Mutation update: The spectra of PLEC sequence variants and related plectinopathies.

Plectin, encoded by PLEC, is a cytoskeletal linker of intermediate filaments expressed in many cell types. Plectin consists of three main domains that determine its functionality: the N-terminal domain, the Rod domain, and the C-terminal domain. Molecular defects of PLEC correlating with the functional aspects lead to a group of rare heritable disorders, plectinopathies. These multisystem disorders include an autosomal dominant form of epidermolysis bullosa simplex (EBS-Ogna), limb-girdle muscular dystrophy (LGMD), aplasia cutis congenita (ACC), and an autosomal recessive form of EBS, which may associate with muscular dystrophy (EBS-MD), pyloric atresia (EBS-PA), and/or congenital myasthenic syndrome (EBS-MyS). In this study, genotyping of over 600 Iranian patients with epidermolysis bullosa by next-generation sequencing identified 15 patients with disease-causing PLEC variants. This mutation update analyzes the clinical spectrum of PLEC in our cohort and in the literature and demonstrates the relationship between PLEC genotype and phenotypic manifestations. This study has integrated our seven novel PLEC variants and phenotypic findings with previously published data totaling 116 variants to provide the most complete overview of pathogenic PLEC variants and related disorders.

Rhabdomyomatous mesenchymal hamartoma presenting as telangiectasia in a 57-year-old man.

Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare congenital malformation of the dermis and subcutaneous tissue. Usually, RMH occurs in the midline of the face and neck region. We described a case of RMH presenting as telangiectasia in a 57-year-old man with a history of pityriasis lichenoides chronicus. Histopathological examination revealed a subepidermal haphazard proliferation of striated muscular tissue perpendicular to the epidermis. These bundles of striated muscular tissue were admixed with adnexal structures. The diagnosis was consistent with RMH. RMH is more common in the neonatal period or in young children, but we should consider it as part of a differential diagnosis in older adults as well.

High-sensitivity C-reactive protein as a biomarker in detecting subclinical atherosclerosis in psoriasis.

Psoriasis is known to be associated with increased risk of cardiovascular diseases. High-sensitivity C-reactive protein (hs-CRP) is a marker of inflammation and an independent risk factor for atherosclerosis. We aimed to assess the correlation between hs-CRP and subclinical atherosclerosis in psoriatic patients. In 60 patients with moderate to severe psoriasis and 60 age- and gender matched healthy controls, we evaluated the serum hs-CRP level and mean intima-media thickness of the common carotid artery (MIMT-CCA). Psoriatic patients had higher levels of hs-CRP (median, 2.25 mg/L; IQR, 0.98-3.80; and range, 0.29-11.60) than did those in the control group (median, 1.03 mg/L; IQR, 0.36-2.15; and range, 0.10-3.35). Psoriatic patients also had higher mean MIMT (0.74 ± 0.19 and 0.54 ± 0.12, respectively, and P < .0001) compared with healthy subjects. The serum level of hs-CRP was significantly correlated with MIMT (P < .0001). Our results indicate that psoriatic patients have a higher risk of subclinical atherosclerosis and hs-CRP may be a useful marker for future risk of cardiovascular diseases in these patients. So, not only does anti-inflammatory drugs play a key role in the treatment of psoriasis, but also they may reduce the risk of cardiovascular diseases by decreasing level of inflammatory markers including hs-CRP.

Can serum level of N-terminal pro B-type natriuretic peptide be used in patients with psoriasis as a predictor of cardiovascular disease?

Past studies have reported associations between psoriasis, metabolic syndrome, and atherosclerotic cardiovascular disease. According to studies, N-terminal pro B-type natriuretic peptide (NT-proBNP) is a useful screening test for cardiac disease. We examined the serum NT-proBNP level in patients with psoriasis and compared them with nonpsoriatic healthy control subjects. Sixty-one patients with psoriasis were enrolled, along with 61 age, sex, and body mass index (BMI) matched control subjects. In both groups, NT-proBNP serum levels and lipid profile parameters were investigated. Means and 95% confidence intervals (CIs) were reported. The median serum concentration of NT-proBNP was higher in psoriatic patients than the control group (26.67 [interquartile range (IQR): 15.15-43.03 and range: 5-250] vs. 17.45 [IQR: 12.35-20.80 and range: 5-45.09, p < 0.0001). NT-proBNP serum level in psoriatic arthritis patients (11%; 55.6 ± 25.7 pg/mL, 95% CI: 31.9-79.4 pg/mL) was higher than psoriasis patients without arthritis (35.8 ± 40.6 pg/mL, CI: 24.7-46.9, p < 0.001). NT-proBNP levels were also positively correlated with BMI, lipid profile, and disease duration. NT-proBNP is elevated in patients with psoriasis, consistent with the high risk of cardiovascular disease associated with psoriasis.

