Part 1: Understanding the role of Malassezia spp. in skin disorders: Malassezia yeasts as commensal or pathogenic organisms of human and animal skin.

INTRODUCTION: Malassezia spp. are a group of lipid-dependent basidiomycetes yeasts acting as commensal organisms of the human and animal skin. However, under some not well-defined circumstances, these yeasts may switch to opportunistic pathogens triggering a number of skin disorders with different clinical presentations. The genus comprises of 18 lipid-dependent species with a variable distribution in the hosts and pathologies thus suggesting a host- and microbe-specific interactions. AREA COVERED: This review highlighted and discussed the most recent literature regarding the genus Malassezia as a commensal or pathogenic organisms highlighting Malassezia-associated skin disorders in humans and animals and their antifungal susceptibility profile. A literature search of Malassezia associated skin disorders was performed via PubMed and Google scholar (up to May 2023), using the different keywords mainly associated with Malassezia skin disorders and Malassezia antifungal resistance. EXPERT OPINION: Malassezia yeasts are part of the skin mycobiota and their life cycle is strictly associated with the environment in which they live. The biochemical, physiological, or immunological condition of the host skin selects Malassezia spp. or genotypes able to survive in a specific environment by changing their metabolisms, thus producing virulence factors or metabolites which can cause skin disorders with different clinical presentations.

MALDI-TOF MS identification of Malassezia species isolated from patients with pityriasis versicolor at the seafarers' medical service in Dakar, Senegal.

Pityriasis versicolor (PV) is a superficial mycosis caused by yeast of the genus Malassezia. The most common isolated Malassezia species in PV lesions differ among M. furfur, M. globosa and M. sympodialis. We purpose to determine the distribution of Malassezia species in PV patients at the seafarers' medical service in Dakar, Senegal and to examine whether any association between identified Malassezia species and patients' profile. From May 2017 to August 2017, first a questionnaire was filled to get informative data before collection of skin scrapings taken from most scaly site using sterile scalpel blade and application of scotch® for direct examination (DE). At the laboratory, DE, culture and identification by MALDI-TOF MS were done. One hundred patients with PV - all men - were included with a mean age of 34 years. Among seafarers, 81% were sailors. Clinical prevalence of PV was highest in aged adults patients with ages of 31 to 60 years (56%). Seafarers with high level of education were less representative with only 2%. The mean duration of the PV was 26.83 months. 20% of subjects suffered lesions in more than one location. The chest was the most affected anatomical site. Furthermore, possible predisposing factors associated with PV were also detected. DE was positive in 95% but culture growth only in 46%. MALDI-TOF MS analysis of the positive cultures could be performed in 84.8% (39/46). Only M. furfur was identified in 100% (39/39). In definitive, M. furfur is the only causative agent of PV in Dakar.

MGL_3741 gene contributes to pathogenicity of Malassezia globosa in pityriasis versicolor.

Dihydroxyacid dehydratase (DHAD) is a key enzyme in biosynthetic pathway of isoleucine and valine. This pathway is absent in human but exists in various organisms such as fungi. Using RNA-seq analysis in this study, we identified MGL_3741gene which encodes DHAD protein in Malassezia globosa (M. globosa). Furthermore, we found that mentioned gene is homologous to the Ustilago maydis, Saccharomyces cerevisiae, Aspergillus flavus, and Aspergillus fumigatus ILV3P. For understanding the probable role of this gene in pathogenicity of M. globosa, we applied Real-time PCR to investigate the differentially expressed of the MGL_3741 gene in healthy and pathogenic states. Our results indicate a significant difference between two mentioned stats. These results revealed that ILV3-like gene in M. globosa can be related to the pathogenicity of this yeast.

[Pityriasis versicolor in infants: unusual clinical presentation and role of corticosteroids used as depigmenting agent for cosmetic purposes in the mother]. / Pityriasis versicolor chez des nourrissons: aspect clinique inhabituel et rôle de la dépigmentation cosmétique par des corticoïdes chez la mère.

We report two cases of Pityriasis versicolor (PV) in infants aged 12 and 18 months. The latter were brought to medical attention because of hypochromic and achromic, round macules involving the limbs and the face. Physical examination of their mothers showed voluntary depigmentation for cosmetic purposes due to the use of corticosteroids and hydroquinone, on average, over a 5-year period. The scotch tape test performed in one of the infants and his mother showed short filaments and clusters of spores. Treatment was based on ketoconazole. After 8 weeks, all patients reported favorable outcomes despite the persistence of some hypochomic macules. The peculiarities of this study are, on the one hand the topography of the lower limbs and on the other hand a positive family history of PV whose occurrence is favored by the use of depigmenting agents based on corticosteroids. Corticosteroids favor the atrophic and achromic feature of the lesions. Indeed, achromic lesions on the lower limbs were described in adults undergoing artificial depigmentation.

