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Chronic bullous dermatosis of childhood (CBDC) is a rare autoimmune subepidermal blistering disease, which can develop following vaccination or medication, or with an autoimmune condition or illness, among other causes.To identify and better understand the clinical features of CBDC by performing a systematic review, in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.Eligible studies included publication since 1980, CBDC diagnosis, case studies, subjects aged 18 years, clinical features and no language restriction. A database search was conducted including Embase, MEDLINE and Scopus on 14 July 2021 (see Appendix for search terms). Data were assessed for risk of bias. Jamovi was used for statistical analysis. Age and sex were compared with mucocutaneous involvement, cutaneous involvement, other symptoms, human leucocyte antigen type and lesion descriptions.After removing duplicate references using Endnote, 351 papers were identified, of which 91 met the inclusion criteria. These papers included 130 cases of CBDC: 110 children and 20 neonates. The ratio of male : female patients was 19 : 1 for neonates and 74:55 for children. χ² analysis with 1 degree of freedom showed that CBDC in neonates was associated with facial (χ²Neonates with CBDC are more likely to have a mucocutaneous distribution of lesions, whereas children are more likely to have cutaneous lesions. The limitations of this study include selection bias, and the small neonate sample size makes the study unrepresentative of the population. The review highlights the need for further research into the clinical features of CBDC in neonates.

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.

This study shows that gain-of-function variants in KLHL24 causing EBS and DCM, do not only originate in the start-codon and suggest that any nonsense-inducing variant affecting nucleotides c.4_84 will likely cause the same effect on protein level and a similar potential lethal phenotype.

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 Epidermolysis bullosa simplex (EBS) comprises a group of rare, blistering genodermatoses. Prior work has been limited by small sample sizes, and much remains unexplored about the disease burden and health-related quality of life (QOL) of patients with EBS. The aim of this study was to characterize the most common patient-reported clinical manifestations and the health-related impact of QOL in EBS, and to examine differences in disease burden by age. Methods Patients with a diagnosis of epidermolysis bullosa (EB) or their caregivers completed a one-time online survey administered by EBCare, an international online EB registry. Survey data from respondents self-reporting a diagnosis of EBS were analyzed for clinical and wound manifestations, medication use, and QOL (using Quality of Life in Epidermolysis Bullosa [QOLEB] scores). Differences across age groups were assessed using Kruskal–Wallis and Fisher’s exact tests. Results There were 214 survey respondents with EBS. The mean age was 32.8 years (standard deviation = 19.2). Many respondents reported blisters (93%), recurrent wounds (89%), pain (74%), chronic wounds (59%), itch (55%), and difficulty walking (44%). Mean QOLEB score was 14.7 (standard deviation = 7.5) indicating a “moderate” impact on QOL, and 12% of respondents required regular use of opiates. Findings were consistent in subgroup analyses restricted to respondents with diagnostic confirmation via genetic testing or skin biopsy (n = 63 of 214). Age-stratified analyses revealed differences in disease burden: younger respondents were more likely to self-report severe disease (24% vs. 19% vs. 5% for respondents aged 0–9 vs. 10–17 vs. 18 + , p = 0.001), failure to thrive (9% vs. 15% vs. 3%, p = 0.02), and use of gastrostomy tubes (15% vs. 12% vs. 1%, p Conclusions In the largest international cross-sectional survey of EBS patients conducted, respondents reported extensive disease burden including significant wounding, pain, itch, difficulty walking, and impact on QOL. Age stratified disease manifestations. These findings suggest significant unmet need, and treatment and counseling for EBS patients should consider age-specific differences.

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

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.

Psoriasis imposes a disease burden that can have a profound negative impact on patients' quality of life (QoL). HOPE was the first non-interventional study conducted in patients with severe chronic plaque psoriasis in Australia that evaluated health-related QoL in response to treatment with secukinumab.HOPE was a prospective, open-label, single-arm, multicentre, non-interventional, exploratory study in patients with severe chronic plaque psoriasis in Australia. The study investigated the change in QoL, using the Dermatology Life Quality Index (DLQI), Assessment Quality of Life-8 Dimension questionnaire (AQoL-8D) and Psoriasis Area and Severity Index (PASI), and safety profile in response to treatment with secukinumab 300 mg SC weekly for 4 weeks followed by monthly maintenance for 58 weeks.At Week 14, the mean percentage reduction in total DLQI score from baseline was -82.4% (n = 65), which indicates a substantial improvement in QoL. This level of improvement was sustained up to Week ≥58, with a mean percentage change of -87.4%. The mean percentage change from baseline for AQoL-8D weighted total score decreased from Week 14 (41.1%) to Week 58 (35.2%), indicating an improvement in patients' QoL. A high proportion of patients achieved PASI 75/90/100 responses at Week 14 (97.0%/71.2%/34.8%), with rates sustained up to Week ≥58 (100%/87.9%/43.1%). The safety profile of secukinumab was favourable, with no cumulative or unexpected safety concerns.Secukinumab treatment demonstrated a striking improvement in patients' QoL in the HOPE study, the first real-world study in patients with severe chronic plaque psoriasis in the Australian clinical setting.

