After the diagnosis of EGPA has been made, three disease phases are often recognizable: the prodrome, eosinophilia/tissue infiltration, and vasculitis.
The prodrome phase is characterized by the presence of allergic disease (typically asthma or allergic rhinitis). This phase often lasts for several years.
During the eosinophilia/tissue infiltration phase, striking peripheral eosinophilia may occur. Tissue infiltration by eosinophils is observed in the heart, lung, gastrointestinal tract, and other tissues.
In the third phase, vasculitis, systemic necrotizing vasculitis affects a wide range of organs, ranging from the heart and lungs to the peripheral nerves and skin (Figure 34–1).
A: Foot of a patient with eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg-Strauss syndrome) showing livedo reticularis and a cutaneous ulcer just superior to the medial malleolus. The patient’s foot is held in extension because of a left foot drop (vasculitis neuropathy of the left peroneal nerve). B: Eosinophilic pneumonia in a patient with EGPA. Biopsy shows dense clusters of eosinophils within the lung parenchyma.
Upper airway disease in EGPA usually takes the form of nasal polyps or allergic rhinitis. A surprisingly high percentage of patients with EGPA have histories of nasal polypectomies, usually long before suspicion of an underlying disease is raised. Although pansinusitis occurs frequently, destructive upper airway disease is not characteristic of EGPA.
Middle ear granulation tissue with eosinophilic infiltrates occurs in some patients, leading to conductive hearing loss. Cases of sensorineural hearing loss (see Chapter 68) have also been reported.
More than 90% of patients with EGPA have histories of asthma. Typically, the asthma represents either adult-onset reactive airway disease or, less commonly, a significant worsening of long-standing disease. Upon encroachment of the vasculitic phase of EGPA, patients’ asthma may improve substantially, even before therapy for vasculitis has begun. Following successful treatment of the vasculitic phase, however, glucocorticoid-dependent asthma persists in many patients.
The pathologic features of lung disease in EGPA vary according to the disease phase. In the early phases, there may be extensive eosinophilic infiltration of the alveoli and interstitium. During the vasculitic phase, necrotizing vasculitis and granuloma may be evident. In the current era, when many patients with asthma are treated with systemic glucocorticoids, lung biopsy specimens showing all three histologic hallmarks of this disease are unusual.
Mononeuritis multiplex occurs with a remarkable frequency in EGPA, with often devastating effects. Vasculitic neuropathy was evident in 74 (77%) of the 96 patients in one series. Nerve infarctions may appear several weeks after the start of appropriate treatment, but do not always indicate the need to intensify therapy, particularly if treatment with both high-dose prednisone and cyclophosphamide has already been initiated. This may be due to continued disease activity but is more likely secondary to thrombosis of vessels that have become severely compromised by previously active inflammation. Clinically, nerve infarctions are heralded by the abrupt occurrence of a foot drop, wrist drop, or some other focal nerve lesion. Muscle wasting secondary to nerve infarctions may continue to appear for weeks after the disease has been brought under control (Figure 34–2).
The ravages of vasculitic neuropathy. Bilateral ankle-foot orthoses required because of bilateral foot drop. Note severe muscle wasting in both legs.
Cardiac involvement also occurs with a disproportionate frequency in EGPA, and is a common cause of death. Some form of cardiac involvement occurred in 12.5% of patients in one large series. Congestive heart failure is the most common cardiac manifestation, although coronary arteritis and valvular abnormalities have also been reported.
Skin disease in EGPA takes many forms, none of which is specific: Palpable purpura, papules, ulcers, and vesiculobullous lesions are common. Nodular skin lesions are usually “Churg-Strauss granuloma” (cutaneous extravascular necrotizing granuloma). These tend to occur on the extensor surfaces of the elbows and other pressure points. Skin biopsy specimens in EGPA reveal eosinophilic infiltration of blood vessel walls. Splinter hemorrhages, digital ischemia, and gangrene associated with inflammation in medium-sized digital arteries are often present at the time of diagnosis.
EGPA is less likely to cause end-stage renal disease than are other forms of ANCA-associated vasculitis. Acute kidney injury may be caused by an eosinophil-mediated interstitial nephritis. When glomerulonephritis does occur, however, the histopathologic findings are often indistinguishable from those of other forms of pauci-immune vasculitis (eg, granulomatosis with polyangiitis [formerly Wegener granulomatosis], microscopic polyangiitis, and renal-limited vasculitis).
Nonspecific arthralgias and frank arthritis often occur early in the course of EGPA. The arthritis of EGPA is migratory in nature and may assume a variety of joint patterns, from a pauciarticular syndrome of lower extremity joints to a polyarthritis of the small joints of the hands.
Eosinophilia (before treatment) is a sine qua non of EGPA. Eosinophil counts may comprise as much as 60% of the total white blood cell count. Eosinophil counts are usually sensitive markers of disease flares, but generally respond very quickly to treatment with high doses of glucocorticoids. Most patients with EGPA also have elevated serum IgE levels. Serum complement levels are usually normal. Immune complexes are not believed to play a primary role in this disease. The erythrocyte sedimentation rate, serum C-reactive protein level, and eosinophil count can be useful in the longitudinal evaluation of disease activity. The reported percentages of EGPA patients with ANCA are variable, with most figures in the literature in the range of 50% (see Chapter 32 for a full discussion of ANCA). Antibodies to either proteinase-3 or MPO (but not to both) may be found. Of the two vasculitis-specific ANCAs, which include antibodies to MPO and proteinase-3, those to MPO are more common in EGPA. MPO-ANCAs usually produce a perinuclear-ANCA (P-ANCA) pattern on serum immunofluorescence testing. Patients who are ANCA-negative tend to have more cardiopulmonary complications, while patients who are ANCA-positive tend to have more of the classic vasculitic manifestations of this disease, although there is considerable overlap between these two groups.
Pulmonary infiltrates are evident in approximately one third of patients with EGPA. These lesions are usually migratory infiltrates that occur bilaterally. Pulmonary hemorrhage is unusual but has been reported. Nodular or cavitary lesions suggest the alternative diagnoses of granulomatosis with polyangiitis (formerly Wegener granulomatosis), infection, or malignancy. Among patients with cardiac involvement, echocardiography or cardiac MRI may confirm poor cardiac function consistent with cardiomyopathy or demonstrate findings compatible with regional myocardial fibrosis.