Rachael Morris-Jones

Synthesis of Melanin-Like Pigments by Sporothrix schenckii In Vitro and during Mammalian Infection

ABSTRACT Melanin has been implicated in the pathogenesis of several important human fungal pathogens. Existing data suggest that the conidia of the dimorphic fungal pathogen Sporothrix schenckii produce melanin or melanin-like compounds; in this study we aimed to confirm this suggestion and to demonstrate in vitro and in vivo production of melanin by yeast cells. S. schenckii grown on Mycosel agar produced visibly pigmented conidia, although yeast cells grown in brain heart infusion and minimal medium broth appeared to be nonpigmented macroscopically. However, treatment of both conidia and yeast cells with proteolytic enzymes, denaturant, and concentrated hot acid yielded dark particles similar in shape and size to the corresponding propagules, which were stable free radicals consistent with identification as melanins. Melanin particles extracted from S. schenckii yeast cells were used to produce a panel of murine monoclonal antibodies (MAbs) which labeled pigmented conidia, yeast cells, and the isolated particles. Tissue from hamster testicles infected with S. schenckii contained fungal cells that were labeled by melanin-binding MAbs, and digestion of infected hamster tissue yielded dark particles that were also reactive. Additionally, sera from humans with sporotrichosis contained antibodies that bound melanin particles. These findings indicate that S. schenckii conidia and yeast cells can produce melanin or melanin-like compounds in vitro and that yeast cells can synthesize pigment in vivo. Since melanin is an important virulence factor in other pathogenic fungi, this pigment may have a similar role in the pathogenesis of sporotrichosis.

Dermatitis caused by physical irritants

Summary Background Although physical irritant contact dermatitis (PICD) is a common occupational dermatosis, it is one of the least well understood because of its multiple types, lack of diagnostic test, and the many mechanisms involved in its production.

Synthesis of Melanin Pigment by Candida albicans In Vitro and during Infection

ABSTRACT Melanins are implicated in the pathogenesis of several important human diseases. This study confirmed the presence of melanin particles in Candida albicans in vitro and during infection. Dark particles were isolated from the digestion of C. albicans cultures and from infected tissue, as established by electron microscopy and immunofluorescence techniques.

The diagnosis and management of tinea

#### Summary points Tinea refers to superficial infection with one of three fungal genera— Microsporum , Epidermophyton , and Trichophyton —collectively known as dermatophytes. These infections are among the most common diseases worldwide and cause serious chronic morbidity. Griseofulvin treatment and school screening programmes almost eradicated tinea capitis (scalp infection) as an endemic condition in the developed world in the 1950s, but it re-emerged as a public health problem in the United Kingdom in the 1990s, with infection rates of at least 12% in school children.1 Increased mass tourism and mobile populations may have contributed to the changing epidemiological trends.2 Newly developed polymerase chain reaction based techniques, although useful in rapid diagnosis of dermatophytosis,3 are still not widely available. Although the number and range of antifungal drugs are limited compared with antibiotics, most are highly effective for fungal disease acquired in temperate climates. This review aims to familiarise the reader with the various clinical presentations of tinea, to outline the steps that should be taken for accurate diagnosis, and to evaluate the most appropriate treatment regimens. #### Sources and selection criteria We based this review on a detailed review of English language publications. We also drew on the British Association of Dermatologists’ clinical guidelines for the management of tinea capitis and the management of onychomycosis, Health Protection Agency guidelines, and extensive clinical experience. All three genera of dermatophytes grow in keratinised environments such as hair, skin, and nails.4 Anthropophilic dermatophytes are restricted to human hosts and produce mild chronic inflammation. The main reservoirs of zoophilic dermatophytes are pets, livestock, and horses; infection with such organisms usually …

Drug reaction with eosinophilia and systemic symptoms: is cutaneous phenotype a prognostic marker for outcome? A review of clinicopathological features of 27 cases

Background  Drug reaction with eosinophilia and systemic symptoms (DRESS) describes a heterogeneous group of severe adverse reactions to medications. The cutaneous phenotype has a number of guises, accompanied by a variety of systemic features including fever, haematological abnormalities and visceral involvement, most commonly the liver. Clinical markers of prognosis have not been identified.

Scytalidium dimidiatum Causing Recalcitrant Subcutaneous Lesions Produces Melanin

ABSTRACT Scytalidium dimidiatum is a pigmented dematiaceous coelomycete that typically causes chronic superficial skin diseases and onychomycosis, as well as deeper infections, such as subcutaneous abscesses, mycetoma, and even fungemia in immunocompromised patients. A second species, Scytalidium hyalinum, has hyaline hyphae and arthroconidia and is considered by some authors to be an albino mutant of S. dimidiatum. This study aimed to confirm the presence of melanin or melanin-like compounds (which have been previously implicated in the virulence of other fungal pathogens) in S. dimidiatum from a patient with multiple subcutaneous nodules. Treatment of the hyphae and arthroconidia with proteolytic enzymes, denaturant, and concentrated hot acid yielded dark particles, which were stable free radicals, consistent with their identification as melanins. Extracted melanin particles from S. dimidiatum cultures were labeled by melanin-binding monoclonal antibodies (MAbs) from Sporothrix schenckii, Aspergillus fumigatus, and Cryptococcus neoformans. Lesional skin from the patient infected with S. dimidiatum contained fungal cells that were labeled by melanin-binding MAbs, and digestion of the tissue yielded dark particles that were also reactive. S. hyalinum was also subjected to the melanin extraction protocol, but no dark particles were yielded.

