Autoimmune Dermatological Diseases Research Articles

Update on protease-activated receptor 2 in inflammatory and autoimmune dermatological diseases

Protease-activated receptor 2 (PAR2) is a cell-surface receptor expressed in various cell types, including keratinocytes, neurons, immune and inflammatory cells. Activation of PAR2, whether via its canonical or biased pathways, triggers a series of signaling cascades that mediate numerous functions. This review aims to highlight the emerging roles and interactions of PAR2 in different skin cells. It specifically summarizes the latest insights into the roles of PAR2 in skin conditions such as atopic dermatitis (AD), psoriasis, vitiligo and melasma. It also considers these roles from the perspective of the cutaneous microenvironment in relation to other inflammatory and autoimmune dermatological disorders. Additionally, the review explores PAR2’s involvement in associated comorbidities from both cutaneous and extracutaneous diseases. Therefore, PAR2 may serve as a key target for interactions among various cells within the local skin environment.

Impactos biopsicossociais enfrentados por pacientes com vitiligo: Uma revisão sistemática

Objective: The aim of this review was to report current knowledge about the main signs and symptoms that affect the quality of life of individuals with vitiligo. Methodology: The searches were carried out through searches in the PubMed Central (PMC) databases. Three descriptors were used in combination with the Boolean term "AND": vitiligo; quality of life; depression; psychosocial impact; Medical Psychology. From this search, 275 articles were found, which were subsequently submitted to the selection criteria. Of which, after applying the inclusion and exclusion criteria, 36 articles were selected from the PubMed database, and a total of 19 studies were used to compose the collection. Discussion: Thus, studies denote that the skin, being the largest organ in the body, is crucial for personal image and diseases that alter its pigmentation, such as vitiligo, reduce the quality of life, especially for young people. From a biological and embryonic point of view, the skin and the brain have an intimate relationship, which suggests that changes in it can be associated with mental health problems, exacerbating or triggering dermatological conditions, which culminate in nervousness, decreased self-confidence, anxiety and even depression. Results: It is known that there may be a biomarker for the activity or severity of vitiligo where it is related to the prevalence of psychiatric problems, creating image distortions. In summary, being a multifactorial autoimmune dermatological disease, it would generate a great impact on the lives of patients, influencing individual self-image and the way the world will perceive it, and thus resulting in a worsening of quality of life.

Metabolomic and lipidomic fingerprints in inflammatory skin diseases – Systemic illumination of atopic dermatitis, hidradenitis suppurativa and plaque psoriasis

Auto-inflammatory skin diseases place considerable symptomatic and emotional burden on the affected and put pressure on healthcare expenditures. Although most apparent symptoms manifest on the skin, the systemic inflammation merits a deeper analysis beyond the surface. We set out to identify systemic commonalities, as well as differences in the metabolome and lipidome when comparing between diseases and healthy controls. Lipidomic and metabolomic LC-MS profiling was applied, using plasma samples collected from patients suffering from atopic dermatitis, plaque-type psoriasis or hidradenitis suppurativa or healthy controls. Plasma profiles revealed a notable shift in the non-enzymatic anti-oxidant defense in all three inflammatory disorders, placing cysteine metabolism at the center of potential dysregulation. Lipid network enrichment additionally indicated the disease-specific provision of lipid mediators associated with key roles in inflammation signaling. These findings will help to disentangle the systemic components of autoimmune dermatological diseases, paving the way to individualized therapy and improved prognosis.

The Serological Evidence of Positive Rheumatoid Factor in Morphea Patients and Its Relation to Disease Severity.

