Rituximab in the Treatment of Epidermolysis Bullosa Acquisita: A Systematic Review.

Objective: Epidermolysis bullosa acquisita (EBA) is a rare dermatosis of the mucous membrane and/or skin. Employing biologic treatment modalities, specifically rituximab (RTX), have become pivotal measure in treating patients with blistering diseases. This study aims to summarize the current evidence on the safety and efficacy of RTX in EBA. Methods: An extensive search was performed in MEDLINE/PubMed, Embase, Scopus, and Web of Science databases until the end of August 19th, 2023. Two independent reviewers screened the papers, and collected data. Two hundred thirty-three studies were screened using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results: Thirty-one studies were enrolled. The most common reason of RTX administration in patients with EBA was recalcitrant diseases. Clinical response and disease remission was recorded as 92.7 percent (63 patients) and 73.8 percent (45 patients) of the patients, respectively. A relapse rate of 39.5 percent (15 patients) in the mean follow-up of 23.0 months was reported in the studies. Of the patients, 28.2 percent (11 patients) experienced RTX-related side events, mostly mild and transient infusion reactions. Conclusion: The results of this systematic review demonstrated that RTX is safe and effective in patients with EBA. This biological treatment modality can be routinely used in managing EBA.

Tracing human papillomavirus in skin and mucosal squamous cell carcinoma: a histopathological retrospective survey.

Worldwide, squamous cell carcinoma (SCC) incidence is rising. The literature debates the human papillomavirus (HPV)'s role in cutaneous SCC development. We examined HPV histopathology in SCC samples in this study. Retrospective study at tertiary referral skin center in 2020. Histopathological features of HPV, including koilocytosis, hyperkeratosis, acanthosis, hypergranulosis, parakeratosis, solar elastosis, papillomatosis, and tumor grade, were examined in SCC specimens. Two dermatopathologists independently reevaluated all samples. We examined 331 SCC cases (male:female ratio = 3.9:1). The mean age was 68.1, with 15.1 standard deviation. Lesions were most common on the face (40.5%), scalp (22.7%), and extremities (20.8%). Koilocytes were found in 50 (15.1%) lesions. Nail (38.1%, p=0.007), oral cavity (36.8%, p=0.014), and genitalia (60.0%, p=0.026) lesions had higher koilocytosis rates. SCCs were found in 6.6% of specimens, but in situ tumors had the highest koilocytosis (64.7%), significantly higher than other grades (p<0.001). SCC pathology often shows HPV and specific koilocyte histopathology. Well-differentiated SCC has a stronger association with nail, oral, and genital lesions.

What is novel in the clinical management of pemphigus vulgaris?

INTRODUCTION: Pemphigus, an uncommon autoimmune blistering disorder affecting the skin and mucous membranes, currently with mortality primarily attributed to adverse reactions resulting from treatment protocols. Additionally, the existing treatments exhibit a notable recurrence rate. The high incidence of relapse and the considerable adverse effects associated with treatment underscore the imperative to explore safer and more effective therapeutic approaches. Numerous potential therapeutic targets have demonstrated promising outcomes in trials or preliminary research stages. These encompass anti-CD-20 agents, anti-CD-25 agents, TNF-α inhibition, FAS Ligand Inhibition, FcRn inhibition, BAFF inhibition, Bruton's tyrosine kinase (BTK) inhibition, CAAR T Cells, JAK inhibition, mTOR inhibition, abatacept, IL-4 inhibition, IL-17 inhibition, IL-6 inhibition, polyclonal Regulatory T Cells, and autologous hematopoietic stem cell transplantation. AREAS COVERED: The most significant studies regarding the impact and efficacy of the mentioned treatments on pemphigus were meticulously curated through a comprehensive search conducted on the PubMed database. Moreover, the investigations of interest cited in these studies were also integrated. EXPERT OPINION: The efficacy and safety profiles of the other treatments under discussion do not exhibit the same level of robustness as anti-CD20 therapy, which is anticipated to endure as a critical element in pemphigus treatment well into the foreseeable future.

DNA repair-related heritable photosensitivity syndromes: Mutation landscape in a multiethnic cohort of 17 multigenerational families with high degree of consanguinity.

