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Background: Epidermolysis bullosa (EB) is an uncommon group of inherited disorders characterized by skin blistering after friction or mechanical trauma. EB affects patients and their families physically, socially, and emotionally. Objective: This study aimed to assess the family quality of life of these patients using the Family Dermatology Life Quality Index (FDLQI) questionnaire. Methods: In this cross-sectional study, we enrolled caregivers of patients with EB registered at the Molecular Dermatology Research Center, affiliated with Shiraz University of Medical Sciences, up to 2020. Participants filled out a demographic data collection form and the FDLQI questionnaire. The data were analyzed using SPSS software, version 22. Results: Overall, 80 participants, consisting of 65 mothers (81.2%) and 15 fathers (18.7%) as primary caregivers, were enrolled in this study. The average FDLQI score was 19.88 ± 4.71. The FDLQI scores of caregivers of patients with EB simplex was significantly lower than scores observed in those with other types of EB (p < .001). There was a significant positive association between the number of patients with EB in the family and FDLQI score (p = .049). FDLQI scores were lower in caregiving mothers who had a higher education (p < .001) and those who were employed (p < .001). Conclusion: Family quality of life is affected in patients with EB. Families with lower socioeconomic status and unemployed caregivers require special attention. More studies are needed to determine the parameters involved in the quality of life of patients with EB and their families.

Background A spectrum of skin disease severity exists in patients with recessive dystrophic epidermolysis bullosa (RDEB). Objective To characterize the patient-reported outcomes and quality of life (QOL) in patients with RDEB. Methods A cross-sectional study of patients with RDEB surveyed through the global EBCare Registry. Patient-reported outcomes included skin disease severity, wound characteristics, pain, itch, extracutaneous symptoms, and medications. QOL was measured by using the validated Quality of Life in Epidermolysis Bullosa instrument. Results A total of 85 patients with RDEB reported 1226 wounds (937 recurrent wounds and 289 chronic open wounds). Overall skin disease severity was self-reported as mild (26%; 22/83), moderate (48%; 40/83), or severe (25%; 21/83). Worsening skin disease severity was significantly associated with larger wounds, increased opiate use, anemia, gastrostomy tube use, infections, osteoporosis, and squamous cell carcinoma. Larger wound size was associated with worse quality of life scores. Limitations All data were self-reported from an online epidermolysis bullosa patient registry. Conclusions This study shows a significant correlation between larger wound size with worsening skin disease severity and quality of life in participants with RDEB. Worsening skin disease severity significantly correlated with key clinical manifestations. These results show that patients with RDEB are able to self-report their skin disease severity and wounds.

Background Previous reports have revealed inadequate resident education and textbook representation of dermatological conditions in patients with skin of color (SoC). This suggests that the literature and continuing medical education are important alternative dermatology educational resources to aid in diagnosing and treating patients of color. Objective This study develops criteria to assess and examine the prevalence of SoC-related publications among top dermatology journals. Methods We developed the first-ever prespecified criteria that allow for the assessment of diversity in the dermatologic literature. The archives of 52 dermatology journals from January 2018 to October 2020, selected based on Scopus ranking, were analyzed for journal characteristics and content regarding skin and hair of color, diversity and inclusion, and socioeconomic/health care disparities that affect underrepresented populations with SoC. Results Our study reveals that the average percentage of overall publications relevant to SoC is quite low. The percent of SoC articles ranged from 2.04% to 16.8% with a mean of 16.3%. The top-performing dermatology journals in SoC were, not surprisingly, from countries with populations with SoC; however, the Journal of Cosmetic and Laser Therapy, Australasian Journal of Dermatology, and Journal of the American Academy of Dermatol Case Reports were among the top 10. Research and higher-impact journals were among the lowest in SoC rankings, including the Journal of Investigative Dermatology, Experimental Dermatology, and Journal of the American Academy of Dermatology, and had Conclusion We believe that the criteria we established could be used by journal editors to include at least 16.8% of SoC-relevant articles in each issue. Increasing SoC content in the dermatological literature, and particularly in high-impact journals, will serve as an invaluable educational resource and aid in promoting excellence in the care of patients with SoC.

