Diagnosis Of Pemphigus Vulgaris Research Articles

Direct immunofluorescence (DIF) versus immunohistochemical (IHC) staining of complements and immunoglobulins (Ig) in pemphigus group.

Pemphigus is a group of bullous disorders of the skin characterized by the formation of autoantibodies present in the intercellular junction of the epidermis. Diagnosis is made by clinical, histopathological examination, and DIF. As DIF needs frozen sections, fluorescent tagged antibodies, UV light microscope for examination, and trained personnel, its non-availability makes a definitive diagnosis challenging. To evaluate the utility of IHC staining of complements and Ig in cases of Pemphigus. Twenty-six diagnosed cases of Pemphigus were stained by Peroxidase immunohistochemical method using monoclonal antibody to IgG, IgA, IgM, IgG4, C3, C4 d with DAB as chromogen. Pemphigus cases include twenty of pemphigus vulgaris (PV), four cases of pemphigus foliaceous (PF), and two of pemphigus vegetans (Pveg). Positivity was defined as the deposition of Ig and complements as distinct, continuous brown staining of keratinocytes at intercellular junctions. On IHC total of 20 PV 17 showed positivity (85%) for IgG, 11 (55%) C4d, 19 (95%) C3d, and 16 (80%) IgG4 deposits at the intercellular junction of the epidermis. All cases of PF showed a deposit of IgG, with three (75%) cases for IgG4, C3d, and C4d. Both cases of Pveg showed positivity for IgG and C4d while one case was negative for IgG4 and C3d. The overall IgG, C3, IgG4, and C4d expression for pemphigus was seen in 88%, 88%, 76.9%, and 61.5% of cases. The relation between these markers, combination of IgG and C3, was best related to each other ( P value = 0.80). The sensitivities for IgG, IgG4, and C3 were 77.8%%, 73%, and 73% resp. We conclude that IHC is a useful tool in the diagnosis of PV with the highest sensitivity of IgG and C3d. The combination of IgG and C3d could replace the DIF in almost all of our cases, so IHC on FFPE sections be used as an alternative method to DIF.

Erythema multiforme-like lip presentation in pemphigus vulgaris patients: a multicenter case series

Pemphigus vulgaris (PV) is a chronic autoimmune mucocutaneous blistering disease. Autoantibodies are directed against desmogleins, leading to the formation of intraepithelial bullae. PV, as with other autoimmune mucocutaneous disorders of the oral cavity, presents diagnostic and therapeutic challenges. Approximately 50–70% of cases present first with oral lesions. The lesions commonly start as vesicles or bullae that rapidly rupture, leading to erosions and ulcerations. The palatal, gingival, buccal, and labial mucosa are the most commonly affected sites. Oral PV can mimic several other diseases that cause mucosal erosions and/or ulcerations, including erythema multiforme (EM). EM is an acute, immune-mediated, self-limited hypersensitivity condition primarily associated with herpes simplex infection. Oral lesions can be variable, but a very characteristic presentation with labial hemorrhagic erosions, ulcerations and crusting is commonly seen. In this case series, we present six cases of PV: one male patient and five female patients whose ages ranged from 34 to 65 years old. All patients presented with hemorrhage and crusting of the lips in addition to multiple intraoral erosions and ulcerations. Three patients presented with oral and skin lesions. All patients underwent biopsies, and a diagnosis of PV was confirmed. All patients were treated with steroids (topical and systemic) and variable steroid-sparing agents. This case series emphasizes that oral PV may be misdiagnosed as EM in a subgroup of patients who present with persistent lip hemorrhage and crusting. Therefore, a comprehensive history, clinical examination and incisional biopsies should be considered in such patients.

Revisiting pemphigus vulgaris: A case report and review of literature

Introduction: Pemphigus is an autoimmune blistering mucocutaneous disease. Production of auto-antibodies against desmosomal glycoproteins is a characteristic feature of the disease. Oral lesions of pemphigus vulgaris are many a times first sign of the disease and hence it is important for a dentist to be familiar with the clinical appearance, diagnosis, and treatment modalities. Case Report: This report describes a case of pemphigus vulgaris in a female patient who presented with ulcers on the gingiva. On the basis of clinical examination and histopathology, we arrived at a diagnosis of pemphigus vulgaris, which was confirmed by immunofluorescence. Conclusion: If left undiagnosed or untreated pemphigus vulgaris may be fatal. Early diagnosis will aid in appropriate treatment and better outcome of the disease.

