Sprue-like enteropathy associated with olmesartan medoxomil use has been recently reported. Its clinical manifestations include diarrhea, weight loss and malabsorption. Duodenal biopsies show villous atrophy (VA) with or without intraepithelial lymphocytosis and inflammation of the lamina propria. Serology for celiac disease (CD) is negative and gluten-free diet does not result in clinical improvement. Symptoms resolve after olmesartan discontinuation. Follow-up biopsies show recovery/improvement of the duodenum. Whether sprue-like enteropathy is a specific adverse reaction to olmesartan or rather a class effect of angiotensin-receptor blockers (ARBs) remains a controversial issue. We report a case of sprue-like enteropathy associated with telmisartan. A 52-year-old man presented with chronic diarrhea, abdominal discomfort and significant weight loss. In the last 3 years, he had been treated with telmisartan 40 mg/day for hypertension after right adrenalectomy for an aldosterone-producing adenoma. Laboratory investigations showed no significant abnormalities: Hb 13.6 g/dL, serum albumin 3.9 g/dL, total cholesterol 193 mg/dL, serum creatinine 0.99 mg/dL, sodium 143.6 mmol/L, K+ 4.3 mmol/L, calcium 9.3 mg/dL, phosphorus 3.9 mg/dL and 25-OH-D3 27.7 ng/mL. Duodenal histology showed subtotal VA and inflammation of the lamina propria. CD serology was negative. HLA-DQ typing showed absence of the DQ2/DQ8 haplotypes. After telmisartan discontinuation, patient’s symptoms subsided, and his body weight increased despite persistence of a gluten-containing diet. Follow-up biopsies at 3 showed progressive duodenal recovery. Very few cases of sprue-like enteropathy associated with ARBs other than olmesartan have been reported. Our case of telmisartan-associated enteropathy further suggests that sprue-like disease may be a class effect of ARBs.

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We have observed five cases of sprue-like enteropathy during treatment with angiotensin II receptor blockers (ARBs) other than olmesartan. To the best of our knowledge, only seven cases 1,3-8 of enteropathy associated with sartans other than olmesartan have been described so far. In Table 1, we summarise the clinicopathological features of these cases including our series.The patients (eight females and four males) ranged in age from 52 to 85 years. They had been treated with ARBs other than olmesartan from 2 months to 13 years and the drugs involved were: irbe- In three cases, there was a collagenous colitis, 3 associated with IELs in two cases. A diffuse involvement of the gastrointestinal tract with collagenous gastritis, ileitis and colitis was documented in the case of Cyrany et al. 3 The possible involvement of almost the entire gut 1,2 is well known in olmesartan-associated enteropathy.Of note, in our series, all the patients underwent colonoscopy, whereas esophagogastroduodenoscopy was performed in two patients. This could explain why duodenal mucosa atrophy was identified only in two cases. In the same two cases, histology revealed also an acute eosinophilic colitis pattern. These cases represent the first report of eosinophilic colitis in patients taking ARBs other than olmesartan. As reported for olmesartan, 10 a milder histological presentation with slight increase in inflammatory cells of the colonic mucosa was present in one case of our series.In all patients, the symptoms ceased after drug withdrawal. In seven cases, the patients underwent follow-up biopsies which confirmed histological recovery 3-8 a few months after drug suspension.In conclusion, the clinicopathological findings in patients taking ARBs other than olmesartan are similar to those described in olmesartan-associated enteropathy.Therefore, we suggest the possibility of a class effect. Clinicians and pathologists should be aware of ARB-induced gastrointestinal injury because its identification has a drastic impact on the patient's health with no other intervention than ARB suspension. LETTERS TO THE EDITORS| 471

ObjectivesThe treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is based on remission-induction and remission-maintenance. Methotrexate is a widely used immunosuppressant but only a few studies explored its role for maintenance in AAV. This trial investigated the efficacy and safety of methotrexate as maintenance therapy for AAV.MethodsIn this single-centre, open-label, randomised trial we compared methotrexate and cyclophosphamide for maintenance in AAV. We enrolled patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), the latter with poor-prognosis factors and/or peripheral neuropathy. Remission was induced with cyclophosphamide. At remission, the patients were randomised to receive methotrexate or to continue with cyclophosphamide for 12 months; after treatment, they were followed for another 12 months. The primary end-point was relapse; secondary end-points included renal outcomes and treatment-related toxicity.ResultsOf the 94 enrolled patients, 23 were excluded during remission-induction or did not achieve remission; the remaining 71 were randomised to cyclophosphamide (n = 33) or methotrexate (n = 38). Relapse frequencies at months 12 and 24 after randomisation were not different between the two groups (p = 1.00 and 1.00). Relapse-free survival was also comparable (log-rank test p = 0.99). No differences in relapses were detected between the two treatments when GPA+MPA and EGPA were analysed separately. There were no differences in eGFR at months 12 and 24; proteinuria declined significantly (from diagnosis to month 24) only in the cyclophosphamide group (p = 0.0007). No significant differences in adverse event frequencies were observed.ConclusionsMTX may be effective and safe for remission-maintenance in AAV.Trial registrationclinicaltrials.gov NCT00751517

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