Obesity and Roux-en-Y gastric bypass drive changes in miR-31 and miR-215 expression in the human rectal mucosa.

BACKGROUND/OBJECTIVES: Obesity increases colorectal cancer (CRC) risk. However, the effects of weight loss on CRC risk are unclear. Epigenetic mechanisms involving microRNAs that lead to dysregulated gene expression may mediate the effects of obesity and weight loss on CRC risk. We examined the effects of obesity and weight loss following Roux-en-Y gastric bypass (RYGB) on microRNA expression in the human rectal mucosa. SUBJECTS/METHODS: We collected rectal mucosal biopsies from obese patients (n = 22) listed for RYGB and age- and sex-matched healthy non-obese Controls (n = 20), at baseline and six months post-surgery. We quantified microRNA expression in rectal mucosal biopsies using Next Generation Sequencing and bioinformatics analysis to investigate the likely functional consequences of these epigenetic changes. RESULTS: Compared with non-obese individuals, obese individuals showed differential expression of 112 microRNAs (p < 0.05). At six-months post-RYGB, when mean body mass had fallen by 27 kg, 60 microRNAs were differentially expressed, compared with baseline (p < 0.05). The expression of 36 microRNAs differed significantly between both i) obese and non-obese individuals and ii) obese individuals pre- and post-RYGB. Quantitative polymerase chain reaction (qPCR) demonstrated that expression of miR-31 and miR-215 was significantly (p < 0.05) higher, 143-fold and 15-fold respectively, in obese than in non-obese individuals. Weight loss, following RYGB, reduced expression of miR-31 and miR-215 to levels comparable with Controls. These differentially expressed microRNAs are implicated in pathways linked with inflammation, obesity and cancer. CONCLUSION: Our findings show, for the first time, that obesity is associated with dysregulated microRNA expression in the human rectal mucosa. Further, surgically-induced weight loss may normalise microRNA expression in this tissue.

Epigenetic adaptations of the masticatory mucosa to periodontal inflammation.

BACKGROUND: In mucosal barrier interfaces, flexible responses of gene expression to long-term environmental changes allow adaptation and fine-tuning for the balance of host defense and uncontrolled not-resolving inflammation. Epigenetic modifications of the chromatin confer plasticity to the genetic information and give insight into how tissues use the genetic information to adapt to environmental factors. The oral mucosa is particularly exposed to environmental stressors such as a variable microbiota. Likewise, persistent oral inflammation is the most important intrinsic risk factor for the oral inflammatory disease periodontitis and has strong potential to alter DNA-methylation patterns. The aim of the current study was to identify epigenetic changes of the oral masticatory mucosa in response to long-term inflammation that resulted in periodontitis. METHODS AND RESULTS: Genome-wide CpG methylation of both inflamed and clinically uninflamed solid gingival tissue biopsies of 60 periodontitis cases was analyzed using the Infinium MethylationEPIC BeadChip. We validated and performed cell-type deconvolution for infiltrated immune cells using the EpiDish algorithm. Effect sizes of DMPs in gingival epithelial and fibroblast cells were estimated and adjusted for confounding factors using our recently developed "intercept-method". In the current EWAS, we identified various genes that showed significantly different methylation between periodontitis-inflamed and uninflamed oral mucosa in periodontitis patients. The strongest differences were observed for genes with roles in wound healing (ROBO2, PTP4A3), cell adhesion (LPXN) and innate immune response (CCL26, DNAJC1, BPI). Enrichment analyses implied a role of epigenetic changes for vesicle trafficking gene sets. CONCLUSIONS: Our results imply specific adaptations of the oral mucosa to a persistent inflammatory environment that involve wound repair, barrier integrity, and innate immune defense.

Measurement of low-grade inflammation of the esophageal mucosa with electrical conductivity shows promise in assessing PPI responsiveness in patients with GERD.

