Rubrum Infection Research Articles

A comparative study of terbinafine versus griseofulvin in ‘dry-type’ dermatophyte infections

We conducted a double-blind comparative study of terbinafine, 250 mg twice daily, versus griseofulvin, 500 mg twice daily, for 6 weeks in chronic dermatophyte infections of the feet or hands. All but three patients (total 31) had Trichophyton rubrum infection. At 12-week follow-up, 100% of the terbinafine-treated group were free from infection compared with 45% of those treated with griseofulvin. Therapy in 75% of the terbinafine-treated group and in 35% of those given griseofulvin was rated as effective overall at long-term follow-up, although these differences were not statistically significant. Six months after treatment all nine patients whose skin had cleared with terbinafine therapy remained in remission versus only one of seven patients treated with griseofulvin. None of the patients in either group experienced serious adverse effects.

Treatment of fungal skin infections: State of the art

The number of cases of mycotic infections are increasing, presenting physicians today with an unprecedented challenge in handling the treatment and prophylactic control of these disorders. The increase in mycotic disorders is due to many factors, such as longer life span, organ transplantation, and the acquired immunodeficiency syndrome. The pharmaceutical industry is providing physicians with newer, more potent drugs to manage mycoses. An overview of current practice in the use of topical and oral agents, especially ketoconazole, are given in the following specific mycoses: tinea capitis, pityriasis versicolor, seborrheic dermatitis, Trichophyton rubrum infections, vaginal candidiasis, and moist intertriginous tineas. The efficacy of ketoconazole in various vehicles and dosage schedules and of traditional agents such as griseofulvin are discussed with relation to each of the mycoses.

The successful treatment of finger Trichophyton rubrum onychomycosis with oral terbinafine

Eleven patients with distal subungal onychomycosis of the fingers by Trichophyton rubrum infection were treated with daily doses of oral terbinafine, a new allylamine derivative. A 125-mg capsule was given twice daily. Each patient's nailplate was marked appropriately following the Zaias and Drachman method for the determination of antifungal efficacy in onychomycosis. Patients were monitored monthly for the antifungal effect of the drug, as well as side-effects, including laboratory values for liver and kidney function tests and a full blood count. At the end of 6 months, all 11 patients were clinically and mycologically normal. It can be concluded that 250 mg (125 mg b.i.d.) oral terbinafine is the most appropriate drug for the treatment of finger onychomycosis. No side-effects of any kind were noted in this 6-month period. Onychomycosis is a common disease of the toenails. No topical treatments have yet been found to be satisfactory. In a very motivated patient-doctor relationship, the use of topically applied thiabendazole has proved effective, particularly after nailplate avulsion. Systemic antifungal treatment is possible with griseofulvin and ketoconazole. Griseofulvin may cause enzyme induction in the liver, which requires a higher dose intake to achieve results. This has been demonstrated using the Zaias and Drachman method of judging successful antifungal clinical effects in onychomycosis. Ketoconazole is a very effective drug which must be carefully monitored. Its difficulties are with liver function, anti-androgenic dysfunction in males, and adrenal dysfunction. There is a great need for an effective and safe oral systemic drug. Terbinafine is an allylamine derivative which is highly antifungal.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent investigations on the relationship between fungal skin diseases and atopic dermatitis.

Atopic dermatitis may be associated with chronic dermatophyte infections and Pityrosporum related disorders. Recent epidemiologic studies in school children and young recruits have confirmed that atopic individuals have an increased susceptibility to Trichophyton rubrum infections of the feet and an increased risk for persistent infections. In contrast, an investigation on skin reactivity in dermatophyte infected atopic patients indicated that a group of these patients is fully able to eliminate the fungi concomitant with the development of a delayed type skin reactivity. Facial erythema and scaling, often including neck and shoulders, is present in many young adults with atopic dermatitis. Preliminary data from a Danish-Swedish investigation have shown that atopic dermatitis patients with head-neck-shoulder dermatitis compared to a group without this disorder and normal individuals more often demonstrate positive prick test, RAST and specific histamine release using extract of Pityrosporum ovale. These findings indicate that the presence of Pityrosporum ovale in the skin may cause an allergic reaction leading to dermatitis.

Drugs affecting Trichophyton rubrum-induced neutrophil chemotaxis in vitro

Summary In Boyden-type experiments, it is shown that corticosteroid drugs inhibit T. rubrum-induced chemotaxis of polymorphonuclear cells (PMNs) in ng 1−1 concentrations; reference is made to reports showing such concentrations are therapeutically achieved by topically applied steroids to the skin under an occlusive dressing. The anti-asthma drugs disodium cromoglycate and ketotifen hydrogen fumarate and the anti-histamine, clemastine, all significantly reduced PMN migration at the ng 1−1 level. The results are discussed in relation to the inflammatory response of the skin in T. rubrum infections.

Experimental chronic dermatophytosis in human skin grafted to nude mouse: inoculation of Trichophytons and histopathological evaluation.