Background and objective Morphea, or localized scleroderma (LS), is an autoimmune skin disorder characterized by inflammation and sclerosis. Its potential causes include infections, genetic predisposition, and trauma. The disease involves cycles of inflammation and fibrosis, leading to skin hardening and scarring, which can cause deformities ifuntreated. Researchexploring the link between morphea and rheumatoid factor (RF), a marker associated with other autoimmune conditions, is ongoing. This study aimed to examine the less-explored role of RF, a marker typically linked to rheumatoid arthritis (RA), in the severityof morphea. It focused on assessing the levels of RFamong morphea patients and its correlation with disease severity, intending to provide deeper insights intothe condition and its management. Methods This study involved a simple randomized cross-sectional analysis to evaluate the role of the RF in measuring morphea severity among patients at the Dermatology and Venereology Department of Al-Sader Teaching Hospitalfrom October 2022 to December 2023. We included participants with clinically and laboratory-confirmed morphea while excluding those with other autoimmune dermatological diseases, recent systemic steroid or immunosuppressive therapy, and pregnant women. The assessment of disease severity was done by utilizing the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT).Statistical analyses were performed using SPSS Statistics version 27 (IBM Corp., Armonk, NY), with a significance threshold of p<0.05. Results Elevated RF levels were significantly associated with increased morphea severity, with severe cases showinghigher RF levels (mean: 30.34 U/mL) compared to moderate (25.83 U/mL) and mild cases (21.56 U/mL) (p = 0.028). However, no significant correlation was found between RF levels and demographic factors such as age, gender, or occupation. Patients with high RF levels had a longer disease duration (mean: 57.15 years) compared to those with normal levels (25.83 years, p = 0.020). Significant differences were observed in lesion distribution on the back (p = 0.002). Logistic regression indicated that severe morphea patients were more likely to have elevated RF levels [odds ratio (OR): 1.158, p = 0.014]. Conclusions This study enriches our understanding of RF's role in morphea, revealing no significant correlation with demographic factors but suggesting its potential role in disease chronicity and severity.

Footprints of Stress in Vitiligo: Association of the 5-HTR2C rs6318 Variant

Abstract Vitiligo is a chronic, progressive autoimmune dermatological disease, and stress is known to have an impact on the development of vitiligo. However, the effect of the serotonin pathway and its impact have not been clearly explained for disease progression. Thus, this study aimed to clarify the stress induced serotonin receptor 5-HTR2C rs6318 variant and its association with vitiligo pathogenesis. Case-control study was conducted with 108 vitiligo patients and 107 age-sex matched, unrelated healthy control group. Real Time-PCR analysis was used for genotyping the 5-HTR2C variation. Genotype and allele frequencies, genotype distributions, Hardy-Weinberg Equilibrium (HWE) and vitiligo-related risk measurements were examined. Genotype correlations of the variant were also analyzed based on gender difference, age onset, Koebner phenomenon history, triggered with stress, clinical subgroups, treatment types, the presence of other autoimmune diseases, vitiligo presence in family members and other auto-immune diseases in relatives. Statistical differences in 5HT-R2C receptor genotypes and allele frequencies between patients and controls were not detected. Genotype frequencies were not in agreement with Hardy-Weinberg Equilibrium in the patients’ group (p&lt;0.00001). The frequency of the risk allele (allele C) was not significantly different between the patient and control groups (p=0.1392). However, in the clinical subgroup analysis, the risk allele presence was detected to be significantly higher for early age onset (&lt;40 years) vitiligo development (p=0.035, OR=Infinity, RR=1.391) and lower in Koebner phenomenon history (p=0.0276, OR= 0.219, RR=0.325). In conclusion, although there was no association between the 5-HTR2C variant rs6318 and vitiligo, current results indicate that there is an association between the 5HTR2C rs6318 variant C allele and early onset vitiligo development.

The Renin-Angiotensin System: The Challenge behind Autoimmune Dermatological Diseases.

Autoimmune dermatological diseases (AIDD) encompass a diverse group of disorders characterized by aberrant immune responses targeting the skin and its associated structures. In recent years, emerging evidence suggests a potential involvement of the renin-angiotensin system (RAS) in the pathogenesis and progression of these conditions. RAS is a multicomponent cascade, primarily known for its role in regulating blood pressure and fluid balance. All of the RAS components play an important role in controlling inflammation and other immune responses. Angiotensin II, the main effector, acts on two essential receptors: Angiotensin Receptor 1 and 2 (AT1R and AT2R). A disturbance in the axis can lead to many pathological processes, including autoimmune (AI) diseases. AT1R activation triggers diverse signaling cascades involved in inflammation, fibrosis and tissue remodeling. Experimental studies have demonstrated the presence of AT1R in various cutaneous cells and immune cells, further emphasizing its potential contribution to the AI processes in the skin. Furthermore, recent investigations have highlighted the role of other RAS components, beyond angiotensin-converting enzyme (ACE) and Ang II, that may contribute to the pathophysiology of AIDD. Alternative pathways involving ACE2, Ang receptors and Ang-(1-7) have been implicated in regulating immune responses and tissue homeostasis within the skin microenvironment. Understanding the intricate involvement of the RAS in AIDD may provide novel therapeutic opportunities. Targeting specific components of the RAS, such as angiotensin receptor blockers (ARBs), ACE inhibitors (ACEIs) or alternative RAS pathway modulators, could potentially ameliorate inflammatory responses, reduce tissue damage and lessen disease manifestations. Further research is warranted to outline the exact mechanisms underlying RAS-mediated immune dysregulation in AIDD. This abstract aims to provide a concise overview of the intricate interplay between the RAS and AIDD. Therefore, we elaborate a systematic review of the potential challenge of RAS in the AIDD, including psoriasis, systemic sclerosis, vitiligo, lupus erythematosus and many more.

