Churg-Strauss Disease 

Updated: Oct 13, 2014
Author: Robert Stanley Rust, Jr, MD, MA; Chief Editor: Amy Kao, MD 

Overview

Background

Churg-Strauss disease (CSD) is one of three important fibrinoid, necrotizing, inflammatory leukocytoclastic systemic small-vessel vasculitides that are associated with antineutrophil cytoplasm antibodies (ANCAs). Of these three conditions, Churg-Strauss disease is the least commonly encountered. 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.[1]

Sir William Osler possibly described the clinical aspects of Churg-Strauss disease in 1900. However, it was not until 1951 that Jacob Churg and Lotte Strauss of Sweden clearly identified the clinical and pathological findings as representative of a distinct entity, setting it apart from polyarteritis nodosa (PAN). They reported 13 individuals who initially manifested severe asthma and subsequently developed fever, eosinophilia, cardiac and renal failure, and peripheral neuropathy.[2] Most also developed pulmonary infiltrates, sinusitis, hypertension, abdominal pain, bloody diarrhea, and skin changes including purpura and subcutaneous nodules. That 11 of the 13 individuals described by Churg and Strauss in their 1951 paper had died of Churg-Strauss disease is not surprising since corticosteroids were only introduced into medical practice in 1951 and did not become readily available for use in medicine until suitable synthetic preparations were prepared.

Because most of the individuals they described had died, Churg and Strauss concentrated particular attention on the distinctive histologic features of CSD. Chumbley and associates used the criteria of Churg and Strauss in their Mayo Clinic series.[3]

Subsequent attempts to refine diagnostic criteria have incorporated more clinical features.[4, 5, 6] The fact that 3 or more sets of criteria are in existence reflect the fact that no single clinical feature is pathognomonic and no discrete measurable biological marker has been identified for this condition. As noted, histologic distinction of Churg-Strauss from a condition that it closely resembled clinically, polyarteritis nodosa (PAN), was particularly important in establishing CSD as a discrete entity. Pathological investigation has established that PAN predominantly affects both medium-sized blood vessels and some small arteries, though it tends to spare capillaries, arterioles, and venules. This tendency is shared with Kawasaki disease.

Churg-Strauss disease chiefly affects small vessels (capillaries, venules, arterioles) by the development of eosinophil-rich granulomatous inflammation of the respiratory tract and small vessels.[6] However, Lie[7] has emphasized the fact that Churg-Strauss disease (and for that matter WG and MPA) may not be restricted to small-vessel vasculitis, a histological fact that is also acknowledged in the Jennette et al[6] "international consensus criteria", which state that CSD, WG, and MPA may involve the medium-sized vessels that are more characteristic targets of PAN.

The identification of antineutrophil cytoplasmic antibodies (ANCA)[1] provided a sensitive, although nonspecific, marker for a particular group of systemic vasculitides including CSD. ANCA with a cytoplasmic staining pattern (cANCA), largely specific for the immunogenic epitopes of antiproteinase 3, was shown to have 98% sensitivity and high specificity for active clinically identified cases of Wegener granulomatosis.[8] ANCA with a perinuclear staining pattern (pANCA) was also identified and shown to have antigenic specificity for epitopes expressed by myeloperoxidase (MPO) as well as other possible epitopes. pANCA is an important marker for CSD,[9, 10] though not as specific as cANCA is for WG. pANCA may also be found in WG, MPA, and PAN.[8, 9, 11, 10]

ANCA provides considerable value in supporting the diagnosis of clinically classified ANCA-related illnesses. Thus, for example, the finding of pANCA in a systemic vasculitic condition arising initially as an asthmatic condition and found to also manifest tissue and blood eosinophilia makes a strong case for the diagnosis of CSD (which invariably involves the lungs).

