AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Churg-Strauss disease is one of the 3 important common leukocytoclastic (ie, fibrinoid, necrotizing, inflammatory) systemic small-vessel vasculitides associated with antineutrophil cytoplasm antibodies (ANCAs). Of these, it is the least common. The others are Wegener granulomatosis (WG) and microscopic polyangiitis (MPA). Although these conditions are not thought to be directly infectious, microbial superantigens may play a role in provoking the onset of the dysregulated immune response that gives rise to these conditions.

In 1951, Jacob Churg and Lotte Strauss of Sweden first made a distinction between Churg-Strauss disease and polyarteritis nodosa (PAN). The Chapel Hill Consensus classification of systemic vasculitides distinguished PAN from Churg-Strauss because PAN predominantly affects medium-sized blood vessels (medium sized and small arteries), while Churg-Strauss predominantly affects small vessels (capillaries, venules, arterioles). The medium-sized vessel predilection of PAN is shared with Kawasaki disease, conditions that spare capillaries, arterioles, and venules. Lie (1994) has emphasized the fact that Churg-Strauss, WG, and MPA are not exclusively small-vessel vasculitides but may also involve the medium-sized vessels that are the characteristic targets of PAN.

In addition to the ANCA-associated small-vessel vasculitides WG and MPA, there are also non-ANCA immune complex associated small-vessel vasculitides such as Schönlein-Henoch purpura (SHP), essential cryoglobulinemic vasculitis (ECV), lupus vasculitis, serum sickness vasculitis, and infection-induced immune complex vasculitis. Churg-Strauss is distinguished from these not only by the presence of ANCA but as well by its association with asthma and by the characteristically associated tissue and blood eosinophilia.

Churg-Strauss disease invariably involves the lungs and may, in addition, affect a wide variety of other tissues and organs of the body, including tissues of the nervous system. However, no single known manifestation of Churg-Strauss disease is pathognomonic. All of the clinical features overlap in some degree with manifestations found in other systemic necrotizing vasculitides.

In most cases of Churg-Strauss disease, the combination of predominantly respiratory tract disease, in association with a characteristic disease evolution involving asthma and eosinophilia is highly suggestive and the diagnosis may usually readily be confirmed by the identification of ANCA-positivity and demonstration of the distinctive eosinophilic vasculitis of small and some medium-sized vessels.

Nonetheless, it should be noted that occasional examples of diseases that straddle the boundaries between PAN, WG, MPA, and Churg-Strauss disease are encountered for which it is difficult with certainty which label is most appropriate. For this reason, a recent classification system by Watts and Scott combined these particular entities under the general heading primary systemic vasculitides.

Churg-Strauss disease also has considerable overlap with idiopathic hypereosinophilic syndrome. In such instances, the distinction of Churg-Strauss from these various other conditions, particularly those that share ANCA positivity, is usually made on the basis of prodromal asthma indicative of Churg-Strauss disease. In instances where the kidney is involved, ANCA-positive vasculitides also share, in distinction to other small-vessel vasculitides, presence of pauci-immune crescentic glomerulonephritis.

Idiopathic hypereosinophilic syndrome (IHES) closely resembles Churg-Strauss disease, differing particularly in that the prodromal asthmatic phase is absent. IHES is defined by (1) peripheral eosinophil count greater than 1500/µL for at least 6 months, (2) evidence of characteristic organ involvement, and (3) absence of other known cause. It affects men aged 20-50 years. The initial manifestations are cardiac, consisting of eosinophilic myocarditis with endocardial damage and confirmed by endomyocardial biopsy. Restrictive cardiomyopathy may ensue as thrombosis develops, promoted by the damaged endocardial surface. Fibrosis then occurs. Mitral or tricuspid incompetence may develop as a result of fibrotic degeneration of the chordae tendineae. In some instances, dilated cardiomyopathy develops.

Cardioembolic disease in IHES may produce neurological manifestations, but a primary encephalopathy also has been described. Sensory or mixed sensorimotor peripheral polyneuropathy, closely resembling that found in Churg-Strauss disease, may develop in a symmetrical or asymmetrical distribution. Mononeuropathy multiplex also may develop. Although prodromal asthma is not a feature, as many as 40% of patients with IHES manifest a persistent, dry cough at some stage of illness. Pulmonary dysfunction also may result from cardiac failure or cardiogenic pulmonary embolism.

Pulmonary infiltrates may be found in as many as 30% of cases of IHES, tending not to be peripheral. Parenchymal eosinophilic infiltration may be found and, rarely, eosinophilic pleural effusions develop. Diarrhea complicates about 20% of cases, while eosinophilic gastritis, enteritis, or colitis occasionally has been reported. Dermatologic manifestations may include urticaria, angioedema, or erythematous pruritic papules and nodules. Raynaud phenomenon, arthralgias, or joint effusions are occasional complications.

Pathophysiology

The pathophysiology of this disorder, particularly the triggering circumstances, is not well understood. Antineutrophil cytoplasmic antibodies (ANCAs) may in part mediate vascular endothelial injury in Churg-Strauss disease, as in PAN, MPA, and WG. In these conditions, ANCAs may promote polymorphonuclear (PMN) cell adherence to vascular endothelial cells, with ensuing lytic vascular endothelial injury. An independent or adjuvant role in this activation may be played by tumor necrosis factor (TNF).

Studies of affected peripheral nerve tissues show that once the stage of epineural necrotic vasculitis has been achieved, activated cytotoxic T-lymphocyte clones (ie, cluster of differentiation 8 [CD8⁺] suppressor/cytotoxic and CD4⁺ helper cells) begin to outnumber eosinophils and predominate in the inflammatory exudate. Occasionally, CD20⁺ B lymphocytes are found in the inflammatory exudate, and deposits of immunoglobulin (IgG), immunoglobulin E (IgE), and C3d antibodies may be detected.

Cytokines undoubtedly participate in this autoimmune process. Patients with Churg-Strauss disease have markedly increased serum levels of interferon alpha and interleukin (IL)–2 and moderate increases of TNF-alpha and IL-1beta similar to those observed in PAN. Elevations of serum IL-6 concentrations have been shown to precede the rise in serum rheumatoid factors that may accompany the onset of an exacerbation of Churg-Strauss vasculitis. Thus, the IL-6 may be an important triggering factor. The rheumatoid factors are chiefly of IgG and immunoglobulin M (IgM) classes, rather than immunoglobulin A (IgA) or IgE.