Effect of Shodhana and Gandhaka Rasayana in Psoriasis - A Case Study

Psoriasis is one of the most common inflammatory autoimmune dermatologic diseases. The major concerns of psoriasis are social stigma which leaves a significant emotional impact for the patient. However, systematic management strategies, diet modification and timely monitoring shows an improvement in health-related quality of life and thus an improvement in social and psychological wellbeing. Severity of psoriasis tends to fluctuate with exogenous factors like diet, environmental factors etc. Spontaneous exacerbations and remissions are usual. There IS no specific treatment protocol in the management of psoriasis. In Ayurveda the symptoms are more similar to Vata kapha predominant Kushta, more specifically Sidhma kushta. The present study is aimed to treat a 22-year-old male patient, a known case of plaque psoriasis admitted in the IPD of Kayachikitsa department, Govt. Ayurveda College, Thiruvananthapuram. Deepana, Pachana Sodhana, Samana and Rasayana were the treatment protocol included. Ayurvedic approach in a single case of psoriasis is found beneficial in correcting the inherent Agnimandya at Koshta and Dhatu level and thus arrest the progression of the autoimmune inflammatory pathology. PASI (Psoriasis Assessment Severity Scale) score was used to assess the severity of lesions. Before treatment PASI score was 5.7 which reduced to 4.2 after 2 weeks. At the time of discharge PASI score was 0. The case report shows no recurrence of symptoms on review after 4 weeks.

A rare case of acquired A haemophilia associated with bullous pemphigoid complicated by cerebral fungal abscesses and multiple opportunistic infections

Acquired A Haemophilia (AHA) is a rare autoimmune disease caused by production of anti VIII factors antibodies that could cause multiple haemorrhagic manifestations. Usually idiopathic, could be related with other conditions, such as Bullous Pemphigoid (BP), an autoimmune dermatologic disease.

Blue light-emitting diodes for the treatment of localized vitiligo: A retrospective study.

Vitiligo is an autoimmune dermatological disease characterized by hypopigmented macules. Treatments include topical agents, phototherapy, and laser therapies. Different lasers should be individually chosen regarding location, extent, activity of the disease. This article aims to demonstrate how blue LED is effective and safe, as its wavelength is very close to the UV spectrum (415 nm vs. 400 nm), but, unlike UV therapy, blue LED have not shown any long-term cancerogenic side effects. We treated 30 patients affected by vitiligo localized on different anatomical areas with blue light-emitting diodes. Complete repigmentation occurred in 75.33% of treated patients (22 out of 30 patients, 14 males, and 8 females). Partial repigmentation occurred in the remaining patients. Blue LED light may be a safe and well-tolerated way to induce repigmentation in patients affected by vitiligo.

