Autosomal recessive congenital ichthyosis: CERS3 mutations identified by a next generation sequencing panel targeting ichthyosis genes

There are at least 38 mutant genes known to be associated with the ichthyosis phenotypes, and autosomal recessive congenital ichthyosis (ARCI) is a specific subgroup caused by mutations in 13 different genes. Mutations in some of these genes, such as CERS3 with only two previous reports, are rare. In this study, we identified mutations in candidate genes in consanguineous families with ARCI with a next generation sequencing (NGS) array that incorporates 38 ichthyosis associated genes. We applied this sequencing array to DNA from 140 ichthyosis families with high prevalence of consanguinity. Among these patients we identified six distinct, previously unreported mutations in CERS3 in six Iranian families. These mutations in each family co-segregated with the ichthyosis phenotype. The patients demonstrated collodion membrane at birth, acrogeria, generalized scaling, and hyperlinearity of the palms and soles. The presence of a significant percentage of CERS3 mutations in our cohort depicts a marked difference between the etiology of ichthyoses in genetically poorly characterized regions and well-characterized western populations. Also, it shows that rare alleles are more prevalent in the gene pool of consanguineous populations and emphasizes the importance of these population studies for better understanding of ichthyosis pathogenesis

Genome-wide single nucleotide polymorphism-based autozygosity mapping facilitates identification of mutations in consanguineous families with epidermolysis bullosa

Autozygosity mapping (AM) is a technique utilised for mapping homozygous autosomal recessive (AR) traits and facilitation of genetic diagnosis. We investigated the utility of AM for the molecular diagnosis of heterogeneous AR disorders, using epidermolysis bullosa (EB) as a paradigm. We applied this technique to a cohort of 46 distinct EB families using both short tandem repeat (STR) and genome-wide single nucleotide polymorphism (SNP) array-based AM to guide targeted Sanger sequencing of EB candidate genes. Initially, 39 of the 46 cases were diagnosed with homozygous mutations using this method. Independently, 26 cases, including the seven initially unresolved cases, were analysed with an EB-targeted next-generation sequencing (NGS) panel. NGS identified mutations in five additional cases, initially undiagnosed due to the presence of compound heterozygosity, deep intronic mutations or runs of homozygosity below the set threshold of 2 Mb, for a total yield of 44 of 46 cases (95.7) diagnosed genetically. © 2018 John Wiley & Sons Ltd

Lichen planus and Hepatitis C: a case-control study

BACKGROUND: The association of lichen planus with hepatitis C (HCV) has been widely reported in the literature. However, there are wide geographical variations in the reported prevalence of HCV infection in patients with lichen planus. This study was conducted to determine the frequency of hepatitis C in Iranian patients with lichen planus at Razi hospital, Tehran. METHODS: During the years 1997 and 1998, 146 cases of lichen planus, 78 (53.1%) women and 69 (46.9%) men were diagnosed. They were diagnosed on the basis of the usual clinical features and, if necessary, typical histological findings. The patients were screened for the presence of anti-HCV antibodies by third generation ELISA and liver function tests. We used the results from screening of blood donors for anti HCV (carried out by Iranian Blood Transfusion Organization) for comparison as the control group. RESULTS: Anti-HCV antibodies were detected in seven cases (4.8%). This was significantly higher than that of the blood donors' antibodies (p < 0.001). The odds ratio was 50.37(21.45–112.24). A statistically significant association was demonstrated between erosive lichen planus and HCV infection. Liver function tests were not significantly different between HCV infected and non-infected patients. CONCLUSION: HCV apears to have an etiologic role for lichen planus in Iranian patients. On the other hand, liver function tests are not good screening means for HCV infection

Updated S2 K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV).

BACKGROUND Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo-like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life. OBJECTIVES AND METHODOLOGY The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence-based or rely on expert opinion. The degree of consent among all task force members was included. RESULTS Treatment depends on the severity of BP and patients' comorbidities. High-potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B-cell-depleting therapy and intravenous immunoglobulins may be considered in treatment-resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations. CONCLUSIONS The guidelines for the management of BP were updated. They summarize evidence- and expert-based recommendations useful in clinical practice