Inoperable infiltrative basal cell carcinoma successfully treated with vismodegib.

Basal cell carcinoma (BCC) is the most common skin cancer but usually has a good prognosis. However, there is a subset of BCC cases with a less favorable prognosis. For patients with locally advanced, recurrent or metastatic BCCs who are not suitable for surgery or radiotherapy, small-molecule drug inhibitors of hedgehog pathway are a new therapeutic opportunity. Here, we present a case of infiltrative BCC with multiple recurrences. Wide excision with reconstructive plastic surgery was performed initially with adjuvant radiotherapy. Due to multiple recurrences afterward, radiotherapy, topical imiquimod and oral itraconazole were used but were not effective. Finally, the patient was treated with vismodegib which led to a complete response. Moreover, the patient's symptoms due to the locally diffused cancer resolved.

Clinical applications of topical ivermectin in dermatology.

Ivermectin (IVM) is a broad-spectrum anti-parasitic drug with significant anti-inflammatory properties. The emergence of treatment resistance to lindane, permethrin, and possibly malathion complicates the global strategy for management of common parasitic skin diseases such as scabies and head lice. In this regard. IVM has been safely and effectively used in the treatment of these common human infestations. In addition, IVM may be useful in inflammatory cutaneous disorders such as papulopustular rosacea where demodex may play a role in pathogenesis. Herein, we review the current applications of topical IVM in dermatology.

Multiple COVID reinfections in a vaccinated psoriatic patient receiving adalimumab.

Currently, psoriasis patients are advised to follow their standard therapeutic regimen, and are advised to be vaccinated against Covid-19. However, the data about the antibody responses, induced by the various kinds of SARS-CoV-2 vaccines in psoriasis patients who require systemic immunosuppressive treatment is scant. In this case report, we describe antibody responses induced by COVID-19 vaccine, in a 26-year-old male patient with psoriasis being treated with anti-TNF biotherapy, adalimumab biosimilar every two weeks. The patient was vaccinated against COVID-19, according to the national protocol. He experienced three episodes of symptomatic COVID-19. His first and second exposures did not result in antibody production. After the third episode of COVID-19, The SARS-CoV-2 anti-spike antibody (IgG) was more than 100 Ru/mL (ELISA; ≥8 Ru/mL is considered positive), and SARS-CoV-2 neutralizing antibody (total) was more than 40 micg/mL (ELISA; ≥2.5 micg/mL is considered positive). This is the first case with weak antibody response to vaccination and multiple episodes of COVID infection in a psoriatic patient with adalimumab biosimilar. However, we cannot assume causality due to the treatment.

A case of severe psoriatic erythroderma with COVID-19.

COVID-19 caused by the SARS-CoV-2, became pandemic very quickly. Management of severe dermatologic disorders in patients who require systemic immunosuppressive treatment is a major concern in COVID-19 pandemic era. Here, we report a 45-year-old homeless addicted male with second flare of psoriatic erythroderma and positive PCR test for COVID 19. His first attack occurred two months earlier, when he was screened for SARS-CoV-2 before admission which all evaluations showed nagative results. The patient was treated and relatively controlled with cyclosporine and therefore he was discharged. During this interval, he not only discontinued his medication, but also became SARS-CoV-2 positive. It seems that both factors participated in flare of his erythroderma.

Soluble biomarkers for diagnosis, monitoring, and therapeutic response assessment in psoriasis.

