The relationship between orofacial granulomatous (OFG) conditions and allergy is evolving. Contact allergies are commonly reported, but the impact of allergy avoidance is unclear, and a current review evaluating this literature has not been performed. We identified 46 studies evaluating the impact of allergen avoidance in OFG (33 case reports, 5 case series, 5 single-arm interventional clinical trials, 1 non-randomized uncontrolled trial, and 2 prospective cohort studies). Patch testing was performed in 158 patients, and the most commonly reported allergens were gold (n = 2), mercury (n = 6), cinnamal/cinnamon (n = 27), sorbic acid (n = 7), grass/silver birch/plant-containing products (n = 22), fragrance (n = 5), nickel (n = 7), and benzoic acid (n = 21). When allergen avoidance was trialed, 123/171 (71%) of patients reported some degree of improvement. A validated scoring/grading system for Granulomatous Cheilitis, Melkerrson-Rosenthal syndrome, and OFG has not been developed, so we were unable to formally assess improvement, instead relying on physician- and patient-reported outcomes in addition to oral disease severity score reporting in several studies. Current literature supports both patch testing and a trial of allergen avoidance/elimination diet to improve OFG in those with a positive result. Few controlled studies have been performed to assess this relationship, and more are needed to evaluate the impact of allergen avoidance. If a patient with difficult-to-treat OFG has a positive patch test and exposure to allergens in their diet, we would recommend a trial of allergen avoidance/elimination diet to facilitate a multimodal approach to improving control of this difficult condition.

This case series describes patients with diffuse dermal immunoglobulin deposition identified using direct immunofluorescence.

Subepidermal blistering diseases are driven by autoantibodies targeted to the basement membrane zone. These autoantibodies can stem from multiple antibody classes (e.g., IgE, IgG, IgM, IgA) and differing antibody classes and antibody targets can impact disease phenotype and potentially management. Despite significant advances, there remains a paucity of data and funding for further elucidating subepidermal blistering disease pathophysiology and the impact this has on management. This review highlights current understanding of subepidermal blistering disease antibody targets, classes, and the impact these have on disease clinical phenotype and management. Highlighted conditions will include bullous pemphigoid, mucous membrane pemphigoid, including ocular cicatricial pemphigoid, linear IgA disease, and epidermolysis bullosa acquisita.

Importance:Direct immunofluorescence (DIF) testing has been an important ancillary tool for the diagnosis of various inflammatory mucocutaneous conditions for more than 50 years. Current DIF test panels are based on historical clinical descriptions; few studies have rigorously addressed preanalytical, analytical, and/or postanalytical aspects, and even fewer have been replicated or validated. Recent unresolved key issues include whether DIF testing and test panels should be triaged or truncated based on clinical indication or histopathologic findings. Objective:To assess levels of consensus regarding practical aspects of DIF testing among immunodermatology testing specialists in the US. Design, Setting, and Participants:Using modified Delphi methods with a priori characterized criteria, a survey containing 54 statements pertaining to DIF testing was created and distributed to assess consensus. Statements not initially reaching consensus were discussed in 2 live virtual sessions, which were supplemented by relevant literature review and free-text survey comments. These statements were then reassessed in a second survey. Immunodermatology testing specialists in US academic institution-based and independent laboratories were invited based on serving as immunodermatology laboratory medical directors, authoring pertinent literature, or delivering relevant talks at major conferences or by referral. The first survey was conducted from January to February 2024, and the second survey was conducted from March to April 2024. Main Outcomes and Measures:The primary measured outcome was degree of consensus for various DIF testing practice, including DIF testing triage by histopathology/dermatopathology findings and DIF testing panel tailored truncations by clinical indication. Results:A total of 23 respondents to the survey invitation had a mean (SD) of 18.5 (11.1) years and median (range) of 20.0 (1.5-46.0) years in immunodermatology laboratory practice. Consensus was achieved for 46 of 54 statements (85.2%) in the initial survey and for an additional 4 statements in the second survey (50 of 54 [92.6%]). Strong consensus was found against tailored truncation of DIF panel based on the clinical indication in the first survey round. The general acceptability of triaging specimens for DIF testing based on histopathology findings remained without consensus after both surveys. Conclusions and Relevance:Overall, participating US specialists in immunodermatology laboratory testing agreed on many practical aspects of DIF testing, including matters not queried previously. The findings also revealed areas of continued controversy and identified issues for prioritized future study.

