Expression of epidermal antimicrobial peptides is increased in tinea pedis.

BACKGROUND: Tinea pedis is often chronic or recurrent, but not all individuals are equally susceptible to this infection. Dermatophytes are able to induce the expression of antimicrobial peptides and proteins (AMPs) in human keratinocytes and certain AMPs can inhibit the growth of dermatophytes. OBJECTIVE: The focus of this study was to analyse the secretion of relevant AMPs, especially RNase 7, human beta-defensin-2 (hBD-2) and the S-100 protein psoriasin (S100A7), in patients with confirmed tinea pedis. METHODS: To verify the diagnosis, skin scales were obtained from all patients (n = 13) and the dermatophytes were identified by potassium hydroxide mount, culture and molecular analysis. To determine the AMP concentrations, the lesional skin area of the foot was rinsed with a buffer that was subsequently analysed by ELISA. The corresponding area of the other unaffected foot as well as defined healthy skin areas of the forearm and forehead and samples from age and gender-matched healthy volunteers served as controls. RESULTS: In tinea pedis patients the AMP concentrations were higher in lesional skin than in non-lesional skin and in healthy skin of controls. In particular, concentrations of hBD-2 and psoriasin were significantly elevated. CONCLUSIONS: The induction of AMPs in tinea pedis might be triggered directly by the dermatophytes; furthermore, attendant inflammation and/or differentiation processes may play a role. Our results indicate that there is no defect in the constitutive expression and induction of the analysed AMPs by dermatophytes in the epidermis of affected patients. However, it is not known why the elevated AMP concentrations fail to efficiently combat dermatophyte growth.

Mycostatic effect of recombinant dermcidin against Trichophyton rubrum and reduced dermcidin expression in the sweat of tinea pedis patients.

Trichophytosis, a common dermatophytosis, affects nearly 20-25% of the world's population. However, little is known about mechanisms for preventing colonization of Trichophyton on the skin. Dermcidin, an antimicrobial peptide that provides innate immunity to the skin and is constitutively secreted even in the absence of inflammatory stimulation, was studied to elucidate its antimycotic activity against Trichophyton. Recombinant dermcidin was determined to have antimycotic activity against Trichophyton rubrum, as evaluated by colony-forming unit (CFU) assays. The killing rate of dermcidin was 40.5% and 93.4% at 50 µg/mL (the average dermcidin concentration in healthy subjects) and 270 µg/mL, respectively. An effect of dermcidin treatment was found to be a reduction of the metabolic activity of Trichophyton as determined by nicotinamide adenine dinucleotide assay. Further, dermcidin concentrations in sweat of tinea pedis patients were found to be lower than those of healthy subjects. These findings suggest a mycostatic role for dermcidin, at normal sweat concentrations. Accordingly, we suspect that dermcidin, at normal sweat concentrations, inhibits growth of Trichophyton, where Trichophyton is subsequently eliminated in conjunction with epidermis turnover. Dermcidin, therefore, appears to play a role in the skin protection mechanism that prevents colonization of tinea pedis.

Recurrent lymphangitic cellulitis syndrome: A quintessential example of an immunocompromised district.

Recurrent lymphangitic cellulitis syndrome (RLCS) occurs when a disordered lymphatic system renders a leg vulnerable to recurrent infection. The underlying immunologic defect is the result of accidental or iatrogenic penetrating wounds on the medial aspect of the thigh or lower limb overlying the greater saphenous vein, because the primary lymphatic drainage vessels are adjacent to this structure. Cracking/fissuring of the skin associated with chronic fungal infection of the feet ("athlete's foot"), most commonly mixed bacterial/fungal interdigital involvement, provides a portal of entry for opportunistic organisms. Bacteria and their products are cleared more slowly in the lymphatic-disrupted and therefore immunologically impaired limb, producing broad areas of dermatitis and around the scars quite distinct from other forms of superficial infection. This rarely develop in otherwise normal limbs. The dermatitis of RLCS and its systemic effects clear with antibiotics but recur intermittently until the tinea pedis is eradicated. The contralateral limb with normal lymphatic structures never develops clinical evidence of infection even though bilateral tinea infection is almost always present. This confirms the central role of an anatomically induced immunocompromised district (ICD) in this syndrome.

