Churg-Strauss Disease Workup

Updated: Jul 21, 2020
  • Author: Nir Shimony, MD; Chief Editor: Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP  more...
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Workup

Approach Considerations

Diagnosis of Churg-Strauss disease (CSD), now known as eosinophilic granulomatosis with polyangiitis (EGPA), is in many cases a process comprised of several tests, clinical visits, and high suspicion. The main reason for this relatively cumbersome diagnosis process is that many of the symptoms and signs change over time, hence delaying clear diagnosis. There is no gold standard diagnostic tool. For all these reasons EGPA diagnosis is mainly clinical with support of lab work and sometimes histopathology and biopsy. As such, when a patient presents with eosinophilic asthma, the clinician must look for a pattern of multisystem disease and investigate for other supportive findings.

Peripheral blood eosinophilia (greater than 10% on differential white blood cell count or greater than 1500 /dl) is the best-known lab hallmark of the disease. Elevated serum IgE is also found in 75% of patients. [101]

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Laboratory Studies

The first (prodromal) phase of Churg-Strauss disease (CSD), now known as eosinophilic granulomatosis with polyangiitis (EGPA), consists of asthma usually in association with other typical allergic features, which may include eosinophilia. During the second phase, the clinical presentation with EGPA, eosinophilia is characteristic (see below) and ANCAs with perinuclear staining pattern (pANCAs) are detected.

Where possible, the diagnosis is confirmed by demonstration of angiographic abnormalities in affected organs and by pathognomonic biopsy findings (see Histologic Findings).

According to the American College of Rheumatology criteria, clinical diagnosis is established when 4 of the following manifestations are documented: (1) allergic history, (2) asthma, (3) eosinophilia, (4) migratory pulmonary infiltrates, (5) paranasal sinus abnormality, (6) mononeuropathy or polyneuropathy, and (7) demonstration of extravascular eosinophilic infiltration of tissues on biopsy.

Eosinophil count

Once the second phase of EGPA is reached, eosinophilia (> 1500/µL or > 10% of total peripheral WBCs) is found on the peripheral blood film of at least 90% of untreated patients.

Mean values for absolute eosinophil counts are in the range of 5,000–9,000/µL, but, in rare instances, counts may exceed 100,000/µL. Thus, the history of asthma with the ensuing development of eosinophilia is highly suggestive of EGPA.

Treatment of asthmatic manifestations of the first stage of EGPA with corticosteroids may promptly resolve this characteristic finding. The prompt resolution of eosinophilia with corticosteroid treatment is itself characteristic of EGPA.

Intermittent elevations of eosinophil counts during the third phase of EGPA may presage a relapse of systemic vasculitis.

Other features

Elevations of ANCA titers are found in 40% of cases of EGPA; these are predominantly pANCAs directed against myeloperoxidase epitopes. [27]

Enzyme-linked immunosorbent assays specific for antimyeloperoxidase antibodies were positive in 10 of 11 patients in whom this test was performed by Guillevin et al. [27]

Serum IgE concentrations are elevated in three quarters of patients in the second or third phase of Churg-Strauss disease.

Erythrocyte sedimentation rate (ESR) and other indices suggestive of the presence of acute-phase reactants may be elevated. Abnormality of sedimentation rate may rapidly (and characteristically, as is also true of eosinophilia) disappear within a few days of treatment with corticosteroids.

Testing for rheumatoid factor is positive in approximately 70% of cases.

False-positive precipitin test results for syphilis have been reported.

Lactate dehydrogenase (LDH) level may be elevated and, as with eosinophilia and elevated sedimentation rate, may correct within a day or a few days after initiation of corticosteroid treatment.

Blood urea nitrogen and creatinine levels may be elevated in individuals who develop ANCA-associated renal vasculitis. Gross or microscopic hematuria and pyuria may be found and are due to inflammatory glomerulonephritis, although they may be misinterpreted as representing urinary tract infection. Dysmorphic red cells or red-cell casts in the urine sediment are consistent with the presence of glomerulonephritis; high-grade proteinemia is also suggestive, although the absence of proteinuria does not exclude glomerulonephritis.

Vasculitis, neurological, and renal manifestations are more common among ANCA-positive patients. [131, 132, 137, 138]  

Serum IgG4 levels and CCL17 levels correlate with disease activity. [133, 113]

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Imaging Studies

Chest radiographs

Chest radiographs demonstrate pulmonary infiltrates in at least half of the patients in the second phase of Churg-Strauss disease (CSD), now known as eosinophilic granulomatosis with polyangiitis (EGPA), and a greater percentage in the third phase of the disease. Typically, these are transient patchy alveolar infiltrates, usually without preferential, lobar, or segmental distribution. In some instances, a diffuse interstitial infiltrative pattern may be apparent.

Lungs may be hyperinflated.

Nonsegmental reticulonodular opacities without cavitation may be found. These may be solitary but may be multiple in more advanced cases. In some patients with advanced disease, striking bilateral reticulonodular opacities are observed.

Bronchial walls may be thickened.

Enlarged intrapulmonary lymph nodes may be found in some cases. This unusual finding suggests EGPA in asthmatic patients who have no history of heavy smoking.

Pleural effusions are not common. Pulmonary hemorrhage is a particularly suggestive and ominous sign in EGPA.

Imaging of the heart may reveal cardiomegaly or pericardial effusion.