HLA class II antigens in Croatian patients with pemphigus vulgaris and their correlation with anti-desmoglein antibodies.

Pemphigus vulgaris (PV) is an acquired autoimmune blistering disease characterized by the production of autoantibodies targeting desmosomal cadherins, primarily desmoglein 1 and desmoglein 3, leading to acantholysis. The etiology of PV is multifactorial, including genetic susceptibility. This retrospective study aimed to evaluate the association of HLA class II alleles and PV and to examine the impact of PV-associated HLA class II alleles on the concentration of anti-desmoglein antibodies. The study group included 30 patients in whom the diagnosis of PV was confirmed by histopathological analysis, immunofluorescence findings, and ELISA testing for detecting antibodies against desmoglein 1 and desmoglein 3. HLA class II alleles were typed by polymerase chain reaction with sequence-specific primers (PCR-SSP). The control group consisted of 190 healthy volunteer blood donors. Data analysis revealed a significantly higher frequency of HLA class II alleles in our population of patients with PV, including HLA-DRB1*04:02, HLA-DRB1*14:54, HLA-DQB1*03:02, HLA-DQB1*05:03, HLA- DQA1*03:01, and HLA-DQA1*01:04, as well as a significantly lower frequency of HLA-DQA1*05:01 compared to the control group. We have also investigated the influence of risk alleles for PV, recognized in almost all study populations, HLA-DRB1*04:02 and HLA-DQB1*05:03, on the concentration of antibodies against desmogleins 1 and 3 in relation to the presence of these alleles. The results showed significantly higher levels of antibodies directed against desmoglein 3 among patients with DRB1*04:02 compared to patients without this allele. No difference was found for anti-desmoglein 1 antibodies. Regarding DQB1*05:03 allele, statistical analysis showed no differences in the concentration of anti-desmoglein antibodies in patients carrying this allele versus those without it.

Pemphigus vulgaris mimicking Steven-Johnson syndrome/toxic epidermal necrolysis: report of an unusual case.

Pemphigus vulgaris (PV) is an autoimmune blistering disease affecting the skin and mucosa. It clinically presents as painful erosions, mainly in the oral cavity, and flaccid blisters and erosions on the skin. Steven-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe mucocutaneous drug hypersensitivity reaction characterized by painful, dusky, erythematous eruptions that often progress to blisters, erosions, and extensive epidermal detachment accompanied by systemic symptoms. Herein, we report the case of a 48-year-old man who presented with extensive skin and mucosal lesions following the ingestion of an unknown medication. The patient's symptoms clinically mimicked SJS, and accordingly, a preliminary diagnosis of SJS/TEN was made. However, clinical investigation of skin biopsy and direct immunofluorescence assay results indicated PV, and a final diagnosis of PV was established.

Kaposi's sarcoma in a patient with pemphigus vulgaris mimicking exacerbation of pemphigus

Kaposi's sarcoma (KS) is a rare multifocal angiogenic tumor often seen in immunocompromised setting such as acquired immunodeficiency syndrome (AIDS) or organ transplantation recipients. Pemphigus vulgaris (PV) is a rare blistering disorder with mucocutaneous involvement for which immunosuppressive therapy has long been the core of treatment. Iatrogenic form of KS has been reported infrequently in pemphigus patients as a result of long-term immunosuppressive therapy. We describe a 39-year-old male patient with confirmed diagnosis of PV who developed KS after receiving immunosuppressive agents for his pemphigus. KS was initially localized to the oral cavity with features mimicking exacerbation of his pemphigus. This interesting case of KS suggests that dermatologists visiting patients with pemphigus with discomfort in the oral cavity should have a high degree of awareness and consider other differential diagnoses along with merely an exacerbation of PV.

SARS-CoV-2 Vaccination Effectiveness in Rituximab-Treated Patients Affected by Pemphigus Vulgaris

SARS-CoV-2 Vaccination Effectiveness in Rituximab-Treated Patients Affected by Pemphigus Vulgaris

Identification of Six microRNAs as Potential Biomarkers for Pemphigus Vulgaris: From Diagnosis to Pathogenesis.

