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PubMed1984

Isotretinoin. A review of its pharmacological properties and therapeutic efficacy in acne and other skin disorders.

Isotretinoin is a new orally active retinoic acid derivative for the treatment of severe refractory nodulocystic acne. The pharmacological profile of isotretinoin suggests that it acts primarily by reducing sebaceous gland size and sebum production, and as a result alters skin surface lipid composition. Bacterial skin microflora is reduced, probably as a result of altered sebaceous factors. Isotretinoin 1 to 2 mg/kg/day for 3 to 4 months produces 60 to 95% clearance of inflammatory lesions in patients with severe, recalcitrant nodulocystic acne, with evidence of continued healing and prolonged remissions in many patients after treatment withdrawal. Doses as low as 0.1 mg/kg/day have also proven successful in the clearance of lesions; however, with such low doses the duration of remission after discontinuation of therapy is usually shorter. Encouraging results have also been seen in small numbers of patients with rosacea, Gram-negative folliculitis, Darier's disease, ichthyosis and pityriasis rubra pilaris, the response in keratinising disorders resembling that with the related drug etretinate. While long term follow-up studies in these patients have not been reported, prolonged remission after withdrawal of isotretinoin in disorders of keratinisation is unlikely, as with other drugs used in these conditions. Isotretinoin is only partially effective in psoriasis, in contrast to etretinate which is very effective in psoriasis but ineffective in severe acne. Some encouraging results have also been reported with isotretinoin in patients with squamous and basal cell carcinomas, but isotretinoin has proven unsuccessful in non-squamous cell epithelial and non-epithelial cancer. Side effects affecting the mucocutaneous system occur in nearly all patients receiving isotretinoin, but rarely lead to drug withdrawal. Raised serum triglyceride levels are also commonly reported. The possibility of long term spinal or skeletal bone toxicity may restrict the use of isotretinoin in severe disorders of keratinisation requiring prolonged administration. Isotretinoin is strictly contraindicated in women of childbearing potential due to its severe teratogenic properties, unless an effective form of contraception is used. Thus, isotretinoin offers an effective advance on the treatment options available in a difficult therapeutic area - those patients with severe, nodulocystic acne not responding to 'traditional' therapy.

Acne Vulgaris↗
PubMed1989

Bifonazole. A review of its antimicrobial activity and therapeutic use in superficial mycoses.

Bifonazole is a substituted imidazole antifungal agent structurally related to other drugs in this group. It possesses a broad spectrum of activity in vitro against dermatophytes, moulds, yeasts, dimorphic fungi and some Gram-positive bacteria. Both non-comparative and comparative clinical trials have clearly demonstrated the efficacy and safety of various formulations of bifonazole 1% (cream, gel, solution and powder) applied once daily in the treatment of superficial fungal infections of the skin such as dermatophytoses, cutaneous candidiasis and pityriasis versicolor. In comparative studies bifonazole was significantly superior to placebo and at least as effective as alternative imidazole antifungal drugs including clotrimazole, econazole, miconazole, oxiconazole and sulconazole. Preliminary studies in other superficial skin and nail infections/dermatoses suggest that bifonazole may be useful for treating onychomycoses (in a combination cream; bifonazole 1% plus urea 40%), otomycoses, erythrasma, sebopsoriasis, seborrhoeic dermatitis and rosacea. However, controlled trials are needed in each of these clinical settings to assess accurately its relative place in therapy. Thus, bifonazole is an effective and well-tolerated treatment for superficial fungal infections of the skin. Compared with the majority of topical antifungal drugs, which need to be applied at least twice daily, bifonazole offers the convenience of once daily administration, which may improve patient compliance.

Antifungal Agents↗
PubMed1992

Terbinafine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in superficial mycoses.