AbstractTwo strains of T. rubrum and one strain of T. mentagrophytes were inoculated into human skin grafted onto BALB/c nude mice by the needle puncture method. Infection was established in 1 of the 10 animals inoculated with fluffy colony type T. rubrum, 2 of the 10 animals inoculated with powdery colony type T. rubrum, and 7 of the 10 animals inoculated with granular colony type T. mentagrophytes, suggesting that the skin grafts are infectible by anthropophilic and zoophilic strains of dermatophytes. T. rubrum infection continued for a maximum of 9 weeks and T. mentagrophytes infection for more than 11 weeks. In the animals inoculated with T. mentagrophytes, fungal elements were localized in the stratum corneum of the human skin grafts. In the acute stage, microabscesses consisting of neutrophils were observed under the stratum corneum in contact with fungal elements; in the chronic stage, epidermal thickening and infiltration, mainly consisting of histiocytes and a smaller number of lymphocytes, was noted in the upper and middle dermis. Ultrastructural findings from the parasites were similar to those of dermatophytosis in man. This experimental system should be useful as a model of chronic dermatophyte infection in the human skin.

Itraconazole therapy for recalcitrant dermatophyte infections

Five patients with recurrent Trichophyton rubrum infections had become unresponsive to topical and oral antifungal therapy. These patients were treated in an open trial of itraconazole, a new oral antifungal medication. Each patient responded promptly to therapy within 1 month and showed marked improvement at the end of 3 to 6 months of therapy. Complete clearing of toenail infections was not achieved in this limited trial and recurrences occurred in the four patients who had toenail infections. The drug was well tolerated and no adverse effects were observed. Itraconazole appears to be an effective drug for relief of clinical aspects of recalcitrant dermatophyte infections. Long-term safety and prevention of recurrence remain to be established.

IgE-mediated sensitivity to Trichophyton rubrum in a patient with chronic dermatophytosis and Cushing's syndrome

Persistent Trichophyton rubrum infection has been observed previously in association with Cushing's syndrome. In this article, we demonstrate IgE-mediated sensitivity to Trichophyton in a patient with chronic dermatophytosis secondary to Cushing's syndrome. Cell-mediated immunity was absent, but Trichophyton extract produced an immediate skin response and also stimulated a concentration-dependent histamine release from basophils of the patient. After adrenalectomy, cell-mediated immunity to Trichophyton was restored, and infection was confined to the nails. Skin and leukocyte sensitivity to Trichophyton extract persisted and was even more pronounced than the sensitivity before adrenalectomy. RAST measurement confirmed the presence of Trichophyton-specific IgE after adrenalectomy. These results provide further evidence that IgE-mediated inflammatory events may be initiated by Trichophyton infection.

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.

Thymopentin in chronicTrichophyton rubrum infection

The case histories of 2 patients with chronic Trichophyton rubrum infections are presented. Both subjects had previously been treated systemically with griseofulvin, but had to be dropped from therapy due to adverse reactions. Topical treatment alone yielded unsatisfactory results. Thymopentin, 50 mg, administered subcutaneously three times weekly for a period of 6 weeks, induced rapid improvement within 3 weeks and almost complete remission 3 weeks later, although the fungi were still present on the skin. This beneficial effect lasted for up to 7 months after cessation of thymopentin therapy. Reinstitution of treatment produced the same response pattern. The clinical and immunological implications of these findings are briefly discussed; thymopentin is believed to enhance the suggested impaired cellular immunity in patients with chronic T. rubum infections.

Clinical features of superficial fungal infections caused by Hendersonula toruloidea and Scytalidium hyalinum.

The clinical appearances of infections in 128 patients caused by the mould fungi Hendersonula toruloidea (102) and Scytalidium hyalinum (37) are described. All the patients originated from the tropics or subtropics but those infected with S. hyalinum came from either the Caribbean or West Africa. Forty-one per cent of those studied had a concurrent dermatophyte infection. While the clinical features of Hendersonula and Scytalidium infections resembled those seen in 'dry type' Trichophyton rubrum infections, there were a number of distinctive features. These included the absence of dorsal infection on the feet, lateral and distal onychomycosis with extensive onycholysis and the development of paronychia on the fingers. The majority of affected patients showed no serious underlying abnormality or predisposing skin disease which could facilitate invasion. The routine incorporation of cycloheximide, which inhibits the growth of these organisms, in mycological media may explain why they are infrequently diagnosed.

Successful Use of Ketoconazole for Invasive Cutaneous

A case of invasive cutaneous Trichophyton rubrum infection complicated the course of a patient undergoing chemotherapy for acute lymphocytic leukemia. This dermatophytic disease was well controlled with ketoconazole. Prior experience with these unusual infections is summarized.

Successful use of ketoconazole for invasive cutaneous Trichophyton rubrum infection

Successful use of ketoconazole for invasive cutaneous Trichophyton rubrum infection

Dermatophytes identified at the australian national reference laboratory in medical mycology 1966-1982

Over a 17 yr period from 1966 to 1982, 4354 dermatophytes were identified at the Australian National Reference Laboratory in Medical Mycology. The most frequently identified species was Trichophyton rubrum, accounting for 35.3% of identifications, followed by Trichophyton mentagrophytes (26.5%), Trichophyton tonsurans (12.8%), Epidermophyton floccosum (10.7%) and Microsporum canis (8.4%). Specimens taken from the feet were the most common source of the Trichophyton rubrum isolates, followed by specimens from the groin. The highest incidence of T. rubrum and other Trichophyton infections was found in males in the age group 21-30 yr. Microsporum species were most commonly isolated from children aged 10 yr or less. In 1.5% of specimens, more than one fungal species was isolated. In most of these instances a yeast (predominantly Candida species) was found in addition to a Trichophyton species.

