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Background

Allergic granulomatosis is the other name for this disorder characterized by:

Asthma
Eosinophilia >10%
Neuropathy, mono or poly
Pulmonary infiltrates, non-fixed
Paranasal sinus abnormality
Extravascular eosinophils

Cardiac and renal involvement may occur. The skin lesions occur on the scalp and extremities forming purpuric patches or nodules which may be painful or urticarial.

As the name implies, an allergic etiology is suspected although this is unproven. Antibodies to hepatitis B virus and HIV have been found in rare cases. Antibodies to p-ANCA are often present suggesting an autoimmune disorder.

Histopathologically, there is a necrotizing vasculitis with tissue eosinophils and extravascular granulomas. Usually small to medium sized arteries and veins are affected. The extravascular granulomas show a palisading necrobiotic granuloma with deep eosinophilia.

OUTLINE

Epidemiology  
Disease Associations  
Pathogenesis  
Laboratory/Radiologic/
Other Diagnostic Testing
 
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Special Stains/
a Immunohistochemistry/
Electron Microscopy
 
Differential Diagnosis  
Prognosis  
Treatment  
Commonly Used Terms  
Internet Links  

EPIDEMIOLOGY CHARACTERIZATION
SYNONYMS Allergic granulomatosis and angiitis
PREVALENCE/
INCIDENCE
 
Incidence of churg-strauss syndrome in asthma drug users: a population-based perspective.

Harrold LR, Andrade SE, Go AS, Buist AS, Eisner M, Vollmer WM, Chan KA, Frazier EA, Weller PF, Wechsler ME, Yood RA, Davis KJ, Platt R.

Meyers Primary Care Institute, University of Massachusetts Medical School and Fallon Foundation, Worcester, MA USA.
J Rheumatol. 2005 Jun;32(6):1076-80. Abstract quote  

OBJECTIVE: To estimate the incidence of Churg-Strauss syndrome (CSS) among a large population of asthma drug users.

METHODS: A retrospective study was conducted among patients who had been dispensed asthma drugs at 3 managed care organizations. Adults who received >/= 3 dispensings of an asthma drug during any consecutive 12-month period between January 1, 1995 and June 30, 2000 were identified. Information on patient age, gender, enrollment status, asthma drugs dispensed, and inpatient and outpatient diagnoses and procedures was obtained from automated databases. Chart reviews were performed on persons identified by combinations of diagnostic and billing codes indicative of CSS. A rheumatologist reviewed abstracted information on all subjects; those who met >/= 2 American College of Rheumatology criteria for CSS were reviewed by 2 clinical experts. Each clinical expert independently rated the cases; disagreements were resolved by consensus. Cases classified as having "probable/definite" CSS were included in these analyses. The incidence of CSS was estimated overall and according to patient gender, age, and calendar year.

RESULTS: From a population of 184,667 asthma drug users contributing 606,184 person-years of exposure, 21 incident cases of CSS were identified (overall incidence of 34.6 per million person-years; 95% confidence interval 21.4 to 53.0). Incidence rates did not differ by gender and age group. The incidence rates for 1995, 1996, 1997, 1998, 1999, and the first 6 months of 2000 were 0, 22, 52, 75, 14, and 14 per million person-years respectively.

CONCLUSIONS: Results from this population-based study suggest a somewhat lower incidence of CSS in asthma drug users than previously reported and provides important information as to the risk of developing CSS from a population-based perspective.

 

DISEASE ASSOCIATIONS CHARACTERIZATION
DRUGS  
Churg-Strauss syndrome associated with hypersensitivity to acetaminophen.

Masuzawa A, Moriguchi M, Tsuda T, Sugawara H, Otsuka M, Yamada S, Tabei K, Kawakami M.

Division of Integrated Medicine I, Omiya Medical Center, Jichi Medical School, Saitama, Japan.
Intern Med. 2005 May;44(5):496-8. Abstract quote  

Acetaminophen is a widely used antipyretic drug. We describe a 64-year-old Japanese woman who developed typical Churg-Strauss syndrome after frequent use of acetaminophen. Following the ingestion of acetaminophen, she exhibited various allergic reactions such as asthmatic attacks, pyrexia and petechiae on legs. In the lymphocyte transformation test, a positive reaction to acetaminophen was detected. A muscle biopsy revealed massive extravascular eosinophil infiltration and a necrotizing vasculitis.