Terbinafine is an orally and topically active allylamine antifungal agent with a primarily fungicidal action in vitro. Its spectrum of in vitro activity includes a broad range of dermatophyte, filamentous, dimorphic and dematiaceous fungi, and some yeast species. In clinical trials, mycological and overall efficacy rates of around 90 and 80%, respectively, have been achieved in cutaneous dermatophyte infections (tinea corporis/cruris and tinea pedis) with terbinafine, administered either orally (250 or 500 mg/day) or topically (a 1% cream applied twice daily). Similar rates of cure have been obtained with oral terbinafine in dermatophyte nail infections after relatively short treatment periods ranging from 3 to 12 months. Topical terbinafine has been effective in approximately 80% of patients with cutaneous candidiasis or pityriasis versicolor. Few comparative data have been published, but generally oral terbinafine appeared to be at least as effective as oral griseofulvin or ketoconazole in tinea corporis/cruris and more effective than griseofulvin in tinea pedis. Both oral and topical terbinafine have been very well tolerated in clinical trials to date, with only minor adverse effects reported. Although further research is required to establish the efficacy of terbinafine in comparison with other available therapies, as well as to fully clarify its tolerability profile, the early results obtained with terbinafine in superficial fungal infections are very encouraging. Terbinafine appears likely to become a first-line therapy for dermatophyte infections, particularly those affecting the nails.

Antifungal Agents↗
PubMed1999

Terbinafine. An update of its use in superficial mycoses.

UNLABELLED: Terbinafine is an allylamine antifungal agent which has fungicidal activity against a wide variety of dermatophytes, moulds and certain dimorphic fungi, and fungistatic activity against Candida albicans. Oral terbinafine 250 mg/day is effective in the treatment of superficial dermatophyte infections such as onychomycosis, tinea pedis and tinea corporis/cruris, generally achieving mycological cure in > 80% of patients. The drug is also effective in children with tinea capitis when administered orally in the dosage range 62.5 to 250 mg/day for 4 weeks. Comparative data indicate that oral terbinafine is more effective than continuous or intermittent intraconazole in dermatophyte onychomycosis, and is as effective as itraconazole 400 mg/day in tinea pedis. The drug has shown greater efficacy than griseofulvin in dermatophyte onychomycosis, tinea pedis and tinea corporis/cruris, and comparable efficacy in children with tinea capitis. Additionally, oral terbinafine is more effective than ketoconazole 200 mg/day in tinea corporis/cruris. Topical terbinafine 1% formulations are effective when applied once or twice daily for up to 2 weeks, achieving mycological cure in > 80% of patients with tinea pedis, tinea corporis/cruris, cutaneous candidiasis and pityriasis versicolor. Its formulations are at least as effective as miconazole 2% cream and naftifine 1% gel in tinea pedis, and more effective than clotrimazole 1% cream, bifonazole 1% cream and oxiconazole 1% lotion. Mycological cure rates achieved with terbinafine generally improve after treatment cessation, reflecting the drug's fungicidal mechanism of action and its residual effect in tissue. Terbinafine is well tolerated after oral or topical administration and has a relatively low potential for drug interactions. Pharmacoeconomic data support the use of terbinafine in dermatophyte infections of the skin or nails. CONCLUSIONS: Evidence suggests that oral terbinafine is the treatment of choice for dermatophyte onychomycosis, as it achieves high rates of mycological and clinical cure, is generally well tolerated and has a relatively low potential for drug interactions. It must also be considered a first-line treatment option, along with itraconazole, in cutaneous mycoses which warrant systemic treatment; topical terbinafine is a treatment of choice in less extensive mycoses. The use of terbinafine in non-dermatophyte or mixed infections has not been fully defined.

Animals↗
PubMed2002

Human herpesvirus 7 in dermatology: what role does it play?