Perinuclear ANCAs (p-ANCAs), directed against myeloperoxidase, are found in patients with Churg-Strauss disease. Antibodies with this pattern of staining and antigenic specificity also are found in the uncertainly classified entity microscopic polyangiitis. Recent work suggests that a mutation in exon 11 of the CD18 gene may be permissive of the elaboration of antimyeloperoxidase antibodies in either of these 2 conditions.

In Wegener granulomatosis, on the other hand, the presence of cytoplasmic ANCAs (c-ANCAs) with antigenic specificity for proteinase-3 is characteristic. A case of one patient with p-ANCAs directed against myeloperoxidase and c-ANCAs against proteinase-3 has been reported; the patient manifested a combination of clinical characteristics suggesting both Churg-Strauss disease and temporal arteritis.

These immunological disturbances may provoke the translocation of proteinase-3 from within the azurophilic granules of PMN cells to the surface of the cell membrane. The attachment of PMN cells to the endothelial surface likely is enhanced by cytokine-mediated induction of adhesion molecules (eg, lymphocyte function-associated protein 1, IL adhesion molecule 1, endothelial-leukocyte adhesion molecule 1). Antiendothelial cell antibodies, detectable in many different primary vasculitic conditions as well as in systemic autoimmune disease with a vasculitic component, also may play a role in Churg-Strauss disease.

Abnormal expression of CD95 cellular receptors (producing a soluble splice variant rather than the usual membrane-bound isoform) may participate in the pathogenesis of Churg-Strauss disease. The result is impairment of normal apoptotic processes whereby lymphocytes and eosinophils are eliminated. This permits abnormal oligoclonal expansion of specific T-cell clones, which may mediate cellular injury. The soluble CD95 isoform has been termed eosinophil survival factor.

Epidemiological association of Churg-Strauss with the utilization of antileukotrienes for the treatment of asthma suggested the possibility that, in some instances, Churg-Strauss might be a drug-induced illness. In particular, an association has been detected with cysteinyl leukotriene 1 receptor antagonists. However, some authorities appear to regard this seeming association as the result of the "unmasking" of preexisting Churg-Strauss, as the introduction of leukotriene inhibitors permits corticosteroid doses to be reduced (Garcia-Marcos, 2003; Kemp, 2003).

Unlike most noninfectious vasculitides, Churg-Strauss disease is distinctive in its pathology, owing to the abundance of eosinophils in the inflammatory perivenular exudate. The vasculopathy is predominantly an arteriopathy, tending to affect small- and medium-sized arteries much more than arterioles, veins, or capillaries. This predilection also is found in PAN and some other conditions. However, the predominance of eosinophils sets Churg-Strauss disease apart from these other conditions. However, epithelioid and giant cells also are found in the inflammatory exudate of patients with Churg-Strauss disease.

The inflammatory arteriopathy evolves into granulomatous fibrinoid necrosis of the vascular media. The result of this process includes the development of collagenolytic or necrobiotic noninfectious granulomata. The granulomatous material surrounds altered vascular elastic fibers and collagen as well as acellular pigmented debris, which is helpful in pathologically distinguishing one form of granulomatous vasculitis from another. Churg-Strauss disease is associated with "red" collagenolytic granulomas.

Lungs are the chief organs involved in patients with Churg-Strauss vasculopathy, and they almost invariably develop regions of angiopathy as the disease progresses. Typical manifestations include granuloma formation, which occurs within vascular walls and in adjacent pulmonary tissues. Similar angiopathic changes develop in the heart (approximately 85%), skin (70%), peripheral nervous system (66%), central nervous system (60%), kidneys (40%), gastrointestinal tract (40%), and musculoskeletal system (20%).

Vasculitic involvement of the heart is found in approximately 85% of cases, typically manifesting as low-output congestive cardiac failure. Churg-Straus disease should be considered in adults with asthma and eosinophilia who develop chest pain, shortness of breath, and cardiogenic shock (Shanks, 2003).

• Evaluation reveals cardiomegaly, restrictive cardiomyopathy/perimyocarditis, diminished myocardial contractility, and pericardial effusion as factors contributing to heart failure.
• Both systolic and diastolic dysfunction may be discerned.
• Steady decline in myocardial shortening fraction often follows.
• Heart failure is the most important cause of death in Churg-Strauss disease and is a major determinant of prognosis.

Skin and nervous tissues are the systems next most commonly involved in patients with Churg-Strauss disease.

• The skin is involved in 65-70% of cases that have progressed to the systemic vasculitic phase. Small-vessel vasculitis of the skin results in purpura or nodules.
• Eosinophilic granulomatous changes in the wall of the gallbladder may result in obstructive jaundice or pain and require cholecystectomy (Tatsukawa, 2003).
• Approximately 64-80% of patients in the systemic phase of Churg-Strauss disease develop peripheral neuropathy, usually in the pattern of mononeuritis multiplex. Mononeuritis multiplex is the second most common initial manifestation of systemic vasculitis in adults with Churg-Strauss disease.
• Initial mononeuritic findings often progress to asymmetrical polyneuropathy, which is restricted to the limbs. As with PAN, both motor and sensory deficits are detectable, especially in the legs, thus, the sciatic nerves (including peroneal and tibial branches) are involved more frequently than radial, median, or cubital nerves.
• Sensory disturbances may include hypoesthesia or hyperesthesia, allodynia, and pain.
• Polyneuropathy may regress with treatment.
• Vasculitis of muscle develops in slightly more than 20% of patients.

Approximately 60% of adults with Churg-Strauss disease develop CNS vasculitis. This is unlike PAN, in which CNS manifestations are rare. However, CNS vasculitis has not been reported in children with Churg-Strauss disease. It does occur in adolescents, albeit rarely.

• Manifestations include intellectual and motor disturbances. These may be abrupt in onset, and seizures may occur.
• Acute cerebral hemorrhage is among the important causes of sudden death in Churg-Strauss disease. In some but not all instances, hemorrhage occurs in individuals who have hypertension.

Gastrointestinal dysfunction develops in 40-60% of patients. Most commonly, this takes the form of mesenteric vasculitis, similar to that seen in PAN.

• The most common manifestations are bloody diarrhea and abdominal pain.

Arteritis of medium-sized blood vessels of the kidneys develops in 20-50% of cases. However, hypertension is less common in Churg-Strauss disease than in PAN.