A device that can easily measure electrical impedance might be a helpful tool for investigating the pathophysiology of gastroesophageal reflux disease. The first aim of this study was to validate our newly developed bioelectrical admittance measurement (BAM) through in vitro experimentation. The second aim was to investigate whether evaluation of BAM by this measurement differed between patients with heartburn according to their response to proton pump inhibitor (PPI) therapy. Caco-2 cell monolayers and three-dimensional tissues were examined by BAM using a frequency response analyzer. BAM was also used to measure the impedance through cell layers. Subsequently, BAM was performed during endoscopy in 41 patients experiencing heartburn without esophageal mucosal breaks. After 2-wk administration of 20-mg rabeprazole twice daily, patient responses to PPI were classified as "good" or "poor" according to their clinical course. In each patient, histological alterations and gene expression levels of inflammation mediators and tight junction proteins were evaluated. Impedance profiles indicated that monolayer Caco-2 cells on top of eight-layered normal human dermal fibroblasts had the highest magnitude of impedance over the range of frequencies. In vivo results revealed that patients with good responses to PPI displayed significantly higher admittance. Severity of low-grade inflammation was significantly associated with esophageal wall admittance. Moreover, esophageal wall admittance may be more closely related to basal zone hyperplasia than dilatation of intercellular spaces. Thus, BAM may be able to detect abnormalities in the subepithelial layer of the esophagus.NEW & NOTEWORTHY Bioelectrical admittance measurement is a new method to evaluate esophageal mucosal permeability vertically during upper gastrointestinal endoscopy. Measurement of low-grade inflammation of the esophageal mucosa with electrical conductivity shows promise in assessing proton pump inhibitor responsiveness in patients with gastroesophageal reflux disease. As various gastrointestinal diseases are associated with changes in mucosal permeability, bioelectrical admittance measurement is expected to be clinically applied to therapeutic decision-making for these diseases in the future.

Risk of metastatic recurrence after endoscopic resection for esophageal squamous cell carcinoma invading into the muscularis mucosa or submucosa: a multicenter retrospective study.

BACKGROUND: We aimed to elucidate the risk of metastatic recurrence after endoscopic resection (ER) without additional treatment for esophageal squamous cell carcinomas (ESCCs) with tumor invasion into the muscularis mucosa (pT1a-MM) or submucosa (T1b-SM). METHODS: We retrospectively enrolled patients with pT1a-MM/pT1b-SM ESCC after ER at 21 institutions in Japan between 2006 and 2017. We compared metastatic recurrence between patients with and without additional treatment, stratified into category A (pT1a-MM with negative lymphovascular invasion [LVI] and vertical margin [VM]), B (tumor invasion into the submucosa ≤ 200 µm [pT1b-SM1] with negative LVI and VM), and C (others). Subsequently, using multivariate Cox analysis, we evaluated risk factors for metastatic recurrence after ER without additional treatment. RESULTS: We enrolled 593 patients, and metastatic recurrence occurred in 38 patients. Metastatic recurrence after additional treatment was significantly lower than that after no additional treatment in category C (9.1% vs. 23.6% in 5 years, p = 0.001), whereas no significant difference was noted in categories A (0.0% vs. 2.6%) and B (0.0% vs. 4.3%). In patients without additional treatment after ER, risk factors for metastatic recurrence were lymphatic invasion (hazard ratio [HR], 5.61), positive VM (HR, 4.55), and tumor invasion into the submucosa > 200 µm (HR, 3.25), and, but near half of the patients with metastatic recurrence had no further recurrence after salvage treatment, resulting in excellent 5-year disease-specific survival in categories A (99.6%) and B (100.0%). CONCLUSIONS: Closed follow-up with no additional treatment may be an acceptable option after ER in pT1a-MM/pT1b-SM1 ESCC with negative LVI and VM.

Gastrointestinal biofilms in health and disease.

Microorganisms colonize various ecological niches in the human habitat, as they do in nature. Predominant forms of multicellular communities called biofilms colonize human tissue surfaces. The gastrointestinal tract is home to a profusion of microorganisms with intertwined, but not identical, lifestyles: as isolated planktonic cells, as biofilms and in biofilm-dispersed form. It is therefore of major importance in understanding homeostatic and altered host-microorganism interactions to consider not only the planktonic lifestyle, but also biofilms and biofilm-dispersed forms. In this Review, we discuss the natural organization of microorganisms at gastrointestinal surfaces, stratification of microbiota taxonomy, biogeographical localization and trans-kingdom interactions occurring within the biofilm habitat. We also discuss existing models used to study biofilms. We assess the contribution of the host-mucosa biofilm relationship to gut homeostasis and to diseases. In addition, we describe how host factors can shape the organization, structure and composition of mucosal biofilms, and how biofilms themselves are implicated in a variety of homeostatic and pathological processes in the gut. Future studies characterizing biofilm nature, physical properties, composition and intrinsic communication could shed new light on gut physiology and lead to potential novel therapeutic options for gastrointestinal diseases.