CSD also has a reasonably characteristic disease evolution, and histologic demonstration of the distinctive pattern of eosinophilic vasculitis of small and some medium-sized vessels results in an even more secure diagnosis. Nonetheless, note 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.[12]

ANCA assays have an even more definitive role in distinguishing the ANCA-related vasculitides from 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 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, the 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 of IHES 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 neurologic manifestations, but a primary encephalopathy has also 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 may also 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 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 Churg-Strauss disease, particularly the triggering circumstances, is not well understood. In their original description of ANCAs, Daives and associates[1] suggested that arboviral infection-related superantigens might stimulate the production of ANCAs that attacked host tissues because of molecular mimicry or some other abnormality of immune tolerance. Triggering of these vasculitides by infection has remained a pathophysiological consideration.[13] ANCAs in part mediate vascular endothelial injury in Churg-Strauss disease, as they do in PAN, MPA, and WG. In these various 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 (CD8+ suppressor and 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 less prominent deposits of immunoglobulin (IgG), immunoglobulin E (IgE), and C3d antibodies may also be detected.

Cytokines undoubtedly participate in this autoimmune process. Patients with CSD have markedly increased serum levels of interferon alpha and interleukin 2 (IL-2) and moderate increases of TNF-alpha and interleukin 1 beta (IL-1beta) similar to those observed in PAN. Elevations of serum interleukin 6 (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, 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.[14]

Typically (approximately 70% of clinically ascertained cases), pANCAs (directed against myeloperoxidase) are found in patients with Churg-Strauss disease. These perinuclear deposits appear as azurophilic granules. pANCA titers in individuals with CSD have been shown to correlate with disease severity; falling titers have been used as indicators of the success or failure of immunosuppressive treatments and, conversely, rising titers have been regarded as indicative of disease exacerbation.[15]

Antibodies with this pattern of staining and similar antigenic specificity are also found in the uncertainly classified entity microscopic polyangiitis (MPA). 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 cANCAs with antigenic specificity for proteinase-3 is characteristic. A case of one patient with pANCAs directed against myeloperoxidase and cANCAs against proteinase-3 has been reported; the patient manifested a combination of clinical characteristics suggesting both Churg-Strauss disease and temporal arteritis.

These immunologic 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). Anti-endothelial cell antibodies, detectable in many different primary vasculitic conditions as well as in systemic autoimmune disease with a vasculitic component, 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.

CSD onset has been associated with immunotherapy for asthma in epidemiologic studies. Immunization with allergen extracts has been suggested to provoke onset of CSD. A particularly important form of immunotherapy in asthma has been the use of drugs designed to reduce leukotriene-mediated airway obstruction.[16, 17, 18] Onset of CSD after the use of antileukotrienes for the treatment of asthma has suggested that these agents may provoke an idiosyncratic drug-induced form of CSD. In particular, an association has been detected with the use of cysteinyl leukotriene receptor type-1 (CysLT1) antagonists (eg, zafirlukast, pranlukast, montelukast) and onset of CSD.[19] However, some authorities appear to regard this association as the result of the "unmasking" of preexisting CSD, as the introduction of leukotriene inhibitors permits corticosteroid doses to be reduced.[20, 19, 21, 18, 22, 23]

On the other hand, zafirlukast treatment has been associated with idiosyncratic development of drug-induced lupus; hence, a primary role for such agents in induction of CSD must also be considered.[24] Despite some continued degree of etiologic uncertainty, it can be said that it remains particularly important to consider unmasked CSD as the underlying cause of CSD-related deterioration in patients with severe asthma undergoing steroid dosage-reduction during a period of antileukotriene therapy–associated improvement in pulmonary disease.

Antiasthmatic agents, such as beclomethasone, cromolyn sodium, or other drugs, may provoke pulmonary eosinophilia. However, it is important to carefully distinguish pulmonary eosinophilia from CSD. Pulmonary disease with eosinophilia has been associated with the use of crack-cocaine.[25, 26]

Pathology

Unlike most noninfectious vasculitides, Churg-Strauss disease is fairly distinctive in its pathology, owing to the abundance of eosinophils in the inflammatory perivenular exudate. However, CSD is a condition with a wide variety of presentations and associated signs and symptoms and other entities may provoke eosinophilic vasculitis. Therefore, CSD remains a clinicopathologic rather than a histopathologic entity.