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 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 Chronic wounds are a fundamental issue for patients with epidermolysis bullosa (EB). Herein, we assess the natural history of wound closure in patients with EB who were randomly assigned to the vehicle-control arm of the multicenter, randomized, double-blind, phase 3 ESSENCE (NCT02384460) trial. Methods ESSENCE was designed to assess the efficacy and safety of a topical cream formulation of 6% allantoin (SD-101 6%) vs vehicle (SD-101 0%) in patients ≥1 month old who had a diagnosis of EB (simplex, recessive dystrophic, or intermediate junctional) and a target wound 10–50 cm2 present for ≥21 days. Time to complete target wound closure and the proportion of patients with target wound closure over time were analyzed overall and by parameters including patient age and baseline body surface area index (BSAi) of total wound burden ( Results The vehicle-control arm included 87 patients. Mean (standard deviation [SD]) time to target wound closure within 3 months was 53.6 (28.6) days, with a range of 14 to 142 days. The proportion of patients with target wound closure increased over time from 7.1% at day 14 to 53.6% at month 3. Mean (SD) changes from baseline in BSAi of total wound burden and BSAi of lesional skin at month 3 were −2.3% (6.3) and −5.0% (13.5) of total body coverage, respectively. Reductions in pain and itching were observed at day 7 and maintained for 3 months. Faster healing times and a greater proportion of patients with wound closure were observed in patients aged 1 month to Conclusions Treatment response observed in the vehicle-control arm of the ESSENCE study was unexpectedly high and may have been due to unforeseen benefits of vehicle or enhanced wound care provided by the clinical trial staff. These observations will help inform the study design of future trials in patients with EB. Trial registration ClinicalTrials.gov, NCT02384460; Date of registration: February 13, 2015; First participant enrollment: March 11, 2015.

BackgroundEpidermolysis bullosa (EB) is a rare genetic disorder that manifests as blistering and/or skin erosion. There is no approved treatment for EB; current standard of care consists of wound and pain management. SD-101 6% is a topical cream containing 6% allantoin that was developed for treating skin lesions in patients with EB. The aim of this phase 3, multicenter, randomized, double-blind, vehicle-controlled study was to assess the efficacy and safety of SD-101 6% cream versus vehicle (0% allantoin) on lesions in patients with EB.MethodsEligible patients were ≥1 month old, had a diagnosis of EB (simplex, recessive dystrophic, or intermediate junctional) and a target wound 10–50 cm2in size that was present for ≥21 days. Patients were randomly assigned to SD-101 6% cream or vehicle, which was applied topically once a day to the entire body for 3 months. Primary efficacy endpoints were time to complete target wound closure within 3 months and the proportion of patients who experienced complete target wound closure within 3 months. Post hoc subgroup analyses were conducted by patient age and in those with body surface area index of total body wound burden ≥5% at baseline.ResultsIn total, 169 patients were enrolled and randomly assigned to SD-101 6% (n = 82) or vehicle (n = 87). Baseline demographics and disease characteristics were similar between treatment groups. There were no statistically significant differences between treatment groups in time to target wound closure (hazard ratio, 1.004; 95% confidence interval [CI] 0.651, 1.549;P = 0.985) or proportion of patients with complete target wound closure within 3 months (odds ratio [95% CI], 0.733 [0.365, 1.474]; nominalP = 0.390). A positive trend toward faster wound closure with SD-101 6% versus vehicle was observed in patients aged 2 to ConclusionsSD-101 6% cream for treatment of EB-associated lesions was not more effective than vehicle in shortening the time to complete target wound closure or achieving complete target wound closure within 3 months.Trial registrationClinicalTrials.gov,NCT02384460; Date of trial registration, February 13, 2015; First participant enrolled, March 11, 2015.