Ketoconazole in Trichophyton rubrum

10 patients with T. rubrum infection were treated with Ketoconazole 200-400 mg a day for 8 weeks. All patients had a skin infection and 2 in addition infection of the toe nails. Previous treatment with Griseofulvin and at least two different antifungal topicals had been ineffective. The infection was evaluated by clinical findings and mycological examination. The skin lesions disappeared in 6 patients, while none of the nail lesions were cured. However, at a follow-up 2 months after the end of the Ketonocazole treatment, recurrence was observed in 3 of 6 patients. It is suggested that Ketoconazole treatment of previously resistant T. rubrum infection should be continued for more than 2 months.

Oral ketoconazole. An effective and safe treatment for dermatophytosis.

This study demonstrates the efficacy and safety of ketoconazole, a broad-spectrum oral antifungal agent administered to 20 patients with severe, extensive, and recalcitrant Trichophyton rubrum infection. The average patient has had continuous infection for 20 years. Sixteen patients had glabrous skin infection that encompassed an average of 40% of their skin surface. The remaining four patients had palmar-plantar infection. Ketoconazole was administered for 27 to 70 days in a daily oral dose of 200 or 400 mg. Initial clinical and mycological response occurred within five to seven days, and the glabrous and/or palmar-plantar skin changes improved at least 90% in all patients. In 13 of these patients, the infection cleared completely. The only side effects experienced--pruritus in four patients and photophobia in two patients--did not necessitate interruption of therapy. Overall, ketoconazole was found to be an effective and safe therapy for dermatophytosis. Follow-up examinations of our cases five months later showed recrudescence in 75% of them, which was not unexpected with these severe infections.

The immunofluorescence staining of fungi in chronic dermatophyte infections.

Summary Indirect immunofluorescence staining of fungi with specific antisera was demonstrated in biopsy specimens taken from six patients with chronic Trichophyton rubrum infections. However, there was no evidence of immunoglobulin or C3 deposition in the vicinity of the organisms or elsewhere in the sections. Circulating antibodies to dermatophyte fungi are often not demonstrable in these patients. However, these results suggest that antibody affinity for epithelium docs not account for their absence in patients' serum.

Oral Ketoconazole

• This study demonstrates the efficacy and safety of ketoconazole, a broad-spectrum oral antifungal agent administered to 20 patients with severe, extensive, and recalcitrant Trichophyton rubrum infection. The average patient has had continuous infection for 20 years. Sixteen patients had glabrous skin infection that encompassed an average of 40% of their skin surface. The remaining four patients had palmar-plantar infection. Ketoconazole was administered for 27 to 70 days in a daily oral dose of 200 or 400 mg. Initial clinical and mycological response occurred within five to seven days, and the glabrous and/or palmar-plantar skin changes improved at least 90% in all patients. In 13 of these patients, the infection cleared completely. The only side effects experienced—pruritus in four patients and photophobia in two patients—did not necessitate interruption of therapy. Overall, ketoconazole was found to be an effective and safe therapy for dermatophytosis. Follow-up examinations of our cases five months later showed recrudescence in 75% of them, which was not unexpected with these severe infections. (<i>Arch Dermatol</i>1981;117:129-134)

The high incidence of Tinea pedis and unguium in patients with Kaposi's sarcoma.

Forty patients suffering from Kaposi's sarcoma (31 males, a females aged from 18 to 80 years) were examined for the presence of mycotic invasion of the toe-webs, toe-nails and soles. Fungi were found without exception in all patients. In 35 patients all three sites were invaded; the remaining 5 showed no involvement of the toe-nails. The causative agent was T. rubrum in 31 patients. T. mentagrophytes in 7, E. floccosum in 2. Four subjects with T. rubrum infection also showed a super-imposed C. albicans infection in the toe-webs. The skin tests with Trichophytin and Candidin yielded a mildly positive response to the former antigen in 4 cases and to the latter in 8 cases. The strikingly high percentage of affected cases in this group of patients with Kaposi's sarcoma is discussed.

Immune responses in patients with chronic Trichophyton rubrum infections.

Summary Thirty-five patients were studied who were infected with Trichophyton species. There was a marked reduction in the incidence of delayed hypersensitivity skin responses in Trichophyton rubrum infections (12%) as compared with those patients who were infected with other dermatophytes (75%). There was no difference in the extent of leukocyte migration in either of the clinical groups infected with Trichophyton rubrum but inhibition was demonstrated in patients infected with other Trichophyton species. Nearly one half of those infected with T. rubrum were atopic as defined by history, present symptoms or a positive immediate wheal and flare reaction to T. rubrum. Reasons for the incidence of atopy and the poor cell-mediated responses are discussed.