive disease may cause ischemic symptoms in the arms (e.g., Raynaud phenomenon, arm claudication); on examination, diminished pulses may be noted and a subclavian bruit heard. The temporal arteries are often spared.

The systemic inflammatory variant is dominated by a wasting syndrome of fever, progressive weight loss, night sweats, and fatigue in association with evidence of temporal artery inflammation, but often without occlusive vascular disease. Interleukin levels are high.

A markedly increased ESR is characteristic of all forms of the disease; a normal sedimentation rate in the absence of strongly suggestive symptoms makes the diagnosis unlikely.

A low-grade anemia of chronic disease and mild elevations of serum liver enzymes are also often present. On occasion, the anemia can be severe.

GCA is a chronic illness that may last for years. Although it tends to be self-limited, the clinical course is highly variable. Complications of late disease are rare, but attempts to discontinue therapy often cause relapses.