Possible microRNA-based mechanism underlying relationship between chronic spontaneous urticaria and Blastocystis.

BACKGROUND: Blastocystis spp. has been proposed as a possible cause of extraintestinal clinical signs such as urticaria pathogenesis. OBJECTIVES: The aim of this study was to investigate the differences between microRNA (miRNA) expression profiles of Chronic spontaneous urticaria (CSU) patients in the presence or absence of Blastocystis spp. as well as healthy controls. Additionally, cellular pathways which are affected in the presence of Blastocystis spp. were identified. METHODS: Twenty patients diagnosed with CSU were enrolled in the study and divided into equally two groups according to the presence of Blastocystis spp. Besides, six healthy individuals were included in the study. The expression profiles of 372 human-derived miRNAs have been investigated in serum samples from CSU patients and healthy controls with miScript miRNA PCR Array Human miRBase Profiler. RESULTS: Compared to Blastocystis-negative (BN)-CSU patients, expression of 3 miRNAs (hsa-miR-3183, hsa-miR-4469, hsa-miR-5191) were found to be downregulated by at least two-fold (p < 0.05) in Blastocystis-positive (BP)-CSU patients. Additionally, the miRNA expression profiles of six healthy individuals (n = 3 Blastocystis-positive, n = 3 Blastocystis-negative) were analyzed and it was determined that the expressions of 7 miRNAs (hsa-miR-4661-5p, hsa-miR-4666a-5p, hsa-miR-4803, hsa-miR-5587-5p, hsa-miR-4500, hsa-miR-5680, hsa-miR-382-3p) increased at least 3-fold in the serum of individuals with Blastocystis-positive compared to Blastocystis-negative subjects. Most down-regulated miRNAs, in BP-CSU patients, affect cell adhesion molecules (CAMs), and signaling pathways therefore, Blastocystis spp. presence may influence the clinical presentation of urticaria by leading to unbalanced immunity. In addition, Blastocystis spp. presence may be influenced TGF- ß signaling pathway through altered miRNAs and may be laying the groundwork for the development of CSU in healthy individuals. CONCLUSIONS: As a consequence, this is the first report to show that the miRNA expression profile is affected by the presence of Blastocystis spp. Further miRNA-based studies are needed in order to enlighten the exact underlying molecular mechanisms of the relationship between Blastocystis spp. and CSU.

Clonal B-cell proliferations developing in the background of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder: A case series.

Clonal B-cell proliferations and B-cell lymphomas may co-occur in the background of follicular helper T-cell (TFH)-derived lymphomas, most associated with EBV, which has been a well-known fact for many years in the prototypical entity "TFH lymphoma, angioimmunoblastic-type." Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (CD4+ PCSM-LPD) is also a TFH-derived clonal proliferation. We searched the archives and identified four cases of CD4+ PCSM-LPD with accompanying clonal B-cell proliferation (one of which showed EBER positivity), and one longstanding case of CD4+ PCSM-LPD, in the background of which a B-cell lymphoma had developed. These five cases broaden experience on CD4+ PCSM-LPD with accompanying B-cell proliferations and also support routine evaluation of these cases with EBV in situ hybridization, to better determine whether or not there is an association with EBV.

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.

Comparison of rituximab and intravenous immunoglobulin in the treatment of autoimmune bullous diseases: Real-life data from a single centre.

BACKGROUND/AIM: Rituximab (RTX) and intravenous human immunoglobulin (IVIG) have been shown to be effective in the treatment of autoimmune bullous diseases (ABD), mainly pemphigus vulgaris (PV). The present study aimed to assess the clinical response of patients with ABD, mainly PV to RTX, IVIG and combined regimen of both. Whether adding IVIG to RTX therapy affects the achievement of complete remission off therapy (CR off), reduces time to CR off, time to steroid cessation, and decreases relapse rate was also investigated. METHODS: Data of 33 patients with ABD [PV (93.9%)], including clinical response to treatment, steroid cessation time, time to CR off and relapse, were recruited from medical charts. RESULTS: CR off and relapse rate, mean time to CR off and relapse was 86.7% (n = 13) vs 60.0% (n = 6) and 53.3% (n = 8) vs 40% (n = 4), 12.77 ± 9.30 vs 11.25 ± 13.40 and 24.1 ± 16.7 vs 13.0 ± 3.6 months in RTX and combination group, respectively. Older age (P = .005), younger age at the time of diagnosis (P = .004), lesser disease duration to the initiation of RTX (P = .004), lesser BMI (P = .026) and female gender (P = .037) were associated factors with CR off. CONCLUSION: Adding IVIG to RTX did not increase CR off rates; it also did not decrease time to CR off, time to steroid cessation, relapse rates and did not increase time to relapse. Patient and disease characteristics, including age, younger age at the time of diagnosis, lesser disease duration before RTX treatment, lesser BMI and female gender, are factors associated with CR off.