Pemphigus vulgaris (PV) is a potentially fatal autoimmune bullous disease. The role of microRNA (miRNA, miR) in the diagnosis and pathogenesis of PV remains unknown. This study aims to provide potential miRNA biomarkers for PV diagnosis and therapy options. Serum samples were obtained from 22 PV patients, 15 mucous membrane pemphigoid (MMP) patients, and 10 normal controls (NC). Total RNA was extracted from the serum samples, and 12 selected miRNAs were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatic analyses including target gene prediction and enrichment analysis were performed. Twelve miRNAs were increased in the serum of the PV group compared with the NC group, in which six miRNAs had good efficacy to diagnose PV from MMP with the area under the receiver operator characteristic curves of 0.970 to 0.988. A series test for the combination of miR-584-5p and miR-155-5p reached the sensitivity and specificity of 95.5% and 100%. Bioinformatic analysis revealed target gene enrichment in the cell adhesion pathways, immune-relating pathways, and P38 mitogen-activated protein kinases signaling pathway. The study provides new insights and targets of miRNAs for the precise diagnosis and the exploration of pathogenesis for PV, which may serve as a reference for further research into autoimmune bullous diseases.

S2310 Esophageal Manifestations of Paraneoplastic Pemphigus Vulgaris Associated With Gastric Neuroendocrine Tumor

Introduction: While pemphigus vulgaris (PV) typically affects the epidermis and oral mucosa, esophageal manifestations are uncommon. The primary symptoms accompanying this manifestation are dysphagia, odynophagia, and hematemesis. In this case report we examine the occurrence of esophageal pemphigus vulgaris associated with a gastric neuroendocrine tumor and note the endoscopic findings of esophagitis dessicans superficialis (EDS) within the esophagus. Case Description/Methods: A 63-year-old female with a history of P-ANCA vasculitis presented for evaluation of dyspnea, hypotension, fatigue, rash, and dysphagia. The patient was thought to have an infectious cause of these signs and symptoms, however given a lack of response to antibiotic and antifungal therapy within 48 hours the differential was broadened to include rheumatologic disease. The patient was treated with intravenous methylprednisolone and continued to experience dysphagia. Esophagogastroduodenoscopy was performed (Figure) and demonstrated a tongue ulceration and extensive desquamation in the distal esophagus appearing similar to a pseudomembrane. Extensive subepithelial hemorrhages were observed in the esophagus, however the gastric and duodenal mucosa were intact. Esophageal and gastric biopsies demonstrated staining for IgG reactive to desmoglein 3 consistent with PV. In addition, a well-differentiated neuroendocrine tumor (NET) in the stomach. The patient was subsequently treated with octreotide for her neuroendocrine tumor, as well as solumedrol and dapsone for her skin lesions. She also received a loading dose of rituximab. She received a second dose of rituximab 21 days after the loading dose and the corticosteroids were tapered as her symptoms of dysphagia gradually improved with immunosuppressive therapy. Discussion: Esophagitis dessicans superficialis has been described as sloughing of the superficial esophageal mucosa and is similar in appearance to the Nikolsky sign of external squamous epithelium seen with immunobullous diseases. Our patient presented with undiagnosed PV and had both esophageal and skin involvement with the concomitant gastric NET. The ultimate diagnosis of PV was confirmed based on the presence of antibodies to desmoglein 3 and it remains unknown if the gastric NET had any role in the development of PV. Clinicians should have a low threshold for endoscopic examination of patients for whom there is suspicion of immunobullous disease to facilitate rapid diagnosis and initiation of appropriate therapy.Figure 1.: Endoscopic images demonstrating tongue ulceration and extensive desquamation in the distal esophagus appearing similar to a pseudomembrane in addition to subepithelial hemorrhages.

系统性红斑狼疮并发寻常型天疱疮1例

A case of systemic lupus erythematosus complicated by pemphigus vulgaris is reported. A 42-year-old female patient presented facial red macules with the joints pain on the limbs for 4 years. She was photosensitive with hematologic abnormal, positive antinuclear antibody, positive antibody to ds-DNA. She got relapsing erosions of mucous membranes in mouth for 2 years. Then extensive, generalized bullae developed, and the bullae soon ruptured to form erosions. The diagnosis of pemphigus vulgaris was confirmed by clinical, histological and immunofluorescent evidences.

Pemphigus herpetiformis with atypical features

Pemphigus herpetiformis (PH) is considered as an uncommon and mild variant of pemphigus. Here, we report the case of a 34-year-old woman who presented with intensely pruritic, annular crusted lesions with vesicles arranged in the periphery over the abdomen, back, and scalp. Cutaneous features were consistent with the clinical diagnosis of PH. However, she had certain unusual clinicoimmunopathological features. She also had oral erosions, which is a rare finding in this variant of pemphigus. The results of histopathological examination and enzyme-linked immunosorbent assay were also in line with the diagnosis of pemphigus vulgaris. She responded well to dapsone with significant objective and subjective improvement in 1-week follow-up.