Human herpesvirus 7 (HHV-7) was discovered in 1989 as a new member of the beta-herpesvirus subfamily. Primary infection occurs early in life and manifests as exanthema subitum, or other febrile illnesses mimicking measles and rubella. Thus, HHV-7 has to be considered as a causative agent in a variety of macular-papular rashes in children. In addition, HHV-7 was found in some cases of other inflammatory skin disorders, such as psoriasis. There are controversial data on the detection of HHV-7 in pityriasis rosea, but so far there is not enough evidence for a pathogenetic association of HHV-7 with this exanthematic skin disease. Although HHV-7 can be found in some cases of Hodgkin's disease, there are no data supporting a direct causative role in this lymphoma type nor in other nodal or primary cutaneous lymphomas. In various epidemiologic forms of Kaposi's sarcoma, infection of monocytic cells with HHV-7 was demonstrated, which may indirectly influence tumor biology. In the context of immunosuppression, HHV-7 has recently been identified as an emerging pathogen in transplant recipients and may exacerbate graft rejection in renal transplant recipients. The ability of HHV-7 to induce cytokine production in infected cells could make HHV-7 an important pathogenetic co-factor in inflammatory and neoplastic disorders. Moreover, the restricted cellular tropism of HHV-7 may render this virus an interesting vector for gene therapy. Thirteen years after the discovery of HHV-7, there has been considerable progress in characterizing its genetic structure, virus-induced effects on infected host cells and in the development of diagnostic tools. Nevertheless, the role of HHV-7 in various skin diseases and the clinical manifestations of reactivation of HHV-7 infection have still to be defined.

Herpesvirus 7, Human↗
PubMed2004

Optimal management of fungal infections of the skin, hair, and nails.

Superficial fungal infections are chronic and recurring conditions. Tinea capitis is a scalp infection, primarily affecting prepubescent children. Ringworm infections, such as tinea corporis and tinea cruris, involve the glabrous skin. Tinea nigra is a rare mycotic infection that may be related to travel abroad. Piedra, black or white, is limited to the hair shaft without involvement of the adjacent skin. Pityriasis (tinea) versicolor and seborrheic dermatitis are dermatoses associated with yeasts of the genus Malassezia that affect the lipid-rich areas of the body. The taxonomy of the Malassezia yeasts has been revised to include nine species, eight of which have been recovered from humans. Tinea pedis, an infection of the feet and toes, is one of the most common forms of dermatophytosis. Onychomycosis is a fungal infection affecting the nail bed and nail plate; it may be chronic and can be difficult to treat. In instances where the superficial fungal infection is severe or chronic, an oral antifungal agent should be considered. Terbinafine, itraconazole, and fluconazole are oral antifungals that are effective in the treatment of superficial mycoses.

Administration, Oral↗
PubMed2000

Seeing through the stratum corneum.

The stratum corneum (SC) provides a vital barrier membrane between the external environment and the vulnerable internal tissues of the skin. It impedes the flow of water, the penetration of xenobiotics, and invasion of pathogenic micro-organisms. It also has protective capacity against ultraviolet radiation and thermal injury. As routine histopathology provides a misleading picture of a disorganized and shadowy SC, we would recommend the skin surface biopsy technique. This painless technique is easy and reliable in obtaining information from the SC. It demonstrates the geometric patterns of the surface, the openings of the eccrine ducts and hair follicles. The skin surface biopsy technique is also ideal for the investigation of the in situ microbiology of skin. Staining with periodic acid Schiff reagent makes it possible to see ringworm fungi, pityriasis versicolor, candida species, or erythrasma micro-organisms. Scanning electron microscopy can be employed when the higher magnification is needed. Histochemical applications include silver staining for melanin particle, potassium ferricyanide staining for blood pigments and lipid staining with Sudan red, for sebum. The rate of movement of topically applied drugs into the skin can be measured using the skin surface biopsy technique. The concentration of radiolabelled drugs can be counted and compared. Comedogenicity and DNA analysis are other applications of this non-invasive technique.

Biopsy↗
PubMed2006

In vitro activity of R126638 and ketoconazole against Malassezia species.