Folliculocentric tinea versicolor.

Tinea versicolor (TV) is typically an asymptomatic fungal infection of the stratum corneum owing to Malassezia overgrowth. It presents as hypo or hyperpigmented macules with fine scale that coalesce into patches on the trunk, neck, and/or arms. Presented in this report is a 34-year-old man with an interesting case of folliculocentric tinea versicolor manifesting as perifollicular hypopigmented macules on the lower back.

Atrophying pityriasis versicolor as an idiosyncratic T cell-mediated response to Malassezia: A case series.

BACKGROUND: Atrophying pityriasis versicolor (PV), first described in 1971, is a rare variant in which lesions appear atrophic. OBJECTIVE: We sought to determine the pathophysiology of atrophying PV. METHODS: A retrospective chart review identified 6 cases of atrophying PV. In all cases, routine light microscopy, an elastic tissue stain, and immunohistochemical assessment for the expression of CD3, CD4, CD8, GATA3 and CXCR3 was performed. RESULTS: All cases demonstrated hyperkeratosis with intracorneal infiltration by pathogenic hyphal forms as well as epidermal attenuation and papillary dermal elastolysis. A supervening, mild-to-moderate, superficial lymphocytic infiltrate was noted and characterized by a focal CD8+ T cell-mediated interface dermatitis along with a mixed T-cell infiltrate composed of GATA3+ and CXCR3+ T cells. LIMITATIONS: Small sample size and the loss of some patients to follow-up. CONCLUSION: Atrophying PV represents the sequelae of a mixed helper T-cell (TH1 and TH2) idiosyncratic immune response to Malassezia and can present as a protracted dermatosis that may clinically mimic an atypical lymphocytic infiltrate. TH1 cytokines can recruit histiocytes, a source of elastases, and upregulate matrix metalloproteinase activity, which may contribute to epidermal atrophy.

Clinicomycological profile of pityriasis versicolor in Assam.

BACKGROUND: Geographical variation in the distribution of Malassezia species associated with pityriasis versicolor (PV) has led to the necessity of studying epidemiological, mycological, and clinical characteristics of PV. AIMS: To study the epidemiological, mycological, and clinical characteristics of PV in a tertiary care hospital. SETTINGS AND DESIGN: The study was carried out with a cross-sectional design. MATERIALS AND METHODS: Two hundred and sixty-two consecutive PV patients were subjected to detailed history, clinical examination, and investigations. Skin scrapings were processed by direct microscopy and culture. Isolates were identified by phenotypic characteristics and polymerase chain reaction-restriction fragment length polymorphism. Association of Malassezia species with clinical and epidemiological characteristics was studied. Statistical analysis of the data was done using statistical software. RESULTS: Maximum number of PV cases (33.9%) belonged to the age group of 21-30 years with a male preponderance. 61.4% of the patients had a sedentary lifestyle, 70.2% showed the gradual onset of the disease, 51.1% presented with pruritus and in 66.4% of the patients symptoms were continuous. Most commonly involved body site was neck (27.8%), 77.09% of the lesions were bilaterally asymmetrical, 87.4% were macular, and 89.3% were hypopigmented. Malassezia furfur (77.3%) was the predominant species. Sedentary lifestyle (61.4%) and increased sweating (48%) were the most commonly associated predisposing factors. CONCLUSION: PV is more common in males. Distribution of Malassezia species varies significantly from those reported in other parts of India. M. furfur was the most common species responsible for PV in our region. Hence, further studies are required to evaluate the exact cause of this variation.

A randomized double-blind, non-inferiority Phase II trial, comparing dapaconazole tosylate 2% cream with ketoconazole 2% cream in the treatment of Pityriasis versicolor.

OBJECTIVES: The objective of this research was to evaluate the efficacy of a new antifungal imidazole, dapaconazole tosylate, in the treatment of Pityriasis versicolor (PV). DESIGN AND METHODS: Sixty patients with clinical and mycological diagnosis of PV were randomly assigned to receive either 1 g dapaconazole tosylate 2% cream or 1 g ketoconazole 2% cream. Treatments were applied once a day for 28 days. A dermatologist evaluated efficacy and safety daily, and weekly laboratorial tests were performed. The primary end point was a clinical and mycological cure of lesions after 28 days of treatment. The secondary end point was the time to clinical healing assessed by Kaplan-Meier analysis and Log-rank testing. RESULTS: Fifty-three patients adhered to protocol rules. Clinical and mycological cure was achieved in 84.6% (22/26) and 92.6% (25/27) of patients treated with ketoconazole and dapaconazole, respectively (difference [effect size] = 8.0%, Standard error of difference: 8.69%, 95% CI: -6.3 to 22.3%). Median time to healing was 23.5 and 21 days for ketoconazole and dapaconazole, respectively (p = 0.126). Adverse events occurred only in ketoconazole-treated patients (13%; 4/30). CONCLUSION: Dapaconazole tosylate is non-inferior to ketoconazole when used at a dose of 20 mg/day for 28 consecutive days for the treatment of PV. Dapaconazole also demonstrated a good safety profile.