• As in PAN, the predominant renal pathology is eosinophilic interstitial pauci-immune segmental glomerulonephritis (Tatsukawa, 2003).
• Crescentic necrotic glomerulopathy may develop in some instances, as is also found in microscopic polyangiitis.
• IgA glomerulonephropathy may develop, as also is the case in microscopic polyangiitis, but rarely. This is a pathological change that is more typical of Schönlein-Henoch purpura.
• In early reports of Churg-Strauss disease, uremia was an occasional cause of death. Current management has considerably reduced the risk of uremia, and in most cases of Churg-Strauss disease, renal involvement is mild. Even if the renal involvement is severe, renal disease usually responds well to corticosteroid treatment.

Testicular pain, with or without epididymitis, may occur in men with Churg-Strauss disease.

Frequency

United States

Churg-Strauss disease is said to account for slightly more than 2% of all vasculitic illnesses. The various primary systemic vasculitides (Churg-Strauss disease, PAN, microscopic polyangiitis, Wegener granulomatosis) together are estimated by Watts et al to affect 15-25 per million individuals in North America annually.

International

Little information is available concerning international variation in the prevalence or incidence of Churg-Strauss disease.

Mortality/Morbidity

• The 5-year survival rate reported in the large series of Chumbley and associates is 62%.
• Morbidity is chiefly cardiopulmonary. Painful arthritis, arthralgia, and myalgia are common troublesome and recurrent manifestations. Abdominal pain, diarrhea, gastrointestinal bleeding, and bowel perforation are less common but important complications.Necrotizing glomerulonephritis occurs in fewer than half of the cases. It tends to affect older patients, who as a group have particularly poor outcomes. Early diagnosis of this renal complication improves outcome (Booth, 2003).Leukopenia due to immunosuppressive therapy enhances risk for sepsis and death, hence should be avoided (Booth, 2003).The chief neurological morbidity is, as in PAN, peripheral neuropathy.
• The chief causes of mortality related to Churg-Strauss disease are severe asthma, cardiopulmonary failure, or gastrointestinal complications. In general, the long-term outcome of Churg-Strauss disease does not differ greatly from that of PAN.

Race

Few data are available regarding racial variations in occurrence or severity of Churg-Strauss disease. In some studies, no racial predilection has been suggested; in others, without clear documentation, it has been suggested that Churg-Strauss disease shares with other systemic vasculitides the tendency toward greater prevalence in whites. Clearly additional data are necessary, using data of greater refinement entailing the casting of a wide socioeconomic and geographic net and greater precision in characterizing populations at risk than what may be based upon genetic markers of skin pigmentation.

Sex

• As with a number of other primary systemic vasculitides, males are slightly more likely than females to develop Churg-Strauss disease.
• The male-to-female ratio for Churg-Strauss disease is estimated by some to be approximately 1.4:1, similar to the sex-related risk ratio for the combined class of Churg-Strauss disease, PAN, microscopic polyangiitis, and Wegener granulomatosis. A higher risk ratio for males is found for one of the important differential considerations, hypereosinophilic syndrome (HES). HES is likely a heterogeneous collection of very severe diseases that are very rare and tend to occur in persons aged 20-50 years, with a male-to-female ratio of 9:1. It is not linked with asthma, but pulmonary disease may be found particularly on the basis of cardiac disease or pulmonary embolization.

Age

Most individuals with Churg-Strauss disease experience the onset of disease in the age range of 15-69 years. Peak risk for vasculitic manifestations is in the middle of the fourth decade of life. Thus, the vasculitic stages of Churg-Strauss disease tend to develop at earlier ages than other primary systemic vasculitides, for which the average age of occurrence is about 60-65 years.

• Churg-Strauss disease is chiefly a disease of adults, occurring in individuals with adult-onset asthma. The vasculitic stages of Churg-Strauss disease seldom, if ever, manifest themselves in small children, although they may do so in teenagers. On the other hand, the premonitory asthmatic stage of Churg-Strauss disease may manifest in children as young as 3 years.
• Although occurrence of the subsequent vascular stages of illness has been regarded as rare even in adolescents, some data suggest that as many as 20% of patients may manifest vasculitic findings in the second decade of life, often preceded by bronchial asthma during the first decade.
• Childhood-onset Churg-Strauss disease is less likely to be complicated by central nervous system vasculitis than cases that develop in middle-aged individuals.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Lanham divided the clinical evolution of Churg-Strauss disease into 3 phases.