Inherited photosensitivity syndromes are a heterogeneous group of genetic skin disorders with tremendous phenotypic variability, characterized by photosensitivity and defective DNA repair, especially nucleotide excision repair. A cohort of 17 Iranian families with heritable photosensitivity syndromes was evaluated to identify their genetic defect. The patients' DNA was analyzed with either whole-exome sequencing or RNA sequencing (RNA-Seq). The interpretations of the genomic results were guided by genome-wide homozygosity mapping. Haplotype analysis was performed for cases with recurrent mutations. RNA-Seq, in addition to mutation detection, was also utilized to confirm the pathogenicity. Thirteen sequence variants, including six previously unreported pathogenic variants, were disclosed in 17 Iranian families, with XPC as the most common mutated gene in 10 families (59%). In one patient, RNA-Seq, as a first-tier diagnostic approach, revealed a non-canonical homozygous germline variant: XPC:c.413-9 T > A. The Sashimi plot showed skipping of exon 4 with dramatic XPC down-expression. Haplotype analysis of XPC:c.2251-1 G>C and XPC:1243 C>T in four families showed common haplotypes of 1.7 Mb and 2.6 Mb, respectively, denoting a founder effect. Lastly, two extremely rare cases were presented in this report: a homozygous UVSSA:c .1990 C>T was disclosed, and ERCC2-related cerebro-oculo-facio-skeletal (COFS) syndrome with an early childhood death. A direct comparison of our data with the results of previously reported cohorts demonstrates the international mutation landscape of DNA repair-related photosensitivity disorders, although population-specific differences were observed.

Bullous pemphigoid, malignant acanthosis nigricans, and erysipeloid carcinoma in a woman with gastric adenocarcinoma.

Key Clinical Message: Bullous pemphigoid did not follow the course of Gastric Carcinoma relapse and remisson, unlike the malignant acanthosis nigricans which was in alignment with the paraneoplastic effect of the Gastric Carcinoma. Abstract: Acanthosis nigricans (AN) is a dermatosis characterized by the presence of hyperpigmented, velvety cutaneous thickening in the flexural areas, posterior neck, and occasionally the extensor surfaces of hand, face, and oral mucosa. AN is commonly associated with insulin resistance, drugs, and rarely internal malignancy (malignant AN). Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by tense blisters involving the skin of mainly elderly patients. The association of BP and malignancy is not well established and the co-existence of BP with AN has not been reported. Here we report a 58-year-old, event-free gastric adenocarcinoma with three types of skin findings with different pathogenesis- BP, malignant AN, and erysipelas-like metastasis.

Pemphigus Disease and Area Index: Unmet needs in the real-world management of pemphigus.

Over the past few decades, a number of scoring instruments have been developed to assess the severity and activity of autoimmune bullous diseases (AIBDs) (Daneshpazhooh et al., 2019; Nili et al., 2020; Nili et al., 2021; Nili et al., 2022). The Pemphigus Disease Area Index (PDAI), developed by the International Pemphigus Definitions Group, is an easy-to-use, quick, and reliable method for determining pemphigus severity. As a reliable and effective tool in clinical trials, PDAI may also have some limitations and might require some revisions to be used on a daily basis. Here, we propose some recommendations to improve the use of PDAI in the clinical setting.

Comparing the efficacy of plasma exeresis and cryotherapy for the treatment of seborrheic keratosis: A randomized controlled trial.

BACKGROUND: Seborrheic keratoses (SK) is a benign epithelial skin tumor and plasma exeresis is a new technique. AIMS: To compare the efficacy and safety of plasma exeresis and cryotherapy for treating SK. METHODS: This study is a randomized controlled trial (RCT). One side of each patient was randomly treated with plasma exeresis (peak-to-peak voltage of 3.44 kV and a frequency of 62.5 kHz) and the other side with cryotherapy. RESULTS: Thirty-five males were enrolled. At week 3, 37.1 % (N = 13) of lesions treated by plasma exeresis were clear, which was higher than those treated by cryotherapy 17.1% (N = 6). However, this difference was not significant (p-value: 0.06). At week 6, 16 (57.1 %) out of 28 remaining lesions, treated by plasma exeresis were clear, which was significantly higher (p-value: 0.005) than those completely cleared by cryotherapy in 6 out of 29 remaining lesions (20.7%). The mean physician assessment scale score was significantly reduced in both groups in the second follow-up (plasma group first follow-up 0.91 ± 0.89 vs. second follow-up 0.5 ± 0.64 and p-value: 0.0031; cryo group first follow-up 1.4 ± 0.84 vs. second follow-up 1.1 ± 0.72 and p-value: 0.0002). Regarding side effects, no significant difference was seen (p = 0.438). The most common complications in the plasma and cryotherapy groups were erythema (10/19, 52.63%) and hypo pigmentation (5/13, 38.46%). CONCLUSIONS: Both cryotherapy and plasma exeresis are effective. We observed a significantly higher cleared lesions treated with plasma exeresis in 6 weeks and after two sessions.

