Clinical and immunological predictors of post-rituximab paradoxical pemphigus flare: A prospective cohort study.

Background Paradoxical flare of pemphigus following rituximab infusion has been reported previously, however, its incidence or risk factors have not been studied in detail. Objectives To evaluate the clinical and immunological predictors associated with post-rituximab paradoxical pemphigus flare. Materials and Methods This was a prospective cohort study including adult patients with pemphigus vulgaris or foliaceus who were treated with rituximab. Patients were administered 1000 mg of intravenous rituximab on days 0 and 14 (Rheumatoid arthritis (RA) protocol), with or without oral prednisolone and/or conventional immunosuppressive agents. Baseline clinical and immunological predictors of post-rituximab pemphigus flares were assessed. Results Fifty patients (mean age 40.44 ± 12.36 years) with a mean pemphigus disease area index (PDAI) score of 27.8 ± 15.48 were administered rituximab. Post-rituximab flare occurred in 10 (20%) patients after a mean of 14.1 ± 4.33 days after the first rituximab infusion. The mean baseline PDAI score (36.4 ± 11.7 vs. 25.6 ± 15.7, P = 0.02) and serum anti-Dsg1 levels (1216.8 ± 850.1 vs. 592 ± 562.12 RU/mL, P = 0.03) were statistically significantly higher in patients experiencing a flare. Using ROC-curve analysis, a PDAI score of 328 (OR 8.3, 95% CI 1.5-44.7) was 80% sensitive and 67.5% specific in predicting post-rituximab flare, while serum anti-Dsg1 level of 31137.78 RU/ml had a sensitivity of 60% and specificity of 85%. There was no significant difference in terms of affected body surface area, type of pemphigus, starting prednisolone dose, oral immunosuppressive adjuvant, serum anti-Dsg3, serum anti-AchRM3, and peripheral CD19+ B cell population. Limitations Our study is limited by a relatively small sample size. Immunological factors were not evaluated at the time of pemphigus flare. Though these unexpected pemphigus flares are likely to be associated with rituximab infusion, the possibility of spontaneous disease exacerbation cannot be entirely excluded. Conclusions Patients with more severe pemphigus or high serum anti-Dsg1 are at risk of post-rituximab paradoxical flare, and may benefit from rituximab administration under close monitoring.

Procedural dermatology and its unmet need.

Procedural dermatology includes invasive conventional dermatologic surgeries which involve significant use of knife and suture, minimally invasive procedures and device-based procedures. Device-based procedures are the easiest to learn and are less prone to human errors due to automation but can lead to monotony, while conventional surgeries require significant skill, craftsmanship and interest. There has been a recent shift in the approach to procedural dermatology as a therapeutic option with complementary and combination models replacing the conventional hierarchical model in which procedures were last in the step-ladder approach. The demand for both conventional dermatologic surgeries and minimally invasive cosmetic procedures is increasing. Unfortunately, this demand has not been met with adequate supply. Consequently, the number of trained professionals with expertise in these procedures is very limited; they are far outnumbered by unqualified practitioners. A limited number of dermatologic surgeons practicing conventional surgeries has resulted in huge waiting lists for vitiligo surgeries, inappropriate excisions for skin cancers and poor cosmetic outcomes of excisions without proper knowledge of flaps and grafts. Increasingly procedures are being performed by inadequately trained personnel, resulting in complications. There is also an absence of good quality research on the subject of procedural dermatology, which has resulted in a lack of standardisation of various procedures and knowledge about the efficacy of various drug-procedure and procedure-procedure combinations. An increasing variety of gimmicky but costly procedures are being offered to the public without much evidence of efficacy. Individual institutional and broad policy directives are needed to address these issues. Special emphasis is required on formal hands-on procedural dermatology training during residency and beyond it.

Lipschutz ulcers in a 4-month-old girl.

Lipschutz ulcers, or non-sexually acquired genital ulcers, typically occur in older children and young adults. A diagnosis of Lipschutz ulcers can only be made after excluding common infectious and non-infectious causes of mucosal ulcers. Herein, we present the case of a 4-month-old girl with painful ulceration of the labia consistent with Lipschutz ulcers.

Asian guidelines for condyloma acuminatum.