Hypersensitivity to acetaminophen may be implicated in the development of Churg-Strauss syndrome in this case.
LEUKOTRINE-RECEPTOR ANTAGONISTS  
Churg Strauss Syndrome and Leukotriene antagonist use: A respiratory perspective.

City Hospital, United Kingdom.

 

Thorax. 2008 May 20. Abstract quote

BACKGROUND: Churg Strauss Syndrome (CSS) is a rare granulomatous small vessel vasculitis that occurs against a background of long-standing asthma. Leukotriene antagonists (LTAs) are used in the management of asthma and may facilitate a reduction in steroid dosage. Reports of the development of CSS in asthmatic patients following the initiation of LTA therapy suggest either a causal association or an unmasking of latent CSS as steroid doses fall. We have undertaken a systematic review to establish whether evidence of a drug induced syndrome exists.

METHODS: Systematic review searching Medline from database inception to August 2007 to identify cases with a possible association between LTAs and CSS. Hill's criteria of causation were used to assess strength of causality.

RESULTS: 62 cases in which CSS developed after the introduction of LTA therapy were identified. Patients were divided into three groups: Group 1 had received no previous steroid therapy, group 2 had been treated with oral and / or inhaled corticosteroids, but had no change in steroid therapy following LTA introduction and group 3 had a clear reduction in steroid therapy following introduction of LTA therapy. The majority of patients from each group exhibited a clear temporal relationship between initiation of LTA and development of CSS with no evidence of pre-existing disease.

CONCLUSIONS: Currently available evidence suggests an association between LTA and CSS that may be causal.
Churg-Strauss syndrome associated with omalizumab.

Department of Rheumatology, Le Mans General Hospital, 194 avenue Rubillard, 72000 Le Mans, France.

Eur J Intern Med. 2008 Jul;19(5):364-6 Abstract quote

Reports have suggested that the leukotriene receptor antagonists may cause Churg-Strauss syndrome following the tapering of oral corticosteroids or even in patients not treated with corticosteroids.

We report a patient not treated with long-term corticosteroids and who developed Churg-Strauss syndrome with myocarditis and central nervous system involvement following the initiation of omalizumab.

Given the possible role of omalizumab in the development of this vasculitis in our patient, we recommend careful monitoring of the appearance of Churg-Strauss symptoms and rising eosinophil count in patients treated with omalizumab.
Drug Induced Churg-Strauss syndrome associated with leukotriene-modifier therapy

JAMA 1998;279:455-457
Chest 2000;117:708-713

Zafirlukast (Accolate) are leukotriene-type receptor 1 antagonists

Churg-Strauss syndrome after reduction of inhaled corticosteroid in a patient treated with pranlukast for asthma.

Hashimoto M, Fujishima T, Tanaka H, Kon H, Saikai T, Suzuki A, Nakatsugawa M, Abe S.

Third Department of Internal Medicine, Sapporo Medical University School of Medicine.

Intern Med 2001 May;40(5):432-4 Abstract quote

Recently, various forms of Churg-Strauss syndrome (CSS) have been reported in association with the use of leukotriene receptor antagonists.

A 53-year-old woman with a 5-year history of asthma associated with chronic sinusitis presented mononeuropathy, hypereosinophilia, and positive P-ANCA in October 1999. She had been treated with pranlukast (450 mg/day) and beclomethasone dipropionate (BDP) at a dose of 1,200 microg/day which had gradually been tapered to 800 microg/day over the previous 17 months. She was found to have CSS, and 60 mg/day of prednisolone was administered instead of pranlukast, resulting in an improvement of her symptoms and eosinophilia. Later, we confirmed that serum P-ANCA had been positive before the pranlukast treatment, but CSS vasculitis had not appeared at that time.

We speculated that an underlying incomplete form of CSS was being masked in this case and that the reduction of inhaled corticosteroid might have been responsible for the unmasking of CSS.

The relationship of asthma therapy and Churg-Strauss syndrome: NIH workshop summary report.

Weller PF, Plaut M, Taggart V, Trontell A.

Division of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

J Allergy Clin Immunol 2001 Aug;108(2):175-83 Abstract quote

The Churg-Strauss syndrome (CSS) is a distinct form of vasculitis that is notable for its eosinophilia and frequent associations with asthma and sinusitis. Because there has been an increasing recognition that CSS can develop in patients with asthma and that CSS might be associated with specific asthma treatments, the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, the Office of Rare Diseases, National Institutes of Health, and the US Food and Drug Administration jointly sponsored a workshop to consider interrelationships among CSS, asthma, and asthma therapeutics and to assess what is known about underlying mechanisms of CSS.