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

Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with intense itch/pruritus and skin lesions. Several modalities of treatment including topical therapy, systemic agents, and biologics are available for the treatment of disease. Despite this, management poses challenge due to chronic nature and recurrent episodes in many patients. Biologics represent an important option of treatment for patients who do not respond to the traditional treatment.In this article, we focused on efficacy and safety of biologics in the treatment of atopic dermatitis. Other therapies are out of the scope of this review. Articles from PubMed and Google scholar and cross references of retrieved articles were used to write the narrative review.Biologics play an important role in the treatment of atopic dermatitis. Every biologic has its own place in the treatment considering pharmacological profile, efficacy, and safety. Several biologics have been studied in the treatment of moderate-to-severe cases who failed to provide adequate response to traditional treatment. Dupilumab, is approved for the treatment of moderate-to-severe atopic dermatitis. Tralokinumab and nemolizumab have shown promising results in patients with atopic dermatitis.

Background Standardized assessments for dystrophic epidermolysis bullosa (DEB) are needed. This prospective, multicenter, 4-week, observational study was designed to evaluate DEB assessments for suitability as clinical trial endpoints. Methods Patients with confirmed DEB diagnosis and ≥ 5 measurable wounds were included. The primary outcome was change from baseline in wound surface area (WSA) of 5 selected wounds by 3-dimensional imaging. Secondary endpoints were change from baseline in clinician global assessment (CGA) of WSA, wound characteristics, disease-related questionnaires and instruments (disease severity, quality of life [QoL], pain and disability, and itch), and tolerability of procedures. Results Of 30 enrolled patients, 29 completed the study (of whom, 28 had recessive DEB). Median age was 17.8 years (range, 3.8–58.7). All patients developed new or recurrent wounds during the 4-week study. Of the wounds selected at baseline, 45/150 (30.0%) healed by week 2; an additional 38 healed by week 4, while 8 of those healed at week 2 had recurred by week 4 for a total of 75/150 (50.0%) healed wounds at week 4. Mean values for WSA, CGA, and disease-related questionnaire and instrument scores remained steady during this 4-week observational study. Of the 10 disease-related questionnaires and instruments assessed, the scores for the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) and the Instrument for Scoring Clinical Outcomes for Research of Epidermolysis Bullosa (iscorEB) did not substantially overlap between moderate and severe disease. Between mild and moderate disease, only the EBDASI scores did not substantially overlap. Conclusions These results stress the dynamic nature of wounds, even during a 4-week period of observation, and suggest that a combination of clinician-assessed outcomes and patient-/caregiver-reported outcomes is needed to provide a comprehensive assessment of DEB severity and impact. In addition, these results support the use of EBDASI and iscorEB to monitor disease severity as both produced scores that did not substantially overlap between disease severity strata. Clinical trial registration ClinicalTrials.gov, NCT02178969. Registered 4 June 2014, https://clinicaltrials.gov/ct2/show/NCT02178969.

Dupilumab is a first-in-class biologic approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of multiple atopic diseases, including atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis. Since gaining traction as an effective treatment modality, multiple reports have highlighted the many ocular side effects associated with dupilumab usage. These range from mild diseases, such as conjunctivitis, dry eyes, and blepharitis, to more severe manifestations such as intraocular inflammation and cicatrizing conjunctivitis. The pathogenesis behind these manifestations remains controversial, but are likely multi-factorial. We review the current evidence surrounding ocular manifestations of dupilumab-associated disease and proposed treatments to provide an overview of this unique disease entity. With increasing usage of dupilumab, formal recommendations regarding the treatment of dupilumab-associated ocular disease are warranted to provide standardized clinical guidance. Furthermore, it is important for health care practitioners to remain abreast with existing literature to counsel and empower patients with the knowledge surrounding contemporary treatments for atopic diseases and their associated sideeffects.

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.

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.

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.

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.

We sought to analyze the existence of skin of color (SOC)-related literature in Pediatric Dermatology. To do so, we applied criteria developed by Wilson et al (Assessment of skin of color and diversity and inclusion content of dermatologic published literature: an analysis and call to action. Int J Women Dermatol. 2021;15:26) to categorize SOC articles. We found that Pediatric Dermatology published 28.4% SOC articles in the last three years, higher than the average (16.8%) found across surveyed dermatology journals. Our findings demonstrate opportunity for improvement through the implementation of keyword standardization and continued prioritization of SOC-related content.

