Case Report: Localized bullous pemphigoid induced by local triggers: a case series and a proposal for diagnostic criteria based on a literature review.

Introduction: Localized bullous pemphigoid (LBP) is an infrequent bullous pemphigoid (BP) variant restricted to a body region. According to the most compelling evidence, LBP occurs in patients with pre-existent serum antibodies against the basement membrane zone, which occasionally acquire the capacity to induce disease after the influence of different local factors acting as triggers. Methods: We hereby present a multicenter cohort of 7 patients with LBP developed after local triggers: radiotherapy, thermal burns, surgery, rosacea, edema and a paretic leg. In addition, we conducted a review of the literature, and we propose a set of diagnostic criteria for LBP, also based on our case series and the 2022 BP guidelines from the European Academy of Dermatology and Venereology. Results: During follow-up, three of the patients from our series evolved to a generalized BP, with only one requiring hospitalization. Our literature search retrieved 47 articles including a total of 108 patients with LBP, with a 63% with a potential local precipitating factor previous to their diagnosis. LBP mostly affected older females, and a subsequent generalized progression occurred in 16.7% of the cases. The most frequently involved areas were the lower limbs. Radiation therapy and surgery were responsible for the inducement of nearly 2 in 3 cases of LBP. We observed a significantly higher risk of generalization in cases where the trigger led to the developing of LBP earlier (p=0.016). Our statistical analysis did not detect any other prognosis factor for generalization when assessing direct immunofluorescence, histological and serological results, or other patient related factors. Conclusion: LBP should be suspected in patients with recurrent localized bullous eruptions. The presence of a trauma history in the same anatomic area is reported in most cases.

Allergen sensitization stratifies IL-31 production by memory T cells in atopic dermatitis patients.

Background: The role of allergen sensitization in IL-31 production by T cells and specifically in the clinical context of atopic dermatitis (AD) has not been characterized. Methods: The response to house dust mite (HDM) in purified memory T cells cocultured with epidermal cells from AD patients (n=58) and control subjects (n=11) was evaluated. AD-associated cytokines from culture supernatants, plasma proteins and mRNA expression from cutaneous lesions were assessed and related with the clinical features of the patients. Results: HDM-induced IL-31 production by memory T cells defined two subsets of AD patients according to the presence or absence of IL-31 response. Patients in the IL-31 producing group showed a more inflammatory profile, and increased HDM-specific (sp) and total IgE levels compared to the IL-31 non-producing group. A correlation between IL-31 production and patient's pruritus intensity, plasma CCL27 and periostin was detected. When the same patients were analyzed based on sp IgE and total IgE levels, an increased IL-31 in vitro response, as well as type 2 markers in plasma and cutaneous lesions, was found in patients with sp IgE levels > 100 kUA/L and total IgE levels > 1000 kU/L. The IL-31 response by memory T cells was restricted to the cutaneous lymphocyte-associated antigen (CLA)+ T-cell subset. Conclusion: IgE sensitization to HDM allows stratifying IL-31 production by memory T cells in AD patients and relating it to particular clinical phenotypes of the disease.

Apremilast improves quality of life and ultrasonography parameters in patients with nail psoriasis: A prospective cohort study.

Specific studies on apremilast for nail psoriasis are lacking. Our objective was to evaluate the nail-specific patient-reported outcomes, clinical efficacy, ultrasound (US) parameters, and safety of apremilast for nail psoriasis. We conducted a prospective cohort study including adult patients with plaque and nail psoriasis with a fingernail Nail Psoriasis Severity Index (NAPSI) score of 12 or more. Patients were treated with apremilast 30 mg b.i.d. for 52 weeks. Forty-five patients were included. At week 52, the Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) Patient Benefit Index global weighted score was 2 or more in 52% of patients and NAPPA Quality of Life and fingernail NAPSI improved by 57% and 53%, respectively. US parameters improved from week 16 onwards. Target nail NAPSI improvements were higher for nail matrix scores (60%) than for nail bed scores (38%, p < 0.001). Baseline target nail bed NAPSI was associated with not achieving a target nail 50% reduction in NAPSI score at week 52 in the bivariate analysis (p = 0.024). Safety was consistent with the known apremilast profile. Results from apremilast therapy for 52 weeks in patients with psoriasis and predominant nail disease show significant improvements in nail-specific quality of life, clinical signs, and structural restoration on US, suggesting that apremilast may be considered in the treatment of nail psoriasis.