Background: Quality of life (QoL) has not been evaluated in Indian patients having epidermolysis bullosa (EB). Aims: The aims of the study were to measure health-related QoL in Indian patients having EB using the quality of life in epidermolysis bullosa (QoLEB) questionnaire, and to find its correlation with clinically measured disease severity. Methods: In this observational cross-sectional study, the QoLEB questionnaire was translated from English to Hindi (QoLEB-Hin) and culturally adapted without a change in concept following standard guidelines. QoLEB-Hin and three clinical scores that have been independently validated in EB, that is, Birmingham Epidermolysis Bullosa severity score (BEBs), Instrument for Scoring Clinical Outcomes of Research for Epidermolysis Bullosa (iscorEB) and Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI), were administered to EB patients/their parents in the presence of an expert. This was followed by validity and correlation studies. Results: Fifty-four patients were recruited (19-females, 35-males; median age 5 years, range 0.025–36 years and 12 patients with an age >13 years). The parents answered the questions for 42 patients (age P < 0.001, Kruskal–Wallis analysis of variance). Cronbach’s alpha coefficient of 0.946 was obtained for all items indicating excellent internal consistency and reliability. Mean sample adequacy was 0.91; absolute fit based off diagonal values was 0.99; indices root mean square error of approximation and root mean square residual were 0.04 and 0.05, respectively, and Tucker Lewis index was >1 indicating overfit. The mean time taken to complete the questionnaire was 6.1 min (range, 6–8 min). QoLEB-Hin correlated significantly (P < 0.001) with BEBs (ρ = 0.79), iscorEB (ρ= 0.63) and EBDASI (ρ = 0.77). Three multiple linear regression models were used to ascertain the strength of relationship between QoL-Hin, and BEBs, iSCOREB and EBDASI, respectively, after adjusting for age, gender and disease subtype. The EBDASI clinical score accounted for approximately 74% (R2 = 0.736, P < 0.001) of the variability in QOL-Hin, as compared to 73% and 55% by BEBs (R2 = 0.731, P < 0.001) and iscorEB (R2 = 0.545, P < 0.001), respectively. Limitations: Parents filled out the questionnaires for many patients and probably led to an overall moderate degree of affliction of QoL. Comparison with Dermatology Life Quality Index and other QoL scores were not done in this study. Furthermore, the scoring was done at one point in time, and test-retest measurements could not be performed. Conclusion: This study validated QoLEB-Hin in an Indian population finding an overall moderate reduction in QoL due to EB. Maximally affected QoL was seen in patients with RDEB. Furthermore, QoLEB-Hin had a variable positive correlation and association with all clinical severity assessment scores.

This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus‐based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue‐bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10–25% of patients laminin 332 is recognized. In 25–30% of MMP patients with anti‐laminin 332 reactivity, malignancies have been associated. As first‐line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first‐line regimens. Additional recommendations are given, tailored to treatment of single‐site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high‐quality randomized controlled trials.

BACKGROUND: Bruton tyrosine kinase (BTK) inhibition targets B-cell and other non-T-cell immune cells implicated in the pathophysiology of pemphigus, an autoimmune disease driven by anti-desmoglein autoantibodies. Rilzabrutinib is a new reversible, covalent BTK inhibitor demonstrating preclinical efficacy as monotherapy in canine pemphigus foliaceus. OBJECTIVES: To evaluate the efficacy and safety of oral rilzabrutinib in patients with pemphigus vulgaris in a multicentre, proof-of-concept, phase II trial. METHODS: Patients with Pemphigus Disease Area Index severity scores 8-45 received 12 weeks of oral rilzabrutinib 400-600 mg twice daily and 12 weeks of follow-up. Patients initially received between 0 and ≤ 0·5 mg kg-1 prednisone-equivalent corticosteroid (CS; i.e. 'low dose'), tapered after control of disease activity (CDA; no new lesions, existing lesions healing). The primary endpoints were CDA within 4 weeks on zero-to-low-dose CS and safety. RESULTS: In total, 27 patients with pemphigus vulgaris were included: nine newly diagnosed (33%) and 18 relapsing (67%); 11 had moderate disease (41%) and 16 moderate to severe (59%). The primary endpoint, CDA, was achieved in 14 patients (52%, 95% confidence interval 32-71): 11 using low-dose CS and three using no CS. Over 12 weeks of treatment, mean CS doses reduced from 20·0 to 11·8 mg per day for newly diagnosed patients and from 10·3 to 7·8 mg per day for relapsing patients. Six patients (22%) achieved complete response by week 24, including four (15%) by week 12. Treatment-related adverse events were mostly mild (grade 1 or 2); one patient experienced grade 3 cellulitis. CONCLUSIONS: Rilzabrutinib alone, or with much lower CS doses than usual, was safe, with rapid clinical activity in pemphigus vulgaris. These data suggest that BTK inhibition may be a promising treatment strategy and support further investigation of rilzabrutinib for the treatment of pemphigus.