Drug Adherence and its Association with Health Literacy Among Patients with Autoimmune Bullous Diseases.

Background: Despite the emergence of novel medications, poor drug adherence is an obstacle toward disease management in patients with autoimmune bullous dermatoses (AIBDs). Objectives: We sought to evaluate medication adherence among patients with AIBDs and determine the impact of health literacy on adherence. Methods: We performed a cross-sectional survey of patients with AIBDs who attended Razi Hospital from May to October 2021. Drug adherence and health literacy were assessed using the Morisky Medication Adherence Scale-8 (MMAS-8; scored 0-8) and Health Literacy for Iranian Adults (HELIA; scored 0-100) questionnaires, respectively. Multivariable ordinal regression, including the covariates age, sex, education level, and annual income, were employed for analyses. Results: Two hundred participants with a mean±standard deviation (SD) age of 50.3±13.5 years were recruited. The female:male ratio was 1.2. About half (53%) of the patients reported good adherence (MMAS-8 score of 8) to their AIBD medications. Moreover, limited health literacy, with a mean±SD score of 57.8±25.8, was noted. Multivariable ordinal regression indicated that literacy score was significantly associated with good drug adherence (odds ratio [OR]: 0.11 per 1 score of health literacy increase, 95% confidence interval [CI]: 0.09-0.14). Conclusion: These findings showed suboptimal drug adherence and health literacy of patients with AIBDs. Improving patient health literacy might be a way to increase drug adherence.

Treatment of persistent chemotherapy-induced hair loss (Alopecia) with human mesenchymal stromal cells exosome enriched extracellular vesicles: A case report.

Introduction: Cancer is among the leading causes of death worldwide and affects a considerable number of individuals. Chemotherapy is one the most common treatment for this condition and hair loss is among one of the most prevalent side effects. In this study, we report successful treatment of a patient suffering from persistent chemotherapy-induced alopecia (PCIA) with extracellular enriched vesicles (EVs) derived from human placental mesenchymal stromal cells (MSCs). Case presentation: The patient was a 36-year-old woman with a history of invasive ductal carcinoma, underwent six courses of chemotherapy with paclitaxel and adriamycin. Following this treatment and for almost 18 months, she, unfortunately, had no regrowth of hair except some light vellus hairs on the scalp. She then received MSC-derived EVs with scalp injection (subcutaneous) every 4 weeks for 3 continuous months at which point she presented complete regrowth of terminal hair on her scalp. Conclusion: This report demonstrates that MSC-derived EVs could be a possible treatment for permanent chemotherapy-induced alopecia; however, further studies and trials are necessary.

Nail abnormalities in subepidermal blistering diseases: a cross-sectional study.

BACKGROUND: Nail involvement in subepidermal autoimmune blistering diseases (SEABD) is not common. Although these changes can be transient, permanent changes can also occur. This study addresses nail involvement manifestations and their associated factors in patients with SEABD. METHODS: From March 2020 to March 2021, we enrolled 56 patients with SEABD who were being examined at a tertiary skin hospital and checked their nail changes. We investigated the association between the SEABD subtypes and treatments that patients were receiving and the nail abnormalities. Additional factors including age, gender, duration since diagnosis, presence of mucosal involvement, and anti-bp230 and anti-bp180 IgG antibody quantitative levels (in those patients with bullous pemphigoid) were analyzed. RESULTS: The most common nail abnormalities were ridging, onycholysis, and onychoschizia. We observed a lower prevalence of onycholysis in EBA, a lower prevalence of periungual bullae in MMP, and a higher prevalence of scarring loss in EBA. Rituximab and dapsone were effective in preventing onycholysis as well as prednisolone in preventing subungual hematoma. Multiple lesions were found to be more common in the foot digits including great toes, probably because of higher exposure to trauma. CONCLUSIONS: In summary, in patients with SEABD and concomitant nail involvement, the underlying disease control, proper treatment, and avoidance of trauma may be helpful.

Infections in Hospitalized Patients with Psoriasis in a Skin Referral Hospital.