There is a reported association between oral contact allergy and oral lichen planus (OLP). Likewise oral squamous cell carcinoma (oSCC) is associated with OLP. It is hypothesized that chronic inflammation may contribute to oSCC risk. Ostensibly, we hypothesized that allergy testing positivity may increase inflammation and thus may be associated with oSCC in OLP. As a secondary objective, we assessed oSCC prevalence in OLP, allergen prevalence in OLP, and associations between allergy testing and OLP phenotype. To do this, we performed a retrospective cohort evaluation of OLP patients seen at the University of Utah from 2015 to 2022. Odds of oSCC occurrence by allergy testing status, clinical/demographic factors and asssociations between allergy testing and OLP phenotype were assessed using univariable and multivariable logistic regression. The prevalence of oSCC and allergy testing (patch + scratch testing) results were summarized descriptively. OLP diagnoses were confirmed by our OLP-specialized clinicians, and/or histologic assessment. Allergy testing was performed by two specialized dermatologists. oSCC diagnosis was identified via chart review and histologic data. Among 587 OLP patients identified, 133 were allergy tested and 77.4

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disorder, primarily presenting with tense bullae and severe pruritus. Diagnosing and treating BP can be challenging due to its variable clinical presentations. We will briefly discuss these phenotypes, highlight diagnostic basics, and briefly summarize recent laboratory advancements that have improved diagnostic sensitivity and accuracy. The treatment landscape for BP has evolved significantly. Newer therapies, including biologics such as rituximab, omalizumab, dupilumab and Janus kinase inhibitors target the immunopathogenesis of BP and can reduce the adverse effects associated with cumulative corticosteroid exposure and conventional immunosuppressants. This article provides a comprehensive overview of BP's clinical features, diagnostic approaches, and emerging therapeutic options, emphasizing personalized medicine and improved patient outcomes.

BACKGROUND:Oral lichen planus (OLP) is an inflammatory disease involving the oral mucosa. It affects roughly 0.5% to 2% of the global population and has an associated risk of oral squamous cell carcinoma. Treatment of moderate to severe OLP often requires immunosuppression. The durability of immunosuppressive medication is currently unknown and is important for understanding therapeutic testing needs. OBJECTIVE:We investigated traditional immunosuppressive drug survival in patients with OLP and evaluated potential discontinuation factors. METHODS:We retrospectively analyzed patients with OLP treated with methotrexate, mycophenolate, azathioprine, or cyclosporine. Time to medication discontinuation was evaluated using the Kaplan-Meier estimator, and Cox proportional hazards regression was used to compare the risk of discontinuing a medication between medications and across patient demographic and disease factors. RESULTS:We identified 125 treatment periods with mycophenolate (n=58), methotrexate (n=34), azathioprine (n=19), or cyclosporine (n=14). Most patients had erosive disease (92%), and median time (IQR) to discontinuation due to adverse events or inefficacy was 9.43 months (6.51-16.1). Overall, only cyclosporine was associated with higher risk of discontinuation compared to methotrexate (hazard ratio [HR]: 2.94; 95% confidence interval [CI]: 1.32-6.45). There was no evidence for risk differences across age or sex for the overall cohort. Within individual medication groups, age was associated with a small increased risk of discontinuing mycophenolate (HR: 1.05; 95% CI: 1.00-1.10) and a small decreased risk in cyclosporine (HR=0.94, 95% CI: 0.89-0.99). Otherwise, no demographic factors were associated with discontinuation. Treatment success was reported 8 times. DISCUSSION:Immunosuppressive medications were frequently discontinued after short time periods, and few were discontinued due to success. These data highlight the need for better systemic therapy in OLP.

Background: Patch-test positivity is common in oral lichen planus (OLP), and allergens may contribute to disease activity. Patch testing provides targeted allergen avoidance and may improve disease.

Aberrant glycan modifications have been hypothesized to drive autoimmune pathogenesis, especially those at the conserved immunoglobulin constant heavy chain domain 2 (CH2)-84.4 site of IgG ( Maverakis et al., 2015 Maverakis E. Kim K. Shimoda M. Gershwin M.E. Patel F. Wilken R. et al. Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: a critical review. J Autoimmun. 2015; 57: 1-13 Crossref PubMed Scopus (343) Google Scholar ). Glycans at this site dictate Ig effector function, with agalactosylated glycans being linked to antibody-mediated autoimmune conditions such as rheumatoid arthritis ( Gudelj et al., 2018 Gudelj I. Salo P.P. Trbojević-Akmačić I. Albers M. Primorac D. Perola M. et al. Low galactosylation of IgG associates with higher risk for future diagnosis of rheumatoid arthritis during 10 years of follow-up. Biochim Biophys Acta Mol Basis Dis. 2018; 1864: 2034-2039 Crossref PubMed Scopus (62) Google Scholar ). Pemphigus vulgaris is an autoimmune blistering disease characterized by autoantibodies directed against desmosomal cadherins.