Ten cases of drug reaction with eosinophilia and systemic symptoms (DRESS) treated with pulsed intravenous methylprednisolone

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, life-threatening, drug-induced illness characterised by a widespread polymorphic eruption, fever and multivisceral involvement. There is little published on the management of DRESS. Prompt recognition and withdrawal of the causative drug is essential, along with supportive treatment. However, the condition commonly progresses despite these measures. Oral corticosteroids are usually given but the response can be suboptimal and result in a prolonged exposure to systemic glucocorticoid. We conducted a prospective single-centre study to determine the efficacy of pulsed intravenous methylprednisolone followed by a short reducing course of oral prednisolone in ten patients with confirmed DRESS. Rash and fever responded rapidly to methylprednisolone in all patients. Compared to pre-treatment assessments, there was a significant reduction in eosinophil count at day 14 and AST level at day 90 post-treatment. One patient developed acute hepatic failure, necessitating a liver transplant, and died 4 months later. In the immediate post-treatment phase, 1 patient developed type 1 diabetes and 1 patient developed a corticosteroid-induced psychosis. Long-term follow-up on 8/10 revealed all patients to be well, although one patient had persistent pruritus. An aggressive corticosteroid regimen in the management of DRESS is associated with good clinical outcome and acceptable tolerance.

Skin Disease Among Human Immunodeficiency Virus-Infected Adolescents in Zimbabwe: A Strong Indicator of Underlying HIV Infection

Background: Southern Africa is witnessing the emergence of an epidemic of long-term survivors of vertically acquired human immunodeficiency virus (HIV) infection presenting with untreated HIV as adolescents. Dermatologic conditions, common in both HIV-infected adults and children, have not been described in this age-group. We investigated the prevalence and spectrum of skin conditions in adolescents admitted to hospitals in Zimbabwe. Methods: A total of 301 consecutive adolescents admitted to 2 central Harare hospitals, underwent a dermatologic examination. Clinical history, HIV serology, and CD4 lymphocyte counts were obtained. Herpes simplex virus-2 serology was used as a surrogate marker for sexual activity. Results: A total of 139 (46%) patients were HIV-1 antibody positive, of whom only 2 (1.4%) were herpes simplex virus-2 antibody positive. The prevalence of any skin complaint among HIV-infected and uninfected participants was 88% and 14%, respectively (odds ratio: 37.7, 95% confidence interval: 19.4–72). The most common HIV-related conditions were pruritic papular eruptions (42%) and plane warts >5% of body area (24%). Having 3 or more skin conditions, a history of recurrent skin rashes and angular cheilitis were each associated with CD4 counts <200 cells/&mgr;L (P < 0.03, P < 0.01, and P < 0.05, respectively). Conclusions: Skin disease was a common and striking feature of underlying HIV-infection in hospitalized HIV-infected adolescents in Zimbabwe. In resource-poor settings with maturing epidemics, the presence of skin disease should be regarded as a strong indication for HIV testing and especially as it may reflect advanced immunosuppression. The high frequency of multiple plane warts has not previously been described, and may be a feature that distinguishes vertically-infected from horizontally-infected adolescents.

Mycobacterium abscessus: a cutaneous infection in a patient on renal replacement therapy

We report a 72‐year‐old man on haemodialysis who presented with multiple abscesses on his lower legs. Routine bacterial culture of abscess pus was reported as ‘sterile’ after 48 h, leading to the suspicion of a mycobacterial infection. Skin biopsy taken for mycobacterial microscopy and culture isolated a heavy growth of Mycobacterium abscessus.

Management of cutaneous viral warts

#### Summary points The prevalence of cutaneous viral warts in the general population is estimated to be 7-12%. Many patients present to primary care with pain and discomfort along with other concerns, such as cosmetic appearance. Although cutaneous viral warts are ubiquitous, no definitive treatment exists. Nevertheless, most warts resolve spontaneously and a large proportion of the remainder respond to simple recommended treatment. For these reasons, potential treatments must have minimal side effects and a favourable risk profile. #### Sources and selection criteria We searched Medline, Embase, and the Cochrane databases for evidence relating to the treatment of cutaneous viral warts. Although a large number of trials have been published, the quality of evidence varied and only a few were randomised and of adequate sample size. Proof of efficacy is challenging, with relatively high rates of spontaneous resolution; furthermore, studies of second and third line treatments are limited as these treatments are typically reserved for recalcitrant warts. High quality evidence based studies are lacking in this discipline owing to confounding factors such as high rates of spontaneous resolution and a subpopulation of warts that seem recalcitrant to most treatments. Occasionally in medicine the longer the list of potential treatments the less effective they seem to be, and this situation is exemplified by viral warts.1 2 This article focuses on the preferred treatment of viral warts in primary care and alternative management in secondary care. Viral warts are benign papillomas that arise from infection of epidermal or mucosal cells with …