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.

Epidermodysplasia Verruciformis After Hematopoietic Stem Cell Transplantation in a Patient With Severe Combined Immunodeficiency Syndrome.

ABSTRACT: Epidermodysplasia verruciformis (EV) is a rare dermatologic disorder that is characterized by skin-colored-to-light brown flat, discrete or confluent papules resembling verruca plana. EV is divided into 2 forms: a classical genetic form and an acquired form. Classical genetic EV is caused by mutations in EVER1 and EVER2 genes. Acquired EV develops in immunocompromised patients such as HIV-positive patients and transplant recipients. Patients with a prior history of hematopoietic stem cell transplantation (HSCT) have tendency to develop generalized verrucosis. We report an extraordinary case of disseminated epidermodysplasia verruciformis seen in a 7-year-old boy diagnosed with severe combined immunodeficiency syndrome who had undergone HSCT. He had plane, brown papules involving his face, forearms, neck, anterior chest, nape, back, and knees. Cutaneous biopsy showed typical characteristic findings of EV: large cells with gray-blue cytoplasm and keratohyaline granules of different sizes in the granular and spinous layers. Herein, we present an unusual case of disseminated EV in a HSCT patient with typical histopathologic findings and treatment options.

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.

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.

Long-term effects of omalizumab on peripheral blood cells and C-reactive protein levels in patients with chronic spontaneous urticaria.

Omalizumab's mechanism of action is not well-understood yet despite its strong therapeutic efficacy in chronic spontaneous urticaria (CSU). To determine the overall effect of omalizumab on peripheral blood cell counts and serum C-reactive protein levels (sCRP) during a 1-year follow-up in patients with CSU. Data of 74 patients (male/female: 20/54) were reviewed from medical charts. Leucocyte counts, percentages of peripheral blood cells(lymphocyte, monocyte, neutrophil [PPBN], eosinophil, basophil [PPBB]) and sCRP were recorded at baseline, 3rd, 6th, 12th months of omalizumab treatment. Although a dramatic increase in the mean PPBB (±SD) was observed at the 3rd month, PPBB (%) gradually decreased after the 3rd month (PPBB: 0.38 ± 0.21 [baseline] vs. 0.59 ± 0.3 [3rd month], p = .002). However, 12th month PPBB remained higher than baseline (PPBB:0.38 ± 0.21 [baseline] vs. 0.46 ± 0.27 [12th month], p = .03). A dramatic decrease in the mean PPBN (%) was noticed within the first 3 months (PPBN:62.85 ± 8.97 [baseline] vs. 58.37 ± 9.07 [3rd month], p = .04), and 12th month PPBN remained lower than baseline values (PPBN: 62.85 ± 8.97 [baseline] vs. 60.31 ± 8.02 [12th month], p = .045).Mean sCRP (mg/dL) decreased rapidly within the first 3 months (sCRP: 1.09 ± 1.53 [baseline] vs. 0.56 ± 0.45 [3rd month], p = .17) and 12th month sCRP still remained lower than baseline levels (sCRP: 1.09 ± 1.53 [baseline] vs. 0.83 ± 1.06 [12th month], p = .01). Omalizumab substantially increases PPBB,and reduces PPBN accompanied by a reduction in sCRP especially in the first 3 months; however, these effects may continue in the long-term. The alterations in peripheral blood cell ratios and sCRP may contribute to the therapeutic effect of omalizumab in CSU.

A Case of Plasma Cell Granuloma Located on the Gingiva.

Plasma cell granuloma (PCG) is an uncommon benign tumor of unknown etiology, primarily located in the lungs. We report a case of PCG on the gingiva mimicking benign and malignant tumors in a 56-year-old woman. Histopathological examination revealed a relatively sharp circumscribed inflammatory cell infiltration under the mucosa-containing plasma cells, predominantly those including Russell bodies. Plasma cells are stained by CD138 immunohistochemistry. Polyclonal status of the lesion was confirmed by kappa and lambda light chaining. The typical histopathological and immunohistochemical findings in combination with the clinical features were consistent with PCG, about which the literature reports very few cases.