Clinical signs and genetic evaluation of patients with neurofibromatosis type 1 with and without optic pathway gliomas in a center in Turkey.

PURPOSE: Optic pathway gliomas (OPGs) occur in 15% of patients with neurofibromatosis type 1 (NF1). Their location renders biopsy or surgical resection difficult because of the risk of vision loss. Therefore, only a few NF1-OPGs have been used for tissue diagnosis, and only a few analyses have been published on the molecular changes that drive tumorigenesis. METHODS: Due to this reason, we evaluated 305 NF1 patients, 34 with OPG and 271 without OPG for germ line mutations. All subjects underwent clinical examination and DNA analysis of NF1, confirming the diagnosis of NF1. RESULTS: Clinically, the group with OPG had a significantly higher incidence of bone dysplasia (P < 0.001) and more café-au-lait spots (P = 0.001) compared to those in the group without OPG. The frequency of Lisch nodules was on the borderline of statistical significance (P = 0.058), whereas the frequency of neurofibromas did not differ significantly (cutaneous, P = 0.64; plexiform, P = 0.44). Individuals with OPG mostly had mutations in the first one-third of the NF1 gene compared with that in patients who did not have OPG. Some identical mutations were detected in unrelated families with NF1-OPG. CONCLUSION: The observation of certain phenotypic features and the correlation between genotype and phenotype might help to determine the risk of developing OPG with NF1.

Assessment of Ecotropic Viral Integration Site 2B (EVI2B) Gene in Juvenile Myelomonocytic Leukemia and Neurofibromatosis Type 1 NF1 Tumors.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease that affects the development and growth of various tissues. NF1 is a major risk factor for the development of malignancies, particularly malignant peripheral nerve sheath tumors, optic gliomas, and leukemia. NF1 encodes a neurofibromin. Three genes, EVI2A, EVI2B, and OMGP, are embedded within intron 27b of NF1. However, the function of these genes remains unclear. EVI2A and EVI2B encode for putative transmembrane proteins. Mouse homologs are associated with viral insertions involved in leukemia in mice. Mouse Evi2b has been identified as a direct target gene of C/EBPα, a transcription factor critical for myeloid differentiation. Also possible is that these genes are related to the leukemia observed in patients with NF1. These genes might act as modifiers of NF1 phenotypic variations. Therefore, we investigated the EVI2B gene in leukemia and NF1 tumors. We analyzed DNA from 10, 20, and 3 patients with NF1, leukemia, and NF1-leukemia, respectively, and six NF1 tumor tissues. DNA sequencing analysis was used to identify the viral integration sequence, and the protein amounts and EVI2B gene expression were analyzed by flow cytometry and quantitative real-time PCR techniques. The EVI2B gene expression was increased in cutaneous neurofibroma compared with the control both at the level of protein and mRNA. However, its expression in plexiform neurofibroma was decreased significantly at protein level and increased at mRNA level compare to control. Moreover, integration of 455 bases near the 3' end of the exon was detected. When this integrated sequence was blasted into the NCBI retroviral genome database, an 87% match with the HIV-1 virus envelope gene was obtained. These preliminary results show that EVI2B might be important in NF1 tumorigenesis and leukemia.

Serum vitamin D levels and vitamin D receptor gene ApaI and TaqI polymorphisms in patients with morphea: a case-control study.

A uncommon inflammatory condition called morphea causes fibrosis in the skin and subcutaneous tissue. The key stages in the pathophysiology are vascular damage, immunological response, and fibrosis. Numerous research have examined the relationships between the immune system, fibrosis, and vitamin D, but the exact pathogenetic pathways of morphea remain poorly understood. The purpose of this study was to investigate serum 25(OH)D levels and the ApaI (rs7975232) and TaqI (rs731236) polymorphisms of the vitamin D receptor (VDR) in morphea patients. There were 48 age- and sex-matched controls and 41 morphea patients total. VDR polymorphisms were found using PCR tests and gel electrophoresis, and serum 25(OH)D levels were determined using liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). The patient group consisted of 37 females (90.2%) and 4 males (9.8%). The patients' mean age was 38.68 ± 17.54 years. In terms of VDR ApaI and TaqI polymorphisms, there was no discernible difference between the patient and control groups. TaqI polymorphism heterozygosity was discovered in all patients with progressive disease, and this finding was statistically significant (p = 0.012). Patients' mean serum 25(OH)D levels were 16.98 ± 11.55 ng/mL, while those in the control group were 18.02 ± 14.30 ng/mL. VDR polymorphisms, vitamin D levels, disease subtype, age of onset, and responsiveness to treatment did not significantly correlate. In our research, we discovered that TaqI polymorphism may be related to the severity of the disease and that the polymorphisms of the VDR ApaI and TaqI were not associated with morphea susceptibility.

