Dapsone hypersensitivity syndrome complicated by Scedosporium apiospermum pneumonia in an immunocompetent patient

Abstract

Dapsone (4,40diaminodiphenyl sulphone) has been used since the middle of the 20th century for leprosy treatment, usually in combination with rifampin and clofazimine. Dapsone hypersensitivity syndrome (DHS) occurs in 0.5-3% of patients treated with this drug. The exact immune mechanism behind this idiosyncratic reaction with multi-organ involvement is unclear. Some genetic and environmental factors, by increasing the production of dapsone-reactive metabolites or affecting the ability of the liver to detoxificate them, may increase the risk of developing DHS. Latency before the onset of symptoms can vary from 2-6 h, in previously sensitised patients, to 6 months [1]. Typical DHS manifestations include high fever, skin rash, malaise, methemoglobinaemia, liver toxicity (jaundice, hepatitis and hepatomegaly) and generalised lymphadenopathy. Acute renal failure, hypersensitivity pneumonia, cholangitis, sensory peripheral neuropathy, pancreatitis and pleural effusion have been reported less frequently [2]. The discontinuation of dapsone and the early initiation of high-dosage systemic corticosteroid therapy are crucial to decrease mortality and morbidity. Scedosporium spp. are hyaline filamentous fungi ubiquitously present in soil, sewage and polluted waters. Although these fungi have a uniform worldwide distribution, they are more commonly found in temperate climates than in tropical climates. The most common species responsible for human disease are Scedosporium apiospermum (teleomorph: Pseudallescheria boydii) and Scedosporium prolificans, both of which are very similar to Aspergillus spp. These pathogens, once mainly known as agents of cutaneous and subcutaneous tissue infections (e.g. maduromycosis) in immunocompetent patients, have recently been reported to cause systemic life-threatening infections in immunocompromised hosts with increasing frequency. Scedosporium-related pneumonia, meningoencephalitis, brain abscesses and endocarditis have been documented in patients with advanced human immunodeficiency virus (HIV) infection and haematological malignancies, as well as in stem cell transplantation recipients. In the international medical literature, there are only a few reports of life-threatening Scedosporium spp. infections in immunocompetent patients. Rodriguez-Tudela et al. [3], in a recent review of 162 cases of scedosporiosis, reported 34 infections in patients with no underlying chronic condition; of note, 23 of these cases (82%) had suffered surgery or traumatism before the acquisition of the infection. Katragkou et al. [4] reviewed 23 cases of Scedosporium apiospermum infection after near-drowning. In this particular condition, Scedosporium apiospermum has been reported to cause severe invasive infections, with frequent central nervous system dissemination, in young and immunocompetent hosts. We report the case of a patient who died of a rapidly progressive pneumonia caused by Scedosporium apiospermum. The patient we describe did not present any typical risk factor for this opportunistic infection, except for a 10-day course of steroid therapy administered to control a DHS. A 53-year-old Indian man presented with a 10-day history of fever, generalised itchy maculopapular rash involving the palms and soles, and jaundice. His past medical history was unremarkable, and he denied taking any medication on a regular basis. He had been living in Italy for the past 26 years, but he had travelled to his L. Ceccarelli G. Calisti (&) D. Delle Rose A. Ricciardi G. Maffongelli P. Sordillo L. Sarmati M. Andreoni Infectious Diseases Unit, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, Italy e-mail: giorgiocalisti@gmail.com