BACKGROUND: Psoriasis is an inflammatory disease associated with multiple comorbidities. Biomarkers for the assessment of psoriasis, its associated comorbidities, and the therapeutic response are not well characterized. A number of possible biomarkers for the diagnosis and monitoring of psoriasis have been proposed. PURPOSE: To assess potential biomarkers for diagnosis of psoriasis, its associated comorbidities and response to treatment. METHODS: We investigated medical databases from 2000 to 2021 and assessed relevant research. In this review, we evaluated the important biomarkers to help predict potential risk of psoriasis and disease activity (Beta-defensin-2, VEGF, Lipocalin-2, and YKL-40) and its possible inflammatory-related comorbidities like cardiovascular diseases (hs-CRP, GlycA, Psoriasin, IL-18, NT-proBNP, and Adipokines). In addition, we described the potential biomarkers for psoriatic arthritis (CXCL10, S100A8 and S100A9, and MicroRNA) and related manifestations such as enthesitis. Finally, we discussed novel markers for monitoring the response to specific treatments (HLA-C 06, PLC, TARC, NLR, and PLR) as well as potentially useful biomarkers for evaluation of therapy-associated adverse events (liver fibrosis-related markers). CONCLUSION: A wide range of genetic, tissue, and serum markers have been investigated in psoriasis; however, most of them are not used in routine clinical practice; and thorough physical examination along with the appropriate application of clinical scoring systems like Psoriasis Area and Severity Index score are still of particular importance.

Fox-Fordyce disease exacerbated by hyperhidrosis.

Fox-Fordyce disease is an uncommon disorder primarily affecting postpubertal females. It is characterized by intensely pruritic, papular eruptions in apocrine-gland bearing regions. Rarity and scant literature have resulted in a lack of definitive treatment options or pathognomonic diagnostic indicators. We report a 16-year-old boy with typical findings of Fox-Fordyce disease including numerous, grouped, rounded (1-3 mm), skin-colored papules confined to the axillary and periareolar areas, bilaterally. These lesions started before puberty, and were exacerbated by hyperhidrosis.

Punctate porokeratotic keratoderma.

We report a 29-year-old woman with multiple small keratotic papules on her lateral fingers and first and second toes. Histopathology revealed a compact parakeratotic column with a poorly developed stratum granulosum, indicating punctate porokeratotic keratoderma (PPK). We discuss demographics, etiology, histopathology, differential diagnosis, and treatment of this disease.

Ocular findings in patients with psoriasis: is it related to the side effects of treatment or to psoriasis itself? A case-control study.

Objectives: To assess ocular abnormalities in psoriatic patients (new-cases versus patients under treatment) in comparison with healthy controls.Methods: A total of 200 psoriatic patients and 100 healthy controls were enrolled in this prospective, observational study. The demographic data of the individuals were recorded. Dermatological and ophthalmologic examinations were conducted; ocular surface disease index (OSDI), Schirmer's and tear break-up time (TBUT) values were also measured.Results: The mean values of TBUT and Schirmer's tests in patients were significantly lower than the controls and significantly higher scores of OSDI were observed among patients compared to the controls (p < .0001); dry eye disease was more frequent in the patients than the healthy subjects (p = .001). Other ocular findings including cataract and uveitis were not significantly different between the groups. Although no significant differences were found between the ocular findings of new cases and patients under treatment, ocular findings in cases under treatment were associated with the type of treatment and more frequent in those treated with methotrexate, followed by acitretin and biologic drugs.Conclusions: Ocular surface problems in psoriatic patients are more common than previously thought; in addition to the role of treatment modalities, psoriasis itself and a probable systemic inflammation may play an important role.Key PointsThere are limited case-control studies about ocular manifestations in psoriasis and also its pathogenesis is not yet clear.This study shows that ocular surface problems in psoriatic patients are higher than healthy subjects; in addition to the role of treatment modalities, psoriasis itself and a probable systemic inflammation may play a pivotal role.Regular ophthalmological evaluations are recommended in psoriatic patients especially those with more severe and chronic form of the disease, to prevent any complications.

Concomitant Hodgkin's lymphoma and atopic dermatitis in a child with Celiac disease.

Celiac disease is an autoimmune disease associated with increased risk of several diseases including a variety of malignancies. This is the first report of the concomitance of atopic dermatitis and Hodgkin's lymphoma in a child with celiac disease. Here, we report an 11-year-old boy with chronic diarrhea, glossitis, chronic dermatitis, and megaloblastic anemia who later developed Hodgkin's lymphoma.

Considerable variation among Iranian dermatologists in the knowledge and attitudes regarding the use of biologic agents to manage psoriasis.

