Clinical features and diagnosis of small-vessel vasculitis

MICROSCOPIC POLYANGIITIS

The history of MPA dates to 1866, with the description of periarteritis nodosa.⁷ The term “microscopic polyarteritis” was introduced in 1948, when glomerular disease was recognized in some patients.⁸ In 1994, the Chapel Hill Consensus Conference defined MPA as a necrotizing vasculitis with few or no immune deposits that affects small vessels (ie, capillaries, venules, or arterioles). Necrotizing arteritis of small- and medium-sized arteries may be present. Necrotizing glomerulonephritis and pulmonary capillaritis commonly occur.⁹ MPA shares many clinical features with GPA and is currently said to be distinguished by the absence of granulomatous inflammation.⁹

Presentations and manifestations

In one assessment of organ system involvement in 85 patients with MPA, investigators observed glomerular syndrome in 82% of patients.¹⁰ They also found a high predilection for involvement of the skin, joints, and lungs. Pulmonary hemorrhage is a particularly important manifestation of MPA because it can be immediately life-threatening.

Differential diagnosis

The differential diagnosis for MPA is similar to GPA in the inclusion of other causes of classic pulmonary-renal syndromes, such as antiglomerular basement membrane disease and systemic lupus erythematosus. Poststreptococcal glomerulonephritis should be considered when the kidney is the predominant organ involved in the absence of lung disease. In the setting of pulmonary infiltrates, infections and neoplasms remain significant in the differential diagnosis.

Diagnostic evaluation

The diagnosis of MPA is based on consistent clinical features and compatible histologic findings. The histologic renal lesion is identical to that seen in GPA. Pulmonary disease typically includes capillaritis and is notable for the absence of evidence of immune deposition, in contrast to antiglomerular basement membrane disease.

Chest imaging is indicated when MPA is part of the differential diagnosis. Computed tomography is the preferred technique, as early alveolar hemorrhage that can occur in MPA may not be visualized on a chest radiograph.

Laboratory assessment should include serum chemistries, complete blood count, erythrocyte sedimentation rate, measurement of C-reactive protein, and urinalysis. Additional testing should be pursued for other diseases as indicated by the clinical features.

Approximately 40% to 80% of patients with MPA have MPO-pANCA.⁵ Approximately 15% of patients are MPO-pANCA positive,⁶ and 0% to 20% are ANCA-negative. As with GPA, ANCA is useful to suggest—but not diagnose—disease in many instances. The absence of ANCA does not rule out MPA.

EOSINOPHILIC GPA

Eosinophilic GPA is a unique entity characterized by eosinophil-rich and granulomatous inflammation involving the respiratory tract and necrotizing vasculitis of small- to medium-size vessels. It is also associated with asthma and eosinophilia.

Different disease phases

Eosinophilic GPA is often thought of as having three phases: prodromal, eosinophilic, and vasculitic.^11,12 Although helpful conceptually, these phases may not always be present and may not occur in sequence.

The prodromal phase is characterized by asthma associated with allergic rhinitis with or without polyposis. The eosinophilic phase is characterized by the presence of eosinophilia in the blood and tissue. Eosinophilia is a prominent feature, although accurate detection and assessment can be challenging in the setting of glucocorticoid use for asthma as this normalizes the eosinophil count.

The vasculitic phase distinguishes EGPA from other eosinophilic disorders. Features of vasculitis may occur in multiple organ sites, including the nerves, lungs, heart, gastrointestinal tract, and kidneys. In one series of 96 patients, nearly 100% had asthma, and peripheral nervous system involvement in the form of mononeuritis multiplex was present in 72%.¹² Cardiac involvement is of particular importance as it is a prominent cause of disease-related mortality. Cardiac manifestations include myocarditis, pericarditis, endocarditis, valvulitis, and coronary vasculitis.

Differential diagnosis

The differential diagnosis of EGPA shares similarities with GPA and MPA, but also includes eosino philic disorders such as hypereosinophilic syndrome, eosinophilic leukemia, and parasitic diseases.

Diagnostic evaluation

Diagnosis is often based on the presence of asthma, a finding of peripheral eosinophilia (> 1,500 cells/mm³), and the presence of systemic vasculitis involving, ideally, two or more extrapulmonary organs. While histologic confirmation remains ideal, demonstration of characteristic findings on biopsy can be difficult. Glomerular involvement is far less common than in GPA and MPA, but, when present, the renal lesion is identical. Pulmonary histologic findings can be diverse and include the classic “allergic-granuloma” as originally described by Churg and Strauss, as well as isolated granulomatous inflammation, eosinophilic inflammation, or small-vessel vasculitis. Tissue eosinophilia is a prominent finding that typically is seen on biopsies of skin, nerve, and gastrointestinal tissues.

Chest imaging should be performed when EGPA is part of the differential diagnosis. Because of the potential for cardiac involvement, a baseline echocardiogram should be obtained. Pulmonary function tests may be useful, particularly in patients who have a strong asthmatic component.

Similar to GPA and MPA, laboratory assessment includes serum chemistries, complete blood count with differential to determine the eosinophil count, erythrocyte sedimentation rate, measurement of C-reactive protein, and urinalysis. With the allergic and asthmatic components, immunoglobulin E levels are frequently elevated. Additional testing for other eosinophilic diseases should be pursued as indicated by the clinical features.

Only about 40% of patients are ANCA-positive.¹³ Most of these are MPO-pANCA, with PR3-cANCA occurring less commonly. Although some reports have suggested differing clinical patterns of EGPA based on ANCA positivity, the presence or absence of ANCA is less helpful in the diagnosis.¹³