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.

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.

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.

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.

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.

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.

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.

Poikiloderma with Neutropenia, Clericuzio-Type Accompanied by Loss of Digits Due to Severe Osteomyelitis.

Poikiloderma with neutropenia (PN), Clericuzio-type is a rare autosomal recessively transmitted genodermatosis caused by biallelic mutations in the USB1 gene and is characterized by early-onset poikiloderma and chronic neutropenia. Nail dystrophy, palmoplantar hyperkeratosis, hypogonadotropic hypogonadism, and recurrent infections can be associated with the disease. Herein, we present a 27-year-old Turkish male patient newly diagnosed as PN, Clericuzio-type after confirmation of a c.531delA (p.His179MetfsX86) homozygous deleterious mutation in exon 5 of the USB1 gene. The presented case highlights the importance of genetic testing for avoiding misdiagnosis based solely on clinical findings, as well as the benefit of a multi-disciplinary diagnostic approach, as he was initially misdiagnosed as Rothmund-Thompson syndrome and subsequently diagnosed as PN, Clericuzio-type at age 27 years.

A novel mutation of keratin 5 in epidermolysis bullosa simplex with migratory circinate erythema.

Epidermolysis bullosa simplex migratory circinate erythema (EBS-Migr) is an uncommon subtype of EBS. We report a case of EBS-MIGR with a novel heterozygous pathogenic mutation in exon 9 (frameshift deletion c.1650delC) and likely benign heterozygous mutation in exon 2 (missense c.591C > A) of keratin 5. This novel pathogenic mutation in KRT5 expands the molecular spectrum of this rare subtype of EBS.

Vascular endothelial growth factor gene polymorphisms in patients with rosacea: A case-control study.

BACKGROUND: Rosacea is a chronic disease that is characterized by facial skin inflammation and vascular abnormality. Vascular endothelial growth factor (VEGF) is a potent mediator of vascular permeability and inflammation that might play a role in the pathogenesis of rosacea. OBJECTIVE: This study aimed to determine the association between VEGF gene polymorphisms and rosacea. METHODS: A case-control study design was used to compare 100 patients with rosacea and 100 age- and gender-matched control subjects in terms of VEGF polymorphisms based on polymerase chain reaction and the serum level of VEGF and VEGF receptors based on enzyme-linked immunosorbent assay. RESULTS: Heterozygous and homozygous +405C/G polymorphism of the VEGF gene was observed to increase the risk of rosacea 1.7-fold (95% confidence interval 1.2-4.2) and 2.3-fold (95% confidence interval 1.2-4.2), respectively. There was a significant positive correlation between the severity of rosacea and +405C/G polymorphism of the VEGF gene in patients with erythematotelangiectatic rosacea. LIMITATIONS: Serum VEGF and VEGF receptor levels were measured in the limited number of patients. CONCLUSION: The present findings indicate that +405C/G polymorphism of the VEGF gene increases the risk of rosacea.

Experience with oral tofacitinib in two adolescents and seven adults with alopecia areata.

Alopecia areata (AA) is a common disease that results in nonscarring hair loss. Recently, tofacitinib (TOFA) has been a novel promising therapy for AA. The aim of this study is to determine the efficacy of oral TOFA treatment for alopecia areata (AA), and alopecia universalis (AU). Data of nine patients treated with oral TOFA with either AA or AU were retrospectively evaluated. Treatment outcome, disease severity, and therapeutic response were evaluated by Severity of Alopecia Tool (SALT) scores along with regular photographic surveillance done at third and sixth months. Treatment response was established on four categories: complete response (90% change in latest SALT score), intermediate response (51-90% change), moderate response (6-50% change), and nonresponse (<5% change). Nine patients aged 13-33 years were reviewed. Four patients (44.4%) did not respond to oral TOFA therapy, three patients (33.3%) were moderate responders, 1 (11.1%) was intermediate responder, and 1 (11.1%) was complete responder at the end of 6 months. The clinical response rate (those who achieved ≥5-100% change in SALT score) was 41.4% for all patients. Most of the patients who responded to TOFA had AA instead of AU. Adverse effects were mild. The clinical response rate of TOFA seems reasonable and TOFA was well-tolerated in this cohort. However, to truly evaluate efficacy, future studies are needed to assess the efficacy, adverse effects, and durability of treatment with TOFA in randomized controlled trials.

A case of bullous pemphigoid induced by vildagliptin.

Bullous pemfigoid (BP), an autoimmune disorder, can also be induced by some medications. Vildagliptin is a new drug used to treat diabetes mellitus (DM). Recently, a few cases of vildagliptin-induced BP have been described in the literature. We report a patient with BP in which vildagliptin was thought to be as a possible causative agent. The awareness of BP development risk during gliptin therapy can prevent unnecessary usage of systemic drugs with serious side effects.

Diaper Dermatitis: A Review of 63 Children.

BACKGROUND/OBJECTIVE: Diaper dermatitis (DD) is a common infantile dermatosis with a highly variable prevalence and incidence. This study aimed to present the demographic and clinical features of babies with DD. METHODS: Data, including demographic and clinical features, obtained from DD patient forms were retrospectively analyzed. RESULTS: The study included 63 babies with DD (female: n = 35 [55.6%]; male: n = 28 [44.4%]; mean age 11.6 mos). Most of the patients (43.5%) were 0 to 6 months of age. In all, 76.3% were breastfed, of whom 31.7% were exclusively breastfed. The number of previous episodes of DD was significantly lower in breastfed babies. The most common diaper area cleansing method was wet wipes (54.1%). Diaper creams were used in 86.2% of patients. DD was severe in 22.2% of patients, moderate in 57.4%, and mild in 20.4%. Candida infection was noted in 77.4% of patients. The median number of previous episodes of DD was significantly higher in patients with Candida infection than in those without (p = 0.02). Treatment yielded greater than 50% improvement (complete and moderate response) in 59.4% of patients at the first follow-up visit (3-5 days) and 82.6% at the second follow-up visit (10 days). CONCLUSION: Most babies with DD were 0 to 6 months of age. Breastfed babies had fewer previous episodes of DD, so mothers should be encouraged to breastfeed their babies to reduce the incidence of DD. Candida infection was common; clinicians should be aware of its association with DD.