Eosinophilic infiltration of the upper respiratory tracts and lungs is the most common finding in CSD, while similar infiltrative pathology is also often found in the gastrointestinal tract. The infiltrative appearance may change into eosinophilic vasculitis with worsening disease. Such clinical manifestations as weight loss, fever, and myalgia are common diagnostic clues to the possibility that CSD is in evolution. These manifestations are found in more than half of all individuals with CSD. Sinusitis has similar prevalence. The characteristic vasculopathy of CSD is predominantly an arteriopathy, tending to affect small- and medium-sized arteries much more than arterioles, veins, or capillaries. This predilection is also found in PAN and some other conditions. However, the predominance of eosinophils sets CSD apart from these other conditions. Epithelioid and giant cells are also found in the inflammatory exudate of patients with CSD.

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. CSD is associated with "red" collagenolytic granulomas.

The lungs are the chief organs involved in patients with Churg-Strauss vasculopathy, and they almost invariably develop regions of angiopathy as the disease progresses. In a series of 96 individuals with CSD, asthma was the first evidence of CSD in 92%; one third developed asthma severe enough to require oral corticosteroid administration.[27] 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 was found in as many as 85% of cases described in early reports, typically manifesting as low-output congestive cardiac failure. However, myocardial involvement (which was associated with poor prognosis) was identified in only 14% of the large series of patients with CSD reported by Guillevin et al.[27] Churg-Straus disease should be considered in adults with asthma and eosinophilia who develop chest pain, shortness of breath, and cardiogenic shock.[28]

  • Cardiac evaluation may demonstrate eosinophilic pericarditis, cardiomegaly, restrictive cardiomyopathy/perimyocarditis, diminished myocardial contractility due to myocardial or endocardial eosinophilic vasculitis or associated tissue infarction. These changes and pericardial effusion are important prognostic factors that obviously bear upon the degree and time course of CSD-associated heart failure.[29]

  • Both systolic and diastolic dysfunction may be discerned.

  • Steady decline in myocardial shortening fraction often follows.

  • Heart failure is an important cause of death in Churg-Strauss disease and is a major determinant of prognosis. In the series by Guillevin et al, 8% of patients with CSD died from cardiac disease in the acute phase of the illness.[27]

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. The pathology most commonly encountered in skin biopsies is small-vessel leukocytoclastic vasculitis with ensuing blood vessel necrosis of either small or large vessels. The cutaneous vasculopathy may be associated with the development of purpura, nodules, or areas of infarction. Similar pathological changes account for mononeuropathy multiplex and myositis due to CSD and are also found in kidneys if glomerulonephritis develops.

  • Eosinophilic granulomatous changes in the gallbladder wall may result in obstructive jaundice or pain and require cholecystectomy.[30]

  • Approximately 64-80% of patients in the systemic phase of Churg-Strauss disease develop peripheral neuropathy, usually in the pattern of mononeuritis multiplex.[27] 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 30-60% of individuals with CSD (prevalence higher in earlier series than in more recent case series). 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.[30]

  • 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.

Epidemiology

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 individuals per million individuals in North America annually.[12]

International

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

Mortality/Morbidity

See the list below:

  • Most (85%) of the index cases reported by Churg and Strauss in 1951 had died from their illness. The development of effective strategies for treatment in ensuing decades (particularly oral corticosteroids) has improved survival considerably, though the disease remains a serious one. To some extent, improved survival may relate to recognition of milder cases. The 5-year survival rate reported in the 30 patient series of CSD that Chumbley and associates reported in 1977 was 62%.[3] In 1999, Guillevin and associates reported a 72% 6-year survival rate in a series of 96 patients with CSD.[27] Elderly patients may have as much as 50% greater risk of death from their CSD and compared to middle-aged or young individuals with this disease.[31]