Issues related to the criteria for defining and diagnosing CSS were reviewed, including the contemporary understanding that diagnostic biopsies need only reveal eosinophilic perivascular infiltrates and that asthma need not be present when CSS develops. From published reports and reports to the US Food and Drug Administration, treatment of patients with asthma with any of 3 cysteinyl leukotriene receptor antagonists, a 5-lipoxygenase inhibitor, and inhaled corticosteroids has been associated with CSS development. It is unknown whether these agents were eliciting CSS. A variety of physiologic and study design issues might lead to the reported associations of these drugs with CSS. Because many asthma patients receiving these therapies were able to diminish their systemic corticosteroid therapy, it is possible that incipient CSS was unmasked by lessened steroid use.

The underlying pathophysiologic mechanisms of CSS, however, are unknown, and there is no means of identifying which patients with asthma might be at risk for CSS. Accordingly, investigations with the goals of defining the underlying pathophysiologic processes of CSS and establishing the relationships of asthma and its therapies to CSS are needed.

THROMBOSIS  

Thrombosis in Churg-Strauss syndrome. Beyond vasculitis?

Ames PR, Roes L, Lupoli S, Pickering M, Brancaccio V, Khamashta MA, Hughes GR.

Coagulation Unit, Cardarelli Hospital, Naples, Italy.

Br J Rheumatol 1996 Nov;35(11):1181-3 Abstract quote

Thromboembolism is considered a rare occurrence in the course of Churg-Strauss syndrome.

We report three patients who experienced vascular occlusions at relapse and at first diagnosis of Churg-Strauss syndrome. The pathogenesis of thrombosis in Churg-Strauss syndrome and the potential role played by the eosinophil are discussed.

 

PATHOGENESIS CHARACTERIZATION
GENERAL  


Evidence for pathogenic involvementof eosinophils and neutrophils in Churg-Strauss syndrome.

Drage LA, Davis MD, De Castro F, Van Keulen V, Weiss EA, Gleich GJ, Leiferman KM.

Departments of Dermatology and Immunology and Medicine, Mayo Clinic/Mayo Foundation, Rochester.

J Am Acad Dermatol 2002 Aug;47(2 Pt 1):209-16 Abstract quote

BACKGROUND: Churg-Strauss syndrome (CSS) is a multi-organ disease with tissue and blood eosinophilia.

OBJECTIVE: Our aim was to study eosinophil and neutrophil involvement in CSS.

METHODS: Eight lesional skin biopsy specimens from 6 patients with CSS and serum and blister fluid from one patient were tested for eosinophil and neutrophil activity. Indirect immunofluorescence on skin specimens used antibodies to eosinophil granule major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and neutrophil elastase (NE). Serum and blister fluid specimens were analyzed for granule protein levels and for eosinophil-activating cytokines.

RESULTS: Indirect immunofluorescence showed prominent cellular and extracellular staining for EDN in skin biopsy specimens; MBP staining was less extensive. Five biopsy specimens showed marked cellular NE staining; 4 showed prominent extracellular NE. Serum and blister fluid specimens contained elevated MBP, EDN, and interleukin 5 levels and enhanced eosinophil survival in culture. Granulocyte-macrophage colony-stimulating factor and interleukin 5 were detected in blister fluid. Blister fluid contained more NE than normal serum.

CONCLUSIONS: Both eosinophils and neutrophils likely participate in skin lesion development in CSS.

 

LABORATORY/RADIOLOGIC/OTHER TESTS CHARACTERIZATION
ANCA Microscopic Polyangiitis Wegener's Granulomatosis Churg-Strauss Syndrome
PR3-ANCA 40% 75% 10%
MPO-ANCA 50% 20% 60%
Negative 10% 5% 30%

 

HISTOPATHOLOGY CHARACTERIZATION
SKIN  
Initial Cutaneous Manifestations Consistent With Mononeuropathy Multiplex in Churg-Strauss Syndrome

Tamihiro Kawakami, MD, PhD; Yoshinao Soma, MD, PhD; Kanade Kawasaki, MD; Ayumi Kawase, MD; Masako Mizoguchi, MD, PhD

 

Arch Dermatol. 2005;141:873-878. Abstract quote

Background  Churg-Strauss syndrome (CSS), also known as allergic granulomatous angiitis, is a rare entity that is characterized by systemic vasculitis in patients with a history of asthma. Patients with CSS show a marked peripheral blood eosinophilia, but the pathogenesis remains unknown.

