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Difficult asthma and Churg‐Strauss‐like syndrome: A cautionary tale

2010; Wiley; Volume: 16; Issue: 1 Linguagem: Inglês

10.1111/j.1440-1843.2010.01884.x

1440-1843

Edmund Lau, Wendy A. Cooper, P.T. Bye, Kwok Yan,

Amyloidosis: Diagnosis, Treatment, Outcomes

A 36-year-old non-smoking, female Caucasian was referred to our institution for management of difficult-to-control asthma. She had developed adult-onset asthma and allergic rhinitis 3 years previously, which subsequently evolved into a Churg-Strauss-like syndrome 2 years later. The diagnosis of Churg-Strauss was made by her community respiratory physician, on the basis of peripheral blood eosinophilia (3.8 × 109/L), positive perinuclear anti-neutrophil cytoplasmic antibody (ANCA) serology (titre 1:80) and pulmonary infiltrates. Serum IgE concentration was 360 ng/mL and a test for Aspergillus precipitins was negative. Thoracoscopic lung biopsy of the right upper lobe demonstrated eosinophilic lung infiltration without vasculitis. Despite the absence of vasculitis on lung biopsy, the clinical features and positive ANCA serology were compatible with a Churg-Strauss-like syndrome, and prednisolone was commenced at a dose of 50 mg/day. Despite a good clinical response to high-dose prednisolone, the patient's asthma symptoms deteriorated once the prednisolone dose was tapered to <20 mg/day. Multiple corticosteroid sparing agents were used without success. Azathioprine caused severe hepatitis and methotrexate induced a worsening of blood eosinophilia. The patient was subsequently treated with omalizumab for 12 weeks. Following the introduction of omalizumab, an attempt was once again made to reduce the corticosteroid dose. The trial of omalizumab was subsequently followed by a severe disease exacerbation when the prednisolone dose was tapered to <20 mg/day. The blood eosinophil count rose dramatically to 22.6 × 109/L and new bilateral lung infiltrates were observed (Fig. 1). The prednisolone dose was increased to 75 mg/day but the patient showed no clinical or radiological improvement. In view of the lack of progress and because a previous biopsy did not demonstrate definitive evidence of vasculitis, a repeat thoracoscopic lung biopsy was performed. This revealed dense eosinophilic infiltration within the alveolar spaces, septa, bronchial walls and pleura. Once again no granulomas or definite vasculitis were observed (Fig. 2). CT scan showing multifocal areas of peribronchial air space opacities. Lung biopsy showing eosinophilic infiltration of the lung parenchyma. Intravenous methylprednisolone (1 g/day) was administered for 5 days, followed by oral prednisolone (100 mg/day). The blood eosinophil count fell to 0.4 × 109/L by day four of pulse methylprednisolone therapy, with rapid clearing of lung infiltrates. Omalizumab therapy was ceased and mycophenolate mofetil (1 g/bd) was introduced. On clinical review at 12 months, the patient's corticosteroid dosage had been successfully tapered to 10 mg/day without recurrence of disease. Churg-Strauss syndrome (CSS), or allergic granulomatosis and angiitis, is a systemic vasculitis characterized by asthma and blood eosinophilia, with the lungs being most commonly involved.1 There may be a long prodromal phase of typical asthma symptoms lasting months and sometimes years, before manifestations of eosinophilic organ damage or vasculitis are observed. Despite a history of asthma, positive ANCA serology and eosinophilic lung infiltration, two thoracoscopic lung biopsies did not demonstrate definitive evidence of vasculitis in the present case. Thus, the differential diagnoses included CSS, hypereosinophilic syndrome and chronic eosinophilic pneumonia. These eosinophilic disorders have overlapping features, which make distinct clinical separation difficult. ANCA positivity and biopsy evidence of vasculitis would support a diagnosis of CSS, whereas negative serology and the absence of vasculitis suggest chronic eosinophilic pneumonia or hypereosinophilic syndrome, depending on limited lung or multi-organ involvement. Therefore, the present case is best described as ‘Churg-Strauss-like syndrome’, in view of the clinical, serological and pathological findings. The mainstay of therapy for CSS are oral corticosteroids and the response is usually favourable. Refractory CSS has been successfully treated by the addition of cyclophosphamide, azathioprine, high-dose i.v. immunoglobulin or interferon alpha. Omalizumab (anti-IgE monoclonal antibody) was tried in this patient because of her uncontrolled asthma, and recent reports of the successful use of omalizumab in CSS, with its efficacy being attributed to the possible blocking of IgE dependent mechanisms of eosinophil proliferation and accumulation.2,3 However, this patient suffered a severe disease exacerbation, which appeared to be temporally related to the introduction of omalizumab. Although the corticosteroid dosage was tapered during omalizumab therapy, there was a dramatic clinical deterioration. The disease exacerbation that followed omalizumab therapy was associated with widespread lung infiltrates, marked blood eosinophilia and a lack of response to high-dose oral prednisolone. Wechsler et al. reported manifestations of CSS following the introduction of omalizumab in patients with severe asthma, although concurrent tapering of corticosteroids likely led to unmasking of CSS in those cases.4 Treatment with mycophenolate appears to have successfully kept the disease in remission in the present patient. As a newer immunosuppressive agent, mycophenolate has already demonstrated its utility, with a favourable side-effect profile in the setting of solid organ transplantation and lupus nephritis, and emerging evidence of efficacy in ANCA-associated vasculitides.5,6 In summary, the present case illustrates the following pertinent points: although it is uncommon, clinicians should consider an underlying eosinophilic disorder in patients with difficult-to-treat adult-onset asthma; further evidence is required to evaluate the safety and efficacy of omalizumab therapy in CSS and omalizumab may unmask CSS during concurrent weaning of corticosteroids; mycophenolate may be successfully used as an alternative immunosuppressive agent.