The in vitro activity of a new triazole R126638 against Malassezia yeasts was compared with that of ketoconazole. With the agar dilution technique, minimal inhibitory concentrations were lower for R126638 compared with ketoconazole against Malassezia globosa, M. obtusa, M. slooffiae, M. restricta and two strains of M. sympodialis. On human stratum corneum in vitro, both R126638 and ketoconazole were very effective in reducing the production of hyphae from 15% to 1% with R126638 and to 2% with ketoconazole. Scanning electron microscopy did not reveal obvious surface differences between untreated cultures and cultures exposed to ketoconazole or R126638 in the concentration range 0.01-1 microg/ml. However, transmission electron microscopy showed partial to complete necrosis of the cytoplasmic organelles of Malassezia yeasts. The combined scanning electron microscopy and transmission electron microscopy findings confirm earlier observations of the "mummifying" effect of azoles against Malassezia spp. In conclusion, R126638 is an interesting new triazole with high activity against the Malassezia yeasts, which are involved in pityriasis versicolor and seborrhoeic dermatitis.

Antifungal Agents↗
PubMed1993

Keratinocyte proliferation in epidermal keratinocyte disorders evaluated through PCNA/cyclin immunolabelling and AgNOR counting.

The assessment of cell proliferation is important to our understanding of hyperproliferative disorders. In this work we evaluated the proliferation characteristics of epidermal keratinocytes in diseases with abnormal keratinization by two different methods (immunostaining for the proliferating cell nuclear antigen--PCNA and histochemical staining for nucleolar organizer region--associated argyrophilic proteins--AgNORs). Twenty-seven specimens from diseases with an abnormal keratinization were studied and compared with specimens of normal human skin. As compared with the latter, the numbers of PCNA-positive epidermal keratinocytes were increased in psoriasis, congenital non-bullous ichthyosiform erythroderma, epidermolytic hyperkeratosis and chronic dermatitis and decreased in ichthyosis vulgaris, X-linked ichthyosis and pityriasis rubra pilaris. In most cases a parallel modification of AgNORs was found. We conclude that although PCNA immunolabelling and AgNOR staining do not provide strictly correlated values, both appear as useful markers for the assessment of keratinocyte proliferation in epidermal disorders.

Autoantigens↗
PubMed1996

The in vitro effect of fluconazole on the filamentous form of Pityrosporum ovale.

The antimycotic activity of fluconazole against the filamentous form of Pityrosporum ovale was studied in vitro. P. ovale was grown on human stratum corneum in vitro with and without the addition of different concentrations of fluconazole. In control cultures hyphae were produced in 25% of the cells compared to only 4% after exposure to fluconazole 1 microgram/ml. In control cultures 16% of the fungal cells showed signs of necrosis, due to the normal turnover rate of the cells, compared to 65% of the fungal cells exposed to 1 microgram/ml of fluconazole. In the transmission electron microscope the typical thick-walled fungal cells with their characteristic budding were observed in control cultures. However, after exposure to 1 microgram/ml of fluconazole that P. ovale cells showed extensive signs of necrosis, with loss of internal organelles and disinterruption of the cell wall. The results obtained in this in vitro model mimic the in vivo situation in pityriasis versicolor. There is a parallel between the good results obtained in this system and the good clinical effect of fluconazole in Pityrosporum-related diseases.

Antifungal Agents↗
PubMed2005

[Genotype analysis of the rRNA gene of Malassezia colonizing the skin surface of patients with atopic dermatitis].

Malassezia species are associated with pityriasis (tinea) versicolor, seborrheic dermatitis, and atopic dermatitis. Presently, eleven species are accepted in the genus Malassezia. Of these, M. globosa and M. restricta colonize the skin surface in atopic dermatitis patients, suggesting that they play a significant role in exacerbating the condition. The two species have different genotypes in the intergenic spacer (IGS) region of the rRNA gene, which correspond to patients and healthy individuals. In addition, the antifungal susceptibilities of the genotypic strains to itraconazole and ketoconazole differ. We found a new analytically significant role of the rRNA gene in Malassezia species, in addition to its use for fungal taxonomy and identification.

