Letter

Disseminated Cryptococcus neoformans after treatment with infliximab for rheumatoid arthritis

This study details the synthesis and biological evaluation of a collection of 19 structurally related Minor Groove Binders (MGBs), derived from the natural product distamycin, which were designed to probe antifungal and antimycobacterial activity. From this initial set, we report several MGBs that are worth more detailed investigation and optimisation. MGB-4, MGB-317 and MGB-325 have promising MIC₈₀s of 2, 4 and 0.25 μg/mL, respectively, against the fungus C. neoformans. MGB-353 and MGB-354 have MIC₉₉s of 3.1 μM against the mycobacterium M. tuberculosis. The selectivity and activity of these compounds is related to their physicochemical properties and the cell wall/membrane characteristics of the infective agents.

Biotherapies targeting TNFα were proven to be effective in the most severe cases of Crohn's Disease, a chronic granulomatous inflammatory bowel disease that can involve any portion of the digestive tract. The tolerance of anti-TNFα therapy is usually good, although several infectious complications have been reported with these drugs.

We report a case of a Crohn's disease patient who developed pulmonary cryptococcosis following chicken manure exposition while he received adalimumab and azathioprine.

A 54-year-old man, with history of severe Crohn's disease and ankylosing spondylitis, was admitted for diarrhea and abdominal pain under azathioprine treatment. In December 2010, he was treated with oral prednisone (1 mg/kg/day), but Crohn's disease relapsed when prednisone dose was lower than 30 mg/a day. The patient was then treated with adalimumab, but six weeks later he developed severe pulmonary cryptococcosis. The patient experienced a good outcome under antifungal therapy. We retrospectively found a high exposure to chicken manure in the last weeks.

Cryptococcosis is an opportunistic infection that can occur under anti-TNFα therapy. The environmental exposure to Cryptococcus spp. (in particular in chicken manure) is a source of contamination. Avoiding exposition to bird manure should be a recommendation for patients who are living in rural areas.

Les agents modulant le tumor necrosis factor alpha (TNFα) constituent une avancée thérapeutique majeure dans l’arsenal thérapeutique de la polyarthrite rhumatoïde, des spondylarthropathies et de la maladie de Crohn. Après 15 ans d’utilisation et la confirmation de leur intérêt thérapeutique, leurs effets indésirables, en particulier infectieux, sont mieux connus. Les infections à pyogènes (principalement pulmonaires, cutanées et urinaires) et la tuberculose constituent les complications infectieuses les plus fréquentes chez les patients traités par anti-TNFα. Toutefois, diverses infections opportunistes ont été observées sous anti-TNFα, notamment à Pneumocystis jiroveci, Histoplasma, Aspergillus, Candida sp. ou encore Nocardia sp. La date de survenue de ces infections opportunistes est variable. Néanmoins, des études ont indiqué qu’elles apparaissaient chez trois quarts des patients durant les 90 premiers jours suivant l’instauration du traitement anti-TNFα. Elles sont grevées d’une morbimortalité élevée. Depuis l’utilisation des anti-TNFα à grande échelle, l’émergence de complications infectieuses opportunistes graves impose au clinicien, d’une part, une grande vigilance lors de l’institution de cette biothérapie, et d’autre part, une surveillance clinique prolongée des patients.

Anti-TNFα agents have revolutionized the treatment of patients with rheumatoid arthritis, spondylarthropathies and Crohn's disease. However, their use is associated with an increased risk of infections. Pyogenic infections (involving the lungs, skin and urinary tract) and tuberculosis are the more commonly observed infectious complications in patients receiving anti-TNFα agents. However, opportunistic infections have been increasingly reported in anti-TNFα-treated patients, and include non tuberculous mycobacteria, fungi (Pneumocystis jiroveci, Candida sp, Aspergillus, Cryptococcus, Histoplasma), opportunistic bacterial (Nocardia), parasitic (Leishmania) and viral (e.g. Cytomegalovirus, human herpes virus 8 [HHV 8]) infections. These infectious complications usually occur within the first months of therapy and are important causes of morbidity and mortality in anti-TNFα-treated patients. It is recommended to rule out infections, especially latent or active tuberculosis, before the initiation of anti-TNFα therapy. However, it is necessary to follow-up closely these patients to detect the possible occurrence of opportunistic infections.