Evaluation of the Role of Oral Mucosal Direct Immunofluorescence and Salivary Desmoglein 1 and 3 Enzyme-Linked Immunosorbent Assay in Patients With Oral Mucosal Pemphigus.

Background:Pemphigus vulgaris (PV) is characterized by antibodies against desmosomal adhesion proteins desmoglein (Dsg) 1 and 3 which can be detected by direct immunofluorescence (DIF) or enzyme-linked immunosorbent assay (ELISA). Oral lesions usually precede cutaneous lesions and an early diagnosis can prevent mortality and morbidity. Dsg antibodies can be detected by ELISA in saliva of patients with oral mucosal pemphigus. This study compares oral mucosal DIF with the salivary Dsg1 and 3 ELISA.Materials and Methods:A total of 26 biopsy and/or DIF-proven PV patients with oral erosions without cutaneous lesions were included in the study. Biopsy of oral mucosa was taken for DIF by standard method. Saliva sample was obtained and processed for ELISA. The results were then compared.Results:Out of 26 patients, 22 (84.6%) had a positive oral mucosal DIF and four patients (15.4%) had negative DIF. Nine patients (34%) had positive salivary Dsg3 ELISA. Seven patients (27%) had positive salivary Dsg1 ELISA. Taking oral DIF as the gold standard, the sensitivity of salivary Dsg1 ELISA was 31.8% and of salivary Dsg3 ELISA was 40.9%.Conclusion:Although DIF is the gold standard for the diagnosis of PV, salivary Dsg1 and 3 ELISA can also be used in the diagnosis of oral pemphigus.

Skin Erosions in a Newborn.

Skin Erosions in a Newborn.

Direct immunofluorescence analysis of oral Tzanck smears for pemphigus vulgaris: A diagnostic test.

Pemphigus vulgaris (PV) is a rare and potentially fatal autoimmune blistering disease. Direct immunofluorescence (DIF) and histopathological analysis are crucial methods for PV diagnosis, but oral tissue biopsy is difficult to perform because of the fragile characteristics of the oral mucosa. However, no well-designed diagnostic studies addressing the validity of DIF analysis of oral Tzanck smears for the diagnosis of PV exist. We aimed to design a diagnostic test based on DIF analysis combined with oral Tzanck smears and evaluate its diagnostic accuracy for PV. We enrolled 81 patients with oral erosive lesions, of whom 41 patients had PV and 40 were non-PV controls. Oral Tzanck smears were obtained from oral mucosal lesions and observed under a fluorescence microscope after fixing and fluorescence staining. The diagnostic efficacy indexes including sensitivity, specificity, predictive value, Youden index, diagnostic odds ratio, and likelihood ratio were calculated. Of the 41 PV patients, 36 showed DIF-positive findings for oral Tzanck smears, and all 36 DIF-positive PV patients showed IgG and/or C3 deposition, with seven also showing IgA and/or IgM positivity. None of the non-PV controls showed DIF positivity. The sensitivity and specificity of DIF analysis with oral Tzanck smears were 87.80% and 100%, respectively. The area under the receiver operator characteristic curve (ROC) was 0.939, with the test demonstrating significantly high diagnostic efficacy. DIF analysis of oral Tzanck smears is a minimally invasive and easy-to-operate technique that can assist the rapid and accurate diagnosis of PV in dental clinic.

Oesophageal involvement in pemphigus vulgaris: a case report

Pemphigus vulgaris is an autoimmune blistering disorder characterised by skin and mucosal involvement and an incidence of 0.5–3.2 per 100,000. It affects men and women with equal frequency, most commonly during 4th and 5th decade of life. It is a potentially life threatening disease, with a mortality rate of 5–15%, attributed to the disease itself as well as complications secondary to corticosteroids and immunosuppressive therapy. Oesophageal involvement is rare and usually presents with dysphagia and odynophagia. Even when present, it may be under-recognised or misdiagnosed without a proper endoscopic and histopathologic evaluation. We present a case of 76-year-old gentleman who developed swollen gums and severe oral ulceration which was associated with pain and difficulty swallowing along with significant loss of weight. He was admitted to hospital and required intravenous fluids and nasogastric tube feeding given substantial dehydration and malnutrition. He went onto develop flaccid blisters on abdomen and upper back. Skin biopsy was performed and histopathology supplemented with direct immunofluorescence (DIF) confirmed pemphigus vulgaris. The patient was commenced on prednisolone and was planned to undergo whole body PET scan, upper GI endoscopy and colonoscopy to rule out paraneoplastic pemphigus. The esophago-gastroscopy revealed multiple ulcers that were biopsied and histopathology showed suprabasal blister formation and acantholysis compatible with the diagnosis of pemphigus vulgaris.