Intraepithelial autoimmune blistering dermatoses are a rare group of skin disorders characterized by the intraepithelial disruption of intercellular connections through the action of autoantibodies. The first article in this continuing medical education series explores the background, epidemiology, clinical features, and diagnostic criteria of each of the major intraepithelial autoimmune blistering dermatoses, including pemphigus foliaceus, pemphigus erythematosus, pemphigus herpetiformis, fogo selvagem, pemphigus vulgaris, pemphigus vegetans, drug-induced pemphigus, IgA pemphigus, IgG/IgA pemphigus, and paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome.

The 2019 novel coronavirus pandemic has tremendously affected health-seeking behaviors. Fear of contracting the disease has been a major factor keeping patients from presenting to hospitals, even when urgent or emergent medical attention is needed. Hospitals limiting staff exposure and capacity to accommodate patients also limits opportunities to seek care. Although physical distancing is encouraged to curb infections, this call needs to be tempered with public health education for what constitutes emergencies and urgent medical conditions needing face-to-face attention. Measures to assuage fears among patients and their caregivers to ensure their safety in the hospital or health care setting need to be communicated and executed effectively. Epidermolysis bullosa is an inherited mechanobullous disorder that is usually stable, but in some patients with underlying comorbidities, close monitoring or face-to-face management is required . We present our experience and provide recommendations pertinent to epidermolysis bullosa patients of all subtypes during the coronavirus crisis.

BACKGROUND Nemolizumab is a humanized anti-IL-31 receptor blocker in phase 3 for atopic dermatitis (AD). OBJECTIVE Analyse onset of action of nemolizumab 30 mg and compare efficacy and safety vs placebo (SC q4wk plus loading dose) in moderate-to-severe AD. METHODS Post hoc analysis of patients with Eczema Area and Severity Index (EASI) scores ≥ 16 from a phase 2b trial of moderate-to-severe AD. Endpoints were change in EASI score at week 16, peak pruritus numeric rating scale (PP-NRS), Investigator's Global Assessment (IGA), changes in sleep and responders with ≥ 4-point improvement on PP-NRS. RESULTS There was a significantly greater itch relief apparent by Day 2 (-22.8% vs -12.3% PP-NRS; P = 0.005) which continued to improve through week 16 (-68.5% vs -30.9% PP-NRS; P

Background The success of clinical trials in Epidermolysis Bullosa (EB) is dependent upon the availability of a valid and reliable scoring tool that can accurately assess and monitor disease severity. The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) and Instrument for Scoring Clinical Outcomes of Research for Epidermolysis Bullosa (iscorEB) were independently developed and validated against the Birmingham Epidermolysis Bullosa Severity Score but have never been directly compared. Objective To compare the reliability, convergent validity, and discriminant validity of the EBDASI and iscorEB scoring tools. Methods An observational cohort study was conducted in 15 patients with EB. Each patient was evaluated using the EBDASI and iscorEB-clinician scoring tools by 6 dermatologists with expertise in EB. Quality of life was assessed using the iscorEB-patient and Quality of Life in EB measures. Results The intraclass correlation coefficients for interrater reliability were 0.942 for the EBDASI and 0.852 for the iscorEB-clinician. The intraclass correlation coefficients for intrarater reliability was 0.99 for both scores. The two tools demonstrated strong convergent validity with each other. Conclusion Both scoring tools demonstrate excellent reliability. The EBDASI appears to better discriminate between EB types and disease severities.

Periostin, an extracellular matrix macromolecule implicated in tumorigenesis, serves as a prognostic marker for many cancer types. However, there are no data on periostin expression in cutaneous squamous cell carcinoma (cSCC). This study examined periostin expression in patients with cSCC and explored its clincopathological relationship and prognosis. Using immunohistochemistry and ImageJ analysis, we compared periostin expression in 95 cSCCs across a spectrum of cSCC aggressiveness: cSCC in situ (SCCIS) (n = 25), low-risk cSCC (LR-cSCC) (n = 26), high-risk cSCC (HR-cSCC) (n = 38), and cSCC in recessive dystrophic epidermolysis bullosa patients (RDEB cSCC) (n = 6). Immunohistochemistry demonstrated periostin expression within the intra-tumoral stroma but not within tumor cells. Periostin levels significantly (P < 0.001) increased from SCCIS, LR-cSCC, HR-cSCC to RDEB SCC. The stroma of most of the cSCCs we evaluated contained cancer-associated fibroblasts with a myofibroblastic (α -SMA-positive) phenotype. Co-localization of periostin with α-SMA, evidence of fibroblast periostin expression, and absence of keratinocyte or tumor cell periostin expression suggest that, in cSCC, periostin is a product of the peritumoral microenvironment and not the tumor cells themselves. Our data indicate that fibroblast periostin expression is highly correlated with the aggressiveness of cSCC, and may thereby provide a molecular marker that will be useful for subtyping and diagnosing cSCCs according to their biological nature.