The Role of Teledermatology and Teledermoscopy in the Diagnosis of Actinic Keratosis and Field Cancerization.

Actinic keratosis (AK) and field cancerization are increasing health problems insufficiently diagnosed by primary care physicians. The objective of this study was to assess the validity and reliability of teledermatology (TD) and teledermoscopy in the diagnosis of AK and field cancerization in a gatekeeper healthcare model. A prospective diagnostic test evaluation was done to assess the diagnostic concordance, accuracy, and performance parameters and the interobserver and intraobserver concordances of TD and teledermoscopy compared with dermatologists' face-to-face evaluation or histopathology. A total of 636 patients with 1,000 keratotic skin lesions were included. TD diagnostic concordance for AK and field cancerization evaluation was very high and superior to primary care physicians' diagnosis (92.4% vs. 62.4% and 96.7% vs. 51.8%, P < 0.001). TD sensitivity, specificity, and positive and negative predictive values for AK diagnosis and field cancerization were high (range = 82.2-95.0) and better than primary care physicians' diagnosis. Teledermoscopy yielded better results in diagnostic concordance, performance parameters, and AK subtypes. Intraobserver and interobserver agreement was >0.83. TD and, to a greater extent, teledermoscopy may be valid and reliable tools for the diagnosis of AK and field cancerization and may improve diagnosis and correct allocation and management in gatekeeper healthcare systems. It can be an alternative tool to training primary care physicians in direct diagnosis of these lesions.

Genetic and experimental evidence for the involvement of the CD6 lymphocyte receptor in psoriasis.

Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors. Available evidence supports CD6, a lymphocyte surface receptor mostly expressed by T cells, as a putative target in autoimmunity. Accordingly, a humanized anti-CD6 antibody has been assayed for the treatment of certain autoimmune disorders, including psoriasis. Here, we present novel evidence in mice and humans for a direct involvement of CD6 in psoriasis pathophysiology. First, an attenuated form of imiquimod-induced psoriasis-like skin inflammation was demonstrated in CD6-deficient mice, as deduced from lower epidermal thickness and local reduced production of pro-inflammatory cytokines, namely, interleukin-17A. Thus, isolated CD4+CD62L+ T cells from CD6-deficient mice displayed decreased in vitro T-helper type 17 polarization. Second, a statistically significant association between CD6 single-nucleotide polymorphisms (rs17824933, rs11230563 and rs12360861) and more severe forms of psoriasis was demonstrated in a cohort of 304 patients at three public hospitals from the metropolitan area of Barcelona. Taken together, these results provide new supportive evidence of the contribution of the CD6 lymphocyte receptor in psoriasis at both experimental and clinical levels.

IgG4 autoantibodies are inhibitory in the autoimmune disease bullous pemphigoid.

The IgG4 subclass of antibodies exhibits unique characteristics that suggest it may function in an immunoregulatory capacity. The inhibitory function of IgG4 has been well documented in allergic disease by the demonstration of IgG4 blocking antibodies, but similar functions have not been explored in autoimmune disease. Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease characterized by autoantibodies directed against BP180 and an inflammatory infiltrate including eosinophils and neutrophils. Animal models have revealed that the NC16A region within BP180 harbors the critical epitopes necessary for autoantibody mediated disease induction. BP180 NC16A-specific IgG belong to the IgG1, IgG3, and IgG4 subclasses. The purpose of this study was to determine effector functions of different IgG subclasses of NC16A-specific autoantibodies in BP. We find that IgG4 anti-NC16A autoantibodies inhibit the binding of IgG1 and IgG3 autoantibodies to the NC16A region. Moreover, IgG4 anti-NC16A blocks IgG1 and IgG3 induced complement fixation, neutrophil infiltration, and blister formation clinically and histologically in a dose-dependent manner following passive transfer to humanized BP180-NC16A mice. These findings highlight the inhibitory role of IgG4 in autoimmune disease and have important implications for the treatment of BP as well as other antibody mediated inflammatory and autoimmune diseases.