Dermatomycosis in lower limbs of diabetic patients followed by podiatry consultation.

BACKGROUND: Diabetic patients are particularly susceptible to fungal infections due to modifications that occur in their immunological system. These modifications compromise natural defences, such as skin and nails, especially from lower limbs. AIMS: Assessing the presence of dermatomycosis in lower limbs of Portuguese diabetic patients followed on Podiatry consultation. Determination of possible predisposing factors and the most frequent fungal species associated with the cases are included in the study. METHODS: A six-month prospective study was carried out in 163 diabetic patients with signs and symptoms of dermatomycosis followed by Podiatry at the Portuguese Diabetes Association in Lisbon. Samples from the skin and/or nails of the lower limbs were collected and demographic and clinical data of those patients were recorded. RESULTS: Trichophyton rubrum was the most frequently isolated dermatophyte (12.1%), followed by Trichophyton mentagrophytes (7.7%) and Trichophyton tonsurans (4.4%). Our study showed positive associations between type 2 diabetes and the presence of dermatomycosis in the studied population (p=0.013); this association was also shown between the occurrence of dermatomycosis and the localization of the body lesion (p=0.000). No other predisposing factor tested was positively associated with infection (p>0.05). CONCLUSIONS: Data on superficial fungal infections in diabetic patients are scarce in Portugal. This study provides information on the characterization of dermatomycosis in lower limbs of diabetic patients.

Hypomethylation and overexpression of CD70 (TNFSF7) in CD4+ T cells of patients with primary Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration and the production of autoantibodies, leading to the destruction of lacrimal and salivary glands. However, very little is known about the pathogenesis of the disorder. CD70 (TNFSF7), a B cell costimulatory molecule, is overexpressed in CD4(+) T cells from patients with systemic erythematosus lupus (SLE) due to the hypomethylation of its promoter. OBJECTIVE: In this study we asked whether the epigenetic regulation of CD70 expression is abnormal in pSS. METHODS: CD70 levels in CD4(+) T cells from pSS patients, tinea pedis and healthy controls were measured by real-time RT-PCR and flow cytometry. Bisulphite sequencing was performed to determine the methylation status of the TNFSF7 promoter region. RESULTS: CD70 expression was significantly elevated and correlated with a decrease in TNFSF7 promoter methylation in pSS CD4(+) T cells compared to controls. CONCLUSIONS: Demethylation of the CD70 promoter regulatory elements contributes to CD70 overexpression in pSS CD4(+) T cells, and may contribute to autoreactivity.

Short-duration oral terbinafine for the treatment of tinea pedis in HIV-positive patients.

Management of tinea pedis in patients who have the human immunodeficiency virus (HIV) is problematic; in those patients, dermatophytoses may be more difficult to treat than in the general population. This prospective, open-label, multicenter, randomized study evaluated the efficacy and safety of a short course of oral terbinafine for tinea pedis in patients who are HIV positive. Twenty-seven patients were randomized to receive oral terbinafine 250 mg once daily for 2 or 4 weeks; 17 patients with positive initial cultures and follow-up cultures were evaluable for efficacy at week 8. Mycological cure (defined as negative potassium hydroxide [KOH] microscopy and culture results) occurred in 47% (8) of patients; and modified mycological cure (defined as negative follow-up cultures) occurred in 65% (11) of patients. All 27 patients were evaluated for safety. Clinical cure (defined as minimal residual signs and symptoms) occurred in 82% (14) of patients. Oral terbinafine was well tolerated, indicating that regimens of 2 or 4 weeks are safe and effective for the treatment of tinea pedis in patients who are HIV positive.

Interferon-gamma production in peripheral lymphocytes of patients with tinea pedis: comparison of patients with and without tinea unguium.