Pemphigus Vulgaris and its Comprehensive Management: Report of Two Cases and Literature Review

In the oral cavity, gingiva lesions may occur that are not associated with bacterial plaque, which require adequate diagnosis and treatment. Desquamative gingivitis is usually related to mucocutaneous disorders, such as pemphigus vulgaris (PV), where oral lesions, including gingival lesions, may precede skin lesions. Management is multidisciplinary and treatment includes topical and systemic pharmacological therapy, require adequate control of dental plaque by the patient and strict supervision over time by the professional for the maintenance and stability of the gingival tissues. Two clinical cases of patients with a diagnosis of PV are presented, which were managed in a timely and integral way to control and stabilize the systemic and local factor.

Ultra-high frequency ultrasound in the differential diagnosis of oral pemphigus and pemphigoid: An explorative study.

Intraoral ultra-high frequency ultrasound (UHFUS) is an emerging technique in oral medicine, due to its possibility to provide submillimeter resolution imaging of superficial mucosal structures. In this study, the potential role of UHFUS in the diagnosis of oral pemphigus vulgaris (PV) and mucous membrane pemphigoid (MMP) is assessed. Consecutive patients with suspected oral PV or MMP were enrolled. All patients underwent clinical examination, laboratory tests, intraoral UHFUS scan, and biopsy. Histology and direct immunofluorescence were set as benchmark for diagnosis confirmation. The sensitivity and specificity of UHFUS compared to histology were assessed. Mann-Whitney test was performed to evaluate the presence of differences in the echogenicity of PV and MMP. P-value was set at P<0.05. Twenty-five patients were included. Thirteen patients were diagnosed with PV, and twelve with MMP. The UHFUS features of PV and MMP lesions were described. Image analysis showed statistically significant differences between the echogenicity of PV and MMP lesions (P<0.05). Good concordance between UHFUS and histology was found. UHFUS showed 75% sensitivity in the diagnosis of PV and 66.7% in the diagnosis of MMP. UHFUS appears a valuable tool in the diagnosis of PV and MMP. Although histology and immunofluorescence remain the gold standard, UHFUS role in the diagnostic algorithm of PV and MMP seems promising as a chair-side tool consistently enhancing clinical evaluation of oral bullous lesions.

Clinical significance of umbilical region involvement in pemphigus vulgaris in a series of 81 ethnic Poles: a comparative analysis of the distribution of lesions in two infrequent locations.

IntroductionAutoimmune bullous diseases are potentially life-threatening dermatoses which present with cutaneous and/or mucosal blisters, diagnosed on the basis of clinical manifestations, direct immunofluorescence of perilesional tissue, and serum testing for circulating autoantibodies. Sometimes, lesions in the navel can lead to the diagnosis of a bullous disease.AimTo assess the frequency of occurrence of pemphigus lesions located in the navel area and nail apparatus in pemphigus vulgaris (PV) in ethnic Poles.Material and methodsEighty one patients (31 males and 50 females, mean age 59 years) with dermatoses of the PV group diagnosed in 2002-2020 were retrospectively analysed using their photographic files. Statistical analysis was performed using the difference test between two proportions to check the difference between the percentage of PV patients with navel area involvement and nail apparatus involvement.ResultsThere was no statistically significant difference between PV patients with nail apparatus involvement (12.3%) and navel area involvement (14.8%) (p = 0.4632). Only females had lesions in the navel area in our series of PV patients.ConclusionsIt is speculated that the causal relationship may exist between the female reproductive system and the pattern of expression of PV lesions around the umbilicus. The awareness that PV can infrequently affect the umbilical region and the nail apparatus should help in some cases to establish the diagnosis of PV. The periumbilical involvement can facilitate the performance of DIF in individuals with lesions in less accessible areas.

Histopathology of Pemphigus Vulgaris Revisited.