The present guidelines aim to provide comprehensive information on genital condyloma acuminata, including the epidemiology, clinical features, diagnosis and management. The guidelines provide evidence-based recommendations on the diagnosis, prevention and treatment of genital condyloma acuminata in adults in Asia, including patients with HIV co-infection. METHODOLOGY: A PubMed search was performed, using the keywords "condyloma acuminata", "anal wart", "anogenital wart", "genital wart" and "genital HPV". A total of 3031 results were found in publications during last six years. A careful review of the titles and abstracts was done to find all the studies pertaining to epidemiology, clinical features, diagnosis, treatment and prevention of condyloma acuminata. DIAGNOSIS: Various diagnostic procedures described are: 1. PCR (LE: 2b). 2. Serology (LE: 2b). 3. In-situ hybridization (LE: 3). PREVENTION: 1. Vaccination (LE: 1a): Quadrivalent vaccine reduced the frequency of anogenital warts in both vaccinated and unvaccinated contacts. According to the update Advisory Committee on Immunization Practices (ACIP) recommendations, the following protocol is recommended: (a). HPV vaccination at age 11 or 12 years for both males and females. (b). Catch-up vaccination for all persons through age 26 years. (c). Shared clinical decision-making regarding potential HPV vaccination for persons aged 27-45 years, who are at risk of new HPV infection. 2. Male circumcision (LE: 2a): conflicting evidence. HIV AND CONDYLOMA ACUMINATA: In HIV-affected individuals, the course of HPV is more aggressive, with a greater risk of treatment resistance, increased chances of intraepithelial neoplasia as well as cancers. TREATMENT: Physician administered. 1. Photodynamic therapy (LE: 1a). 2. Laser (LE: 2b). 3. Surgery (LE: 1a). 4. Electrosurgery (LE: 2c). 5. Cryotherapy (LE: 1b). 6. Immunotherapy (LE: 1b). 7. Podophyllin (LE: 1b). Provider administered. 1. Imiquimod 5%(LE: 1a). 2. Podophyllotoxin (LE: 1b). 3. Sinecatechins (LE: 1a). 4. Cidofovir (LE: 3). 5. 5- Fluorouracil (LE: 1a). 6. Interferon (LE: 1a).

Autoimmunity in vitiligo: Therapeutic implications and opportunities.

Vitiligo is an acquired chronic pigmentary disorder affecting the melanocytes, mainly in the skin and mucosae. It occurs due to the dynamic interaction between genetic and environmental factors leading to autoimmune destruction of melanocytes. Defects in melanocyte adhesion and increased oxidative stress further augment the immune response in vitiligo. It is a cosmetically disfiguring condition with a substantial psychological burden. Its autoimmune nature with resultant chronicity, variable responses to therapeutic modalities, and frequent recurrences have further diminished the quality of life. Hence, treatment should aim to provide more extended remission periods, prevent recurrences, provide good cosmetic outcomes and ensure patient satisfaction. These treatment goals seem plausible with the recent progress in our understanding of the complex pathogenic mechanisms underlying vitiligo at a molecular and genetic level. We provide a literature review of the pathogenic mechanisms and the therapies targeting these mechanisms.

Acquired cutis laxa type II (Marshall syndrome) in a 3-month-old boy.

Acquired cutis laxa type II (Marshall syndrome) is a post-inflammatory elastolysis occurring in infancy and childhood. It is challenging to treat with very few effective treatment options available. Herein, we describe the case of a 3-month-old boy with acquired cutis laxa type II secondary to a neutrophilic dermatosis. Early treatment of the initial inflammatory phase is essential to reduce the permanent sequelae.

Pemphigus Oral Lesions Intensity Score (POLIS): A Novel Scoring System for Assessment of Severity of Oral Lesions in Pemphigus Vulgaris.

Background: Many patients with pemphigus vulgaris (PV) in India present with predominant/exclusive oral mucosal lesions. Current validated scoring systems for pemphigus do not adequately represent the clinical variability of oral lesions. Objective: To develop and validate a novel scoring system exclusively for oral lesions in PV. Methods: In this cross-sectional study, the Delphi method was used to build an initial scale that was administered in 115 patients with PV. Exploratory factor analysis was used to examine the underlying factor structure of the new scale. The psychometric properties of the new scale were studied. Correlations between the new scale and Autoimmune Bullous Skin Disorder Intensity Score (ABSIS), Pemphigus Disease Area Index (PDAI), and Physician Global Assessment (PGA) were also assessed. Results: Content validity of the initial scale was established with an average content validity index (CVI) of 0.8. Exploratory factor analysis resulted in a 3-factor structure with a total of 9 items. Corrected item-total correlation, a measure of data quality, was more than 0.30 for all items in the new oral mucosal scale-Pemphigus Oral Lesions Intensity Score (POLIS). Significant correlations were observed between POLIS and oral ABSIS (r = 0.85, p < 0.001), mucosal PDAI (r = 0.70, p < 0.001), and PGA (r = 0.60, p < 0.001). POLIS was also reliable with good internal consistency (Cronbach's α = 0.86) and strong inter-rater agreement. Limitations: The study cohort included participants from a single center. Usability and time taken to administer the scale were not assessed. Conclusions: The new scale, POLIS, has adequate validity and reliability. It includes both quality of life and clinical disease severity parameters, assessing disease severity holistically. Further studies evaluating the scale's responsiveness to change are in progress.