Churg-Strauss Syndrome (Allergic granulomatosis)

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.

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

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.

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.