Pemphigus vulgaris (PV) is a severe, potentially life-threatening autoimmune blistering disease, which is common in India. Although there is abundant literature on clinical and immunologic features, comprehensive studies on its histopathology are lacking. The aim of this study was to describe the histopathologic and immunofluorescence features as well as discuss various diagnostic pitfalls of PV. Histopathologic and immunofluorescence (DIF/IIF) findings were reviewed for 169 biopsies from 2007 to 2017 (11 years). The 169 samples included 152 skin, 16 oral mucosal, and 1 corneal biopsy. Maximum prevalence was noted in the fifth decade (57%) with a slight male preponderance. Vesicles were seen in 149 cases (88%), the level of which was suprabasal in 91(61%) and both suprabasal and intraepidermal in 50 cases (33.5%). Acantholytic cells were present in 142 cases (95%). Acantholytic keratinocytes showed rounded and polygonal acantholysis. 86 (51%) cases showed evidence of regeneration. Adnexal involvement was seen in 92 cases, commonest in the hair follicles. Unusual histologic findings included: intraepidermal bulla, absence of dermal inflammation, free floating hair shafts, multinucleated epithelial cells, eosinophil predominance; all of which are discussed. DIF was performed in 166 cases, of which 163 were positive (98%), and IgG was the commonest immunoreactant (96%). IIF was performed in 11 cases, of which 9 cases were positive for Dsg3. Although the diagnosis of PV rests on combined clinical, histologic, and IF features, histopathology as the sole means is also a powerful tool. It is important to be aware of the diagnostic pitfalls to optimize its utility.

S1930 Lisinopril-Induced Oroesophageal Pemphigus Vulgaris: A Previously Unreported Side Effect

INTRODUCTION: Pemphigoid diseases (PD) are a group of blistering autoimmune pathologies including pemphigus vulgaris (PV) and pemphigus foliaceous (PF), which affect mucocutaneous tissues. NSAIDs, penicillamine, and angiotensin-converting enzyme inhibitors (ACEI) such as captopril and enalapril are associated with drug-induced pemphigoid (DIP). We present a case of lisinopril-associated PV which has not been previously reported. CASE DESCRIPTION/METHODS: A 35-year-old male with essential hypertension presented with multiple oral ulcers associated with dysphagia, odynophagia, and a 20-lb weight loss in six weeks since starting lisinopril. Multiple white-colored lesions were noted along the buccal mucosa (Figure 1) and posterior pharynx. Tests for ANA, HIV, and a chronic hepatitis panel were negative. Fluconazole, Nystatin, and Valganciclovir were initiated without improvement. As such, he subsequently underwent an intralesional incisional biopsy of the buccal mucosa which revealed changes compatible with PV (Figure 2). On EGD, two blood-filled blisters in the mid-esophagus were noted (Figure 3). Considering a pre-established diagnosis of PV, they were not biopsied. Lisinopril was discontinued and the patient was started on prednisone and mycophenolate with a subsequent resolution of symptoms. DISCUSSION: PD are characterized by IgG antibodies directed against epithelial antigens, desmoglein 1 and 3, leading to separation of keratinocytes (acantholysis) and formation of intraepidermal bullae. ACEI such as captopril, enalapril, and cilazapril have been associated with DIP. One case report of lisinopril induced PF has been reported. However, mucinous nor cutaneous PV secondary to its use has not been previously detailed. The etiology of lisinopril-induced DIP is not fully understood. All ACEI contain an amide-group which is noted to modify keratinocyte proteins to make neoantigens and can stimulate acantholysis. Patients on ACEI are also noted to have circulating autoantibodies against keratinocyte surface antigens which can be contributory. Cessation of ACEI is essential to halt progression while immunotherapy with steroids and other immunomodulators such as rituximab, azathioprine, or mycophenolate are the mainstay of management. A thorough drug reconciliation should be performed on presentation to allow for possibly early discontinuation of the offending agent(s), limit duration, and decrease side-effects of subsequent immunomodulatory therapy.Figure 1.: Well circumscribed, whitish ulceration of the buccal mucosa with adjacent erythema and swelling.Figure 2.: Hematoxylin-eosin (HE) stain of the buccal mucosa showing mucosal epithelium exhibiting a suprabasal split and associated acanthloysis with an underlying relatively brisk perivascular and interstitial lymphoplasmacytic infiltrate; with 40X (A) and 100X (B) magnification.Figure 3.: Two blood-filled blisters of the mucosa in the mid-esophagus, each measuring 6-7 mm in length.