  • Morbidity is chiefly cardiopulmonary. Painful arthritis, arthralgia, neuritis, 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 patients. It tends to affect older patients, who as a group have particularly poor outcomes. Early diagnosis of this renal complication improves outcome.[32] Leukopenia due to immunosuppressive therapy enhances risk for sepsis and death and therefore should be avoided.[32] The chief neurologic 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. In addition to overall severity of CSD, both myocardial disease and severe gastrointestinal disease were found by Guillevin et al to be independent predictors of poor prognosis.[27]

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 (eg, Wegener granulomatosis) a tendency toward greater prevalence in whites or individuals of Nordic ancestry.[31] 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 such tentative and possibly irrelevant indirect genetic markers as skin pigmentation. Nonetheless, there is some support in selected diseases for the notion that disease prevalence or severity for certain autoimmune conditions may be greater in individuals with heavier 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 in small children, although they may 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.

 

Presentation

History

Lanham divided the clinical evolution of Churg-Strauss disease into 3 phases.[4]

First phase

The first phase is prodromal to the 2 subsequent vasculitic phases. Bronchial asthma is the initial disease manifestation in as many as 80-90% of cases of Churg-Strauss disease.[27] The asthma is severe in as many as one third of all patients. An additional 6% will develop asthma within a year of onset of manifestations in other organ systems. In most series, bronchial asthma is the first clinical feature and is the nearly constant finding of the first phase, preceding fever or eosinophilia. Some authorities have estimated that less than 3% of all individuals who develop CSD have no asthma as an element of their CSD.

  • Additional findings that often precede or accompany the first phase of CSD include allergic rhinitis, nasal polyposis, sinusitis, and recurrent bronchitis, or pneumonia. Nasal rhinitis and polyposis, in particular, are likely to precede the onset of reactive airway disease.

  • 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.[33]

  • 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 other organ systems that may be present in ensuing stages of the disease.

  • Recurrent fevers of unclear etiology and weight loss, either of which may occur in the first phase of illness in more than half of individuals developing CSD, 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.

  • Exceedingly rarely, Churg-Strauss pathogenesis may result in development of the systemic vasculitic stages of CSD in individuals who do not have either asthma or eosinophilia.

  • However, also remember 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 as comprising the systemic vasculitic stages of CSD.

  • 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.

  • The frequency of CSD–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

See the list below:

  • 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.[28]

  • 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 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.

    • Neurologic 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.

    • Testicular pain may occur in men with Churg-Strauss disease.

Physical

See the list below:

  • 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 the skin, heart, abdomen, joints, peripheral nerves, and muscles may reveal evidence for the various characteristic changes of Churg-Strauss disease as 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 reveals 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).

    • Neurologic findings tend to develop late. Pulmonary manifestations with eosinophilia usually establish the diagnosis of Churg-Strauss disease prior to the development of neurologic disease.

    • The examination may disclose CNS manifestations due to intraparenchymal or subarachnoid brain hemorrhages.

    • Optic neuritis, cranial neuritis, and psychosis 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

See the list below:

  • Genetic factors

    • Several lines of evidence suggest a genetic predisposition, which may entail an inherited tendency to dysregulation of the cellular immune system. The features of this dysregulation are discussed in Pathophysiology.

    • The variation in age at onset of illness is not understood, but this variation 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. 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 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.

    • In summary, 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.

 

DDx

Diagnostic Considerations

Other problems to be considered include the following:

  • 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)

Differential Diagnoses

 

Workup

Laboratory Studies

See the list below:

  • The first (prodromal) phase of Churg-Strauss disease (CSD) consists of asthma usually in association with other typical allergic features, which may include eosinophilia. During the second phase, the clinical presentation with CSD, 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 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 promptly resolve this characteristic finding. The prompt resolution of eosinophilia with corticosteroid treatment is itself 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 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.

Imaging Studies

See the list below:

  • 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, 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 the lungs

    • CT scan of the 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, whereas more widespread consolidation is discerned occasionally.