LASER THERAPY IN THE TREATMENT OF ORAL MANIFESTATION OF PEMPHIGUS VULGARIS: CASE REPORT

Pemphigus vulgaris is an autoimmune dermatological disease that results from the production of autoantibodies against desmogleins 1 and 3. A 41-year-old brown-skinned female patient reported to the emergency of a hospital with reports of painful sores in the mouth and skin. On physical examination, ulcers on the body and blisters on the palms of the hands were observed. On intraoral examination, ulcerated lesions were observed on the lateral border of the tongue, hard palate, buccal mucosa, and crusts on the lips. The diagnostic hypotheses were pemphigus vulgaris, Stevens-Johnson syndrome, and bullous pemphigoid. The hypothesis of pemphigus vulgaris was confirmed through biopsy and histopathologic analysis. Systemic corticosteroid treatment and 14 sessions of red laser treatment were performed to promote analgesia and repair. Laser therapy proved to be effective as a complementary treatment for lesions in the mouth, providing comfort due to the reduction of painful symptoms and total regression of the lesions. Pemphigus vulgaris is an autoimmune dermatological disease that results from the production of autoantibodies against desmogleins 1 and 3. A 41-year-old brown-skinned female patient reported to the emergency of a hospital with reports of painful sores in the mouth and skin. On physical examination, ulcers on the body and blisters on the palms of the hands were observed. On intraoral examination, ulcerated lesions were observed on the lateral border of the tongue, hard palate, buccal mucosa, and crusts on the lips. The diagnostic hypotheses were pemphigus vulgaris, Stevens-Johnson syndrome, and bullous pemphigoid. The hypothesis of pemphigus vulgaris was confirmed through biopsy and histopathologic analysis. Systemic corticosteroid treatment and 14 sessions of red laser treatment were performed to promote analgesia and repair. Laser therapy proved to be effective as a complementary treatment for lesions in the mouth, providing comfort due to the reduction of painful symptoms and total regression of the lesions.

Esophageal Bullous Pemphigoid.

Bullous pemphigoid is a rare autoimmune dermatologic disease that usually occurs in the elderly. Mucous membrane lesions occur in about 10–35% of patients and are almost always limited to the oral mucous membrane. Esophageal involvement is very rare (4% of cases) and usually presents with chest pain, dysphagia, and odynophagia, though patients are frequently asymptomatic. We report the case of newly diagnosed bullous pemphigoid in a 76-year-old man with a past medical history of dementia. He presented with cutaneous manifestations but also severe gastrointestinal bleeding due to extensive esophageal involvement. Although bullous pemphigoid is mainly a skin disease, mucous membrane lesions should not be overlooked as they are associated with an even poorer outcome. A high index of suspicion for esophageal involvement is needed as its presentation can be fatal, as with our patient.LEARNING POINTSBullous pemphigoid is a rare autoimmune disease that should be suspected in elderly patients with itchy cutaneous lesions.Mucous membrane lesions should always be evaluated, as they are associated with a poor prognosis, even if asymptomatic.Early diagnosis should be the main focus, as steroids, the mainstay of treatment, may not be effective in severe cases.

Drug Reaction with eosinophilia and systemic symptoms with alopecia universalis and vitiligo

Drug reactions with eosinophilia and systemic symptoms (DRESS) are rare and potentially fatal adverse hypersensitivity reaction to some drugs, especially anticonvulsants. The syndrome affects not only the skin but also other organs, especially the liver. The incidence can vary from 1 to 5 cases per 10.000 patients exposed to anticonvulsants.The recognition of the syndrome is of fundamental importance since the mortality rate is between 10 and 40%. Once the diagnosis is established, the triggering drug must be identified and discontinued. Corticosteroids are usually associated with therapy. Autoimmune sequelae have been reported, including vitiligo and rarely alopecia. Alopecia universalis is a variant of alopecia areata, characterized by hair loss throughout the body. We report a case of DRESS, associated with two autoimmune dermatological diseases: alopecia universalis and vitiligo.

The oral manifestations of scurvy in the 21st century

Scurvy is a vitamin deficiency historically associated with pirates and sailors that affects collagen synthesis, leading to hemorrhage, skin, and oral lesions. In the 18th century, the lack of consumption of foods rich in vitamin C was found to cause such a severe condition, whose early diagnosis increases the likelihood of a better prognosis. A 58-year-old female patient complained of fatigue, body pain, and gingival bleeding for nearly 24 months. In 2001, she was diagnosed with lupus, now in remission, and osteoporosis more recently. On clinical examination, gingivitis with spontaneous bleeding was observed, despite the patient’s good hygiene, as well as some petechiae over the body. Due to the hypothesis of a possible autoimmune dermatological disease, the patient was referred to a dermatologist, who requested a series of tests, including vitamin C dosage. The results showed a concentration below 0.25mg / dL (IR, 4 to 2.0 mg / dL), and thus the diagnosis of scurvy was established. The patient was administered vitamin C replacement and in about 3 months, the symptoms started to improve. In some cases, such as this, hospitalization is required for intravenous replacement due to bleeding risks. This case report highlights the importance of the dentist in the early diagnosis and treatment of scurvy. This condition causes oral lesions that are often confused with other more common conditions, such as gingivitis or autoimmune dermatological response. Therefore, we recommend a comprehensive physical examination and anamnesis, including dietary history.

Alopecia areata: A psychodermatological perspective.