Background Epidermolysis bullosa (EB) patients have multiple risk factors for osteoporosis. There is limited literature describing the prevalence of bone health in EB, particularly in adults and less severe EB types. Objectives To investigate the prevalence of osteopenia or osteoporosis in EB patients from the Australasian Epidermolysis Bullosa Registry (AEBR). Methods Of 417 AEBR patients, 72 underwent a dual energy X-ray absorptiometry scan. Bone mineral density (BMD) T and Z-scores, EB Disease Activity and Scarring Index (EBDASI), and Quality of Life in EB (QOLEB) scores were obtained. Results T-scores of RDEB patients were significantly lower than the diagnostic cut-off value for osteopenia. EBDASI and QOLEB scores were inversely correlated with Z-scores. The prevalence of osteoporosis in adults was 75% in severe EB types (RDEB and JEB). In adults with less severe types (EBS and DDEB), the prevalence of osteopenia was 50% and 33%, respectively. Conclusions This is the largest study of osteoporosis in EB to date and the first to include adult patients with EBS. The high prevalence of osteoporosis and osteopenia identified in these patients warrants larger, collaborative international studies. Nevertheless, EB patients with high disease severity and QOL scores, irrespective of type, should receive early osteoporosis screening and prophylaxis.

In recent years, calcineurin inhibitors have been used as the first line alternative to topical corticosteroids in the treatment of discoid lupus erythematosus (DLE). We aim to evaluate the efficacy and safety of topical tacrolimus 0.1% vs topical halobetasol propionate 0.05% in patients with DLE. This comparative study was carried out in the Department of Dermatology and Venereology, Chittagong Medical College Hospital (CMCH), Bangladesh between the period of July 2018 and June 2019. The change of DLE activity assessed with the cutaneous lupus erythematosus disease area and severity index was used as a primary outcome measure. The effective sample was 40 patients in each group. Both groups were similar in terms of baseline demographic and clinical characteristics. After 8 weeks of treatment, the mean total erythema score decreased significantly in both groups (in tacrolimus treated group [TTG] from 12.53 ± 8.05 to 8.03 ± 5.69, [P < .001] and in halobetasol propionate treated group [HTG] from 11.83 ± 7.17 to 7.30 ± 4.56 [P < .001]), as well as the mean total scale/hypertrophy score (in TTG from 8.08 ± 5.30 to 4.33 ± 3.21; [P < .001] and in HTG from 7.40 ± 4.73 to 3.68 ± 2.01, [P < .001]. The magnitude of reduction was significantly better in HTG [P = .032]). The mean total activity score decreased significantly in both groups (in TTG from 22.95 ± 13.40 to 14.33 ± 8.89, [P < .001] and in HTG from 22.15 ± 11.95 to 13.7 ± 7.22, [P < .001]). The present study demonstrated that tacrolimus 0.1% ointment and halobetasol propionate 0.05% ointment had a comparable efficacy in DLE patients; however, halobetasol showed significantly better improvement regarding scaly, hypertrophic lesions.

Coronavirus 2019 (COVID 19) was first detected in December 2019 in China. It has become a pandemic. With concern about therapies that may decrease immunity and enhance the severity of an indivduals's COVID‐19 infection, leading to a possibly fatal outcome, use of immunosuppressants has become an important concern. This work focuses on management of various skin diseases individuals lacking immunity to COVID‐19 but requiring a systemic immunosuppressant, keeping in view the challenge of the COVID 19 pandemic and that our knowledge of this virus and its effects on the immune system are incomplete including knowledge as to an individual's immunity after COVID‐19 infection. This article is protected by copyright. All rights reserved.

SARS‐COV‐2 is a highly virulent positive‐sense single stranded RNA virus that spreads rapidly via respiratory droplets, causing severe acute respiratory syndromes with significant mortality and morbidity. Currently 210 countries and territories are affected around the world with a reported 2.6 million confirmed cases.1 The COVID 19 pandemic has changed the way patients attend their specialist appointments and receive medical care. Whilst some specialist clinics have closed we have implemented strategies and restructured our academic practice in Australia to minimize the spread of disease whilst treating patients who need urgent care. We hope to share these strategies in the hope they may be useful to the dermatology community. This article is protected by copyright. All rights reserved.