• First phase
• • The first phase is prodromal to the 2 subsequent vasculitic phases. Bronchial asthma is the nearly constant finding of the first phase. The presence of an asthmatic condition (usually steroid-dependent) is the historical feature that most commonly prompts consideration of Churg-Strauss disease in individuals who manifest any of the many vasculitic abnormalities of various organ systems that may be present in ensuing stages of the disease.
  • However, it must be noted that it is possible for asthmatic individuals to develop vasculitic or inflammatory diseases other than Churg-Strauss disease as explanations for the disease of either pulmonary or nonpulmonary organ systems. The occurrence of tissue and blood eosinophilia provides an additional important clue in the individual who has asthma and abnormalities of sudden onset in several organ systems that Churg-Strauss disease is the likely cause of the various organ system disease manifestations noted below.
  • An additional historical fact of importance is the recent addition of leukotriene receptor antagonists to the treatment regimen for asthma. This association is found in perhaps half of the cases, in three quarters of these patients, the addition of those drugs was made within 3 months prior (Kawakami, 2005).
  • It must further be noted that exceedingly rarely, Churg-Strauss pathogenesis may result in disease of various organ systems in individuals who do not have either asthma or eosinophilia (Sharma, 2004).
  • Additional common findings are allergic rhinitis, nasal polyposis, sinusitis, and recurrent bronchitis or pneumonia. Nasal rhinitis and polyposis often precede the onset of reactive airway disease. The severity of asthma ranges from mild to quite severe and steroid-dependent.
  • The duration of the first phase, prior to progression of illness, averages about 28 months (range 4-72 mo). However, a few patients remain in the prodromal stage of illness for 30 years or more before the second or third phase of Churg-Strauss disease manifests.
  • Recurrent fevers of unclear etiology and weight loss, either of which may occur during the first phase of Churg-Strauss disease, enable the careful clinician to suspect that Churg-Strauss disease underlies the allergic and asthmatic manifestations. Another clue is the fact that the reactive airway component of Churg-Strauss disease tends to develop at a later age (commonly, the fourth decade of life) than is typical for idiopathic asthma. However, fairly typical early childhood-onset asthma may presage the development of the vasculitic stages of Churg-Strauss disease in adolescence.
  • The frequency of Churg-Strauss disease–related reactive airway disease increases, and the severity of the disease worsens, as the vasculitic stage of Churg-Strauss disease is reached. In some cases, an unexpected remission of asthma occurs with the onset of vasculitic manifestations of the second phase of Churg-Strauss disease.
• Second phase
• • During the second phase of illness, hypereosinophilia of blood develops in association with tissue eosinophilia and Loeffler syndrome. During this phase, the eosinophils comprise on average 40% of the WBC count on peripheral blood film (range, 18-65%). Particularly characteristic complications of this phase of illness are chronic eosinophilic pneumonia and eosinophilic gastroenteritis. Hemoptysis may occur. Patients experience a relapsing and remitting course of eosinophilic infiltrative disease and blood eosinophilia.
  • In some instances, the second phase of illness consists of the combination of chest pain, shortness of breath, and development of cardiogenic shock. ECG may suggest myocardial infarction, although coronary arteries may appear normal on angiography. Valvular insufficiency and segmental or global hypokinesis of the myocardium may be found. These findings suggest Churg-Strauss myocarditis (Shanks, 2003).
  • Fever always is present during periods of exacerbation.
• Third phase
• • Months to many years of such intermittent bouts precede the third phase, that of systemic vasculitis. Patients with continued reactive airway manifestations may experience remission, often to a remarkable extent, at the onset of this third phase of Churg-Strauss disease. As vasculitis develops and worsens, weight loss may be noted.
  • On average, progression from the initial stage of Churg-Strauss disease to fully developed systemic vasculitis takes about 3 years. In some quite fulminant cases, systemic vasculitic manifestations may develop without a prior second phase of relapsing-remitting complications. In other cases, the second and third phases of Churg-Strauss disease develop simultaneously. The interval between first and third phases of Churg-Strauss disease is prognostically significant. As might be expected, the shorter the duration of that interval, the worse the prognosis.
• Signs and symptoms may include any of the following:
• • Symptoms related to congestive heart failure ranging from congestive heart failure to cardiogenic shock. ECG may suggest myocardial infarction, although coronary arteries may appear normal on angiography. Valvular insufficiency and segmental or global hypokinesis of the myocardium may be found, all in keeping with Churg-Strauss myocarditis.
  • Neurological findings are most commonly peripheral polyneuropathy, usually mononeuritis multiplex pattern with motor and sensory deficits unexplainable by a single central lesion. Deficits tend to be asymmetrically distributed, involving individual peripheral nerves without reference to specific fiber types. The distribution is not in the "glove-stocking" distribution suggestive of toxic neuropathies. Peripheral muscle stretch reflexes may be diminished or lost. Sensory disturbances may include hypoesthesia, hyperesthesia, allodynia, or other forms of pain. Pain and paraesthesia tend to involve the legs. However, other manifestations may result in vasculitic disease of the brain with stroke or hemorrhage. These may result in abrupt onset of motor, intellectual, or sensory deficits, brainstem signs, stupor, or coma. Seizures may occur.
  • Eosinophilic gastroenteritis may result in abdominal pain, weight loss, or bloody diarrhea.
  • Skin changes may include the development of petechiae and palpable purpura.
  • Acute renal failure, developing rapidly over several weeks, is a characteristic feature of the rapidly progressive glomerulonephritis of Churg-Strauss disease. Gross hematuria or pyuria may be found. These findings, due to inflammatory glomerulonephritis, may be misinterpreted as urinary tract infection.
  • Abdominal pain, bloody diarrhea
  • Testicular pain

Physical

• In the first phase of Churg-Strauss disease, examination reveals nasal polyposis, intermittent fever, and findings consistent with sinusitis, allergic rhinitis, and bronchial asthma. The signs of reactive airway disease gradually worsen over time.
• During the systemic vasculitic phase, examination of skin, heart, abdomen, joints, peripheral nerves, and muscles may reveal evidence for the various characteristic changes of Churg-Strauss disease that have been noted in History. Two thirds of patients in this advanced state of illness are found to have cutaneous purpura or nodules.
• Cardiopulmonary findings that are consistent with congestive heart failure, low output state, or pericardial effusion may be discerned.
• Abdominal tenderness and evidence for gastrointestinal bleeding may be found on examination. Occasionally, the examination will reveal evidence of bowel obstruction. The findings of acute abdomen develop in patients with bowel perforation.
• Arthritis may be noted; any joint may be involved.
• Neurologic examination
• • In patients in the systemic vasculitic phase of illness, neurologic examination may reveal evidence of peripheral neuropathy limited to the extremities. At first, the pattern usually is that of mononeuritis multiplex, but with progression of illness, asymmetrical sensory and motor polyneuropathy is found (legs > arms).
  • Neurological findings tend to develop late. Pulmonary manifestations with eosinophilia usually establish the diagnosis of Churg-Strauss disease prior to the development of neurological disease.
  • The examination may disclose CNS manifestations due to intraparenchymal or subarachnoid brain hemorrhages.
  • Optic neuritis, cranial neuritis, and psychosis also have been described in adults with Churg-Strauss disease.
  • Children seldom manifest CNS findings. One girl with Churg-Strauss disease, who was in the early years of the second decade of her life, developed chorea.

Causes

• Genetic factors
• • Several lines of evidence suggest genetic predisposition, which may entail inherited tendency to dysregulation of the cellular immune system. The features of this dysregulation are noted in Pathophysiology.
  • The variation in age at onset of illness is not understood, but suggests the possibility that secondary factors, such as environmental influences, may hasten the onset of disease for some individuals.
• Environmental factors
• • Environmental factors may contribute to the development of Churg-Strauss disease. Thus, for example, the inhalation of fungal spores, such as those produced by actinomycetes and Aspergillus species, has been implicated in the pathogenesis of some cases.
  • Exposure to pigeons and the molds associated with their roosts also may provoke the development of Churg-Strauss disease.
  • Smoking of free-base cocaine was documented carefully as a circumstance preceding individual bouts of an illness similar to or identical to Churg-Strauss disease in one individual. The illness in that case was not sustained endogenously, recurring only with additional episodes of cocaine smoking.
  • Thus, some environmental factors appear to provoke transient effects that resemble Churg-Strauss disease but do not represent a chronic and self-perpetuating disease.
• Drugs
• • Carbamazepine, macrolide antibiotics, and cysteinyl leukotriene-receptor antagonists have been implicated as provocative causes of Churg-Strauss disease. Leukotriene-receptor antagonists may be especially important in terms of provoking chronic Churg-Strauss disease that does not resolve with discontinuation of the inciting drug.
  • Leukotriene-receptor antagonists are used in some patients who are undergoing withdrawal of steroid treatment of asthma. This has prompted some clinicians to ascribe the onset of Churg-Strauss disease to steroid withdrawal rather than to direct effects of the leukotriene-receptor antagonist. They propose that Churg-Strauss manifestations were masked or perhaps prevented by the higher steroid doses. However, several patients who were not in the midst of a steroid taper have developed Churg-Strauss disease after administration of leukotriene-receptor antagonists. Some authorities now recommend the use of inhaled steroids rather than leukotriene-receptor antagonists when attempting to taper systemically administered steroid treatment of asthma.
• Churg-Strauss disease has developed in the wake of Basedow disease with autoimmune thyroiditis; whether this is a chance association is not known.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Microscopic polyangiitis (microscopic polyarteritis)
Idiopathic hypereosinophilic syndrome
Essential cryoglobulinemic vasculitis
Strongyloidosis with hyperinfection syndrome
Loeffler syndrome (simple pulmonary eosinophilia)
Chronic eosinophilic pneumonia
Acute eosinophilic pneumonia
Allergic bronchopulmonary aspergillosis
Bronchocentric granulomatosis
Tropical pulmonary eosinophilia (wuchereriasis, brugiosis)