Observations  A retrospective review was performed in 9 cases of CSS in whom cutaneous findings were present as an initial manifestation. All 9 patients had purpura and petechiae as well as severe pain and paresthesias of the lower extremities. Four patients (44%) used leukotriene receptor antagonists to treat their asthma, and 3 (75%) of them developed CSS within 3 months. Five patients (56%) were positive for perinuclear antineutrophil cytoplasmic antibodies before therapy, but in all 5 the levels of perinuclear antineutrophil cytoplasmic antibody normalized. Serum IgE levels were elevated in all patients before treatment but decreased after treatment. Histologically, all patients demonstrated leukocytoclastic vasculitis and eosinophilic infiltration. Eight biopsy specimens (73%) revealed marked eosinophilia around the nerve fibers in the dermis. Palisading granulomas in association with vessel-based changes were present in 4 (36%) of 11 biopsy specimens.

Conclusions  These characteristic cutaneous clinical patterns that are consistent with the presence of mononeuropathy multiplexes in the lower extremities may help physicians establish an earlier diagnosis. Both eosinophils and IgE, as well as perinuclear antineutrophil cytoplasmic antibodies to some degree, likely participate in skin lesion development in CSS. Furthermore, there appears to be a correlation between treatment with leukotriene receptor antagonists and the onset of CSS in some cases.

Cutaneous manifestations of Churg-Strauss syndrome: a clinicopathologic correlation.

Davis MD, Daoud MS, McEvoy MT, Su WP. Department of Dermatology, Mayo Clinic, Rochester, MN 55905, USA.

J Am Acad Dermatol 1997 Aug;37(2 Pt 1):199-203 Abstract quote

BACKGROUND: Allergic granulomatosis of Churg-Strauss (Churg-Strauss syndrome) is a distinct clinical disease of multisystem vasculitis.

OBJECTIVE: We characterize the clinical and histologic features of cutaneous findings in Churg-Strauss syndrome.

METHODS: All patients with Churg-Strauss syndrome seen between 1976 and 1995 were retrospectively reviewed.

RESULTS: Ninety patients with the diagnosis of Churg-Strauss syndrome were identified; 36 (40%) had cutaneous findings. Five patients (6%) had skin lesions as the initial manifestation. The most frequent cutaneous findings were purpura and petechiae on the lower extremities and cutaneous nodules and papules on the elbows. In 37 biopsy specimens from 29 patients, the most common findings were extravascular necrotizing granuloma (15 specimens) and leukocytoclastic vasculitis (16 specimens).

CONCLUSION: Cutaneous lesions in Churg-Strauss syndrome are common. Their characteristic clinical and histologic pattern may help establish the diagnosis.

 

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
Lung lesions Am J Clin Pathol 2000;114:767-772
EOSINOPHILIC PNEUMONIA  
HYPEREOSINOPHILIC SYNDROME  
Hypereosinophilia with systemic thrombophlebitis.

Kanno H, Ouchi N, Sato M, Wada T, Sawai T.

Hum Pathol. 2005 May;36(5):585-9. Abstract quote  

Summary A 34-year-old Japanese woman developed subcutaneous induration in the left thigh, then showed extreme eosinophilia, and died of hemorrhagic infarction of the brain. Autopsy revealed endocarditis with eosinophil infiltration and systemic thrombophlebitis, including pulmonary veins and intrahepatic branches of the portal vein. Arterial structure was relatively preserved.

She had no clinical history of asthma and had anti-ascarid IgE antibody at postmortem serological examination; thus, her disease does not fulfill the diagnostic criteria of Churg-Strauss syndrome and idiopathic hypereosinophilic syndrome (HES). Her organ involvement is, however, consistent with that of HES; thus, her pathophysiological conditions would resemble those of HES.

Systemic thrombophlebitis without arterial lesion in patients with hypereosinophilia has never been reported, and this case would broaden the spectrum of vascular lesions in these patients.
Allergic bronchopulmonary aspergillosis)  
Wegener granulomatosis  
INEFECTIONS Dirofilarial nodules
PNEUMOTHORAX Eosinophilic vascular infiltration of pneumothorax

 

PROGNOSIS AND TREATMENT CHARACTERIZATION
PROGNOSIS  

Churg-Strauss syndrome: outcome and long-term follow-up of 32 patients.

Solans R, Bosch JA, Perez-Bocanegra C, Selva A, Huguet P, Alijotas J, Orriols R, Armadans L, Vilardell M.

