Toxicity of nifurtimox as second-line treatment after benznidazole intolerance in patients with chronic Chagas disease: when available options fail.

OBJECTIVE: To describe the tolerability and rate of nifurtimox discontinuation when administered as a second-line treatment to patients with previous treatment interruptions due to adverse reactions with benznidazole. METHODS: We studied a prospective cohort study of adult patients with chronic Chagas disease in a referral centre in Spain treated from July 2007 to July 2017. We analysed the tolerability profile and treatment interruption rate due to adverse reactions (ARs) to nifurtimox in patients previously incompletely treated (less than 30 days) with benznidazole due to ARs. RESULTS: A total of 472 patients initiated treatment with benznidazole during the study period. Of these, 118 (25%) developed ARs that led to treatment discontinuation before 30 days of therapy. Fifty-three (44.9%) of 118 initiated nifurtimox as second-line treatment; most were women (79.3%), were of Bolivian origin (98.1%) and had a median age of 37.3 years (interquartile range, 29.8-43.2). The most common ARs with nifurtimox were cutaneous hypersensitivity (24.1%), digestive disorders (22.2%), fever (12.9%), neurologic disturbances (11.1%), depression, anxiety or insomnia (9.2%), dyspnoea (7.4%), myalgia (5.5%), and dizziness, asthenia or malaise (7.4%). Twenty-six (49.1%) of 53 patients discontinued nifurtimox due to ARs, all of them before the required minimal therapy duration of 60 days. There were no deaths. CONCLUSIONS: Treatment of chronic Chagas disease relies on two drugs with a poor tolerability profile. In our cohort, 12.3% of the patients who initiated benznidazole and subsequently nifurtimox in case of nontolerance developed ARs that led to permanent treatment discontinuation. Most were women of childbearing age, a group for whom therapy has the added benefit of interrupting vertical transmission.

Colonic perforation secondary to metastatic lung adenocarcinoma during anti-TNF treatment for ankylosing spondylitis.

Biological agents targeting inflammatory cytokines such as tumour necrosis factor alpha (TNF-α) have emerged in recent years as effective medications for a variety of inflammatory arthropathies. Although the relationship between the use of anti-TNF drugs and an increase in the rate of infections is well established, the role of these drugs in the development of different types of cancer is unclear. Randomized clinical trials and national registries have not demonstrated a significant increase in the risk of cancer in patients treated with anti-TNF drugs, but numerous cases of the appearance of malignant tumors in patients receiving these drugs have been reported. We describe the case of a 73-year-old man, ex-smoker, who developed a lung cancer during treatment with infliximab further complicated by perforation of a metastasis in the sigmoid colon, which is a very infrequent event in the course of this malignancy. A few similar cases previously reported in the literature are reviewed.