Skin-related quality of life (SRQL) in autoimmune bullous disease (AIBD) may be different between diseases and flare states. We sought to evaluate SRQL during patient-reported flare and non-flare. We also examined Skindex-16 construct validity as development cohorts did not contain AIBD. Diagnoses included: pemphigus, pemphigoid, dermatitis and herpetiformis (DH). Skindex-16 assessed SRQL (three domains [emotions, symptoms, functioning] scored 0-100, higher scores = worse SRQL). Differences in median Skindex-16 score were calculated with quantile regression. Internal consistency and standard error of measurement (SEM) were calculated using Cronbach's alpha. Convergent validity between Skindex-16 and other patient reported outcomes was assessed with Spearman's rank correlation. We identified 148 AIBD patients not experiencing flare and 65 experiencing flare. SRQL was worse for all conditions during flare than non-flare (SRQL difference > SEM and p<0.05). Desmoglein-1 and 3 were likewise significantly different between flare and non-flare, whereas other labs were not associated with flare. Compared with pemphigus, non-flare emotional SRQL was worse in pemphigoid (+7; 95% CI -0.41-14.4), and DH (+14.3; 3.62-25.0). During flare, pemphigoid had better emotional- (-14; -45.1-16.6) and symptom-related (-25; -53.6-3.64) SRQL. Cronbach's alpha was >0.80 for all domains and disease states. Skindex-16 showed moderate correlation with PROMIS Depression and patient-reported disease severity. Low correlation was seen with PROMIS Physical Functioning. Overall floor effects >20% were seen during non-flare, but ceiling effects were rare (<10% for all domains). SRQL was severely impacted by AIBD, especially during flare. Patients with pemphigoid and DH had worse SRQL during non-flare, highlighting possible therapeutic gap. These data support the construct validity of Skindex-16 in patients with AIBD.

BACKGROUND:Dermatitis herpetiformis (DH) is a rare gluten-induced skin disorder characterized predominantly by IgA autoantibodies against endomysium, tissue transglutaminase (TG2/tTG), epidermal transglutaminase (TG3/eTG) and deamidated gliadin. To date, circulating autoantibody reactivity has not been systematically described.OBJECTIVES:Characterization of serum reactivities in DH.METHODS:This multicentre international study analysed sera from 242 patients with DH taken at the time of initial diagnosis. DH-specific IgA and IgG serum autoantibodies were analysed by indirect immunofluorescence (IF) on monkey oesophagus, and by enzyme-linked immunosorbent assay (ELISA) based on recombinant TG2/tTG, TG3/eTG and deamidated gliadin (GAF3X).RESULTS:IgA indirect IF microscopy on monkey oesophagus revealed the highest reactivity (84.3%; specificity 100%) followed by IgA TG2/tTG ELISA (78.5%, specificity 99.0%), IgA TG3/eTG ELISA (72.7%, specificity 95.0%) and IgA GAF3X ELISA (69.0%, specificity 98.5%).CONCLUSIONS:Serum IgA and IgG autoantibodies against endomysium, TG2/tTG, TG3/eTG and deamidated gliadin are highly prevalent in DH. Indirect IF microscopy on monkey oesophagus (IgA) provides the highest diagnostic accuracy that can be further enhanced by 4.5% when combined with IgA TG2/tTG ELISA.

Oral lichen planus (OLP) is a recalcitrant, relapsing autoimmune condition that poses a significant treatment challenge. Allergies to dental metals, fragrances, and additives have been documented in the setting of OLP. Likewise, oral squamous cell carcinoma (OSCC) has been reported to evolve in lesions of OLP. We hypothesized that the chronic inflammation of allergy-driven OLP may increase the odds of developing OSCC. Our primary objective was to compare the odds of OSCC between patch test negative and positive patients. A query was performed of all patient charts at the University of Utah Health from 01/01/2015 to 09/01/2022 for ICD-10 codes for lichenoid dermatitis. Results/Conclusions: We identified 587 patients with OLP. Of these, 131/587 (22%) were patch tested and 98/131 (72%) reacted to an allergen on patch/scratch testing. 55/98 (56%) reacted to a dental metal or product found in fillings/crowns, and 43/98 (44%) reacted to a flavoring, additive, or fragrance. Reactions to metals were: cobalt (n=7), mercury (n=6), palladium (n=13), gold (n=8) and nickel (n=24). Reactions to additives, flavorings, preservatives, and fragrances were observed to Balsam of Peru (n=31), benzoic acid (n=26), cinnamic aldehyde (n=17), and fragrance mix (n=17). 43/587 (7%) of OLP patients developed an OSCC and 33% (14/43) of these patients had been patch tested. 9/14 (64%) reacted to a dental metal, and 2/14 to Balsam of Peru. There was insufficient evidence to support an increased risk of OSCC in the setting of a positive patch test (Odds ratio 1.26, 95% CI 0.33-4.84). In this cohort, we did not find sufficient evidence to support an association between patch test positivity and OSCC. However, we did find a high rate (72%) of patch test positivity to pertinent allergens, supporting the practice of patch testing in these patients. This data also highlights that OSCC is relatively common in these patients and regular oral examinations and biopsy of changing lesions is critical.