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• The first (prodromal) phase of Churg-Strauss consists of asthma usually in association with other typical allergic features, which may include eosinophilia. During the second phase, clinical presentation with Churg Strauss disease, eosinophilia is characteristic (see below) and ANCAs with perinuclear staining pattern (p-ANCAs) are detected. Where possible, the diagnosis is confirmed by demonstration of angiographic abnormalities in affected organs and by pathognomonic biopsy findings. According to 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 Churg-Strauss disease 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 Churg-Strauss disease.
  • Treatment of asthmatic manifestations of the first stage of Churg-Strauss disease with corticosteroids may obscure this characteristic finding. The prompt resolution of eosinophilia with corticosteroid treatment is itself quite characteristic of Churg-Strauss disease.
  • Intermittent elevations of eosinophil counts during the third phase of Churg-Strauss disease may presage a relapse of systemic vasculitis.
• Elevations of ANCA titers are found in 50-65% of cases of Churg-Strauss disease; these are predominantly p-ANCAs. In Churg-Strauss disease, the p-ANCAs usually are directed against myeloperoxidase antigens.
• 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.
• Testing for rheumatoid factor is positive in approximately 70% of cases.
• False-positive precipitin tests for syphilis have been reported.
• 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.

Imaging Studies

• Chest radiographs
• • Chest radiographs demonstrate pulmonary infiltrates in at least half of the patients in the second phase of Churg-Strauss disease 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, quite 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 Churg-Strauss disease 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 Churg-Strauss disease.
  • Imaging of the heart may reveal cardiomegaly or pericardial effusion.
• CT scan of lungs
• • CT scan of lungs demonstrates the above-mentioned findings of Churg-Strauss disease 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, while more widespread consolidation is discerned occasionally.
  • Occasional finding of centrolobular nodular densities within the background ground-glass opacity also is highly suggestive of Churg-Strauss disease. 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 Churg-Strauss disease, representing an opportunity for diagnostic biopsy.
  • Pleural or pericardial effusions occasionally are detected.
• Results of abdominal or renal angiography usually are negative in Churg-Strauss disease. However, Churg-Strauss disease may account for less than 5% of all cases of ANCA-associated renal vasculitis, while MPA accounts for approximately half, and WG approximately one third of such cases.
• MRI imaging of 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 also may be found.

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.

Procedures

• Procedures that may be valuable in the diagnosis of Churg-Strauss disease have been reviewed and include the following:
• • Biopsy of skin, hilar lymph nodes, lung parenchyma, or peripheral nerve demonstrates the characteristic vasculitis. Kidney biopsy may show segmental necrotizing glomerulonephritis with crescent formation, possibly including highly characteristic eosinophilic infiltration of the renal interstitium.
  • Electrophysiological studies of peripheral nerves

Histologic Findings

• Histopathologic studies of a biopsy of affected skin areas reveal small-vessel arteriopathy with granuloma formation in the vascular walls. 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 also may be discerned.
• 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 also are found, with small numbers of CD20⁺ B cells. Scarce deposits of IgG, IgE, and C3d antibodies may be detected.
• Kidney biopsy may disclose eosinophilic interstitial pauci-immune segmental glomerulonephritis. Occasionally, glomerulonephritis with IgA deposition is found.

Staging

Lanham divided the clinical evolution of Churg-Strauss disease into 3 phases (see History).

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Medical management of cardiovascular, cardiac, renal, and gastrointestinal complications of Churg-Strauss disease falls under the purview of subspecialty consultation. Drugs used in the treatment of Churg-Strauss disease are described in the Medication section.

Surgical Care

• Surgical procedures in patients with Churg-Strauss disease most commonly entail biopsy of affected tissues.
• In addition, surgical intervention may be indicated in patients who experience catastrophic complications, such as acute abdomen or intracranial hemorrhage.

Consultations

• Consultations for Churg-Strauss disease depend on the manifestations of the disease. The cardiopulmonary manifestations typically are most important. Consultations with the following may be required:
• • Pulmonologists
  • Cardiologists
  • Rheumatologists
  • Gastroenterologists
  • Urologists

Diet

No dietary factors are clearly known to assist in the management of Churg-Strauss disease, except as are related to the management of congestive heart failure, renal failure, or gastrointestinal complications. The management of these factors falls under the purview of subspecialists involved in the care of these organ systems.

Activity

No clear evidence suggests that particular activities influence the course of the illness once it is established. Environmental exposures and medical treatment of asthma that may influence the chances for development of Churg-Strauss disease have been discussed in Causes.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The recommended initial medications for treatment of severe manifestations of Churg-Strauss disease, including patients with Churg-Strauss disease–related peripheral neuritis, are corticosteroids, which are administered at high doses. Intravenous administration of methylprednisolone at doses of 15 mg/kg on 1-3 successive mornings is one of the most common initial approaches to severe cases. This is followed by oral prednisone at a dose of approximately 1 mg/kg/d (usual, but absolute maximal daily dose should not exceed 80 mg/d), with ensuing taper once clinical improvement is noted.

Many patients with Churg-Strauss disease manifest a favorable response to this monotherapeutic approach within a few days; however, in many cases persistence of asthma prevents oral prednisone from being tapered to doses lower than 10-15 mg/d. In milder cases, initial treatment can be undertaken with the administration of oral corticosteroids at doses of 1 mg/kg/d (60 mg/d is the usual but not absolute maximal dose).

