Treatment of difficult-to-treat-dermatophytosis: results of a randomized, double-blind, placebo-controlled study.

INTRODUCTION: Difficult-to-treat dermatophytosis is an emerging public health problem in Sri Lanka. Safe, effective and affordable treatment is needed to solve this problem. Therefore this study has assessed the effectiveness and safety of modified Whitfield ointment applied twice daily with oral griseofulvin 500 mg daily given over 8 weeks in patients with difficult-to-treat dermatophytosis. METHODOLOGY: A randomized, double-blind, within-patient-placebo-controlled trial was conducted in patients with clinico- mycologically (history, physical examination, direct light microscopy examination of scales in potassium hydroxide mount) confirmed difficult-to-treat dermatophytosis. Lesions were randomized to receive modified Whitfield ointment (5% benzoic acid and 5% salicylic acid) or emulsifying ointment. All patients were given oral griseofulvin 500mg once daily. The outcome measures were clinical assessment of disease severity, the total surface area of the lesions and the patient's perception of the disease severity at baseline and every two weeks up to a maximum of 8 weeks. RESULTS: Thirty patients completed the study. At two weeks, there was a statistically significant improvement in modified Whitfield ointment arm in the clinical assessment of disease severity and the patients' perception. There was a 7.59% reduction in the surface area of lesions in modified Whitfield ointment arm and a 5.83% increase in the surface area of lesions in the emulsifying ointment arm at two weeks. The difference between the two arms in surface area changes was not statistically significant (p = 0.107, df = 29). CONCLUSIONS: A combination of modified Whitfield ointment with griseofulvin is significantly effective, safe and affordable option for treating difficult-to-treat dermatophytosis in the tropics.

Pathogenesis of tinea.

Dermatophytes are hyphomycetes that can degrade keratin. This puts them in a position to cause infections of the keratin-containing superficial skin. The resulting clinical picture is called tinea. The pathogenesis and course of tinea is decisively determined by pathogen-related factors and by the defense mechanisms of the host. An infection starts with an adherence of fungal propagules, followed by the formation of hyphae that can spread within the tissue. This process is accompanied by a release of fungal enzymes and other pathogenic factors. Next keratinocytes are activated, the epidermal barrier is destroyed, epidermal proliferation is enhanced and defensins are expressed within the epidermis. In addition, innate and specific immune responses are initiated, involving neutrophilic granulocytes, macrophages, antibodies and T cells. The cellular mechanisms are thought to be crucial for healing. Special conditions apply to nail infections, because within nail plates the fungi are not accessible to effective defense mechanisms, as well as to infections of hair follicles that contain specific concentrations of steroid hormones. Dermatophytes that penetrate into the dermis can cause granulomatous inflammatory reactions and systemic immune reactions are supposed to be a trigger of so-called id reactions.

Modeling dermatophytosis: Guinea pig skin explants represent a highly suitable model to study Trichophyton benhamiae infections.

Dermatophyte infections are a growing health concern worldwide with increasing patient numbers, especially in children. However, detailed knowledge about infection mechanisms and virulence factors are scarce. This study aimed to establish an infection model based on guinea pig skin explants mimicking the in vivo situation as closely as possible to survey the pathogenesis of dermatophytoses. A fundamental prerequisite was the detailed description of native guinea pig skin and its morphological changes during tissue culture because comprehensive data on guinea pig skin characteristics were not available. Skin explants were harvested from healthy, adult guinea pigs and transferred to cell culture inserts. One group was inoculated with defined suspensions of colony-forming units of zoonotic Trichophyton benhamiae isolates; others served as controls to assess the tissue viability during the 10-day culture. Samples were taken on days 3, 5, 7 and 10 and processed for histological and immunohistochemical analysis. Standard tissue culture conditions provoked acantholysis and regional orthokeratotic alterations. The reduced desquamation caused hyperkeratosis paralleled by hypogranulosis or regional hyperplasia. During T. benhamiae infection, keratinocyte proliferation came to a complete halt on day 5 whereas the number of terminal deoxynucleotidyl transferase dUTP nick end labeling assay-positive cells increased moderately up to day 7. Hyphae grew massively into the skin explants causing strong keratinolysis and tricholysis. By the end of the culture, complete disintegration of the basement membrane and dermal tissue was observed. A realistic and reliable skin infection model was established to study dermatophytoses in general and cutaneous T. benhamiae infections in particular.

Hair loss due to scalp ringworm irradiation in childhood: health and psychosocial risks for women.