Background The current standard in the serologic diagnosis of autoimmune bullous diseases (AIBD) is a multistep procedure sequentially applying different assays. In contrast, the BIOCHIP Mosaic technology combines multiple substrates for parallel analysis by indirect immunofluorescence. Methods Sera from 749 consecutive, prospectively recruited patients with direct immunofluorescence–positive AIBD from 13 international study centers were analyzed independently and blinded by using (1) a BIOCHIP Mosaic including primate esophagus, salt-split skin, rat bladder, monkey liver, monkey liver with serosa, recombinant BP180 NC16A, and gliadin GAF3X, as well as HEK293 cells expressing recombinant desmoglein 1, desmoglein 3, type VII collagen, and BP230 C-terminus and (2) the conventional multistep approach of the Department of Dermatology, University of Lubeck. Results In 731 of 749 sera (97.6%), specific autoantibodies could be detected with the BIOCHIP Mosaic, similar to the conventional procedure (725 cases, 96.8%). The Cohen κ for both serologic approaches ranged from 0.84 to 1.00. In 6.5% of sera, differences between the 2 approaches occurred and were mainly attributed to autoantigen fragments not present on the BIOCHIP Mosaic. Limitations Laminin 332 and laminin γ1 are not represented on the BIOCHIP Mosaic. Conclusions The BIOCHIP Mosaic is a standardized time- and serum-saving approach that further facilitates the serologic diagnosis of AIBD.

Background: Pemphigus encompasses a group of life-threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of immunosuppressive treatment, the prognosis of pemphigus was almost always fatal. Due to its rarity, only few randomized controlled therapeutic trials are available. Recently, rituximab has been approved as first-line treatment for moderate and severe pemphigus vulgaris in Europe and the USA.Objectives: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology (EADV) has initiated a throughout update of the guideline for the management of patients with pemphigus. Results: The guidelines for the management of pemphigus were updated and the degree of consent among all task force members was included. The final version of the guideline was consented by the European Dermatology Forum (EDF) and several patient organisations.

Background Esophageal strictures are the common gastrointestinal complications in patients with epidermolysis bullosa (EB) requiring dilation. There is limited information on the best type of intervention, outcomes, and predictors for re-stenosis. Objectives We aimed to investigate the frequency, clinical presentation of esophageal strictures in EB patients, and to ascertain the predictors of re-stenosis. Methods We conducted a retrospective, multicenter cohort study involving 7 specialized, international EB centers on patients who were 0 to 50 years of age. Descriptive statistics and hazard risks for re-stenosis were calculated. Results We identified 125 patients with 497 esophageal stricture episodes over a mean period of observation of 17 (standard deviation [SD] = 11.91) years. Dilations were attempted in 90.74% of episodes, using guided fluoroscopy 45.23%, retrograde endoscopy 33.04%, and antegrade endoscopy 19.07%. Successful dilation was accomplished in 99.33% of attempts. Patients experienced a median of 2 (interquartile range [IQR]: 1-7) stricture episodes with a median interval between dilations of 7 (IQR: 4-12) months. Predictors for re-stenosis included: number of strictures (2 vs 1 stricture: χ = 4.293, P = 0.038, hazard ratio [HR] = 1.294 (95% confidence interval [CI]: 1.014--1.652 and 3 vs 1 stricture:χ = 7.986, P = 0.005, HR = 1.785 [95% CI: 1.194, 2.667]) and a long (≥1 cm) segment stricture (χ = 4.599, P = 0.032, HR = 1.347 (95% CI: 1.026--1.769). Complications were more common with the endoscopic approach (8/86, antegrade endoscopy; 2 /149, retrograde endoscopy vs 2/204, fluoroscopy; χ = 17.39, P-value Conclusions We found excellent dilation outcomes irrespective of the dilation procedure; however, with higher complications in the endoscopic approach. Long (>1 cm) segment involvement and multiple locations were predictive of stricture reoccurrence.