CT scan of the lungs

CT scan of the lungs demonstrates the above-mentioned findings of EGPA even more clearly. In most cases of advanced disease, thin-section lung CT scan also reveals the highly suggestive finding of bilateral, ground-glass pulmonary opacity.

Subpleural airspace consolidation is an additional feature in about half of cases, whereas more widespread consolidation is discerned occasionally.

Occasional finding of centrolobular nodular densities within the background ground-glass opacity is highly suggestive of EGPA. This change is much more apparent on CT scan than on plain radiographs, as is the thickening of interlobular septi and bronchial wall.

Increased vascular wall caliber also may be discerned.

Enlarged hilar or mediastinal lymph nodes also are apparent on pulmonary thin-section CT scan in many patients with EGPA, representing an opportunity for diagnostic biopsy.

Pleural or pericardial effusions can be seen in up to 30% of the cases.

Other imaging studies

Results of abdominal or renal angiography usually are negative in EGPA. However, EGPA may account for less than 5% of all cases of ANCA-associated renal vasculitis, whereas microscopic polyangiitis (MPA) accounts for approximately half, and Wegener granulomatosis (WG) approximately one third of such cases.

MRI of the brain in patients with CNS manifestations may reveal vascular territory infarction, with or without hemorrhage. Areas of bright signal on T2-weighted MRI suggestive of vasculitis may be found. [34]

Upper respiratory obstruction is present in respirometry  in up to 70% of the cases, and can be persistent after treatment in up to 40% of the cases. [103]

Because of the devastating results of untreated cardiac manifestations, cardiac investigation including MRI should be considered in some of the cases.

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Other Tests

Electrophysiological studies

Electrophysiological studies of peripheral nerves may reveal deficits referable to both myelinated and unmyelinated sensory and motor fibers, especially those subserving the lower extremities.

Abnormalities in the findings of electrophysiological studies of the sciatic nerve (including tibial and peroneal branches) typically are more profound than those in the radial, median, and cubital nerves. The absence of conduction blocks may be helpful in distinguishing Churg-Strauss mononeuritis multiplex from chronic inflammatory demyelinating polyneuropathy.

Patients may be found to manifest acute-onset reduction or absence of sensory nerve action potentials.

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Procedures

Procedures that may be valuable in the diagnosis of Churg-Strauss disease (CSD), now known as eosinophilic granulomatosis with polyangiitis (EGPA), have been reviewed and include the following:

  • Biopsy specimens of skin, hilar lymph nodes, lung parenchyma, or peripheral nerve demonstrate the characteristic vasculitis. Kidney biopsy sample may show segmental necrotizing glomerulonephritis with crescent formation, possibly including highly characteristic eosinophilic infiltration of the renal interstitium.

  • Electrophysiological studies of peripheral nerves.

Biopsy

Biopsy results in Churg-Strauss disease (CSD), now known as eosinophilic granulomatosis with polyangiitis (EGPA), may demonstrate eosinophilic vasculitis, especially involving the outer zone of the adventitia of medium (10–150 μ m) to small (30–50 μ m) arteries. However, it may be found that infiltrating cells are predominantly lymphocytic while eosinophils may be less prominent or even rare. Vascular wall necrosis with loss of inner elastic vascular lamina and associated hyaline degeneration may be observed. Involved vessels often show occlusion and recanalization. Granuloma formation is rare. The region of arteriopathic change chiefly consists of a central eosinophilic core surrounded by an inflammatory exudate consisting of macrophages, epithelioid cells, and giant cells. Similarly constituted inflammatory exudate may infiltrate the perivascular surround. Fibrinoid necrosis of the vascular media may be discerned.

Nerve biopsy specimens may show similar vascular changes in the epineural space in as many as half of all cases with EGPA neuropathy. Sural nerve biopsy is hence the gold standard test in documenting peripheral neuropathy. Evidence of axonal degeneration is the most common finding, and necrotizing vasculitis and perineural eosinophilic infiltration can only be confirmed in half of the cases. Focal loss of myelinated nerves and subperineural edema is characteristic. Immunohistochemical changes on biopsy specimens may confirm the presence of CD4-, CD45 RO- or CD8+ T cells, CD3+ Pan-T lymphocytes, or CD-68 positive macrophages. MHC-class I cells (beta2-microglobulin positive) and MHC class II cells (HLA-DR) may be found—the later particularly in the endoneurium, accompanied by CD68+ macrophages. CD20+ B cells are comparatively rare as are deposits of IgG or C3d complement.

Histopathologic studies of a biopsy specimen of affected skin areas reveal small-vessel arteriopathy with granuloma formation in the vascular walls. Enlarged intrapulmonary, hilar, or mediastinal lymph nodes or pulmonary nodules, if biopsied, may reveal similar characteristic histologic abnormalities.

Biopsy of lung parenchyma may show tissue injury and eosinophilia without necrotizing vasculitis or the presence of extravascular granulomata.

Nerve biopsies reveal vasculitic epineural necrosis in more than half of patients with clinical neuropathy. As has been noted, the predominant cell type within the epineural inflammatory exudate is lymphocytes expressing CD8+ or CD4+ T-cell markers. Lesser numbers of eosinophils are found, with small numbers of CD20+ B cells. Scarce deposits of IgG, IgE, and C3d antibodies may be detected.

Kidney biopsy may reveal eosinophilic interstitial pauci-immune segmental glomerulonephritis. Occasionally, glomerulonephritis with IgA deposition is found.

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