Department of Internal Medicine, Department of Pathology, Department of Pneumology and. Department of Preventive Medicine, Vall d'Hebron University General Hospital, 08035 Barcelona, Spain.

Rheumatology (Oxford) 2001 Jul;40(7):763-71 Abstract quote

OBJECTIVES: To study the clinical spectrum and evolution of Churg-Strauss syndrome in order to assess the clinicopathological features of the disease, the response to treatment and the long-term outcome.

METHODS: Thirty-two patients with proven allergic and granulomatous angiitis (Churg-Strauss syndrome) and followed up at a single institution were evaluated. They were recruited between 1977 and 1999 from internal medicine departments. Data were obtained retrospectively from medical files in 15 cases and prospectively, using a standardized form, for the remaining patients.

RESULTS: All patients had asthma and hypereosinophilia. The lungs, skin and peripheral nervous system were the organs most frequently involved. Antineutrophil cytoplasmic antibodies with antimyeloperoxidase specificity (MPO-ANCA) were detected in 77.8% of tested patients but they were not useful for monitoring disease activity. Extravascular granulomas were rarely seen in tissue biopsies. Forty per cent of the patients were treated with steroids alone. Immunosuppressive agents were added to the treatment when severe neurological, cardiac or gastrointestinal involvement was present. The outcome and long-term survival were good. Clinical relapse was rare after the first year of therapy. Dysaesthesiae of the distal limbs, neurophatic pain and cardiac failure were the most frequent sequelae.

CONCLUSIONS: Churg-Strauss syndrome is a rare disorder characterized by hypereosinophilia and systemic vasculitis occurring in patients with asthma and allergic rhinitis. Vasculitis commonly affects the lungs, skin and peripheral nervous system. Outcome and long-term survival is usually good with steroids alone or in combination with immunosuppressive agents. The syndrome has a low mortality rate compared with other systemic vasculitides.

Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: analysis of four prospective trials including 278 patients.

Gayraud M, Guillevin L, le Toumelin P, Cohen P, Lhote F, Casassus P, Jarrousse B

French Vasculitis Study Group. H pital Avicenne, Bobigny, France.

Arthritis Rheum 2001 Mar;44(3):666-75 Abstract quote

OBJECTIVE: To determine the long-term outcome of patients with polyarteritis nodosa (PAN), microscopic polyangiitis (MPA), and Churg-Strauss syndrome (CSS), to compare the long-term outcome with the overall French population, to evaluate the impact on outcome of the type of vasculitis, prognostic factors, and treatments administered at diagnosis, and to analyze treatment side effects and sequelae.

METHODS: Data from PAN, MPA, and CSS patients (n = 278) who were enrolled between 1980 and 1993 were collected in 1996 and 1997 and analyzed. Two prognostic scoring systems, the Five-Factors Score (FFS) and the Birmingham Vasculitis Activity Score (BVAS), were used to evaluate all patients at the time of diagnosis.

RESULTS: The mean (+/- SD) followup of the entire population was 88.3 +/- 51.9 months (range 3 days to 192 months). Of the 85 deaths recorded, at least 41 were due to progressive vasculitis or its consequences. Death rates reflected disease severity, as assessed by the FFS (P = 0.004) and the BVAS (P < 0.0002), and the 2 scores were correlated (r = 0.69). Relapses, rarer in hepatitis B virus (HBV)-related PAN (7.9%) than in MPA (34.5%) (P = 0.004), occurred in 56 patients (20.1%) and did not reflect disease severity. Survival curves were similar for the subpopulation of 215 patients with CSS, MPA, and non-HBV-related PAN who were given first-line corticosteroids (CS) with or without cyclophosphamide (CYC). However, CS with CYC therapy significantly prolonged survival for patients with FFS scores > or =2 (P = 0.041). Relapse rates were similar regardless of the treatment regimen; only patients treated with CS alone had uncontrolled disease. CYC was associated with a greater frequency of side effects (P < 0.00001).

CONCLUSION: Rates of mortality due to PAN (related or unrelated to HBV), MPA, and CSS reflected disease severity and were higher than the mortality rate in the general population (P < 0.0004). Rates of relapse, more common in MPA than HBV-related PAN patients, did not reflect disease severity. Survival rates were better among the more severely ill patients who had received first-line CYC. Based on these findings, we recommend that the intensity of the initial treatment be consistent with the severity of the disease. The use of the FFS and BVAS scores improved the ability to evaluate the therapeutic response.

Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008


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Last Updated June 19, 2008

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