Chronic widespread dermatophytosis due to Trichophyton rubrum: a syndrome associated with a Trichophyton-specific functional defect of phagocytes

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.

The menace of chronic and recurrent dermatophytosis in India: Is the problem deeper than we perceive?

“…[ 5 ] The dermatophytic clearance from the skin is secondary to the activation of cell-mediated immunity (CMI) and is Th1/Th17-dependent. [ 6 ] It is of interest to note that acute dermatophytosis is associated with Th1 response, whereas in cases of chronic dermatophytosis, the immunity is skewed toward Th2 cytokines with high levels of IgE and IgG4 antibodies. [ 5 ] One could propose that individuals with defective tilt of immunity toward Th2 cytokines would be more predisposed to chronic dermatophytic infection.…”

“…In patients who suffer from chronic dermatophytosis, defective phagocytosis of the fungal hyphae is observed. [ 6 ] Mannans produced by T. rubrum work by inhibiting the critical steps in antigen processing and presentation. [ 4 ] The free radicals and nitric oxide release have been found to be 20–30% lower than that of controls in patients of chronic dermatophytosis, indicating a defective killing mechanism as well.…”

In vitro activity of azole derivatives and griseofulvin against planktonic and biofilm growth of clinical isolates of dermatophytes

“…Dermatophytes are keratinophilic fungi involved in superficial mycoses, whose incidence has increased in recent years, particularly chronic and recurrent forms, with Trichophyton rubrum as the most common species in human cases . Studies conducted over the past few years have reported an increase in resistance to antifungal agents commonly used to treat cutaneous mycoses, including dermatophytosis .…”

“…Some features, including the ability to form biofilms, may be associated with dermatophyte unresponsiveness to antifungals . In general, biofilms are commonly implicated in the antifungal tolerance of microorganisms, commonly requiring high minimum inhibitory concentration (MIC) values to inhibit their growth …”

“…6,10,11 In general, biofilms are commonly implicated in the antifungal tolerance of microorganisms, commonly requiring high minimum inhibitory concentration (MIC) values to inhibit their growth. 1,2,[12][13][14] To better understand the in vitro antimicrobial susceptibility of dermatophytes, the aim of this study was to, primarily, determine the MICs of itraconazole, voriconazole and griseofulvin against planktonic growth of T. rubrum, Trichophyton tonsurans, Trichophyton mentagrophytes, Microsporum canis and Microsporum gypseum and, subsequently, evaluate the impact of these antifungals on biofilms of these dermatophytes.…”