Tongue lesions in psoriasis: a controlled study

BACKGROUND: Our objective was to study tongue lesions and their significance in psoriatic patients. METHODS: The oral mucosa was examined in 200 psoriatic patients presenting to Razi Hospital in Tehran, Iran, and 200 matched controls. RESULTS: Fissured tongue (FT) and benign migratory glossitis (BMG) were the two most frequent findings. FT was seen more frequently in psoriatic patients (n = 66, 33%) than the control group (n = 19, 9.5%) [odds ratio (OR): 4.69; 95% confidence interval (CI): 2.61–8.52] (p-value < 0.0001). BMG, too, was significantly more frequent in psoriatic patients (28 cases, 14%) than the control group (12 cases, 6%) (OR: 2.55; 95% CI: 1.20–5.50) (p-value < 0.012). In 11 patients (5.5%), FT and BMG coexisted. FT was more frequent in pustular psoriasis (7 cases, 53.8%) than erythemato-squamous types (56 cases, 30.4%). On the other hand, the frequency of BMG increased with the severity of psoriasis in plaque-type psoriasis assessed by psoriasis area and severity index (PASI) score. CONCLUSIONS: Nonspecific tongue lesions are frequently observed in psoriasis. Further studies are recommended to substantiate the clinical significance of these seemingly nonspecific findings in suspected psoriatic cases

Original article title: "Comparison of therapeutic efficacy of topical corticosteroid and oral zinc sulfate-topical corticosteroid combination in the treatment of vitiligo patients: a clinical trial"

<p>Abstract</p> <p>Background</p> <p>Vitiligo is the most prevalent pigmentary disorder which occurs worldwide, with an incidence rate between 0.1-4 percent. It is anticipated that the discovery of biological pathways of vitiligo pathogenesis will provide novel therapeutic and prophylactic targets for future approaches to the treatment and prevention of vitiligo. The purposes of this study were evaluating the efficacy of supplemental zinc on the treatment of vitiligo.</p> <p>Methods</p> <p>This randomized clinical trial was conducted for a period of one year. Thirty five patients among 86 participants were eligible to entrance to the study. The patients in two equal randomized groups took topical corticosteroid and combination of oral zinc sulfate-topical corticosteroid.</p> <p>Results</p> <p>The mean of responses in the corticosteroid group and the zinc sulfate-corticosteroid combination group were 21.43% and 24.7%, respectively.</p> <p>Conclusion</p> <p>Although, the response to corticosteroid plus zinc sulfate was more than corticosteroid, there was no statistically significant difference between them. It appeared that more robust long-term randomized controlled trials on more patients, maybe with higher doses of zinc sulfate, are needed to fully establish the efficacy of oral zinc in management of vitiligo.</p> <p>Trial Registration</p> <p>chiCTRTRC10000930</p

International bullous diseases group: consensus on diagnostic criteria for epidermolysis bullosa acquisita

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a complex autoimmune bullous disease disease with variable clinical presentations and multiple possible diagnostic tests, making an international consensus on the diagnosis of EBA essential. ----- OBJECTIVES: To obtain an international consensus on the clinical and diagnostic criteria for EBA. ----- METHODS: The International Bullous Diseases Group (IBDG) met three times to discuss the clinical and diagnostic criteria for EBA. For the final voting exercise, 22 experts from 14 different countries voted on 50 different items. When > 30% disagreed with a proposal, a discussion was held and re-voting carried out. ----- RESULTS: In total, 48 of 50 proposals achieved consensus after discussion. This included nine diagnostic criteria, which are summarized in a flow chart. The IBDG was unable to determine one procedure that would be applicable worldwide. A limitation of the study is that differential diagnosis of bullous systemic lupus erythematosus has not been addressed. ----- CONCLUSIONS: This first international consensus conference established generally agreed-upon clinical and laboratory criteria defining the clinical classification of and diagnostic testing for EBA. Holding these voting exercises in person with the possibility of discussion prior to voting has advantages in reaching consensus over Delphi exercises with remote voting

Evaluation of Oral Mucosal Lesions in 598 Referred Iranian Patients

The mucosal membrane of the oral cavity displays at times classical developmental lesions considered to be variations of normal structures rather than having disease characteristics. Of these lesions leukoedema, Fordyce granules, geographic-, fissured- and hairy tongue, median rhomboid glossitis and lingual varices were studied in 598 patients referred to the School of Dentistry, Tehran, Iran. The prevalence was studied in relation to age, gender, occupation, education, smoking habits, general health, addictions and or drug therapies. Oral developmental lesions were seen in 295 patients (49.3%). Only Fordyce granules (27,9%), fissured tongue (12,9%), leukoedema (12,5%) and hairy tongue (8,9%) had enough cases for statistical analysis. Three of these lesions increased with age but not fissured tongue. All were more common in men. After adjusting for age, the parameters education, occupation and complaints upon referral had little influence on the prevalence of the lesions. Fewer Fordyce granules were seen in oral mucosa of smoking men. Leukoedema and hairy tongue were significantly associated with smoking, leukoedema with diabetes mellitus. We conclude that there was a highly significant association between these oral lesions and age, gender and smoking. Few significant associations were found between oral lesions and general diseases