Background Milia are superficial keratinous cysts seen as pearly white, dome-shaped lesions 1–2 mm in diameter. Milia are associated with diseases that cause subepidermal blistering, such as hereditary forms of epidermolysis bullosa, epidermolysis bullosa acquisita, bullous pemphigoid, bullous lichen planus, and porphyria cutanea tarda. Multiple eruptive milia are rare and more extensive in number than primary milia. Objective The aim of this study was to search the literature for cases of blistering diseases with multiple milia formation, especially in areas of the skin where there was no evidence of blistering or trauma, and review the interpretations of their pathogenesis. Methods We performed a literature search with the terms multiple milia and bullous diseases, pemphigoid, and pemphigus. Results Very few studies have investigated the origin of milia. Primary milia are thought to originate from the sebaceous collar of vellus hairs, and secondary milia are believed to derive from eccrine ducts more commonly than from overlying epidermis, hair follicles, or sebaceous ducts. Milia secondary to blisters or trauma are speculated to be produced through the regeneration process of disrupted sweat glands or hair follicles. Immunological predisposition, aberrant interaction between the hemidesmosomes, and the extracellular matrix components beneath the hemidesmosomes have been described with regard to the formation of numerous milia during recovery. Multiple milia could be a primary manifestation of dystrophic epidermolysis bullosa in skin areas without evidence of blistering. Conclusion The exact etiology of multiple milia remains unknown. Immunological predisposition and improper interaction between hemidesmosomes and extracellular matrix components are speculated to play a role in the formation of milia during recovery of bullous lesions in blistering diseases. Still, further studies on the triggering mechanisms of keratinocyte dysfunction in cases of multiple milia formation without evidence of prior blistering are needed.

Background: Nemolizumab targets the IL-31 receptor a subunit involved in atopic dermatitis (AD) pathogenesis. Objective: We sought to evaluate a new dosing strategy of nemolizumab in patients with AD. Methods: We performed a 24-week, randomized, double-blind, multicenter study of nemolizumab (10, 30, and 90 mg) subcutaneous injections every 4 weeks versus placebo, with topical corticosteroids in adults with moderate-to-severe AD, severe pruritus, and inadequate control with topical treatment (n 5 226). The Eczema Area and Severity Index (EASI), the peak pruritus (PP) numeric rating scale (NRS), and the Investigator’s Global Assessment (IGA) were assessed. Standard safety assessments were performed. Results: Nemolizumab improved EASI, IGA, and/or NRS-itch scores, with the 30-mg dose being most effective. Nemolizumab (30 mg) reduced EASI scores versus placebo at week 24 (268.8% vs 252.1%, P 5 .016); significant differences were observed by week 8 (P _4-point decrease) were greater for 30 mg of nemolizumab versus placebo at week 16 (P

Multiple synostoses syndrome type 4 (SYNS4; MIM 617898) is an autosomal dominant disorder characterized by carpal-tarsal coalition and otosclerosis-associated hearing loss. SYSN4 has been associated with GDF6 gain-of-function mutations. Here we report a five-generation SYNS4 family with a reduction in GDF6 expression resulting from a chromosomal breakpoint 3′ of GDF6. A 30-year medical history of the family indicated bilateral carpal-tarsal coalition in ~50% of affected family members and acquired otosclerosis-associated hearing loss in females only, whereas vertebral fusion was present in all affected family members, most of whom were speech impaired. All vertebral fusions were acquired postnatally in progressive fashion from a very early age. Thinning across the 2nd cervical vertebral interspace (C2-3) in the proband during infancy progressed to block fusion across C2-7 and T3-7 later in life. Carpal-tarsal coalition and pisiform expansion were bilaterally symmetrical within, but varied greatly between, affected family members. This is the first report of SYNS4 in a family with reduced GDF6 expression indicating a prenatal role for GDF6 in regulating development of the joints of the carpals and tarsals, the pisiform, ears, larynx, mouth and face and an overlapping postnatal role in suppression of aberrant ossification and synostosis of the joints of the inner ear (otosclerosis), larynx and vertebrae. RNAseq gene expression analysis indicated >10 fold knockdown of NOMO3, RBMXL1 and NEIL2 in both primary fibroblast cultures and fresh white blood cells. Together these results provide greater insight into the role of GDF6 in skeletal joint development.

