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.

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.

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.

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.

Chromoblastomycosis caused by Alternaria infectoria, concurrent with myiasis, in a recipient of a kidney transplant: a compelling case report.

Neglected tropical diseases (NTDs) pose a significant threat to the health of millions of people worldwide, particularly in impoverished populations in tropical and subtropical regions. The World Health Organization (WHO) considers certain fungal infections, such as chromoblastomycosis, as NTDs. Chromoblastomycosis is a chronic fungal infection affecting the skin and subcutaneous tissue, primarily found in tropical and subtropical regions of Latin America, Africa, and Asia. This case report presents a 46-year-old female patient with chromoblastomycosis who had a history of renal transplantation and was receiving immunosuppressive therapy. The patient exhibited dark, verrucous, and ulcerative lesions on the legs, and the diagnosis was confirmed through the microscopic examination of skin scrapings by observing medlar bodies. Two sequential fungal tissue cultures and ITS sequencing verified the presence of Alternaria infectoria, not formerly described in chromoblastomycosis. Moreover, observation of fly larvae in the lesions verified the diagnosis of myiasis. Treatment with voriconazole and terbinafine resulted in complete resolution of the lesions after 5 months. This case emphasizes the importance of considering chromoblastomycosis in individuals with occupational exposure in tropical areas, as well as the challenges associated with its diagnosis, coinfections, and treatment.

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.