The precise mechanism of the host defense that protects the nail from dermatophyte invasion is not known. Recent immunological findings in dermatophytosis suggest the hypothesis that the T helper 1 (Th1) response may play a role in protecting the nail from dermatophyte invasion. Our present study focused on interferon-gamma (IFN-gamma) release in patients with tinea pedis with or without tinea unguium, and pathogenesis of tinea unguium is discussed in relation to the association with a possible deficiency of Th1 response in the host defense mechanism. The production of IFN-gamma by peripheral blood mononuclear cells from the patients with tinea unguium in response to stimulation with trichophytin was not impaired in contrast to that from the patients without tinea unguium. Comparable lymphocyte proliferation to trichophytin was observed in both groups. Normal healthy persons with no clinical evidence of tinea could be divided into two groups based on lymphocyte proliferation and IFN-gamma production in response to trichophytin: high responder and low responder, with high responders being correlated with a clinical history of previous tinea pedis. In this study, a lack of a Th1 response to dermatophyte antigen was not shown in patients with tinea unguium by measuring the release of IFN-gamma, which plays a role in the effector phase of the delayed-type hypersensitivity reaction. A deficiency in the Th1 response to dermatophyte antigen, therefore, does not appear to play an important role in the establishment of tinea unguium.

Tinea pedis.

Tinea pedis is a term used to encompass several clinically distinctive infections of the skin of the foot. Dermatophytic fungi are primarily responsible for these infections. Several nondermatophytes have been implicated in some patients, particularly for nail infections. The major clinical variants are (1) interdigital infections in which dermatophytes initiate the process by damaging the stratum corneum while the subsequent maceration and leukokeratosis results from overgrowth of bacteria such as Micrococcus sedantarius, Brevibacterium epidermidis, Corynebacterium minutissimum and gram-negative organisms; (2) plantar mocasin type of hyperkeratosis due to T rubrum and found primarily in those with an atopic background; (3) vesiculo-bullous infections in the arch and side of the foot due to an immune response of delayed hypersensitivity to T mentagrophytes.

Langerhans cell accumulation in chronic tinea pedis and pityriasis versicolor.

Persistence of chronic tinea pedis (CTP) and pityriasis (tinea) versicolor (PIVE) has been tentatively attributed to an impaired cellular immune response. Therefore immunophenotyping of the inflammatory infiltrates in both disorders was performed in order to detect possible defects in cellular defence. The results of the present study show a dominance of memory T cells, an accumulation of macrophages and lack of B cells. A very prominent feature in CTP and especially PIVE was a marked accumulation of Langerhans cells (LCs) in the epidermis, mostly without expression of CD4. Furthermore, reduced expression of cellular activation markers and the presence of suppressor T cells was noted. In general, the cellular response in PIVE appeared to be slightly stronger than in CTP. This composition of the inflammatory infiltrates in chronic dermatomycoses is similar to previous findings in a variety of dermatoses. However, in PIVE and CTP local reduction of delayed-type hypersensitivity may occur. The function of LCs in these infections is therefore of special interest.

[The nonspecific correction of phagocytosis in patients with foot mycoses]. / Nespetsificheskaia korrektsiia fagotsitoza u bol'nykh mikozami stop.

A clinico-cytochemical examination of 47 patients with mycosis pedis is presented. The author established that these patients showed an inhibition of the phagocytic activity of neutrophils due to imbalance of acid and alkaline phosphatases. It is considered justified to use diuciphon as a means of unspecific immunocorrection.

[A comprehensive assessment of the phagocytic activity of the blood neutrophils in patients with rubromycosis treated with griseofulvin and nizoral]. / Kompleksnaia otsenka fagotsitarnoi aktivnosti neitrofilov krovi u bol'nykh rubrofitiei, lechennykh grizeoful'vinom i nizoralom.

The neutrophilic phagocytic activity (absorption and enzymic bactericidal) is intensified in rubromycosis patients treated with nizoral vs. those administered griseofulvin. it is advisable to combine griseofulvin therapy with biogenic stimulants (pyrogenal, aloe, fiBS, vitreous body).

[Immunologic shifts in tanners under the influence of potassium bichromate contact]. / Immunologicheskie sdvigi u rabochikh-kozhevnikov pod vliianiem kontakta s bikhromatom kaliia.

Immunologic examinations of leather-dressers, suffering from eczemas and dermatitis due to exposure to potassium bichromate have revealed immunologic shifts, particularly marked in combinations of the dermatoses with mycoses of the soles. This fact has lead to a conclusion on the contribution of mycoses of the soles to sensitization of the body to industrial allergens.