Bruton Tyrosine Kinase (BTK) has a key role in multiple pathways involved in inflammation and autoimmunity. Therefore, BTK has become a new therapeutic target for a group of hematologic and autoimmune disorders. The pharmaceutical industry has invested in the clinical development of BTK inhibitors during the last decade. Ibrutinib, for example, which was the first BTK inhibitor to be used in clinical trials, has two approved indications, mantle cell lymphoma and chronic lymphocytic leukemia, and remains under evaluation for additional indications. Rillzabrutinib (PRN1008) is a new, highly potent and selective inhibitor of BTK. Early studies performed in canine pemphigus demonstrated effectiveness. A proof-of-concept, multicenter, phase 2 trial has recently showed the efficacy and safety of oral rilzabrutinib in pemphigus vulgaris. In this mini review, we present evidence regarding the mechanisms affected by BTK inhibition and the concept of BTK inhibition as an emerging new treatment in pemphigus.

Objective The Quality of Life in Epidermolysis Bullosa (QOLEB) score is an Epidermolysis Bullosa (EB) specific quality of life (QoL) measurement tool. It is a statistically valid and reliable questionnaire which has benefits over generic QoL tools in QoL evaluation in EB. It also has important implications in the evaluation of the clinical efficacy of new interventions in EB. The utility of this score would be increased if the clinical relevance of individual scores and changes in QOLEB scores could be further understood.Methods In order to achieve this, the minimal clinically important difference (MCID) was calculated using both anchor-based and distribution-based techniques. Banding techniques were also applied to the QOLEB questionnaire in order to stratify scores into “very mild”, “mild”, “moderate”, “severe” and “very severe” categories.Results Using these methodologies, the MCID for the QOLEB score was calculated at a 6 point change in QOLEB scores, and the QOLEB bands were calculated as: 0-4 points for ‘very mild’, 5-9 points for ‘mild’, 10-19 points for ‘moderate’, 20-34 points for ‘severe’ and 35-51 points for ‘very severe’ impact on QoL.Conclusions Calculating the MCID and clinical bands for the QOLEB questionnaire increases the breadth of clinical applications for the QOLEB questionnaire. It now has direct utility in determining the clinical significance of interventions in EB by evaluating changes in QOLEB scores and how they correlate to the MCID and clinical bands.

Introduction: Pemphigus, an autoimmune disease group characterized by blisters and erosions of the skin and/or mucosal membranes has been treated with systemic corticosteroids (CS) and immunosuppressive therapies for the past few decades. Areas Covered: However, common adverse effects and complications of long-term CS and immunosuppressive drugs are limiting their long-term use. The disease results in death if not treated. Thus, currently, researchers are trying to develop new and safer therapeutic approaches. Specifically, targeted therapies to pathogenic immune pathways are under investigation. The B cell inhibitors which block CD20 and CD19 are the main new drugs investigated in clinical trials as alternatives to systemic steroids. Expert Opinion: Randomized controlled trial (RCT) Level evidence shows that rituximab and short course CSs are more effective and safer than standard CS treatment. Specific BTK inhibitors have shown promise in data from a phase II international open-label study. Further studies are ongoing.

Glucocorticosteroids (GCs), have been the mainstay treatment for several dermatological diseases such as autoimmunebullous diseases (AIBDs). However, they come with a great cost of GCs-associated adverse events causingmortality and morbidity. Recently, a new measure to evaluate toxicity due to GCs’ use has been demonstrated to bereliable.This review aimed to summarise toxicity attributed to GCs use and give more insight about this new toxicity index.

Background The BIOCHIP is a novel multiplex indirect immunofluorescence technique used in the serological diagnosis of bullous pemphigoid and pemphigus. The BIOCHIP method combines the screening of autoantibodies and target antigen-specific substrates in a single miniature incubation field. Objective To evaluate the diagnostic accuracy of the new immunofluorescence BIOCHIP multiplex tool in pemphigus and bullous pemphigoid. Methods For the validation of the BIOCHIP, sera from patients with BP (n = 38), PF (n = 8) and pemphigus vulgaris (PV) (n = 23) were used. In addition, sera from disease control patients (n = 63) and healthy volunteers (n = 39) were used. The multiplex BIOCHIP and direct immunofluorescence (DIF) were performed for all BP, PF and PV patients. Additional indirect immunofluorescence (IIF) was performed on patients with BP, and ELISA was performed on patients with pemphigus. Results The BIOCHIP mosaic showed a sensitivity of 86.8% and specificity of 85% for BP180 or BP230 being positive in BP. It demonstrated a sensitivity of 75% and specificity of 97.7% for Dsg1 in PF. The BIOCHIP was found to have a sensitivity of 60.9% and specificity of 73.6% for Dsg3 in PV. Conclusion The BIOCHIP mosaic-based immunofluorescence test is potentially a simple, time and effort saving test that can aid in the diagnosis and screening of BP, PV and PF. However, there is potential for interpretation bias and a learning curve that needs to be taken into consideration.