Corticosteroid treatment, whether oral or intravenous, has been combined with plasma exchange or plasmapheresis for cases that were difficult to treat. This combination appears to have conferred benefit in some patients. Some patients have demonstrated marked clinical improvement, accompanied by declining circulating p-ANCA titers, after treatment with intravenous immunoglobulin (IVIg). Some patients have been treated, either initially or during a subsequent phase of therapy, with the combination of daily oral prednisone and cyclophosphamide. This approach may enhance disease control and may have a sparing effect upon steroid dosage, thus diminishing steroid-related adverse effects. Prednisone taper in patients responding to the combined therapy can be undertaken after approximately 2 weeks.

The combination of high-dose corticosteroids and dapsone has been used in patients with severe Churg-Strauss and has proven effective in instances of Churg-Strauss myocarditis (Shanks, 2003). Corticosteroid doses may be reduced after improvement in myocarditis is achieved.

Cyclophosphamide treatment (titrated to the neutrophil count) generally is continued for 6-12 months after remission is established. Pulse intravenous cyclophosphamide therapy in combination with corticosteroids appears to diminish the risk for various adverse effects seen in patients receiving oral cyclophosphamide daily. This form of therapy also is considered in patients whose disease responds poorly to corticosteroids. Dose, frequency, and total number of cyclophosphamide pulses are adjusted to disease response, blood counts, and renal function. Efficacy of this form of therapy is not, as yet, fully established.

Usually, collaborating with physicians specializing in renal medicine is the best way to undertake this form of therapy. Protocols must be employed to ensure that renal function is preserved with regard to additionally administered medications and hydration. These protocols entail intense hydration and coadministration of 2-mercaptoethanesulfonate (mesna). Some studies have employed initial pulse intravenous cyclophosphamide at doses as high as 0.6 g/m² of body surface, but this dose must be reduced in accordance with the degree of impairment of renal function exhibited by the patients.

Azathioprine, methotrexate, or ribavirin have possible roles in the treatment of Churg-Strauss disease, but these drugs require additional study and should not be employed without the participation of a subspecialist who can provide recommendations concerning dosage, anticipated benefits, and adverse effects.

The suggestion has been made that males with Churg-Strauss disease might attain some benefit from treatment with thalidomide. This approach requires considerable additional study and the participation of an expert who can provide information concerning appropriate dosage, anticipated benefits, and adverse effects. The use of thalidomide is contraindicated in women of childbearing age. None of the drugs noted in this paragraph should be employed without the collaboration of subspecialists skilled in their use and familiar with the relative indications, dosage adjustments, potential benefits, and adverse effects. Therefore, none of these agents will be reviewed in the following drug section, since the complex issues entailed with their use fall beyond the scope of this review.

Drug Category: Corticosteroids

These medications decrease the activity of the immune system in inflammatory reactions. The immune system is of critical importance in the pathophysiology of this disease.

Drug Category: Cytotoxic agents

These agents inhibit cell growth and proliferation, reducing the activity of the immune system.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Patients hospitalized for treatment of Churg-Strauss disease should be assessed, as should any hospitalized patient, for the risk of deep vein thrombosis, pulmonary embolus and, if cardiac dysfunction has been noted, cardiogenic embolus.
• Treatment with steroids entails risks for gastrointestinal hemorrhage, electrolyte disturbance, and infection, which also must be considered. When steroids are administered, antacids or appropriate histamine-blocking agents should be administered to reduce the risk for gastrointestinal hemorrhage.

Further Outpatient Care

• Administration of antacids or histamine-blocking agents to reduce the risk for gastrointestinal hemorrhage should be continued as long as patients are administered oral corticosteroids.
• Long-term corticosteroid administration entails risk for electrolyte disturbances, infections, and fractures because of diminished bone mass. These risks must be reassessed continually during the course of therapy.
• Alternative steroid-sparing anti-inflammatory therapies, selected from among the options noted in the treatment section, should be considered in patients requiring long-term corticosteroid therapy.

Deterrence/Prevention

• A number of authorities believe that the administration of cysteinyl leukotriene-receptor antagonists for the treatment of asthma may provoke development of Churg-Strauss disease in some individuals. The use of inhaled steroids, rather than cysteinyl leukotriene-receptor antagonists during the taper phase of steroid treatment of an acute exacerbation of asthma may be a valuable alternative for avoiding this potentially provocative circumstance.

Complications

• Particularly characteristic complications of the second phase of Churg-Strauss disease are chronic eosinophilic pneumonia and eosinophilic gastroenteritis.
• Abdominal pain, diarrhea, gastrointestinal bleeding, and bowel perforation are important complications.
• Raynaud phenomenon, arthralgias, or joint effusions are occasional complications.