    • Occasional finding of centrolobular nodular densities within the background ground-glass opacity 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, 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]

Other Tests

See the list below:

  • 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

See the list below:

  • Procedures that may be valuable in the diagnosis of Churg-Strauss disease 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

Histologic Findings

See the list below:

  • Biopsy results 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 Churg-Strauss neuropathy. 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.

 

Treatment

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 Medication.

Surgical Care

See the list below:

  • 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

See the list below:

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

    • Pulmonologist

    • Cardiologist

    • Rheumatologist

    • Gastroenterologist

    • Urologist

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 are discussed in Causes.

 

Medication

Medication Summary

For most patients, Churg-Strauss disease (CSD) is a readily treatable illness, and reports over the past few decades have shown better outcomes than were demonstrated in earlier case series. In part, this may be due to the inclusion of milder cases due to improved recognition. In particular, diagnostic sensitivity has been greatest for individuals whose initial presentation is with asthma (90% of cases in some case series). However, a major factor has been the availability of corticosteroids. Milder CSD may respond well to orally administered corticosteroids.

The recommended initial medications for treatment of severe manifestations of CSD, including patients with CSD–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. Rapid correction of eosinophilia, leukocytosis, and elevations of sedimentation rate and LDH are characteristic of CSD. Failure to provoke such corrections early in the course of therapy is associated with elevated risk for poor long-term outcome.

Intravenous treatment 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 CSD 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 pANCA 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 disease and has proven effective in instances of Churg-Strauss myocarditis.[28] 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 is also 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 utilized 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 used 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 patient.

Azathioprine, methotrexate, or ribavirin have possible roles in the treatment of CSD, but these drugs require additional study and should not be used 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 CSD 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 used 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 are reviewed in the following Medication section because the complex issues entailed with their use fall beyond the scope of this article.

Corticosteroids

Class Summary

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.

Methylprednisolone (Medrol, Solu-Medrol, Depo-Medrol)

Moderate or severe cases often treated for 1-3 d with IV methylprednisolone (or equivalent dose of some other anti-inflammatory corticosteroid). Administer initial dose under close supervision, since rare instances of anaphylaxis after initial dose have been reported.

Prednisone (Sterapred)

Useful in initial management of mild cases (especially for asthma) and in taper and maintenance phases of therapy for Churg-Strauss disease.

Cytotoxic agents

Class Summary

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

Cyclophosphamide (Cytoxan)

Synthetic drug, chemically related to nitrogen mustards, developed as antineoplastic agent. Biotransformed in liver, where constituent alkylating metabolites activated. These activated compounds interfere with growth of susceptible rapidly proliferating cells. Mechanism of action with regard to tumor cells may involve cross-linking of tumor cell DNA.

 

Follow-up

Further Outpatient Care

See the list below:

  • Administration of antacids or histamine-blocking agents to reduce the risk for gastrointestinal hemorrhage should be continued for 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 Medication section, should be considered in patients requiring long-term corticosteroid therapy.

Further Inpatient Care

See the list below:

  • 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 must be considered. When steroids are administered, antacids or appropriate histamine-blocking agents should be administered to reduce the risk for gastrointestinal hemorrhage.

Deterrence/Prevention

See the list below:

  • 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

See the list below:

  • 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.

  • Treatment-related complications include those associated with immunosuppression (eg, risk for infection) and other effects of anti-inflammatory medications such as Cushing ulcer with or without gastrointestinal perforation.

Prognosis

See the list below:

  • Once an appropriate therapeutic intervention is undertaken, a good response usually is achieved within 4 weeks. Thereafter, the disease can usually be well controlled with low maintenance steroid doses.

  • Most individuals who showed favorable response to corticosteroid treatment of Churg-Strauss associated neuropathy do not manifest disease relapse within the ensuing 8 months.

  • Individuals with neuropathy associated with Churg-Strauss disease who show poor response to initial corticosteroid treatment may experience improvement once cyclophosphamide is administered.

  • 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 guarded because 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.