High Prevalence of Terbinafine Resistance Among Trichophyton mentagrophytes/T. interdigitale Species Complex, a Cross-Sectional Study from 2021 to 2022 in Northern Parts of Iran.

Treatment-resistant dermatophytosis caused by the members of the Trichophyton mentagrophytes/Trichophyton interdigitale species group (TMTISG) is increasing worldwide. We aimed to determine the prevalence of TMTISG in patients with dermatophytosis in two centers from north of Iran and detect the possible mutations in the squalene epoxidase (SQLE) gene in relevant terbinafine (TRB) resistant pathogenic isolates. From November 2021 to December 2022, 1960 patients suspected to dermatophytosis and referred to two mycology referral laboratories in the north of Iran were included in the study. Identification of all dermatophyte isolates was confirmed by RFLP of rDNA internal transcribed spacer (ITS) regions. Antifungal susceptibility testing against five common antifungals using the CLSI-M38-A3 protocol was performed. The TMTISG isolates resistant to TRB, were further analyzed to determine the possible mutations in the SQLE gene. Totally, 647 cases (33%) were positive for dermatophytosis of which 280 cases (43.3%) were identified as members of TMTISG. These were more frequently isolated from tinea corporis 131 (44.56%) and tinea cruris 116 (39.46%). Of 280 TMTISG isolates, 40 (14.3%) were resistant to TRB (MIC ≥ 4 µg/mL), all found to be T. indotineae in ITS sequencing. In SQLE sequencing 34 (85%) of TRB-resistant isolates had coincident mutations of Phe397Leu and Ala448Thr whereas four and two isolates had single mutations of Phe397Leu and Leu393Ser, respectively. Overall, the resistance of Iranian TMTISG isolates to TRB greatly occurred by a mutation of Phe397Leu in the SQLE gene as alone or in combination with Ala448Thr. Nevertheless, for the occurrence of in vitro resistance, only the presence of Phe397Leu mutation seems to be decisive.

KTWS (Klippel-Trenaunay-Weber syndrome): A systematic presentation of a rare disease.

BACKGROUND: Klippel-Trenaunay-Weber syndrome (KTWS) is a rare disease with a wide range of manifestations. KTWS is characterized by a clinical triad of varicosities of the extremities, cutaneous vascular malformations, and hypertrophy of soft tissues and long bones. The diagnosis is made clinically supplemented with magnetic resonance imaging and computed tomography. AIM: Hereby we aim to highlight the significance of the possible life-threatening first-time presentations associated with the GI system in previously undiagnosed KTWS patients. PATIENT: We report the case of a 47-year-old male with KTWS, who presented with various symptoms such as rectorrhagia since childhood, digestive problems and abnormal lateral vascular malformations of the left buttock which extended all the way to the leg, vascular malformations of the left fourth and fifth toes as well as soft tissue swelling of the left foot. There was no evidence of other clinical presentations. The patient was hospitalized with severe rectorrhagia and a hemoglobin level of 3/9. Physical examination revealed a blood pressure of 85/55 and pulse rate of 115. Ruptured aneurysm of the superior mesenteric artery was found on angiography and subsequently treated with embolization. Dermatologic evaluation showed pitting edema of the left leg and foot and multiple vascular lesions. Thus a diagnosis of KTWS was established. Pulsed dye laser therapy and compression bandage was performed for the patient. The patient's follow-up was done 3 months after discharge for which the patient was again consulted by a dermatologist and gastroenterologist. Lymphedema of the left leg had improved to a great extend so treatment with compression bandage was continued. Colonoscopy was repeated for the patient to evaluate and control possible active sources of bleeding, due to potential life-threating complications. RESULTS: According to previous findings, there have been few case reports of KTWS presenting with gastrointestinal manifestations, fewer of which have covered acute life-threatening bleedings associated with this system.

Lipoid proteinosis: A systematic presentation of an unusual disease.

BACKGROUND: Lipoid proteinosis (LP) or Hyalinosis Cutis et Mucosae or Urbach-Wiethe disease is a rare autosomal recessive genodermatosis characterized by an amorphous hyaline material deposition in the skin mucosa and viscera. The clinical symptoms of this disease often begin in childhood, which persist throughout life. Skin manifestations include inflammation, scaling, acne, and eventually ulceration, and hyaline amorphous deposits in these areas of the wound cause a waxy and thick appearance on the skin. In addition, wounds leave atrophic scars like chickenpox. AIM: Herein, we present the first case of LP in the north of Iran; although LP is a sporadic disease, it occurs all around the world, with about 400 cases worldwide having been reported thus far. PATIENT: We report the case of a 28-year-old female patient with a history of skin lesions on her face, scalp, extremities, and buttock, as well as hoarse cry, respiratory problems, dysphagia, and migraine since childhood. There was no evidence of other clinical presentations. A biopsy was taken from the lesions, and the patient was diagnosed with LP. A laryngeal laser was performed for the patient, and peeling creams were used for her skin lesions. RESULT: According to previous findings, there has been no case report of LP with systemic symptoms in the north of Iran.