Alopecia Areata (AA) is an autoimmune dermatological disease that could be influenced by psychological factors as part of the pathophysiology of the illness. This review article aims to report on psychodermatological and psychopathological aspects involved in the etiopathogenesis and comorbidities of AA, as well as on the psychiatric and psychological management of affected patients. We conducted a literature search on PubMed and Google Scholar from January 1980 to May 2021 employing the search terms of alopecia areata, psychological factors, psychological impact, psychodermatology, and psychopathology. All lists of references from the identified articles were screened for further relevant studies. The search was limited to English and Spanish language articles and was supplemented with themed books and book chapters. No specific quality criteria were used for the studies selection. Several authors have found a high comorbidity rate between AA and mental disorders, concluding that stress and psychological factors are involved in both the development and exacerbation of the illness. More evidences are needed in order to describe the associations between the immune response, stress, and the physiological factors observed in AA patients. AA is a complex illness characterized by multifactorial etiology. An interaction between genetic, autoimmune, hormonal, neural, and psychological factors is supposed. Psychopathological aspects of illness need to be better described and considered in the clinical setting.

27978 Psoriasis and methotrexate: A systematic review and meta-analysis of nonmelanoma skin cancer risk

Background: Psoriasis is a chronic, autoimmune dermatologic disease that often requires systemic treatment. Of the immune regulating therapies, methotrexate (MTX) is a commonly used systemic therapy. Both MTX and psoriasis are associated with an increased risk of developing nonmelanoma skin cancers (NMSCs). Currently, the risk associated with combining these factors is not well quantified.

The role of autophagy-related gene 9B in lichen planus.

Lichen planus (LP) is an idiopathic, chronic, relapsing, inflammatory, autoimmune dermatological disease. The etiopathogenesis of LP is still unclear. Autophagy is a strictly regulated lysosomal degradation pathway that is crucial for maintaining intracellular homeostasis and normal development. The dysregulation of autophagy-associated genes was recognized to increase the susceptibility to multiple diseases, including inflammation, autoimmune disorders and cancer. Our study aimed to detect the expression of autophagy-related gene 9 b (ATG9B) in LP patients compared to normal control persons to investigate the possible role of autophagy in pathogenesis of this disease. This case-control study included 30 LP patients and 30 age-, gender-matched healthy controls. Four millimeters punch skin biopsies were obtained from LP lesions and from the controls and they were kept in lysis solution for the stability of the studied parameters and were kept frozen at -80°C till analysis of ATG9B using real-time polymerase chain reaction. The level of ATG9B in lesional skin of LP was significantly decreased compared to normal control persons (P < 0.01); also, there was a non-significant relation between ATG9B level and age, sex, duration and family history among LP patients. Limited number of patients included in our study (30 patients). Autophagy may play a role in the pathogenesis of cutaneous LP.

Anti-Angiogenic Efficacy of PSORI-CM02 and the Associated Mechanism in Psoriasis In Vitro and In Vivo.

Psoriasis is a chronic proliferative autoimmune dermatologic disease characterised by abnormal angiogenesis. Thus, regulating angiogenesis in the skin is an important treatment strategy for psoriasis. PSORI-CM02, an empirical Chinese medicine formula optimised from Yin Xie Ling, was created by the Chinese medicine specialist, Guo-Wei Xuan. Clinical studies have shown that PSORI-CM02 is safe and effective for the treatment of psoriasis. However, its anti-psoriatic mechanisms remain to be further explored. In this study, we investigated the effects of PSORI-CM02 on angiogenesis in the skin and the underlying mechanisms in IL-17A-stimulated human umbilical vein endothelial cells (HUVECs) and a murine model of imiquimod (IMQ)-induced psoriasis. In vitro, PSORI-CM02 significantly inhibited the proliferation and migration of IL-17A-stimulated HUVECs in a dose-dependent manner. Further, it markedly regulated the antioxidative/oxidative status and inflammation; suppressed the expression of VEGF, VEGFR1, VEGFR2, ANG1, and HIF-1α; and reduced the phosphorylation of MAPK signalling pathway components in IL-17A-stimulated HUVECs. In vivo studies showed that PSORI-CM02 markedly reduced angiogenesis in the skin of mice with IMQ-induced psoriasis, while significantly rebalancing antioxidant/oxidant levels; inhibiting the production of IL-6, TNF-α, IL-17A, and IL-17F; and repressing the synthesis of angiogenic mediators. In addition, PSORI-CM02 markedly reduced the activation of the MAPK signalling pathway in psoriatic skin tissue. Taken together, our results demonstrated that PSORI-CM02 inhibited psoriatic angiogenesis by reducing the oxidative status and inflammation, suppressing the expression of angiogenesis-related molecules, and inhibiting the activation of the MAPK signalling pathway in vitro and in vivo.