INTRODUCTION: Psoriasis and its treatments may predispose patients to various infections. This is considered one of the most significant complications in patients with psoriasis. OBJECTIVES: In the present study, we aimed to determine the prevalence of infection in hospitalized psoriasis patients and its relationship with systemic and biologic treatments. METHODS: All hospitalized patients with psoriasis from 2018 to 2020 in Razi Hospital in Tehran, Iran, were studied and cases of infection were recorded. RESULTS: Overall, 516 patients were studied and 25 types of infection in 111 patients were found. The most common types of infection were pharyngitis and cellulitis, followed by oral candida, urinary tract infections, common cold, fever of unknown origin, and pneumonia. Female sex and pustular psoriasis were significantly associated with infection in psoriatic patients. Those patients who received prednisolone had a higher risk of infection, and those under treatment with methotrexate or infliximab had a lower risk of infection. CONCLUSION: Overall, 21.5% of psoriasis patients in our study had at least one episode of infection. This demonstrates that the prevalence of infection in these patients is not low. Using systemic steroids was associated with a higher risk of infection, while using methotrexate or infliximab was concomitant with a lower risk of infection.

Whole transcriptome-based skin virome profiling in typical epidermodysplasia verruciformis reveals α-, ß-, and γ-HPV infections.

HPVs are DNA viruses include approximately 450 types that are classified into 5 genera (α-, ß-, γ-, µ-, and ν-HPV). The γ- and ß-HPVs are present in low copy numbers in healthy individuals; however, in patients with an inborn error of immunity, certain species of ß-HPVs can cause epidermodysplasia verruciformis (EV), manifesting as recalcitrant cutaneous warts and skin cancer. EV presents as either typical or atypical. Manifestations of typical EV are limited to the skin and are caused by abnormal keratinocyte-intrinsic immunity to ß-HPVs due to pathogenic sequence variants in TMC6, TMC8, or CIB1. We applied a transcriptome-based computational pipeline, VirPy, to RNA extracted from normal-appearing skin and wart samples of patients with typical EV to explore the viral and human genetic determinants. In 26 patients, 9 distinct biallelic mutations were detected in TMC6, TMC8, and CIB1, 7 of which are previously unreported to our knowledge. Additionally, 20 different HPV species, including 3 α-HPVs, 16 ß-HPVs, and 1 γ-HPV, were detected, 8 of which are reported here for the first time to our knowledge in patients with EV (ß-HPV-37, -47, -80, -151, and -159; α-HPV-2 and -57; and γ-HPV-128). This study expands the TMC6, TMC8, and CIB1 sequence variant spectrum and implicates new HPV subtypes in the pathogenesis of typical EV.

Dermoscopy of cutaneous granulomatous disorders: A study of 107 cases.

BACKGROUND: Cutaneous granulomatous disorders (CGDs) can share some features, but an accurate assessment of various findings and their pattern can be useful in differentiating them. In addition to common dermoscopic findings for CGDs, some peculiar dermoscopic characteristics can be helpful in distinguishing them. OBJECTIVE: Herein, we aimed to evaluate dermoscopic findings in patients with CGDs and determine the dermoscopic criteria that could suggest the type of granulomatous disorder. MATERIAL AND METHODS: A total of 107 cases including 75 (70.09%) males and 32 (29.90%) females with an established diagnosis of cutaneous leishmaniasis (n = 49), cutaneous sarcoidosis (n = 23), granuloma annulare (GA) (n = 18), and tattoo granuloma (n = 17) confirmed by clinical and pathological studies were included. Based on the previous studies available in the literature, we wrote a checklist containing dermoscopic features of CGDs. Afterward, two dermatologists independently reviewed all dermoscopic images for the presence or absence of each item on the checklist. Descriptive analysis, fisher exact, chi-square, and t-test were used. The granulomatous disorders with larger sample sizes were selected for further analysis, including the univariate and conditional multivariate logistic regressions. RESULTS: The most prevalent nonvascular findings in all of our CGD patients were white scaling (N = 67%, 62.61%), diffuse or localized orange structureless areas (N = 53%, 49.53%), and diffuse erythema (N = 48%, 44.85%). Furthermore, the most frequent vascular findings in all of our CGD cases were branching and arborizing vessels (N = 30%, 28.03%), linear irregular (N = 30%, 28.03%), and dotted vessels (N = 27%, 25.23%). CONCLUSION: For differentiating leishmaniasis from sarcoidosis by dermoscopy, white scaling and white scarring areas are more suggestive of cutaneous leishmaniasis, whereas the presence of arborizing vessels would be more in favor of sarcoidosis. When comparing GA to cutaneous leishmaniasis, the latter significantly shows more linear irregular vessels, hairpin vessels, white scaling, and white scarring areas. In the case of differentiating sarcoidosis from GA, the presence of hairpin vessels would be suggestive of sarcoidosis.