Mesalazine-induced Churg-Strauss syndrome in a patient with Crohn's disease and sclerosing cholangitis.

Sirs, Churg-Strauss syndrome (CSS) is a rare disorder characterized by asthma, eosinophilia and systemic vasculitis (1). Three different phases can usually be recognized in CSS: asthma and atopic allergies such as rhinitis may precede of months, and sometimes of several years, the development of an eosinophilic infiltrative disease with eosinophilic pneumonia or gastro-enteritis followed by the vasculitic phase (1). The etiology of CSS is unknown but putative triggering factors have been identified, including desensitization, vaccination, rapid discontinuation of oral corticosteroid and, more recently, some drugs such as macrolide antibiotics and leukotriene receptor antagonists (2, 3). We report a case of Churg-Strauss syndrome in a patient with Crohn’s disease associated with use of mesalazine, a compound known to induce rarely eosinophilic pneumonia (4). A 39-year-old man with a 10-year history of atopic rhinitis, nasal polyposis, and asthma presented with weakness, fever, weight loss, arthralgias, vertigo, and paresthesias. He was on salbutamol, mesalazine and ursodeoxycholic acid. Mesalazine had been started 10 months before presentation for Crohn’s disease and sclerosing cholangitis, both histologically proven. At presentation, his eosinophil count was 12,124 x mm3 (56% of total), erythrocyte sedimentation rate 41 and C-reactive protein 7 mg/L (nv < 5). A urine specimen revealed haematuria (1 plus). Antineutrophil cytoplasmic antibody (ANCA), antinuclear antibodies (ANA), and rheumatoid factor were negative. A nuclear magnetic resonance of the skull revealed pansinusitis, whereas a computed tomography of the lung showed initial centrolobular emphysema. Pulmonary function tests disclosed a mild obstructive disease. Electromyography of peripheral nerves was indicative of mononeuritis multiplex. A bone-marrow biopsy specimen showed extensive eosinophilic infiltration. Since a stool specimen was positive for Blastocystis hominis, the patient was discarded with metronidazole treatment. One month later, the patient was admitted again because of worsening of vertigo. Laboratory tests confirmed the presence of eosinophilia (46.4%), and increased inflammatory markers. An ENT doctor examination revealed vestibular decompensation and right perceptive hypacusia. Subsequently, there was the occurrence of spontaneous nystagmus and a left third cranial nerve palsy. A repeat nuclear magnetic resonance of the skull showed new multiple small ischemic lesions. Because of the presence of asthma, marked eosinophilia, sinusitis, and neuropathy a diagnosis of Churg-Strauss syndrome was made and treatment with prednisone 1 mg/Kg was started with prompt clinical improvement, normalization of inflammatory indices and of eosinophilia. Since no reports on the association of Churg-Strauss syndrome with Crohn’s disease were found in a literature search, and based on the well-known recognition that drugs can act as triggering factors in ChurgStrauss vasculitis (2, 3), mesalazine was stopped. Eight months after diagnosis the patient is well under treatment with prednisone 15 mg/day. His eosinophil count is normal as well as his erythrocyte sedimentation rate and C reactive protein. The cause(s) of Churg-Strauss syndrome is usually not known, but among putative triggering factors vaccinations, desensitisation, antibiotics and, more recently, leukotriene receptor antagonists have been described (2-3, 5). Mesalazine is known to induce eosinophilic pneumonia and can cause activation of eosinophil (4, 6). More rarely, it has been associated with vasculitis-like syndromes and, in a single case, with Churg-Strauss syndrome in a patient with ulcerative colitis (4, 6-10). In most cases blood eosinophilia was present (6-8). To our knowledge this is the first report of a case of Churg-Strauss syndrome in a patient with Crohn’s disease and sclerosing cholangitis. Even though we could not demonstrate a cause-effect relationship between mesalazine and Churg-Strauss syndrome, we believe that our patient’s illness was probably caused by this drug because of its capacity to induce eosinophil activation and hypersensitivity reactions. We suggest that mesalazine should be used with caution in patient with asthma.