First report of tamoxifen-induced baboon syndrome.

BACKGROUND: Baboon syndrome is a rare, type IV hypersensitivity reaction causing a maculopapular rash. Tamoxifen is an antineoplastic agent, working as an estrogen receptor antagonist, also called a selective estrogen receptor modulator. A variety of rashes were reported with Tamoxifen use to-date except baboon syndrome. The Tamoxifen-induced baboon syndrome seems to be reversible, as discontinuation of the drug improves clinical outcomes. AIM: Herein, we present the first case of Tamoxifen-induced baboon syndrome which occurred 8 years after initiation of Tamoxifen use. PATIENTS: A 44-year-old woman presented with papulovesicular eruption on her body and erythema on her face for a duration of 6 months. There was no evidence of ocular or mucosal involvement. She was diagnosed with breast cancer and treated with tamoxifen 10 mg twice daily over the past 8 years. She was not taking other medications or over-the-counter supplements at the time of presentation. The patient underwent urgent skin biopsies of two lesions on her buttock and thigh. No organisms were seen on Gram stain. The patient's skin biopsy revealed extensive hyperorthokeratosis, minimal parakeratosis, hypergranulosis, and lichenoid interface dermatitis in the irregularly acanthotic epidermis supporting diagnosis of fixed drug eruption. Following a multidisciplinary discussion, the patient was diagnosed with baboon syndrome or symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) associated with Tamoxifen. RESULTS: Hence, Tamoxifen was immediately discontinued and treated with oral steroid along with topical agents. She showed improvement of clinical abnormalities within days after discontinuation of Tamoxifen. CONCLUSIONS: Given the widespread use of Tamoxifen in the management of patients with breast cancer, it is important that healthcare professionals monitor for rare, however clinically significant, and potentially life-threatening dermatological manifestations of Tamoxifen use, such as baboon syndrome.

Co-localization of alopecia areata and lichen planopilaris in a patient receiving immunosuppressants: A rare case.

BACKGROUND: AA is an acquired dermatosis distributed universally, with multifactorial etiology. It affects the hair follicle with or without nail involvement, resulting in an acute nonscarring alopecia with a relapsing course.1 Being a relatively common skin disease, LPP (lichen planopilaris) is initiated by a chronic lymphocytic inflammation that selectively destructs the hair follicles and eventually leads to scarring alopecia. Also, even though there is enough literature available for the co-existence of AA and LPP with each other and their association with other autoimmune conditions, there are only very few reports on the anatomical concomitance of both disorders.3 AIMS: Although the incidence of not only one but two autoimmune diseases in an immunosuppressed individual is very unusual, we hereby report a case of co-localization of AA and LPP in a patient receiving immunosuppression due to a previous history of SLE (Systemic lupus erythematosus). PATIENTS: A 37-year-old woman, housewife, presented to our office with general alopecia on the scalp since about two years ago (Figure 1), particularly on the vertex which was accompanied by mild itching and trichodynia. She had a history of hypothyroidism and lupus erythematosus arthritis. She had been receiving long-term treatment with prednisolone, hydroxychloroquine, azathioprine, and levothyroxine but had not been treated for hair loss. Despite being on all of the above-mentioned immunosuppressants, the patient developed AA and LPP which are both immune-mediated diseases. RESULTS: In addition to continuing her oral immunosuppressants, the patient was treated with Minoxidil 5% and Clobetasol solution as well as a higher dose of Azathioprine than she was receiving beforehand. Approximately, 3 months into the treatment, the follicular hyperkeratosis and scalp erythema resolved. Also, hair growth could be seen on AA spots. CONCLUSION: Our case report is indicating the possibly mutual immunopathogenesis of these two T cell-mediated disorders. Furthermore, we want to bring attention to the probability of new autoimmune diseases occurring even during treatment with immunosuppressive medications.

The necessity of patch testing in determining the causative drug of AGEP.

BACKGROUND: Acute Generalized Exanthematous Pustulosis (AGEP)is a rare, severe skin reactionmainly caused by medications such as antibiotics, anti fungals, Calcium channel blockers and Anti malarias. Although it resolves spontaneously in most patients, systemic corticosteroids are neededin severe cases. AIMS: In order to determine the drug that is causing this condition, patch testing must be performed. Hydroxychloroquine is a medication that is used for the treatment of rheumatic and dermatologic conditions. And although it has been rarely seen to cause this reaction, we report a case of Hydroxychloroquine-induced (HCQ) AGEP which was confirmed by Patch testing. PATIENTS: A woman 49 years of age with an18 month history of mild, untreated Rheumatoid Arthritis experienced an acute episode of arthritis in her right elbow. Upon going to a rheumatologist, Prednisolone 5 mg BID and HCQ 200 mg daily were administered for a 30-day period. But after only 17 days of this treatment, the patient developed generalized erythema and painful pustular eruptions. Prednisolone dosage was changedto 7.5 mg per day andHCQ was discontinued one day afterthe appearance of eruptions. The diffuse erythema started improving a week after the patient's hospitalization.Considering the factthat our patient was receiving multiple potentially causative medications, patch testing was necessary to distinguish the drug responsible for this reaction. RESULTS: After the patch testing was done, HCQ-induced AGEP was confirmed. CONCLUSIONS: Patch testing is the gold standard of determining the responsible drug for an AGEP reaction. It should also be kept in mind that HCQ, although rarely, can cause this condition.