Prognosis

• Once an appropriate therapeutic intervention is undertaken, a good response usually is achieved within 4 weeks. Thereafter, the disease usually can be well controlled with low maintenance steroid doses. With modern therapy, the outlook for Churg-Strauss disease appears to be much better than in early reports. More than 90% of patients achieve remission after initial steroid treatment. Whether the apparently improved outlook, as compared to earlier reports, represents a change in the average severity of disease, improved recognition and diagnosis of milder cases, or improvements in therapy is not well understood. Patients demonstrating a favorable response usually retain an independent existence on steroid maintenance therapy. The relapse rate is approximately 25-30%.
• Characteristically, patients with severe systemic vasculitis have a poor response to the initial phases of treatment. Both systolic and diastolic dysfunction associated with cardiomyopathy may improve with steroid therapy, although very low myocardial shortening fractions may not improve with this therapy. The outlook for patients with severe systemic vasculitis is quite guarded, since they have a considerable risk for dependent existence and progressive decline or premature death. The overall mortality rate may be as high as 25% within 5 years of diagnosis, half of these patients dying directly from vasculitis and half from secondary complications of vasculitis. The patients at highest risk for death or severe morbidity are those with severe myocardial or gastrointestinal vasculitis.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• These do not differ in any significant way from other areas of practice in medicine.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Abril A, Calamia KT, Cohen MD. The Churg Strauss syndrome (allergic granulomatous angiitis): review and update. Semin Arthritis Rheum. Oct 2003;33(2):106-14. [Medline].
• Azzopardi C, Montefort S, Mallia C. Cardiac involvement and left ventricular failure in a patient with the Churg-Strauss syndrome. Adv Exp Med Biol. 1999;455:547-9. [Medline].
• Barry C, Davis S, Garrard P, Ferguson IT. Churg-Strauss disease: deterioration in a twin pregnancy. Successful outcome following treatment with corticosteroids and cyclophosphamide. Br J Obstet Gynaecol. Jun 1997;104(6):746-7. [Medline].
• Berger JR, Wei T, Wilson D. Idiopathic granulomatous angiitis of the CNS manifesting as diffuse white matter disease [letter; comment]. Neurology. Dec 1998;51(6):1774-5. [Medline].
• Bili A, Condemi JJ, Bottone SM, Ryan CK. Seven cases of complete and incomplete forms of Churg-Strauss syndrome not related to leukotriene receptor antagonists. J Allergy Clin Immunol. Nov 1999;104(5):1060-5. [Medline].
• Boggi U, Mosca M, Giulianotti PC, et al. Surviving catastrophic gastrointestinal involvement due to Churg-Strauss syndrome: report of a case. Hepatogastroenterology. Jul-Aug 1997;44(16):1169-71. [Medline].
• Booth AD, Almond MK, Burns A, et al. Outcome of ANCA-associated renal vasculitis: a 5-year retrospective study. Am J Kidney Dis. Apr 2003;41(4):776-84. [Medline].
• Brooklyn TN, Prouse P, Portmann B, Ramage JK. Churg-Strauss syndrome and granulomatous cholangiopathy. Eur J Gastroenterol Hepatol. Jul 2000;12(7):809-11. [Medline].
• Bruce IN, Bell AL. A comparison of two nomenclature systems for primary systemic vasculitis. Br J Rheumatol. Apr 1997;36(4):453-8. [Medline].
• Burke AP, Sobin LH, Virmani R. Localized vasculitis of the gastrointestinal tract. Am J Surg Pathol. Mar 1995;19(3):338-49. [Medline].
• Caballero J, Zayas R, Arana R, et al. [Churg-Strauss syndrome with pericardial and myocardial involvement]. Rev Esp Cardiol. Sep 1999;52(9):745-7. [Medline].
• Chen KR, Su WP, Pittelkow MR, Leiferman KM. Eosinophilic vasculitis syndrome: recurrent cutaneous eosinophilic necrotizing vasculitis. Semin Dermatol. Jun 1995;14(2):106-10. [Medline].
• Cho KH, Kim YG, Yang SG, et al. Inflammatory nodules of the lower legs: a clinical and histological analysis of 134 cases in Korea. J Dermatol. Aug 1997;24(8):522-9. [Medline].
• Chumbley LC, Harrison EG Jr, DeRemee RA. Allergic granulomatosis and angiitis (Churg-Strauss syndrome). Report and analysis of 30 cases. Mayo Clin Proc. Aug 1977;52(8):477-84. [Medline].
• Churg A, Brallas M, Cronin SR, Churg J. Formes frustes of Churg-Strauss syndrome. Chest. Aug 1995;108(2):320-3. [Medline].
• Churg J, Strauss L. Allergic granulomatosis, allergic angiitis, and periarteritis nodosa. Am J Pathol. Mar-Apr 1951;27(2):277-301. [Medline].
• Cohen P, Guillevin L, Baril L, et al. Persistence of antineutrophil cytoplasmic antibodies (ANCA) in asymptomatic patients with systemic polyarteritis nodosa or Churg-Strauss syndrome: follow-up of 53 patients. Clin Exp Rheumatol. Mar-Apr 1995;13(2):193-8. [Medline].
• Davis MD, Daoud MS, McEvoy MT, Su WP. Cutaneous manifestations of Churg-Strauss syndrome: a clinicopathologic correlation. J Am Acad Dermatol. Aug 1997;37(2 Pt 1):199-203. [Medline].
• Dietz A, Hubner C, Andrassy K. [Macrolide antibiotic-induced vasculitis (Churg-Strauss syndrome)]. Laryngorhinootologie. Feb 1998;77(2):111-4. [Medline].
• Dillon MJ. Childhood vasculitis. Lupus. 1998;7(4):259-65. [Medline].
• Dinc A, Soy M, Pay S, et al. A case of Churg-Strauss syndrome presenting with cortical blindness. Clin Rheumatol. 2000;19(4):318-20. [Medline].
• Eustace JA, Nadasdy T, Choi M. Disease of the month. The Churg-Strauss Syndrome. J Am Soc Nephrol. Sep 1999;10(9):2048-55. [Medline].
• Falk RJ, Nachman PH, Hogan SL, Jennette JC. ANCA glomerulonephritis and vasculitis: a Chapel Hill perspective. Semin Nephrol. May 2000;20(3):233-43. [Medline].
• Ferro JM. Vasculitis of the central nervous system. J Neurol. Dec 1998;245(12):766-76. [Medline].
• Gross WL, Csernok E. Immunodiagnostic and pathophysiologic aspects of antineutrophil cytoplasmic antibodies in vasculitis. Curr Opin Rheumatol. Jan 1995;7(1):11-9. [Medline].
• Guillevin L, Fain O, Lhote F, et al. Lack of superiority of steroids plus plasma exchange to steroids alone in the treatment of polyarteritis nodosa and Churg-Strauss syndrome. A prospective, randomized trial in 78 patients. Arthritis Rheum. Feb 1992;35(2):208-15. [Medline].