Diagnostic Role of Direct Immunofluorescence Assay in Determining The Etiology of Erythroderma: Experience in a Tertiary Referral Hospital.

Introduction: Erythroderma is a life-threatening dermatologic emergency which is characterized by diffuse erythema and exfoliation affecting more than 90% of the body surface area. Most common cutaneous diseases associated with erythroderma are systemic contact dermatitis, psoriasis, drug eruption and atopic dermatitis. Clinical-pathological correlation is used to determine the underlying disease. In addition, direct immunofluorescence (DIF) may provide significant clues for etiology of erythroderma especially in the case of autoimmune bullous skin diseases (ABSDs). Objectives: In our study, we aimed to analyze the demographic data, clinical pre-diagnoses, final diagnosis, histopathological and DIF examination findings, accompanying systemic signs and laboratory abnormalities of erythrodermic patients. Methods: We conducted a retrospective study of 31 erythroderma patients in a referral hospital between 2014 and 2021. Cutaneous biopsies were taken from all patients for H&E and DIF examination. Results: Average age was 54.6 ± 23 years, 48.4% of the patients were female (N = 15) whereas 51.6 % of the patients were male (N = 16). Average time between the onset of rash and biopsy was 18.8 days. DIF analysis showed immune deposits in 19.4% (N = 6) of the patients; whereas no immune deposits were detected in 80.6% (N = 25) of the patients. The most frequent final diagnosis was adverse cutaneous drug eruption followed by ABSDs. Conclusions: Our findings suggest that DIF may be used in conjunction with clinical-pathologic and clinical findings to reveal the associated skin diseases in erythrodermic patients. Erythrodermic patients presenting with clinical findings of ABSD should be considered for DIF examination.

Dermatology consultation requests from a university hospital's pediatric and adult emergency departments: A 5-year retrospective analysis.

BACKGROUND: Unnecessary dermatology consultation requests from emergency departments (EDs) are a common occurrence worldwide. AIM: This study aimed to analyze the demographic and clinical characteristics of patients consulted to the dermatology department for dermatologic disorders by a university hospital's pediatric ED (PED) and adult ED (AED). MATERIALS AND METHODS: The electronic medical records of 2316 dermatology consultation requests from the PED and AED during a 5-year period were retrospectively reviewed. Patient demographic and clinical characteristics, dermatological diagnoses, and time of day of dermatology consultation requests from the PED and AED were retrospectively analyzed. RESULTS: The electronic medical records of 1845 consultation requests with complete data were included in the study. There were 969 (52.5%) consultation requests from the PED and 876 (47.5%) from the AED. Mean time from onset of dermatological symptoms to ED presentation was 31.6 d. Herpes zoster infections (18.5%), adverse cutaneous drug reactions (8.1%), and urticaria with angioedema (7.9%) were the most common skin disorders resulting in consultation requests from the AED, versus non-specific viral infections (9.2%), insect bites (8.3%), and atopic dermatitis (8.2%) from the PED. In all, 11.5% of ED patients that received dermatology department consultation required hospitalization due to dermatologic disorders. CONCLUSION: As patients commonly present to EDs with non-urgent dermatological diseases, ED physicians should receive training on common dermatological diseases so as to decrease the number of unnecessary dermatology consultation requests.

TMC8 mutation in a Turkish family with epidermodysplasia verruciformis including laryngeal papilloma and recurrent skin carcinoma.

The vast majority of primary immunodeficiencies (PIDs) occur due to the defects in cells originating from hematopoietic stem cells, while in some PIDs, there are defects in various genes responsible for non-leucocyte immune response such as seen in epidermodysplasia verruciformis (EV). EV caused by the mutations in TMC6, TMC8, and CIB1 genes is called "typical." "Atypical" EV may develop in patients with primary immunodeficiencies originating from hematopoietic stem cells, which include severe T-cell failure, caused by inactivating biallelic mutations of STK4, RHOH, CORO1A, ITK, TPP2, DCLRE1C, LCK, RASGRP1, or DOCK8 genes. Here, we present a family with TMC8 gene mutation leading to disseminated epidermodysplasia verruciformis including laryngeal papilloma and recurrent cutaneous squamous cell carcinomas. Typical EV with impaired local, keratinocyte-intrinsic immune response should be considered when routine immunological examinations are normal in patients presenting with clinical signs of EV. Although it is not possible to prevent EV lesions, early and appropriate surveillance for malignancy is mandatory.