Dermatitis, Atopic↗
PubMed2005

[Malassezia species in patients with seborrheic dermatitis and atopic dermatitis].

Malassezia species, organisms normally colonizing the skin surface, are thought to play a role as either the cause or an exacerbating factor in a number of skin conditions, including pityriasis versicolor, Malassezia folliculitis, seborrheic dermatitis (SD) and atopic dermatitis (AD). Using a non-cultural PCR method, we analyzed Malassezia spp. extracted from the skin surface of SD and AD patients. The species most commonly detected in both patient groups were M. globosa and M. restricta, and the number of Malassezia spp. In these patients was higher than in healthy subjects. After a topical application of 2% ketoconazole cream, changes in the population of Malassezia spp. in 20 intractable cases of AD were recorded. The addition of the 2% ketoconazole cream to the standard topical treatments was found to have reduced the Malassezia spp. population by 90%, and showed a clinical efficacy rate of 70%. Furthermore, a combination of azole agents and tacrolimus produced a synergistic anti-fungal effect against Malassezia spp. in vitro. A clinical trial using this drug combination conducted on the face and neck of patients with intractable AD showed a 66.6% efficacy rate in both the reduction of the flora and in clinical improvement. From these results it was evident that Malassezia is one of the factors exacerbating AD, and that removal of the organism results in an improvement in the clinical condition of the patient.

Dermatitis, Atopic↗
PubMed2005

[Molecular analysis of Malassezia species isolated from three cases of Akatsuki disease (pomade crust)].

Malassezia spp. which normally colonize on the skin surface, are known as being either the cause or an exacerbating factor in a variety of skin conditions, including pityriasis versicolor, folliculitis, seborrheic dermatitis and atopic dermatitis. We report here three cases of Akatsuki disease (pomade crust). Scales and crusts were collected from the lesional skin and analyzed using a PCR-based non-culture method. Malassezia microflora in Akatsuki disease was compared to that of healthy subjects and atopic dermatitis patients. Samples were collected from upper and lower eyelids (Case 1), an operation scar (Case 2) and parietal scalp (Case 3). DNA was extracted from the scales and nested PCR was performed using specific primers for each species. Our analysis detected only M. obtusa and M. slooffiae in Cases 1 and 3 and only M. slooffiae in Case 2. Our previous data indicated that while M. globosa, M. restricta and M. sympodialis were common in healthy subjects, the two aforementioned species were rare, suggesting that the presence of M. obtusa and M. slooffiae in the subjects in the present study is correlated to the pathogenesis of Akatsuki disease.

Aged↗
PubMed2005

Mycology in the Philippines, revisited.

The warm tropical climate of the Philippines and its interaction with cultural practices, occupation and immune responsiveness contribute to the increased susceptibility of Filipinos to fungal infections. An investigation to determine the prevalence of fungal infections in dermatology training institutions over a 4-year period was conducted. The results showed that fungal infections rank as the second leading cause of consultation with a prevalence of 12.98%. Pityriasis versicolor (25.34%), tinea corporis (22.63%), tinea cruris (16.7%) and tinea pedis (16.38%) were the most frequently encountered cases. Fungal culture yield is low and Candida sp. is the most common isolate, obtained predominantly from specimens taken from the oral mucosa and nails. Candidiasis is still the most common opportunistic infection followed by coccidioidomycosis, cryptococcosis and aspergillosis. Imidazoles are the most commonly prescribed systemic and topical treatment by Filipino dermatologists. Initial data collected would serve as reference for future research and may be used to compare with epidemiologic data obtained from other Asian countries.

Candidiasis↗
PubMed2005

Superficial fungal infections seen at the National Skin Centre, Singapore.