Importance Autoimmune bullous diseases (AIBDs) are chronic relapsing-remitting conditions with significant morbidity. Skin-related quality of life (SRQL) may vary by AIBD subtype and disease type. Disease severity and flare severity can be difficult to define; SRQL can offer a key insight. Objectives To investigate the Skindex-16 score as an SRQL measure in AIBD subtypes during flare and nonflare states and to evaluate Skindex-16 construct validity. Design, Setting, and Participants This retrospective cross-sectional study was conducted from September 1, 2016, to February 1, 2020, among 192 patients at the University of Utah Health autoimmune dermatology clinic with pemphigoid, pemphigus, dermatitis herpetiformis, and linear immunoglobulin A disease. Patients had an encounter-associated diagnosis, Skindex-16 scores, and self-reported flare status. Statistical analysis was performed from March 2022 to June 2023. Exposure Autoimmune bullous disease subtype and patient-reported flare status. Main Outcomes and Measures Skindex-16 domain scores (emotions, symptoms, and functioning; range, 0-100, where 0 indicates no effect on SRQL and 100 maximum effect) and individual item scores were described by disease and flare status. Flare scores were expected to be higher by at least the standard error of measurement (SEm). Convergent validity was assessed using Spearman correlation among Skindex-16 scores, serologic titers, and other patient-reported outcome measures. Floor or ceiling domain scores (<20% of sample scoring either lowest or highest possible domain scores, respectively) were assessed for Skindex-16. Structural validity was assessed using confirmatory factor analysis (CFA). Results The study included 192 patients with 212 visits (median age, 68 years [IQR, 58-76 years]; 123 of 212 women [58.0%]) with Skindex-16 scores (64 in flare state and 148 in nonflare state). Median Skindex-16 domain scores were higher for all disease categories among patients in the flare state compared with those in the nonflare state (pemphigoid [emotions: flare, 52.4 (IQR, 38.1-69.0); nonflare, 7 (IQR, 0-17); symptoms: flare, 37.5 (IQR, 29.2-58.0); nonflare, 13 (IQR, 0-25); functioning: flare, 26.7 (IQR, 10.0-56.7); nonflare, 0 (IQR, 0-3)]; pemphigus [emotions: flare, 54.8 (IQR, 31.0-81.0; nonflare, 0 (IQR, 0-19); symptoms: flare, 58.3 (IQR, 41.7-70.8); nonflare, 4 (IQR, 0-12.5); functioning: flare, 26.7 (IQR, 13.3-83.3); nonflare, 0 (IQR, 0-3.33)]; dermatitis herpetiformis [emotions: flare, 72.6 (IQR, 34.7-90.5); nonflare, 14.3 (IQR, 2.4-26.2); symptoms: flare, 69 (IQR, 31.3-85.4); nonflare, 12.5 (IQR, 0-29.2); functioning: flare, 38.3 (IQR, 5.0-63.2); nonflare, 0 (IQR, 0-13.3)]. This difference exceeded SEm cut points. Cronbach α was greater than 0.80 for all domains and AIBDs. Moderate or low correlations were seen with desmoglein 1 and bullous pemphigoid 180 titers. Moderate correlation existed between Skindex-16 and Patient-Reported Outcomes Measurement Information System Depression scores (emotions: ρ = 0.40; symptoms: ρ = 0.41; functioning: ρ = 0.48), and strong correlation existed between Skindex-16 and patient-reported disease severity (emotions: ρ = 0.71; symptoms: ρ = 0.73; functioning: ρ = 0.66). Floor domain scores greater than 20% were seen among patients in the nonflare state, but ceiling domain scores were rare (<10% for all domains); CFA model fit was poor. Conclusions and Relevance In this cross-sectional study, SRQL was highly associated with flare of AIBDs. Skin-related quality of life was worse during periods without flare among patients with pemphigoid and dermatitis herpetiformis compared with pemphigus, highlighting residual SRQL morbidity. Skindex-16 showed good construct validity, but the poor CFA model fit needs further research. Clinical measurement of SRQL in AIBDs can add critical disease-severity information.