The effect of COVID-19 on patients with chronic spontaneous urticaria treated with omalizumab and antihistamines: A cross-sectional, comparative study.

INTRODUCTION: Chronic spontaneous urticaria (CSU) is defined as recurrent attacks of urticaria present for more than six weeks. The monoclonal anti-immunoglobulin E antibody, omalizumab, was approved for the treatment of CSU in patients who remain refractory to H1-antihistamines. Biologic agents are shown not to increase the risk of COVID-19 infection in different studies. OBJECTIVE: In the present study, we aimed to determine the prevalance of COVID-19 infection in relation to the age, gender, presence of other comorbidities, and treatment given for CSU. METHODS: We conducted a descriptive cross-sectional study of 233 patients diagnosed with CSU in a tertiary referral hospital. Demographical data, treatment given for CSU, the presence of COVID-19-related symptoms, history of close contact to a person with COVID-19 and COVID-19 real-time polymerase chain reaction (RT-PCR) results were determined via a telephone survey and checked from medical data records. RESULTS: One hundred sixty patients were female; whereas 73 were male. The mean age was 44.76. Out of 233 patients with chronic urticaria, 125 had symptoms related to COVID-19 infection. RT-PCR testing for COVID-19 was performed in 156 patients. Of 156 patients with COVID-19 RT-PCR test, RT-PCR result was positive in 15 cases. CONCLUSIONS: No statistically significant relationship was found between COVID-19 RT-PCR positivity and the type of treatment administered for chronic urticaria when the patients are divided into omalizumab ± oral antihistamines and only oral antihistamines treatment groups (p = 0.150). Omalizumab seems to be safe in the era of COVID-19.

The effect of the COVID-19 pandemic on dermatology consultation requests from adult and paediatric emergency departments.

AIM: This study aimed to determine the characteristics of dermatology consultation requests from the adult and paediatric emergency departments (EDs) of a university hospital during 8 months of the COVID-19 pandemic in 2020 and to compare them with the same 8 months of 2019. MATERIALS AND METHODS: Electronic medical records of dermatology consultation requests from adult and paediatric EDs between 15 March 2019 and 15 November 2019, and between 15 March 2020 and 15 November 2020 were retrospectively reviewed. RESULTS: The study included 495 consecutive dermatology consultation requests. In total, 283 (57%) consultation requests occurred in 2019, vs 212 (43%) between in 2020 during the COVID-19 pandemic. The number of consultation requests per day was significantly lower in 2020 (0.9 ± 0.1 per day) than in 2019 (1.15 ± 0.1 per day; P = .002), and was significantly lower in March, April and May 2020, as compared with March, April, and May 2019 (P = .004, P = .001, and P = .001, respectively). The median time from onset of dermatological symptoms to ED presentation was significantly longer in 2020 than in 2019 (4 days in 2019 vs 7 days in 2020; P < .001). Dermatological emergencies in 2019 and 2020 constituted 6.7% of all emergency presentations, with no significant difference between the 2 years (7.1% of all ED presentations in 2019, vs 6.1% in 2020; P = .795). CONCLUSION: COVID-19 restrictions and fear of COVID-19 infection might have discouraged patients from presenting to EDs because of skin problems; however, the easing of COVID-19 restrictions might lead to an increase in ED presentations, including non-urgent dermatological disorders. In order to reduce unnecessary use of EDs and prevent ED overcrowding, the general public should be educated about what constitutes a dermatological emergency.

Paediatric lichen sclerosus et atrophicus: A retrospective analysis of 38 paediatric patients.

