Facial demodicosis in the immunosuppressed state: a retrospective case series from a tertiary referral center.

BACKGROUND: Data on Demodex in the immunosuppressed state is limited, focusing mainly on patients with human immunodeficiency virus and hematological malignancies. The aim of this study was to describe the manifestations of facial demodicosis in diverse immunosuppressive states. METHODS: The medical records of all patients followed at a Demodex outpatient clinic of a tertiary medical center from January 2008 to November 2020 were retrospectively reviewed. Data on patients who were immunosuppressed while with demodicosis were retrieved. RESULTS: The cohort included 28 patients (17 women and 11 men; median age, 58 years). Types of immunosuppression included treatments with hydroxyurea for polycythemia vera/essential thrombocytosis, mycophenolic acid, tacrolimus, and prednisone for liver and/or kidney transplantation, prednisone with cyclosporine/methotrexate/azathioprine/rituximab mainly for autoimmune diseases, mercaptopurine with/without anti-tumor necrosis factor alpha (TNF-α) for Crohn's disease, chemotherapy for neoplasms, anti-TNF-α for psoriasis, and Cushing's syndrome. The clinical types of demodicosis included: papulopustular, erythematotelangiectatic and fulminant rosacea, hyperpigmented, pityriasis folliculorum, pustular folliculitis, and dermatitis. The diverse clinical presentations led to various differential diagnoses. Topical treatment with ivermectin (monotherapy/combination with other treatments) was effective. CONCLUSION: Clinicians treating immunosuppressed patients should be familiar with the different forms of demodicosis and include them in the differential diagnosis of facial eruptions.

Pigmented demodicidosis - an under-recognized cause of facial hyperpigmentation.

BACKGROUND: There is a paucity of data regarding demodicidosis-associated facial hyperpigmentation. OBJECTIVE: To delineate the clinical, dermoscopic, and histopathologic features of demodicidosis-associated facial hyperpigmentation. METHODS: Clinical and diagnostic data were collected from the medical files of patients who were referred to our outpatient dermatology clinic in 2006-2019 for evaluation of facial hyperpigmentation and were diagnosed with demodicidosis. RESULTS: The cohort included 19 patients (13 male) aged 42-76 years, all with Fitzpatrick skin type 3-4. All presented with mostly asymptomatic dusky, brown-gray, facial pigmentation, localized or diffuse with background erythema in 36.8% of cases, and skin roughness in 26.3%. Dermoscopy yielded characteristic findings of white gelatinous or opaque protrusions from hair follicles or infiltration of follicular openings with an amorphic material. A specific finding was perifollicular and reticulated pigmentation of the affected areas. Findings were confirmed on microscopic (n = 7) and histopathologic (n = 5) studies. Anti-demodectic treatment led to complete (73.6%) or partial (23.4%) resolution of pigmentation within 2 years. CONCLUSION: We describe unique clinicopathological and dermoscopic findings associated with an under-recognized type of facial hyperpigmentation caused by demodex for which we propose the term "pigmented demodicidosis." Demodicidosis should be added to the list of causes of facial hyperpigmentation.

[DISSEMINATED CRYPTOCOCCOSIS IN A LIVER TRANSPLANT RECIPIENT DIAGNOSED BY TZANCK SMEAR].

INTRODUCTION: Cryptococcus neoformans is an opportunistic fungus which causes severe morbidity and mortality among immune-compromised patients. Cutaneous manifestations of systemic cryptococcosis are rare and may include a papulo-nodular rash, ulcers, cellulitis, molluscum contagiosum-like papules and more. The Tzanck smear is a well-known simple diagnostic test which can be performed bedside, in order to characterize cell cytology. Its classic use was in diagnosis of autoimmune blistering diseases or herpes virus infections. However, in recent years it has been used as an efficient diagnostic tool for other dermatologic conditions. We present a case of a 47-year old liver transplant recipient who presented with numerous cutaneous manifestations of disseminated cryptococcosis, initially diagnosed with bacterial cellulitis and non-melanoma skin cancer. With the aid of the Tzanck smear we rapidly established the correct diagnosis leading to swift treatment.

Evaluation of multiplex real-time PCR for identifying dermatophytes in clinical samples-A multicentre study.