Malassezia species and their associated skin diseases.

Malassezia spp. are lipophilic fungi that occur on all skin surfaces of humans and animals as commensal and pathogenic organisms. In the 2000s, several new species were added to the Malassezia genus by Japanese researchers. The genus Malassezia now includes 14 species of basidiomycetous yeast. Culture-independent molecular analysis clearly demonstrated that the DNA of Malassezia spp. was predominantly detected in core body and arm sites, suggesting that they are the dominant fungal flora of the human body. Malassezia spp. have been implicated in skin diseases including pityriasis versicolor (PV), Malassezia folliculitis (MF), seborrheic dermatitis (SD) and atopic dermatitis (AD). While Malassezia spp. are directly responsible for the infectious diseases, PV and MF, they act as an exacerbating factor in AD and SD. The fatty acids generated by Malassezia lipase can induce inflammation of the skin, resulting in development of SD. Patch and serum immunoglobulin E tests revealed that AD patients were hypersensitive to Malassezia. However, these findings only partially elucidated the mechanism by which Malassezia spp. induce inflammation in the skin; understanding of the pathogenetic role of Malassezia spp. in SD or AD remains incomplete. In this article, the latest findings of Malassezia research are reviewed with special attention to skin diseases.

Can pityriasis versicolor be treated with 2% ketoconazole foam?

BACKGROUND: Pityriasis (tinea) versicolor is a superficial fungal infection of the stratum corneum caused by Malassezia species. The diagnosis is made clinically by its classic appearance of round or oval macules with fine scale that may be hyperpigmented or hypopigmented. Diagnosis may also be confirmed with microscopic evaluation of skin scrapings that reveal both short, stubby hyphae, and spores under KOH preparation. Ketoconazole is an important treatment of pityriasis versicolor but is primarily used in cream formulas. A foam vehicle has been shown to improve drug absorption through the stratum corneum and distribution in the skin. This study has assessed the safety and efficacy of ketoconazole 2% foam in treatment of pityriasis versicolor. METHODS: Ketoconazole 2% foam was evaluated in a single-center, open-label, one-arm pilot study which enrolled eleven subjects to gain 10 evaluable subjects aged 21 years and older with a clinical diagnosis of tinea versicolor and positive KOH using calcofluor. The subjects came for 4 scheduled visits (baseline, week 1, week 2, and week 4) and were instructed to apply ketoconazole 2% foam to all affected areas twice daily for 2 weeks. At each visit, mycological and clinical assessment of a target area was done, along with static global assessment and body surface area estimation of the disease in each subject. Patient questionnaires were given at baseline and at week 2 to rate pruritus and satisfaction with the foam. RESULTS: At the week 2 visit, following the treatment period, three out of ten evaluable subjects had negative skin samples prepared with KOH/calcifluor. Of these three, one subject later showed recurrence of fungal elements consistent with tinea versicolor at the week 4 follow-up visit. The other negative subjects remained negative and four additional subjects tested negative at week 4. Three subjects with positive samples at week 4 had only yeast forms without hyphae present. Investigator ratings of the target area were averaged for each clinical feature and demonstrated improvement in scale, hyper- or hypopigmentation, erythema, and induration throughout the study. Average pruritus score increased slightly 1 week after the baseline visit, but then improved steadily over the remaining visits. The investigator's static global assessment rating showed improvement from mild to moderate disease at baseline to minimal or no disease at week 4 in 7 subjects. The remaining subjects showed neither improvement nor progression of the disease throughout the study. One out of the eleven subjects enrolled did not complete the study. One subject noted mild skin burning sensation after application of medicine. Post-treatment patient questionnaires indicated overall satisfaction with the foam vehicle. LIMITATIONS: This was a single-arm, open-label, noncomparative trial. CONCLUSION: Ketoconazole 2% foam improved overall clinical assessment and microscopic evidence of pityriasis versicolor in all subjects with favorable patient feedback regarding the novel foam vehicle.