UNLABELLED: Cutaneous fungal infections are common in Singapore. The National Skin Centre is a tertiary referral centre for dermatological diseases in the country, and sees more than 2,500 cases of superficial fungal infections annually. AIM: This study analyses data collated from the centre's medical record office as well as fungal culture results from the mycology laboratory. RESULTS: From 1999 to 2003, there were a total of 12,903 cases of superficial fungal infections seen at the centre. The majority of patients (n=9335) (72.3%) were males. The most common infection was tinea pedis (n=3516) (27.3%), followed by pityriasis versicolor (n=3249) (25.2%) and tinea cruris (n=1745) (13.5%). Candidal infections were also common (n=1430), the majority of which were cases of candidal intertrigo. There were very few cases of tinea capitis, which is uncommon in Singapore. The number of cases of onychomycosis has shown a rising trend over the past 5 years. Trichophyton rubrum was the most prevalent fungal pathogen isolated from all cases of superficial fungal infections of the skin, except for tinea pedis, where Trichophyton interdigitale was the most frequently isolated organism. Dermatophytes remain the most commonly isolated fungal pathogens isolated in toenail onychomycosis, whilst Candida species accounted for the majority of isolates in fingernail onychomycosis. CONCLUSION: Current epidemiologic trends of superficial fungal infections in Singapore show some similarities to recent studies from the United Kingdom and United States.

Candidiasis, Cutaneous↗
PubMed1994

A survey to determine the prevalence of leprosy in a community in east Trinidad.

A house-to-house survey was conducted in a community in East Trinidad, where a clustering of cases had been observed. There were 1355 residents, of whom 73.5% had a complete visual skin examination. No new cases of leprosy were found but a variety of skin disorders were diagnosed. The most common disorder was pityriasis versicolor, which is one of the differential diagnoses of hypopigmented skin lesions. This has serious implications for the delayed diagnosis of leprosy. In all, 5 of the 9 old cases residing in the survey area suffered from paucibacillary disease, and had a history of contact with a lepromatous case. They were not listed initially as contacts of this index case. Contact lists should therefore include nonfamilial persons having frequent contact with an index case. The definition of 'frequent' should be determined by each programme. It may also be necessary to review the duration of surveillance of contacts. The survey was estimated to have cost about US $2,500 and was not considered to be cost-effective.

Adolescent↗
PubMed1977

Methotrexate.

The folic acid antagonists, aminopterin and then methotrexate, have been the primary systemically administered drugs for the treatment of severe psoriasis for 25 years. Methotrexate was finally approved by the FDA 5 years ago and was recently estimated to be used for approximately 25,000 psoriatic patients annually. With the small but chronic doses used for psoriasis, methotrexate has been relatively safe, except for a limited occurrence of significant hepatotoxicity. The good to excellent results obtained in most patients must, therefore, be weighted against the small risk of liver damage. Methotrexate has also been used with some effectiveness in several other dermatologic conditions, including mycosis fungoides, dermatomyositis, pityriasis rubra pilaris, and others, although they are not yet FDA-approved indications. The recent successful introduction of photochemotherapy (psoralen and ultraviolet light) for moderate and severely affected psoriatics will probably lead to a substantial decrease in the number of patients requiring methotrexate.

Chemical and Drug Induced Liver Injury↗
PubMed1976

[Dermatomyositis with spinulosis (Wong type dermatomyositis). Histologic study. Attempt at pathogenic interpretation].

The authors present a case of dermatomyositis with generalised spinulosis of pilose pityriasis rubra (lichen ruber acuminatus) type, giving a highly characteristic appearance of linear verruciform spinulosis of the back of the hands. They describe the histological lesions and feel that this spinulosis is probably due to marked degenerative smooth muscle myositis of the erector pili muscles. They recall the earlier cases of O'Leary and Christianson and above all those of Wong. The case reported is the first in a child.

Child↗