• Hagen EC, Andrassy K, Csernok E, et al. Development and standardization of solid phase assays for the detection of anti-neutrophil cytoplasmic antibodies (ANCA). A report on the second phase of an international cooperative study on the standardization of ANCA assays. J Immunol Methods. Sep 13 1996;196(1):1-15. [Medline].
• Hauschild S, Csernok E, Schmitt WH, Gross WL. Antineutrophil cytoplasmic antibodies in systemic polyarteritis nodosa with and without hepatitis B virus infection and Churg-Strauss syndrome--62 patients. J Rheumatol. Jun 1994;21(6):1173-4. [Medline].
• Hellemans S, Dens J, Knockaert D. Coronary involvement in the Churg-Strauss syndrome. Heart. Jun 1997;77(6):576-8. [Medline].
• Hellmich B, Gross WL. Recent progress in the pharmacotherapy of Churg-Strauss syndrome. Expert Opin Pharmacother. Jan 2004;5(1):25-35. [Medline].
• Hellmich B, Csernok E, Gross WL. Proinflammatory cytokines and autoimmunity in churg-strauss syndrome. Ann N Y Acad Sci. Jun 2005;1051:121-31. [Medline].
• Hellmich B, Ehlers S, Csernok E, Gross WL. Update on the pathogenesis of Churg-Strauss syndrome. Clin Exp Rheumatol. Nov-Dec 2003;21(6 Suppl 32):S69-77. [Medline].
• Hoffman PM, Godfrey T, Stawell RJ. A case of Churg-Strauss syndrome with visual loss following central retinal artery occlusion. Lupus. 2005;14(2):174-5. [Medline].
• Jennette JC, Wilkman AS, Falk RJ. Anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and vasculitis. Am J Pathol. Nov 1989;135(5):921-30. [Medline].
• Kawakami T, Soma Y, Kawasaki K, et al. Initial cutaneous manifestations consistent with mononeuropathy multiplex in Churg-Strauss syndrome. Arch Dermatol. Jul 2005;141(7):873-8. [Medline].
• Kim Y, Lee KS, Choi DC, et al. The spectrum of eosinophilic lung disease: radiologic findings. J Comput Assist Tomogr. Nov-Dec 1997;21(6):920-30. [Medline].
• Klemmer PJ, Chalermskulrat W, Reif MS, et al. Plasmapheresis therapy for diffuse alveolar hemorrhage in patients with small-vessel vasculitis. Am J Kidney Dis. Dec 2003;42(6):1149-53. [Medline].
• Lamprecht P. TNF-alpha inhibitors in systemic vasculitides and connective tissue diseases. Autoimmun Rev. Jan 2005;4(1):28-34. [Medline].
• Lamprecht P. Off balance: T-cells in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Clin Exp Immunol. Aug 2005;141(2):201-10. [Medline].
• Lane SE, Watts R, Scott DG. Epidemiology of systemic vasculitis. Curr Rheumatol Rep. Aug 2005;7(4):270-5. [Medline].
• Langford CA, Sneller MC. New developments in the treatment of Wegener''s granulomatosis, polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome. Curr Opin Rheumatol. Jan 1997;9(1):26-30. [Medline].
• Lanham JG. Churg-Strauss syndrome. Br J Hosp Med. May 6-19 1992;47(9):667-73. [Medline].
• Lhote F, Cohen P, Genereau T, et al. Microscopic polyangiitis: clinical aspects and treatment. Ann Med Interne (Paris). 1996;147(3):165-77. [Medline].
• Lie JT. Histopathologic specificity of systemic vasculitis. Rheum Dis Clin North Am. Nov 1995;21(4):883-909. [Medline].
• Lie JT. Nomenclature and classification of vasculitis: plus ca change, plus c''est la meme chose [editorial]. Arthritis Rheum. Feb 1994;37(2):181-6. [Medline].
• Martin-Suarez I, D'Cruz D, Mansoor M, et al. Immunosuppressive treatment in severe connective tissue diseases: effects of low dose intravenous cyclophosphamide. Ann Rheum Dis. Aug 1997;56(8):481-7. [Medline].
• Matsuo K, Tomioka T, Tajima Y, et al. Allergic granulomatous angitis (Churg-Strauss syndrome) with multiple intestinal fistulas. Am J Gastroenterol. Oct 1997;92(10):1937-8. [Medline].
• Metzler C, Lamprecht P, Hellmich B, et al. Leucoencephalopathy after treatment of Churg-Strauss syndrome with interferon {alpha}. Ann Rheum Dis. Aug 2005;64(8):1242-3. [Medline].
• Muschen M, Warskulat U, Perniok A, et al. Involvement of soluble CD95 in Churg-Strauss syndrome. Am J Pathol. Sep 1999;155(3):915-25. [Medline].
• Niles JL. Antineutrophil cytoplasmic antibodies in the classification of vasculitis. Annu Rev Med. 1996;47:303-13. [Medline].
• Pellissier JF, Figarella-Branger D, Serratrice G. [Neuromuscular diseases with eosinophilia]. Med Trop (Mars). 1998;58(4 Suppl):471-6. [Medline].
• Primack SL, Muller NL. Radiologic manifestations of the systemic autoimmune diseases. Clin Chest Med. Dec 1998;19(4):573-86, vii. [Medline].
• Rutgers A, Heeringa P, Tervaert JW. The role of myeloperoxidase in the pathogenesis of systemic vasculitis. Clin Exp Rheumatol. Nov-Dec 2003;21(6 Suppl 32):S55-63. [Medline].
• Sable-Fourtassou R, Cohen P, Mahr A, et al. Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann Intern Med. Nov 1 2005;143(9):632-8. [Medline].
• Sakamoto S, Ohba S, Eguchi K, et al. Churg-Strauss syndrome presenting with subarachnoid hemorrhage from ruptured dissecting aneurysm of the intracranial vertebral artery. Clin Neurol Neurosurg. Aug 2005;107(5):428-31. [Medline].
• Sanders JS, Stegeman CA, Kallenberg CG. The Th1 and Th2 paradigm in ANCA-associated vasculitis. Kidney Blood Press Res. 2003;26(4):215-20. [Medline].
• Sharma BK, Daga MK, Sharma M. A limited form of Churg-Strauss syndrome presenting without asthma and eosinophilia. Med J Aust. Nov 1 2004;181(9):498-9. [Medline].
• Somogyi A, Muzes G, Molnar J, Tulassay Z. Drug-related Churg-Strauss syndrome?. Adverse Drug React Toxicol Rev. Jun-Sep 1998;17(2-3):63-74. [Medline].
• Sonneville R, Lagrange M, Guidoux C, et al. [The association of cardiac involvement and ischemic stroke in Churg Strauss syndrome]. Rev Neurol (Paris). Feb 2006;162(2):229-32. [Medline].
• Steinfeld S, Golstein M, De Vuyst P. Chronic eosinophilic pneumonia (CEP) as a presenting feature of Churg-Strauss syndrome (CSS) [letter; comment]. Eur Respir J. Nov 1994;7(11):2098. [Medline].
• Sudo K, Tashiro K. Idiopathic granulomatous angiitis of the CNS manifesting as diffuse white matter disease [letter; comment]. Neurology. Dec 1998;51(6):1774; discussion 1775. [Medline].
• Sullivan EJ, Hoffman GS. Pulmonary vasculitis. Clin Chest Med. Dec 1998;19(4):759-76, ix. [Medline].
• Tatsis E, Schnabel A, Gross WL. Interferon-alpha treatment of four patients with the Churg-Strauss syndrome. Ann Intern Med. Sep 1 1998;129(5):370-4. [Medline].
• Terasaki F, Hayashi T, Hirota Y, et al. Evolution to dilated cardiomyopathy from acute eosinophilic pancarditis in Churg-Strauss syndrome. Heart Vessels. 1997;12(1):43-8. [Medline].
• Thuy GN, Cuguilliere A, Arteaga C, et al. [Idiopathic chronic eosinophilic pneumonia]. Med Trop (Mars). 1998;58(4 Suppl):455-8. [Medline].
• Vital C, Vital A, C