Toll-like receptor 9 promoter polymorphism as a predictive factor of narrow-band UVB phototherapy response in patients with psoriasis.

BACKGROUND: Prediction of response to ultraviolet B (UVB) phototherapy in psoriatic patients mainly relies on clinical criteria, although some genetic predictors have been identified. Toll-like receptors (TLRs) have been involved in psoriasis pathogenesis through activation of the innate immune system. Their polymorphisms may condition not only the clinical profile of psoriasis but also the response to therapy. METHODS: We analyzed the role of functional single-nucleotide polymorphisms (SNPs) of TLR2, 5, 4, and 9 in clinical response to a standard narrow-band UVB (NBUVB) therapy in 39 patients with moderate to severe psoriasis. RESULTS: We found a significant relationship between TLR9-1486T/C SNP variants and a better response to NBUVB phototherapy. Patients with TC and CC genotype showed a higher improvement of Psoriasis Area and Severity Index (PASI) than patients with TT genotype. Results of multivariate analysis indicate that the differences in PASI improvement at the end of phototherapy attributed to TRL9 SNP genotype were not dependent on the patients' phototype, age, gender, body mass index, basal PASI, or disease evolution. CONCLUSIONS: We describe a functional genetic variant in TLR9 gene that might affect the susceptibility to antipsoriatic treatment. The search of genetic predictive factors may be helpful in therapy selection and optimization of therapeutic regimes in psoriatic patients.

The role of Fcγ receptor polymorphisms in the response to anti­tumor necrosis factor therapy in psoriasis A pharmacogenetic study.

IMPORTANCE: Variability in genes encoding proteins involved in the immunological pathways of biological therapy may account for the differences observed in outcomes of anti­tumor necrosis factor (TNF) treatment of psoriasis. OBJECTIVE: To assess the role of 2 Fcγ receptor (FcγR) polymorphisms in the response to anti-TNF therapy in psoriasis. DESIGN: Retrospective series of patients with psoriasis who received anti-TNF therapy(infliximab, adalimumab, or etanercept) from January 1, 2007, through December 31, 2010. Patients were followed up for 12 weeks. SETTING: Two psoriasis referral centers. PARTICIPANTS: Seventy treatment-naive patients with moderate to severe psoriasis who received anti-TNF agents. INTERVENTION: Patients underwent FcγRIIA-H131R and FcγRIIIA-V158F polymorphism genotyping. MAIN OUTCOMES AND MEASURES: The Psoriasis Area and Severity Index and the body surface area were assessed at baseline and at treatment weeks 6 to 8 and 12. The polymorphism genotypes were correlated with the treatment outcomes. RESULTS: Bivariate analysis showed a nonsignificant association between FcγR low-affinity genotypes and greater improvement in the Psoriasis Area and Severity Index and body surface area at the end of treatment. Conversely, patients harboring high-affinity alleles presented a greater reduction in body surface area at the intermediate point, which remained independent in the multivariate analysis. We also detected an additive effect of both polymorphisms in the multivariate analysis. High-affinity alleles may contribute to a quicker response owing to a more efficient removal of relevant cells expressing TNF. CONCLUSIONS AND RELEVANCE: Preliminary results of this pilot study on the pharmacogenetics of FcγR and biological therapy in psoriasis suggest a role with clinical implications for FcγRIIA-H131R and FcγRIIIA-V158F polymorphisms in the outcome of anti-TNF treatment of psoriasis. These results might help dermatologists in guiding therapeutic decisions, especially in very severe cases where a quick response is needed.