The gold-standard method for dermatophyte identification involves direct microscopy and culture, which have inherent shortcomings. Only few molecular methods have been standardised for routine clinical work. This study aimed to develop and test a platform for identifying the most common dermatophytes in Israel using multiplex real-time polymerase chain reaction (RT-PCR). Specific primers were designed for the multiplex system (LightCycler 480) according to known cultures and validated by reference isolates. The dermatophyte detection rate was compared to smear and culture in 223 clinical samples obtained from a tertiary medical centre. Inconsistencies between methods were evaluated by sequencing. The RT-PCR was further evaluated in 200 community-based samples obtained from a health maintenance organisation and 103 military-personnel-based samples analysed at a central laboratory. In hospital-based clinical samples, complete concordance between methods was observed in 190 samples (85%; Kappa = 0.69). In most cases of non-concordance, sequencing was consistent with RT-PCR results. RT-PCR correctly identified all smear- and culture-positive cases in community and military-personnel samples. The results were available within 4 hours. The multiplex RT-PCR platform is a rapid and efficient method for identifying dermatophyte species in clinical samples and may serve as a first step in the diagnostic algorithm of superficial fungal infections.

Mycetoma (Madura Foot) in Israel: Recent Cases and a Systematic Review of the Literature.

AbstractMycetoma is a chronic soft tissue infection caused by fungal or bacterial pathogens, and is endemic in tropical and subtropical regions. Cases in developed countries outside the mycetoma belt are rare and usually imported by immigrants. Sporadic cases have been reported in Israel. Unpublished cases in the participating medical centers are reported. In addition, a systematic review of the literature was performed. All published mycetoma cases diagnosed in Israel were included with relevant variables collected. Twenty-one cases of mycetoma were diagnosed in Israel between 1942 and 2015, including four unpublished cases and 17 published cases. The mean age at diagnosis was 42 years (range 23-73), and 16 of the patients were male. The foot was the primary involved organ. Fifteen patients were immigrants from Yemen, Ethiopia, and Sudan. Five cases were autochthonous. One case was travel related. Among patients who developed symptoms after immigration, the mean time from exposure to symptom onset was 5.6 years (range 1-10 years). The mean time from symptom onset to diagnosis was 6.6 years (range 0.2-35 years). The autochthonous cases demonstrate that Israel is endemic of mycetoma. The immigrant population represents two distinct waves of immigration to Israel in the past century. Two unpublished cases of Ethiopian immigrants are the first reported cases of mycetoma acquired in Ethiopia. The diagnostic and therapeutic challenges along with the epidemiological data emphasize the need of raising the awareness of physicians to this devastating condition even in developed countries.

A Unique Clinicopathological Manifestation of Fungal Infection: A Case Series of Deep Dermatophytosis in Immunosuppressed Patients.

BACKGROUND: Dermatophytes are the most common cause of superficial fungal infections in humans. Deep dermatophytosis, however, is rare, described to date only in isolated case reports, usually in the setting of systemic immunosuppression. OBJECTIVE: To present the 15-year experience of a tertiary dermato-mycology clinic with the diagnosis and treatment of deep dermatophytosis. METHODS: Patients were identified by database search. Clinical, mycological, histological, and treatment data were collected from the medical files. RESULTS: Ten patients were identified: nine after solid-organ transplantation and one undergoing chemotherapy, all diagnosed within 3 years after beginning immunosuppression (average 7.5 months). The infective agent in nine cases was Trichophyton rubrum. All patients presented with concurrent superficial fungal infections. Complete resolution was noted in response to systemic antifungal agents. There was no histological evidence of hair-follicle involvement. LIMITATIONS: The limitations of the study were the retrospective design and the small cohort size. CONCLUSION: This case-series study suggests that deep dermatophytosis is a separate entity, distinct from Majocchi's granuloma. It occurs only in immunocompromised patients and is characterized by discrete nodules, an indolent course, the absence of follicular invasion, and proximity to a superficial dermatophyte infection. Systemic antifungal treatment leads to complete resolution. The urgent need for the treatment of superficial fungal infections in immunocompromised patients is emphasized.

Onychomycosis in Israel: epidemiological aspects.