BACKGROUND: Until 1960, hundreds of thousands of children worldwide had been treated for scalp ringworm by epilation via irradiation. The discovery of late health effects in adulthood prompted investigation of the medical aspects of irradiation in childhood and led to the establishment of strict protocols for the use of X-ray irradiation. These studies ignored alopecia, which affects some individuals who underwent irradiation for scalp ringworm as children. This study examined the impact of alopecia due to irradiation for scalp ringworm on the health and psychosocial status of affected women. METHODS: We analysed a random sample of 130 medical files of women recognised by Israel's state committees as suffering from permanent hair loss as a result of scalp ringworm irradiation in childhood. The coded medical data included demographic variables, self-reported mental health conditions, self-reported physical health conditions, self-reported social conditions, and spousal relationship. RESULTS: Compared with the general population of women in Israel, research participants reported significantly higher rates of depression, anti-depressant and/or anti-anxiety drug use, psychotherapy or psychiatric hospitalisation, attempted suicide, migraines, cancer, and divorce. Many described humiliating social experiences due to their appearance, both in childhood and adulthood, that led them to curtail their social interactions. The participants also reported that alopecia negatively affected their spousal relationships. CONCLUSIONS: Life with hair loss from scalp ringworm irradiation in childhood has a negative impact on women's health status and psychosocial state. Health policy-makers must broaden their approach to women who underwent scalp ringworm irradiation by addressing the effects of their hair loss in addition to the effects of the radiation treatment per se. This may be achieved by guiding physicians who provide medical services to these women to take into account the psychosocial and health risks related to hair loss in their diagnosis and treatment as well as by creating a cadre of specially trained mental health professionals who can address their unique psychosocial needs. They must also consider including the specialized mental health services tailored for these women's unique needs in the Healthcare Basket.

Tinea cruris in children.

Tinea cruris is an intensely pruritic fungal infection of the groin and adjacent skin. Also known as crotch rot and jock itch, it can be a troubling important entity that at times is a clinical, diagnostic, and therapeutic challenge. Predisposing factors include heat, humidity, and hyperhidrosis, common accompaniments of high school-aged athletes. Furthermore, obesity and diabetes mellitus, additional risk factors for tinea cruris, are reaching unprecedented levels in adolescents. Treatment options range from improving hygiene to topical antifungal agents and systemic antifungal agents, the latter with potentially dangerous side effects.

[The pathophysiology and defense mechanism against superficial and subcutaneous fungal infection].

To determine the pathophysiology of the fungal infection and defense mechanisms against superficial dermatomycosis, two series of experimental infections of Trychophyton mentagrophytes were made on the forearm of a male volunteer. One series was applied topical steroid ointment, the other the vehicle alone. The infected sites were biopsied from each row weekly up to the 4th week, and the set of sites were studied and compared clinically, histopathologically and immunohistochemically. For the study against subcutaneous fungal infection, the same experiments were studied using the subcutaneous inoculation of Sporothrix schenckii. The pathophysiology of the superficial dermatophytosis was thought to be the same as those of the contact (allergic) dermatitis, including the physiodynamics of CD-1 cells. The principal mechanism of the defense lay in the removal of the foreign materials (fungi) together with keratinocytes whose turnover increased because of the eczematous reaction. It was proved that the topical application of steroid ointment suppressed the immune reactions locally, thus forming a paradoxical feature with little inflammatory reaction and abundant fungal elements (so-called atypical tinea). The pathophysiology of the subcutaneous fungal infection was thought to be a suppurative granulomatous reaction and pathologically showed a mixed cell granuloma. The neutrophils and macrophages engulfed and digested the fungi in the forefront, but the circumference was surrounded by epithelioid cells and/or foreign body granuloma. Transepithelial elimination also played some role in the defense. It was proved that when the defense mechanism was weakened by the topically applied steroid ointment, not only the clinical symptoms but also the fungicidal tissue reaction were subdued, and histocytes only engulfed fungi to protect them from dispersion. The trichophytin reaction turned positive on the 14th day, and the sporotrichin reaction on the 7th day.

Epidermal cell proliferation in guinea pigs with experimental dermatophytosis.

To elucidate the mechanisms underlying the self-healing process of experimental dermatophytosis produced in guinea pigs by an occlusive method with Trichophyton mentagrophytes, epidermal proliferative activity was evaluated by the in vivo tritiated thymidine-labeling technique performed at various intervals after the first and second infections. Determination of labeling indices disclosed that an increased epidermal proliferation correlated well with the severity of inflammatory changes, i.e., a peak activity was noted after 10 days in primary infection and at 2 days in reinfection, respectively, and was followed by subsequent spontaneous lesion clearance after 10 days. Application of a heat-killed spore suspension produced inflammatory changes with enhanced epidermopoiesis, similar to those induced by reinoculation of living spores, only in immune animals. The present results indicate that the dermatitic changes occurring in experimental dermatophytosis increase epidermopoiesis which facilitates elimination of the fungus from the stratum corneum and that host immune activity, particularly contact sensitivity to fungal antigen, exerts a crucial role to induce these changes.

