Abstract
Dermatophytes are agents of typically benign superficial infections. However, an increasing number of severe infections in immunocompromised hosts has been reported. We aimed to understand the factors underlying the existence of a cohort of patients presenting with chronic widespread dermatophytosis (CWD) due to Trichophyton rubrum, but with no signs of immunodeficiency. Their disease is usually recurrent and difficult to manage. Fourteen patients meeting the following criteria for CWD were studied: T. rubrum culture-proven skin lesions of ≥10 cm in at least one dimension; the involvement of at least three non-contiguous localizations of >1 year’s duration; and no predisposing conditions. For comparison, we also studied 13 acute Tinea pedis patients. Macrophages and neutrophils were isolated and tested for T. rubrum conidia phagocytic and killing activity. H2O2, NO, and pro- and anti-inflammatory cytokine release were measured. All experiments were run with age- and sex-matched healthy donors’ cells in parallel. CWD patients’ macrophages and neutrophils presented with reduced T. rubrum–phagocytic and killing abilities, and reduced H2O2 and NO release when compared with those of healthy donors. CWD patients’ macrophages secreted lower levels of the proinflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α, but enhanced levels of the anti-inflammatory cytokine IL-10. Neutrophil secretion closely followed this unbalanced pattern. In contrast, responses to the positive controls zymosan, lipopolysaccharide, and phorbol myristate acetate were comparable with those of healthy donors. The same experiments were performed with macrophages and neutrophils from the acute Tinea pedis patients and showed no differences when compared with the matched healthy donors. Patients with CWD have a T. rubrum-related functional deficiency of phagocytes and may represent a distinct clinical entity in the complex spectrum of the Trichophyton–host interaction.
Highlights
Dermatophytes are agents of typically benign superficial infections, of which the non-inflammatory, scaly lesions of toe webs due to Trichophyton rubrum are known as the most common example (Seebacher et al, 2008)
Patients were diagnosed with chronic widespread dermatophytosis (CWD) if they had T. rubrum culture-proven dermatophytosis involving at least three non-contiguous localizations, with lesions of ≥10 cm in at least one of its extensions, for more than 1 year
A second part of the study involved the recruitment of individuals presenting with Tinea pedis (Tp), the most common and benign form of dermatophytosis due to T. rubrum in Brazil (Costa-Orlandi et al, 2012)
Summary
Dermatophytes are agents of typically benign superficial infections, of which the non-inflammatory, scaly lesions of toe webs due to Trichophyton rubrum are known as the most common example (Seebacher et al, 2008). There are numerous reports of severe and occasionally life-threatening dermatophytic infections in the increasing population of immunocompromised patients, showing that dermatophytoses may pose a more serious threat to these patients (Marconi et al, 2010). The immune–genetic background underlying deep (invasive) dermatophytic infections afflicting some members of consanguineous families in Northern Africa has been elucidated (Lanternier et al, 2013). This syndrome was associated with an autosomal recessive CARD9 deficiency that accounts for the patients’ failure to limit the invasiveness of dermatophytes such as T. rubrum and T. verrucosum. There are frequent reports of patients presenting with recurrent or chronic widespread dermatophytosis (CWD) of the skin which, not invasive, is difficult to manage (Sentamilselvi et al, 1997– 1998; Vittorio, 1997; Gorani et al, 2002; Cordeiro et al, 2006; Seyfarth et al, 2007; Balci and Cetin, 2008; Kong et al, 2015)
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