A first case of fixed drug eruption due to Tamsulosin.

BACKGROUND: Fixed Drug Eruption (FDE) is a drug reaction involving the skin and less commonly the mucosal membranes. Tamsulosin is an alpha-1 adrenergic receptor blocker used to treat benign prostatic hyperplasia. Dizziness and headache are among its most common side effects (Singapore Med J, 2018;59:336). Although cutaneous drug eruption has been reported with other alpha-1 adrenergic receptor blockers. AIMS: Drug rash due to Tamsulosin is relatively uncommon (Singapore Med J, 2018;59:336). In this case we report an incidence of fixed drug eruption due to Tamsulosin. PATIENTS: A 54 year old male, with benign prostatic hyperplasia was referred to our office for evaluation of certain eruptions, having developed his hyper-pigmented patches after 2 weeks of using oral 0.4 mg Tamsulosin per day. Based on the clinical course and the skin biopsy we diagnosed the condition as Tamsulosin associated fixed drug eruption. The most important therapeutic measure was discontinuing Tamsulosin medication. Following this, his eruptions improved remarkably in a few days without complications. RESULTS: According to previous findings, there has been no case report on fixed drug eruption caused by Tamsulosin. CONCLUSION: Our case is a relatively mild form of fixed drug eruption. Therefore it should be kept in mind that a severe cutaneous drug eruption might occur after Tamsulosin administration.

In vitro antifungal susceptibility of Candida speciesisolated from diabetic patients.

INTRODUCTION: This study aims to evaluate the antifungal susceptibility of different species of Candida isolated from diabetic patients against eight antifungal agents. METHODS: Susceptibility testing of 111 clinical isolates of Candida species was performed against 8 antifungals using the M27-A3 protocol of the Clinical and Laboratory Standards Institute (CLSI). RESULTS: Voriconazole, lanoconazole, and caspofungin showed the highest in vitro activity against all the isolates of C. albicans. Resistance against the tested antifungals was only observed in the C. albicans isolates. CONCLUSIONS: Our finding revealed that resistance against amphotericin B, itraconazole, ketoconazole, posaconazole, and fluconazole can be observed in C. albicans.

In vitro antifungal susceptibility of Candida speciesisolated from diabetic patients

Abstract INTRODUCTION This study aims to evaluate the antifungal susceptibility of different species of Candida isolated from diabetic patients against eight antifungal agents. METHODS Susceptibility testing of 111 clinical isolates of Candida species was performed against 8 antifungals using the M27-A3 protocol of the Clinical and Laboratory Standards Institute (CLSI). RESULTS Voriconazole, lanoconazole, and caspofungin showed the highest in vitro activity against all the isolates of C. albicans. Resistance against the tested antifungals was only observed in the C. albicans isolates. CONCLUSIONS Our finding revealed that resistance against amphotericin B, itraconazole, ketoconazole, posaconazole, and fluconazole can be observed in C. albicans.

Reflectance confocal microscopy: a useful and non-invasive tool in the in vivo differentiation of benign pigmented skin lesions from malignant melanoma. Report of a case.

The diagnosis of seborrheic keratoses (SK) undergoing regression can be challenging clinically and dermoscopically. We report a case of a SK with a history of change and equivocal dermoscopic features, thereby showing confocal features suggestive of solar lentigo/early SK. The present case emphasizes the potential value of reflectance confocal microscopy (RCM) in the differentiation of malignant from benign pigmented skin lesions.

Dermoscopy and in vivo reflectance confocal microscopy of a congenital nevus of the nipple.

We report a 26-year-old male with a 4 mm diameter, asymmetric, irregularly pigmented and bordered, brown maculopapular lesion on the right nipple present since childhood with enlargement of the lesion within the last 3 months. Dermoscopy revealed a global globular pattern with the presence of focally light brown globules and irregular black globules in its centre. In vivo reflectance confocal microscopy (RCM) revealed dense junctional and dermal melanocytic nests of different sizes and shapes that appeared as sharply demarcated round to oval reflective structures; cellular outlines of single melanocytes were not always detected. In the centre of the lesion within the upper dermis, irregularly shaped, homogeneously reflecting structures were observed. As a clear differentiation between clusters of melanophages and melanocytic nests could not be made with certainty, an excisional biopsy was performed to establish the diagnosis of compound nevus with features of congenital nevus. Therefore, to prove that dermoscopic globules correlated with melanophages, the correlation between dermoscopic RCM and histopathology was necessary.