Autoimmune bullous diseases during pregnancy pose a therapeutic challenge for medical dermatologists. There are main concerns with regard to the regimen, dose, route of administration, and potential harm to the fetus. Many therapeutic options may be safe during pregnancy despite official classifications. Furthermore, there are always questions regarding management during the lactation period. Additionally, issues exist about male and female fertility and the time of discontinuation of certain medications before conception. In this article, we present an overview of the literature based on answers to these issues to solve common and uncommon management problems that arise about a spectrum of autoimmune bullous diseases before conception, as well as during pregnancy and the lactation period. Keywords: Pemphigus, pemphigoid, bullous, pregnancy, lactation fertility

This is an updated review of the literature on the emerging therapeutic options for the treatment of pemphigus to provide better care for patients. There is an increasing range of molecules targeted for pemphigus therapy against CD20, Bruton tyrosine kinase, chimeric antigen receptor, T-cell immune components, B-cell activating factor, proliferation-inducing ligand (APRIL), CD25, p38 mitogen-activated protein kinase (p38MAPK) and cytokine modulation therapies (anti-IL-4, anti-IL-6). The main aim of the current new therapies is to provide specific pathology-focused therapeutic options which have long-term sustainable therapeutic effects on disease progress, cause less side effects without systemic immunosuppression, and have less risk of getting antibodies against the medication during treatment.

Background There is limited evidence to suggest patients with epidermolysis bullosa (EB) have more postoperative wound complications than the general population. Despite this, the authors have noted reluctance among some surgeons to operate on these patients. Objective A cross-sectional study was designed to investigate postoperative wound and scar healing outcomes in patients with EB. Methods Patients were asked to complete the "Surgical Wound and Scar Healing in EB" questionnaire, and data gathered were analyzed. Results Forty-six patients completed the questionnaire for a total of 94 different surgical procedures. Five patients reported blistering at the surgical wound site. All 5 had generalized forms of EB. Four patients reported wound infections, and 1 patient reported wound dehiscence. The postoperative scar healed with keloid or hypertrophic scarring after 26% of the reported surgical procedures. Conclusion Blistering at the postoperative site seems to be uncommon and particularly unlikely to occur in localized forms of EB. Postoperative wound infections and dehiscence are uncommon. Patients with EB may have a propensity to develop keloid or hypertrophic scarring. With these data, the authors hope clinicians have greater confidence in referring patients with EB for surgery, and surgeons more reassured about postoperative wound healing.

Background: Autoimmune blistering diseases (AIBD) are characterised by the body’s production of autoantibodies against structural proteins in the epidermis and/or the basement membrane on cutaneous and mucosal surfaces. Alopecia is a complication of AIBD that has generally been overlooked in patients with severe blistering diseases because it is regarded as a cosmetic issue. Yet recent research into quality of life tools has found that stigmatisation by appearance plays a significant role in blistering diseases. Aim: To review the current literature detailing the pathogenesis and clinical presentations of alopecia in AIBD patients. Method: We searched Medline, PubMed and EMBASE electronic databases up to September 2018, for empirical human and animal studies. Results: Only 36 human studies including 223 patients (190 pemphigus, 25 pemphigoid, 5 epidermolysis bullosa acquisita, 2 dermatitis herpetiformis and 1 linear IgA disease) detailed demographic and clinical manifestations of alopecia. A range of hair evaluation methods was demonstrated to reach alopecia diagnosis. Furthermore, with no universal validated scoring system for alopecia severity, alopecia patterns have been summarised. Conclusion: Previous randomised trials have not highlighted alopecia as an important outcome of AIBD, so epidemiological evaluation of the available literature has been helpful in summarising trends between existing studies and demonstrating inconsistencies.

The definition of IgG4-related diseases incorporates a broad range of systemic diseases particularly a subset dominated by fibroinflammation. CD4+cytotoxic T cells have emerged as the major driving force for the fibroinflammation, and the pathogenetic role of IgG4 still remains to be determined. Cutaneous involvement is uncommon and is not well defined as elevated tissue IgG4 plasma cells are not a specific marker and prominent cutaneous fibroinflammation is often absent in cutaneous disease. We report the case of a patient with longstanding alopecia universalis and severe atopic dermatitis who presented with diffuse induration and mottled dyspigmentation of his scalp. Multiple scalp biopsies revealed diffuse interfollicular fibroinflammation and IgG4 plasma cells with induction of distinctive dedifferentiated follicles not seen in alopecia areata. This complex case may provide insight into the role of specific subsets of T cells not only in respect to the fibroinflammation linked to IgG4-related diseases but also the capacity to modify disease, follicular stem cell activation, immune privilege, cytotoxicity in alopecia areata, and the presence of atopy that may have contributed to the pathogenesis of this case.

