Search

Glucocorticoid use in patients with autoimmune bullous disease is associated with significant morbidity, and in some cases, excess mortality. The hyperglycaemic complications arising from glucocorticoid use have been well-documented and range from mild hyperglycaemia to diabetic ketoacidosis. Patients with pre-existing glucose intolerance or type 2 diabetes mellitus are at increased risk of developing complications. Several other factors have been investigated for their association with steroid-induced hyperglycaemia, including patient age, sex, family history, dose, regimen and duration of therapy. Findings in the current literature, however, are largely conflicting and evidence is limited by methodological weaknesses. Glucocorticoids should be used with caution, and patients using steroids should be closely monitored for adverse effects.

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.

PDF file - 79K, A: Average array signal intensities �SD for the single probe representing COL7A1, n=3-5. B: Western blotting shows the level of type VII collagen varies between sample groups, increased in both UVSCCF samples compared with NHF. Type VII collagen is identified in RDEB fibroblast samples from patients with the following COL7A1 genotypes: x79 6501G>A/unknown and 2470insG/2470insG, and RDEBSCC fibroblasts samples from patients with x31 3832-1G>A/Unknown and x73 6075delC/unknown COL7A1 genotype.

PDF file - 56K, Unsupervised clustering of the core serum response gene set is able to cluster NHF but not RDEBSCCF sample groups in culture

XLS file - 36K, Table describing the patient samples used in this study

PDF file - 382K, Includes Microarray and Expression Analysis, BRB Array Clustering Analysis, and Tumorigenicity assays

PDF file - 190K, A: RDEBSCCF derived matrix promotes adhesion of keratinocytes compared with matrix derived from other fibroblast groups (* = p

XLS file - 8K, describing KEGG pathway analysis results

BackgroundIn two severe congenital ichthyosis subtypes, autosomal recessive lamellar ichthyosis (ARCI-LI) and X-linked recessive ichthyosis (XLRI), cutaneous manifestations include widespread scaling. Approved topical treatment options are limited to emollients and keratolytics.AimThis analysis from the randomized phase IIb CONTROL study assessed whether the efficacy and safety of TMB-001, a novel topical isotretinoin ointment formulation, differed between ARCI-LI and XLRI subtypes.MethodsParticipants ≥ 9 years with genetically confirmed XLRI or ARCI-LI and ≥ 2 (of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with ≥ 3 scaling score were randomized 1 : 1 : 1 to TMB-001 0.05%/TMB-001 0.1%/vehicle, twice daily for 12 weeks. The proportion of participants with ≥ 50% reduction vs. baseline in VIIS scaling (VIIS 50; primary endpoint) and ≥ 2-grade reduction in Investigator’s Global Assessment (IGA)-scaling score vs. baseline (key secondary endpoint) were evaluated. Adverse events (AEs) were monitored.ResultsAmong enrolled participants (TMB-001 0.05%, n = 11; 0.1%, n = 10; and vehicle, n = 12), 52% had ARCI-LI and 48% XLRI subtypes. Mean age was 33.6 and 35.4 years for participants with ARCI-LI and XLRI, respectively. Overall, 33%, 50% and 17% of participants with ARCI-LI and 100%, 33% and 75% of participants with XLRI achieved VIIS 50 in the TMB-001 0.05%, TMB-001 0.1% and vehicle groups, respectively (nominal P = 0.24 for 0.05% vs. vehicle, intent-to-treat population). Improvement of ≥ 2-grade IGA score was observed in 33%, 50% and 0% of participants with ARCI-LI and 83%, 33% and 25% of participants with XLRI in the TMB-001 0.05%, TMB-001 0.1% and vehicle groups, respectively (nominal P = 0.03 for 0.05% vs. vehicle, intention-to-treat population). Most AEs were application-site reactions.ConclusionRegardless of congenital ichthyosis subtype, TMB-001 demonstrated greater proportions of participants achieving VIIS 50 and ≥ 2-grade IGA improvement vs. vehicle.

BP is a rare autoimmune skin-blistering disorder with a profound negative impact on quality of life, associated with burdensome morbidity and possible mortality. There is a need for effective targeted therapies with a demonstrated safety profile for BP. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation that may play a role in BP. Published case series describes the use of dupilumab in patients with BP, but it has not been formally assessed in a clinical trial for BP. We describe the design of the LIBERTY-BP ADEPT trial (NCT04206553) that aims to investigate the efficacy and safety of dupilumab in achieving sustained remission off oral corticosteroids (OCS) in patients with moderate-to-severe BP. LIBERTY-BP ADEPT is a global, randomized, double-blind, placebo-controlled, parallel-group study consisting of a 35-day screening period, a 52-week double-blind treatment period and a 12-week follow-up period. Inclusion criteria include age 18–90 years and clinical features of BP with a confirmed diagnosis based on histopathology, immunopathology, and serology. Exclusion criteria include previous treatment with IL-4 or IL-13 antagonists or systemic or medium-to-high potency topical corticosteroids within 7 days of the baseline visit. All patients receive standard OCS to control disease activity at the start of the treatment period. Post randomization, after 2 weeks of sustained remission, OCS is to be gradually tapered and discontinued as long as disease control is maintained. The primary endpoint is the proportion of patients achieving sustained remission at week 36. Key secondary endpoints include total cumulative OCS dose, percent change in weekly average daily Peak Pruritus Numerical Rating Scale (NRS) score, and proportion of patients with improved daily Peak Pruritus NRS score ≥4 from baseline to week 36. LIBERTY-BP ADEPT aims to enroll 98 patients; enrollment is ongoing and will include more than 17 sites in Europe. BP shares pathophysiological pathways with type 2 inflammatory diseases mediated by IL-4 and IL-13. The ongoing LIBERTY-BP ADEPT study is the first randomized, controlled trial designed to evaluate the efficacy and safety of dupilumab in patients with moderate-to-severe BP.

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.

THE ANNIVERSARY edition of the European Academy of Dermatology and Venereology’s (EADV) 30th Congress was held between 29th September and 2nd October 2021. As COVID-19 remains a barrier to global travel, the EADV’s 30th Anniversary Congress was staged virtually, providing access to the latest research, breakthroughs, and scientific advances to dermato-venereology professionals.

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.

Rituximab (RTX) combined with short-term glucocorticoids (GC) is an effective therapeutic option for pemphigus. The newly developed Glucocorticoid Toxicity Index (GTI) tool provides the possibility to measure GC toxicities over time. To compare 1-year GTI between two groups of RTX-treated and RTX-naïve patients with pemphigus. The responsiveness of the GTI was also investigated. A prospective cohort of 129 adults with newly diagnosed pemphigus was conducted. GC-related toxicities were assessed at 3-month intervals according to Composite and Specific lists of the GTI. Of the patients, 76.7% (n = 99) received RTX. Throughout the time intervals, RTX-treated patients had lower GTI compared to RTX-naïve ones (p = 0.036). The mean GTI at 1-year was 34.3 in the RTX-treated group and 50.8 in the RTX-naïve group (p = 0.04). The most commonly observed GC-related toxicity was neuropsychiatric manifestations for 34% (224 events). The relapse rate of RTX-treated patients (1%) was significantly lower than RTX-naïve patients (10%) (p = 0.037). The GTI showed no correlation with cumulative GC consumption in both groups (p 0.05, both). Patients treated with GC alone had remarkably higher GTI than patients treated with GC plus RTX. The GTI is an applicable tool to quantitatively capture GC toxicities at the patient level in pemphigus.

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.