Invasive trichophyton rubrum infection in an immunocompromised host. Case report and review of the literature.

Typically confined within the keratinized, epithelial layer of the skin and hence categorized among the dermatophytoses, Trichophyton rubrum infections usually present as superficial, scaling eruptions. In certain clinical settings, however, such as in immunosuppressed hosts, deep local invasion, multivisceral dissemination, and even death due to T. rubrum granulomas have been described. A case of multiple, subcutaneous, neutrophilic abscesses due to T. rubrum in an immunosuppressed renal allograft recipient is described. The pathogenesis, diagnosis, and immunology of invasive T. rubrum infections in immunocompromised hosts are reviewed.

Tinea incognito and "over-the-counter" potent topical steroids.

The term tinea incognito has been used to describe a dermatophyte infection modified by corticosteroid treatment. Lesions are often atypical appearing and the diagnosis is frequently delayed or missed. This difficulty is often exacerbated by the random misuse of potent dermatologic preparations that can alter the initial presentation to the dermatologist. Recently, we have encountered an increasing number of patients who have obtained potent superpotent topical steroids "over the counter" to self-treat various dermatoses. We report two such cases of tinea incognito that were exacerbated and altered clinically by the use of such preparations.

Experimental medication of equine ringworm due to Trichophyton equinum var. autotrophicum.

Twelve medicaments were tested for their efficacy in the treatment of Trichophyton equinum var. autotrophicum; povidone iodine, thiabendazole ointment, captan ointment and Burroughs Wellcome Ringworm Ointment gave satisfactory results but their usefulness may be limited for treatment of large numbers of horses. Aqueous washes containing 0.5% hexetidine or 0.3% chloramine-T did not prevent fungi being isolated from lesions for up to 7 days after treatment. Similarly neither etisazole nor thiabendazole suspension prevented fungi from being isolated from lesions for up to 15 days after treatment. Commonly used aqueous solution of 2.5% lime sulphur and 2% captan were least successful, as fungi could still be isolated from lesions for up to 30 days after treatment. The need to treat large numbers of horses may dictate the use of such solutions rather than ointments because of ease of application and cost factors. Treatments consisting of 10% nystatin ointment, 10% iodine fortis, 10% Medol and a proprietary ointment, Queensland Itch Dressing, were not satisfactory. Clinical appraisal and a scratch test must be used together to evaluate progress of treatment. Mass medication of large numbers of horses should be primarily aimed at reduction of spread of infection; normal hair growth should not be used as an indication of the removal of infective agents in the hair as regrowth was altered very little by medication. Hence assessments of cure on the basis of regrowth of hair alone are of dubious value.

Pimecrolimus-induced tinea incognito.

A 6-year-old boy was brought to his primary care provider by his mother, who complained of a pruritic rash near his right eye. The eruption was described as a small, erythematous, slightly scaly plaque at the lateral margin of the right eyelid. The child was in good health and took no medications. The diagnosis of eczema was made; the patient was treated with pimecrolimus cream b.i.d. to the affected area. After 2-3 days of treatment, the itching and erythema completely resolved; however, a rough and scaly plaque persisted. After 1-2 weeks of treatment, the itching gradually returned, and the lesion began to increase in size. Multiple, similar lesions appeared several centimeters from the initially affected area. Pimecrolimus was discontinued; topical nystatin/triamcinolone ointment was prescribed. The eruption continued to spread, and the patient was referred to dermatology for further evaluation. The patient presented to the dermatology clinic with multiple annular, scaly papules and plaques with central clearing. Excoriations and mild inflammation were noted around all affected areas (Figure). A potassium hydroxide examination of the lesions revealed numerous hyphae. The nystatin/triamcinolone ointment was discontinued; oral griseofulvin was prescribed. The eruption improved dramatically after 3 weeks and eventually cleared completely after 5 weeks of treatment. Topical 2% ketoconazole cream was applied b.i.d. for the final 2 weeks of treatment.

Disruption of barrier function in dermatophytosis and pityriasis versicolor.