Onychomycosis is a fungal infection treated orally for prolonged periods of treatment, caused primarily by Dermatophytes, Candida species and non-dermatophyte moulds (NDMs). The prevalence of specific aetiology may differ in dependence of environmental, geographic and demographic factors, and may affect management of the infection. The objective of this survey was to analyse epidemiologic parameters of onychomycosis in Israel. Data of a cohort of 27,093 patients were collected from six centres during a 2- and 10-year period. The diagnosis was based on microscopy of KOH/calcofluor mounts of nail scrapings and culture isolation. A positive result indicates isolation of a fungus in culture. Data were analysed for each centre and expressed as range for the whole cohort, using the spss v18 software. Analysis included three epidemiologic parameters: fungal aetiology in toe- and fingernails; association with gender; association with age group. Dermatophytes were the major causative agents and Trichophyton rubrum the most frequent isolate. Candida species were more frequent in women fingernails; frequency increased with age and C. parapsilosis the most frequent species. NDMs were isolated at low rate and Aspergillus terreus was the most frequent isolate. This is a first large cohort of onychomycosis patients from Israel analysed by defined epidemiological parameters.

Dermoscopy as a diagnostic tool in demodicidosis.

BACKGROUND: The in vivo demonstration of Demodex infestation is traditionally based on the microscopic identification of Demodex mites, which is time consuming and requires specific equipment and a trained observer. OBJECTIVE: The aim of this study was to describe for the first time the use of polarized-light dermoscopy for the diagnosis of demodicidosis in patients with variable clinical presentations. METHODS: A total of 72 patients with variable facial eruptions were examined clinically, microscopically, and dermoscopically for the presence of Demodex mites. RESULTS: Of the 72 patients, 55 were found to have demodicidosis. In 54 patients, the dermoscopy examination yielded a specific picture consisting of Demodex "tails" and Demodex follicular openings. In patients with an inflammatory variant of demodicidosis, reticular horizontal dilated blood vessels were also visualized. Microscopically, skin scrapings demonstrated Demodex in 52 patients. Overall, the dermoscopy findings showed excellent agreement with the microscopy findings (kappa value 0.86, 95% CI 0.72­0.99, P < 0.001). In the remaining 17 patients, there was no evidence of Demodex infestation either microscopically or dermoscopically. LIMITATIONS: The study was not blinded. As there are no standards for the diagnosis of demodicidosis, our results were based on criteria developed by our research group. CONCLUSIONS: This is the first description of the specific dermoscopic findings associated with variable clinical presentations of demodicidosis. Dermoscopy may serve as a valuable tool for the real-time validation of Demodex infestation and the evaluation and follow-up of affected patients.

CD4+ and CD8+ T cells mediated direct cytotoxic effect against Trichophyton rubrum and Trichophyton mentagrophytes.

BACKGROUND: The cellular immune system is the most dominant factor in curing acute dermatophytosis. However, the exact immune mechanisms involved in generating this defense are complex and still obscure. The aim of this study was to investigate the fungicidal mechanism of T cells in the normal population versus patients with chronic fungal infections. METHODS: Thirty patients were included in the study: 15 patients with chronic dermatophytosis and 15 normal healthy patients with a history of acute dermatophytosis. The procedures were performed as follows. 1) Proliferation and cytotoxic activity of lymphocytes cultured with various dermatophytes homogenate such as, Trichophyton rubrum, Trichophyton mentagrophytes and Microsporum gypseum. 2) CD4(+) and CD8(+) T cells were separated by magnetic beads before culture with fresh spores of either T. mentagrophytes or T. rubrum. 3) Routine histology and ultrastructural study were performed to illustrate the mode of activity of the T cells against the dermatophytes. RESULTS: The study showed that both CD4 and CD8 possess cytotoxic activity against dermatophytes. However, the results demonstrated a suppression of lymphocyte proliferation response and a significant lower cytotoxic effect in chronic patients. Ultra structure and histological evaluation of the culture of hyphae with CD4(+) or CD8(+) T cells showed more prominently destructive effects in the culture of cells that had been obtained from normal population than those of patients with long-lasting fungal infections. CONCLUSION: The study suggests a selective impairment of lymphocyte function against dermatophytes, in patients with chronic dermatophytoses.