BACKGROUND: Many international guidelines have been introduced with the aim of helping clinicians by providing evidence-based advice for the prescription of biologic therapies in psoriasis. Because no local or regional guideline is available, the treatment of psoriasis with biologics is mainly based on clinical experiences regarding the international guideline among Iranian dermatologists. OBJECTIVE: To assess the knowledge and attitudes among Iranian specialists regarding the use of biologic agents to manage psoriasis. METHODS: Data were collected using an electronic questionnaire specifically designed for this study based on a review of the literature. The designed Google form consisted of 53 multiple choice questions divided into five sections. RESULTS: A total of 111 dermatologists agreed to participate in this study. There was considerable variation among the responding dermatologists in terms of their knowledge and attitudes toward biologics. There were some significant associations between knowledge and attitudes of dermatologists toward biologics and their personal and professional characteristics. CONCLUSIONS: More comprehensive educational approaches, both in the dermatology residency and postgraduation periods, could be very beneficial to promote the knowledge and attitude of the dermatologist in treating psoriasis with biologic agents. This study could be one of the first steps to develop a country-based or a region-based plan to improve the knowledge and attitude among dermatologists regarding the use of biologic drugs in psoriasis and possibly to reach a better status to prescribe these agents in the management of psoriasis.

Pentoxifylline: a drug with wide spectrum applications in dermatology.

Pentoxifylline (PTX) is a methylxanthine derivative with a variety of anti-inflammatory effects. Currently, PTX is approved by the Food and Drug Administration for the treatment of intermittent claudication, but studies have shown that it has a variety of physiological effects at the cellular level, which may be important in treating a diverse group of diseases.

Electrocardiographic changes after high-dose corticosteroid pulse therapy in pemphigus patients.

PURPOSE: The objective of the current study was to evaluate the effect of intravenous methylprednisolone pulse therapy on myocardial repolarization alterations, especially QT dispersion in anticipation of cardiovascular risks in patients with pemphigus vulgaris. METHODS: The current study is a prospective-controlled study on the electrocardiographic changes after methylprednisolone pulse therapy in 50 patients with pemphigus vulgaris. RESULTS: A total of 50 patients (28 female and 22 male) were included in our study. The mean heart rate was significantly higher in male patients both before (92 ± 10.80 versus 82.75 ± 12.01 ms) and after pulse therapy (102.73 ± 14.26 versus 91.07 ± 15.02 ms) (p value < .01). The value of heart rate was significantly greater after receiving steroid pulse therapy. Corrected QT dispersion before pulse therapy was 19.92 ± 8.2 ms that increased to 40.68 ± 18.12 ms after treatment (p value < .001). CONCLUSION: Our study shows that there is a relationship between pulse steroid infusion and increased predisposition to the occurrence of cardiac arrhythmias. QT dispersion could be a good marker to assess this risk in these patients.

Nodular colloid milium mimicking keloid.

Colloid milium is a rare cutaneous deposit disease that usually presents clinically by the development of yellowish translucent or flesh-colored papules or plaques on sun-exposed skin. Histologically, it is characterized by the presence of colloid in the dermal papillae. In this case report, we present a 52-year-old man who presented with a nodule on his upper lip that mistakenly was diagnosed and treated as keloid.

A novel mutation in ST14 at a functionally significant amino acid residue expands the spectrum of ichthyosis-hypotrichosis syndrome.

BACKGROUND: Mutations in the ST14 gene, encoding the serine protease matriptase, have been associated with ichthyosis-hypotrichosis syndrome (IHS), a Mendelian disorder with skin and hair manifestations which include, in addition to ichthyosis and hypotrichosis, hypohidrosis and follicular atrophoderma. However, the understanding of the specific consequences of mutations in ST14 on the development of this syndrome is incomplete. RESULTS: Using a targeted next-generation sequencing array of 38 ichthyosis-associated genes on a large cohort of 180 ichthyosis patients from a primarily consanguineous background, a previously unreported homozygous p.Asp482Asn mutation in ST14 was identified in a patient with IHS. This mutation affects an essential site within a ligand-binding domain of matriptase. Comparison with previous reports of IHS allowed further delineation of the phenotype of IHS in correlation with mutations present in these patients. Histological and ultrastructural analysis of skin and hair identified novel features in this disorder. CONCLUSIONS: This study correlates genotypic and phenotypic features of the rare disorder, IHS, expands the spectrum of pathology associated with the disorder, and provides clinical evidence of the importance of the Asp482 amino acid, previously shown to have an essential role in matriptase activation.