Dermatophytes have the ability to form molecular attachments to keratin and use it as a source of nutrients, colonizing keratinized tissues, including the stratum corneum of the skin. Malassezia species also affect the stratum corneum of the skin. Therefore, dermatophytosis and pityriasis versicolor of the skin are thought to be important factors of profound changes in skin barrier structure and function. We aimed to describe the changes in transepidermal water loss (TEWL), stratum corneum hydration, and skin pH in the lesions of the dermatophytosis and pityriasis versicolor. Thirty-six patients with dermatophytosis (14 with tinea cruris, 13 with tinea corporis and nine with tinea pedis or tinea manus) and 11 patients with pityriasis versicolor were included in this study. TEWL, stratum corneum conductance and skin pH were determined by biophysical methods to examine whether our patients exhibited changes in barrier function. Dermatophytosis and pityriasis versicolor except tinea pedis and tinea manus showed highly significant increase in TEWL compared with adjacent infection-free skin. Hydration was significantly reduced in lesional skin compared with adjacent infection-free skin. From this study, infections with dermatophytes and Malassezia species on the body can alter biophysical properties of the skin, especially the function of stratum corneum as a barrier to water loss. On the contrary, infections with dermatophytes on the palms and soles little affect the barrier function of the skin.

Invasive Trichophyton rubrum infection occurring with infliximab and long-term prednisone treatment.

BACKGROUND: A 64-year-old woman presented with erythematous plaques, tender nodules, and pustules of the dorsal right hand and both legs following long-term treatment with systemic steroids and infliximab. Skin biopsy demonstrated dermal inflammation with foci of necrosis and multinucleated giant cells containing fungal spores. Tissue culture grew Trichophyton rubrum. OBJECTIVE: To report a case that demonstrates the pathophysiology of invasive T. rubrum infection, the mechanisms of action and uses of tumor necrosis factor alpha (TNF-alpha)-inhibiting drugs, and how these drugs may increase patients' risk of invasive dermatophytosis. CONCLUSION: Dermatophytes such as T. rubrum rarely cause invasive disease. This unusual presentation of invasive T. rubrum occurred with immunosuppression by infliximab and systemic steroids. Patients should have a thorough examination for signs of latent infection before TNF-alpha inhibitors are prescribed, including inspection of the skin and nails for signs of dermatophytosis.

Exacerbated inflammatory reaction to Trichophyton rubrum infection on an HIV-positive patient successfully treated with fluconazole.

A 33 year-old HIV-positive Brazilian female patient was diagnosed with a cutaneous inflammatory reaction on her left forearm. The lesion spread rapidly affecting most of her forearm. The clinical diagnosis of tinea corporis (ringworm) was confirmed by wet mount preparations on 20% KOH and by the isolation of Trichophyton rubrum on pure cultures. Treatment with Fluconazole for a period of four weeks successfully cured the infection.

Barrier function, epidermal differentiation, and human beta-defensin 2 expression in tinea corporis.

Tinea corporis is a superficial mycotic infection resulting in substantial epidermal changes. We determined skin barrier function, epidermal differentiation, and human-beta-defensin 2 (hBD-2) protein expression in 10 patients with tinea corporis caused by Trichophyton rubrum (T. rubrum). We found disturbed skin barrier function as shown by a significant increase in transepidermal water loss (TEWL) and specific ultrastructural changes including disturbed formation of extracellular lipid bilayers, lamellar body extrusion, and deposit of clotted material at the stratum granulosum/stratum corneum interface. Epidermal proliferation in tinea increased several fold and accordingly, proliferation and inflammation-associated keratins K6, K16, and K17 were expressed. Expression of basal keratins K5 and K14 increased, whereas differentiation-associated K10 was reduced. Reduction of the cornified envelope proteins involucrin, loricrin, and the S100 protein filaggrin was also seen. Reduced filaggrin expression correlated with reduced skin hydration; protein breakdown products of filaggrin have been shown to be important for water binding. Surprisingly, we found pronounced epidermal protein expression of hBD-2, which may be related to disturbed epidermal differentiation and inflammation. hBD-2 showed a weak, although significant, antifungal activity against T. rubrum in the turbidimetric assay and the immunohistological staining was somewhat less pronounced in areas directly underneath fungal hyphae in the stratum corneum. Together, we describe profound changes in skin barrier structure and function, epidermal proliferation, and differentiation including pronounced protein expression of hBD-2 in tinea corporis.

Characteristics of dermatophytoses among children in an area south of Tehran, Iran.

The aim of this study was to determine the prevalence and etiological agents of dermatophytoses, and also their distribution according to age, gender, and body site among children in an area south of Tehran. A total of 382 children aged