The clinical trials industry faces a number of challenges during the evolving coronavirus disease 2019 (COVID-19) pandemic, for example, site closures, mandatory self-isolation, travel restrictions, interruptions to delivery of investigational product, or staff or participants becoming infected with severe acute respiratory syndrome coronavirus 2. These challenges can pose difficulties in adhering to visit schedules, performing laboratory testing, conducting protocol-specified procedures, and administration of investigational product. As a result, clinical trial sites, contract research organizations, and sponsors have had to act swiftly to ensure that trial patients are safe and systems are in place for continuing trials. Protocols should also be amended to reflect changes and approved by an ethics board. The authors provide practical considerations and recommendations for dermatology clinical trial operations during the COVID-19 pandemic.

Pemphigus represents a group of rare autoimmune bullous diseases that affect the skin and mucous membranes. This group has a chronic course leading to high morbidity and mortality. Because of the painful chronic-recurring blisters and/or erosions on skin and mucosa, pemphigus can impair quality of life (QOL). Therapeutic modalities, anxiety and depression can also have an additional negative impact in the QOL of the pemphigus patients. Since the nature and course of the pathology and the fact that pemphigus worsens the quality of life of affected patients, scoring systems to objectively evaluate the clinical activity of the disease and to correlate that with the QOL are needed. Nowadays the most used global scales to assess the clinical activity of pemphigus are the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS), the Pemphigus Disease Area Index (PDAI) and the Pemphigus Visual Activity Scale (PVAS). To evaluate the patient's generic QOL the most used score is the Dermatology Life Quality Index (DLQI), but all the sponsered clinical trials in pemphigus are using ABQOL this rather than DLQI.

Background Mentorship can have a profound impact on the success and happiness of a mentee while also providing a sense of fulfillment and enrichment for the mentor. Both officially designated or spontaneously chosen mentors can be useful for the proteges as they navigate through their training and professional work environment, meanwhile striving to obtain the optimal work-life balance. Different genders can have variable experiences, in both their personal lives managing family obligations, as well as their professional lives as dermatologists, which may affect the advice and guidance offered. Objective We studied the impact of gender on the mentor-mentee relationship for both official and spontaneous mentorships through a voluntary survey with a focus on reported outcomes from the perspective of the mentee. Methods Participants were selected through e-mail invitation via the Women's Dermatologic Society and program directors of the Association of Professors of Dermatology membership lists and given a link to the anonymous survey tool. The survey included 13 questions looking at official and spontaneous mentorships, the role of gender, and success in the dermatology field. Results Of the 288 respondents, 69.9% (n=202) were women, 29.8% (n=86) were men, and one identified as other. Of the survey participants, 81% had official mentors while 91% had spontaneous ones with the overlap indicating there may have been a history of multiple mentors per individual. Mentoring had an overall significant positive impact, and 98.5% of those in the spontaneous mentor group rated the mentor as helpful compared with 87.6% in the official mentor cohort. For official mentorships, 60.1% involved gender similar mentors, and of those who had officially designated mentors of any type, 55% indicated a preference for mentors of the same gender. Specifically looking at respondents who participated in same gender official mentorships, 65.5% preferred this type, but of those who had a gender dissimilar equivalent, only 36.7% indicated a preference for gender similarity in a mentor. Comparably, 59% of the proteges with spontaneous mentors had a gender similar one, and of those who had spontaneous mentors of any type, 59.2% preferred gender similarity. Considering only those in gender similar spontaneous mentorships, 74.5% favored a same gender pairing compared with 32.9% of those in the gender dissimilar group. For female-female official mentorships, 75% preferred a female mentor similar to 80.5% of the spontaneous mentor cohort. Conclusions Spontaneous mentors may provide greater benefit than officially designated ones. For the majority of the categories, there was no statistical difference between female same gender mentorships and gender dissimilar relationships, which is in contrast to previously published literature. Overall, based on the feedback provided, the respondents felt that the quality of the relationship was the most important defining factor, but some noted that same gender mentorships can provide additional benefit geared towards similar interests and experiences in life.