Evaluation of corneal densitometry changes in patients with lichen planus.

To investigate the corneal topography and densitometry changes in patients with lichen planus (LP). Anterior segment parameters and corneal densitometry of patients with LP and age- and gender-matched individuals with healthy eyes were evaluated using Scheimpflug corneal topography. A 12mm corneal area was divided into 4 annular zones and 3 regions-in-depth anterior, central and posterior-for densitometry evaluation. The study included 45 patients with LP and 50 individuals with healthy eyes. The two groups were similar in age and gender, and they showed no significant differences in anterior segment corneal topography parameters. Schirmer's I test results were significantly lower in the patients with LP than in the control group (P˂.001). The total corneal densitometry was higher in patients with LP than in the control group (P=.030). The anterior, central and posterior corneal densitometry in the 0-2mm and 2-6mm annular zones was higher in the LP group than in the control group. Correlation analysis between disease duration and corneal densitometry values showed a strong positive correlation in the anterior segment and a moderate positive correlation in the central and posterior segments (r=0.632, P˂.001; r=0.572, P˂.001; and r=0.562, P˂.001, respectively). Corneal densitometry values were higher in patients with LP than in individuals with healthy eyes, even if the patients had a clinically transparent cornea. More studies are needed to evaluate the changes that may occur in corneal transparency in patients with LP and other autoimmune dermatologic diseases that may affect the eye.

Implication of Human Bacterial Gut Microbiota on Immune-Mediated and Autoimmune Dermatological Diseases and Their Comorbidities: A Narrative Review.

During the last decade, the advent of modern sequencing methods (next generation techniques, NGS) has helped describe the composition of the human gut microbiome, enabling us to understand the main characteristics of a healthy gut microbiome and, conversely, the magnitude of its disease-related changes. This new knowledge has revealed that healthy gut microbiota allow the maintenance of several crucial physiological functions, such as the ability to regulate the innate and adaptive immune systems. Increasing evidence has pointed out a condition of dysbiosis in several autoimmune/immune mediated dermatological conditions and specific gut microbial signatures have also been reported to correlate with clinical and prognostic parameters of such diseases. Based on a literature search of relevant published articles, this review debates the current knowledge and the possible pathogenic implications of bacterial gut microbiota composition assessed through NGS techniques in systemic lupus erythematosus, atopic dermatitis, psoriasis, and alopecia areata. Evidence of a potential role of specific gut microbiota signatures in modulating the clinical course of such diseases and their main comorbidities has been also reviewed.

Disproportionality analysis of bullous pemphigoid adverse events with PD-1 inhibitors in the FDA adverse event reporting system

ABSTRACTObjectives: Bullous pemphigoid, an autoimmune dermatological disease, may be associated with the use of a relatively new anti-cancer drug class, PD-1 inhibitors, which includes pembrolizumab and nivolumab. This paper analyzes the signals between PD-1 inhibitors and bullous pemphigoid based upon the reported real-world data.Methods: A pharmacovigilance analysis was performed on the publicly available Adverse Event Reporting System database of Food and Drug Administration. Disproportionality ratios were used to examine a signal between PD-1 inhibitors and bullous pemphigoid. A heat map was generated to depict the signal between PD −1 inhibitor use and skin toxicity adverse events.Results: The analysis indicated that there is a significant signal (PRR = 13.82 [95% CI: 9.99–19.11], Chi-squared with Yates’ correction = 420.48) between pembrolizumab use and bullous pemphigoid and that there is a significant signal (PRR = 13.19 [95% CI: 10.57–16.46], Chi-squared with Yates’ correction = 869.71) between nivolumab use and bullous pemphigoid. The signals remained statistically significant after stratifying for sex and age for both pembrolizumab and nivolumab. The signal is supported by 35 case reports in which there was evidence of PD-1 inhibitor use and a pemphigoid adverse event.Conclusion: When prescribing PD-1 inhibitors, physicians should monitor closely for symptoms of bullous pemphigoid.