BACKGROUND: Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory cutaneous disease. AIM: To evaluate the characteristics of paediatric LSA patients in Turkey. MATERIAL AND METHODS: Data for patients aged <18 years who were diagnosed with LSA by a paediatric dermatologist were retrospectively reviewed. Patient demographic characteristics, clinical features, disease duration, the vitamin D level, accompanying diseases, presence of atopy, therapeutic approach and treatment response were recorded. RESULTS: The study included 38 patients, of whom 35 (92.1%) were female and 3 (7.9%) were male. Mean age at onset of disease was 6.4 ± 3.3 years in females versus 3.1 ± 2.6 years in males. Mean diagnostic delay was 20.6 ± 28.9 months in females and 2 ± 1.7 months in males. In 28 (80%) patients the time from onset of lesions to diagnosis was ≥3 months. The majority (76.3%) of the patients were asymptomatic, whereas five had itching, two had itching and burning, and two had pain. Among the females, 12 (34.3%) and 23 (65.7%) presented with isolated extragenital and anogenital involvement + extragenital lesions, respectively. All three males had isolated extragenital involvement. The most commonly recommended treatments were topical calcineurin inhibitors and calcipotriol/betamethasone ointment. Accompanying diseases were as follows: alopecia areata (n = 2); atopic dermatitis (n = 2); vitiligo (n = 2); ulcerative colitis and juvenile idiopathic arthritis (n = 1); Hashimoto's thyroiditis (n = 1). Among the 28 patients whose vitamin D level was measured, 24 (85.7%) had vitamin D deficiency. CONCLUSION: LSA can be asymptomatic in the majority of affected children. Diagnostic delay was noted in 80% of the study's LSA patients, highlighting the lack of awareness of the condition among parents and clinicians.

Early recognition of chronic rejection in a face allotransplant patient with alopecia.

The features of chronic rejection (CR) in full-face vascularized composite allotransplantation (VCA) are not well-known. Herein, we report a full-face transplant patient that experienced two episodes of acute rejection (AR) and three episodes of AR/CR over the course of 6-years. The patient noticed a small, round patch of hair loss in his beard 9 months after the second AR episode, which occurred 21 months post-transplantation. Biopsy of the alopecic patch showed lichen-planopilaris-like features, which were suggestive of early CR. Despite an increase in immunosuppressive dosages, the alopecia progressed. Following the second and third AR/CR episodes, the alopecia became more pronounced, with the addition of hyperpigmentation as well as sclerosis and telangiectasia. The findings of multiple biopsies showed CR. Based on these findings we think that alopecia with lichen-planopilaris-like histopathological features similar to grade III AR features, particularly in hair follicles appears to be an early finding of CR in the presented patient. The findings further indicate that follicular involvement may be a significant feature of CR in VCA patients and that it can present prior to sclerosis, vasculopathy, or loss of adnexa. The present case is uniquely important because of the distinctive presentation of CR, with hair follicles clinically and histopathologically affected, leading to progressive and irreversible alopecia with lichen-planopilaris-like histopathology.

Hydroxychloroquine treatment for Alopecia Universalis: Report of six cases.

Recent reports indicate that hydroxychloroquine is a potential new treatment option for alopecia universalis; thus, we aimed to report on the safety and efficacy of hydroxychloroquine in 6 patients with refractory alopecia universalis that were treated with 400 mg/d continuously for ≥6 months. The treatment outcome was retrospectively evaluated using the Severity of Alopecia Tool (SALT), and at the end of 6 months, patients with a ≥50% decrease in the SALT score were considered as strong responders, a 5%-50% decrease as intermediate responders and a <5% decrease as non-responders. The present findings indicate that hydroxychloroquine is not an effective treatment since in 5 of the 6 patients it was discontinued at the end of 6 months due to lack of hair regrowth, whereas only a 6-year-old boy responded with a SALT score change of 8% after the 12th month.

Serial Quantiferon-TB Gold test results in 279 patients with psoriasis receiving biologic therapy.

The risk of active tuberculosis is still a concern in patients receiving biologics. To determine the risk of latent tuberculosis infection (LTBI) reactivation by Quantiferon-TB Gold (QFT) assay in psoriatic patients treated with biologics in 11 years' follow-up, along with chest radiography alterations. This retrospective study included 279 patients with plaque-type and/or pustular, or nail psoriasis who were treated with biologics, and had results for ≥2 LTBI tests. The QFT outcomes were defined according to the baseline and the follow-up QFT results; seroconversion as from negative to positive, seroreversion as from positive to negative, persistently seronegative as invariantly negative, persistently seropositive as invariantly positive, and other any result was accepted as indeterminate. Demographic features, the presence and the type of any chest X-ray abnormality was noted during the follow-up. Of 279 baseline QFT tests, the vast majority were negative (n = 193; 69%), with a less of positive (n = 86; 31%). Ten (5.2%) of 193 patients converted from negative to positive QFT status after starting biologic therapy (P < 0.001) during 11 years' follow-up. Although these 10 patients exhibited seroconversion of QFT from negative to positive, only one patient was diagnosed with active TB. There was no statistically significant difference among biologics as regards with QFT seroconversion risk (P = .09). This study showed that 5.2% of patients showed seroconversion. Annual QFT testing remains a necessary and mandatory tool to prevent further TB reactivation in psoriasis patients taking biologic therapy although only one patient was diagnosed with active TB in this cohort.