Intermittent hypoxia induces turbinate mucosal hypertrophy via upregulating the gene expression related to inflammation and EMT in rats.

PURPOSE: Chronic intermittent hypoxia (IH) plays a pivotal role in the consequences of obstructive sleep apnea (OSA). It has been demonstrated that IH impairs nasomaxillary complex growth to reduce nasal airway cavity size in rodent models. Although turbinate dysfunction with inflammatory mucosal hypertrophy is related to OSA, the role of IH in turbinate hypertrophy with inflammation-driven fibrosis is unknown. Here, we aimed to clarify the pathogenesis of inflammatory mucosal hypertrophy and epithelial-mesenchymal transition (EMT) in the nasal turbinate under IH. METHODS: Seven-week-old male Sprague-Dawley rats were exposed to IH (4% O2 to 21% O2 with 0% CO2) at a rate of 20 cycles/h. RESULTS: Hypertrophy of the turbinate mucosa occurred after 3 weeks, with the turbinate mucosa of the experimental group becoming significantly thicker than in the control group. Immunostaining showed that IH increased the expression of TGFß and N-cadherin and decreased E-cadherin expression in the turbinate mucosa. Quantitative PCR analysis demonstrated that IH enhanced the expression of not only the inflammatory markers Tnf-a, Il-1b, and Nos2 but also the EMT markers Tgf-b1, Col1a1, and Postn. CONCLUSIONS: Collectively, these results suggest that IH induced turbinate hypertrophy via upregulation of gene expression related to inflammation and EMT in the nasal mucosa.

Protection and regeneration of esophageal, pharyngeal, and laryngeal mucosa as a major element in therapy of patients with esophageal and extraesophageal reflux symptoms.

Treatment of esophageal and extraesophageal reflux syndromes is mainly focused on inhibiting the secretion of hydrochloric acid. In spite of the high efficacy of proton pump inhibitors, approx. 30-60% of GERD patients experience daily symptoms. Beside acid reflux, other factors such as abnormal esophageal peristalsis, visceral hypersensitivity, ineffective esophageal clearance mechanisms, and impaired mucosal barrier also play an important role in generating GERD symptoms. An additional therapeutic proposition is a procedure aimed at improving the defense mechanisms of esophageal mucosa rather than inhibiting the damage-inducing factors. The preparation consisting of hyaluronic acid (HA), chondroitin sulfate (SC) and poloxamer 407 protects against harmful factors (hydrochloric acid, pepsin) and accelerates mucosal healing and regeneration, constituting a substantial element of monotherapy or add-on therapy in patients with gastroesophageal reflux disease.

Mucosal Immunity and Liver Metabolism in the Complex Condition of Lactation Insufficiency.

Lactation insufficiency is variously defined and includes the inability to produce milk, not producing enough milk to exclusively meet infant growth requirements, and pathological interruption of lactation (e.g., mastitis). Of women with intent-to-breastfeed, lactation insufficiency has been estimated to affect 38%-44% of newly postpartum women, likely contributing to the nearly 60% of infants that are not breastfed according to the World Health Organization's guidelines. To date, research and clinical practice aimed at improving feeding outcomes have focused on hospital lactation support and education, with laudable results. However, researchers' reports of recent rodent studies concerning fundamental lactation biology have suggested that the underlying pathologies of lactation insufficiency may be more nuanced than is currently appreciated. In this article, we identify mucosal biology of the breast and lactation-specific liver biology as two under-researched aspects of lactation physiology. Specifically, we argue that further scientific inquiry into reproductive state-dependent regulation of immunity in the human breast will reveal insights into novel immune based requirements for healthy lactation. Additionally, our synthesis of the literature supports the hypothesis that the liver is an essential player in lactation-highlighting the potential that pathologies of the liver may also be associated with lactation insufficiency. More research into these biologic underpinnings of lactation is anticipated to provide new avenues to understand and treat lactation insufficiency.

Transient Receptor Potential Vanilloid 4 Regulation of Adenosine Triphosphate Release by the Adenosine Triphosphate Transporter Vesicular Nucleotide Transporter, a Novel Therapeutic Target for Gastrointestinal Baroreception and Chronic Inflammation.

BACKGROUND: Transient receptor potential vanilloid 4 (TRPV4) is activated by stretch (mechanical), warm temperature, some epoxyeicosatrienoic acids, and lipopolysaccharide. TRPV4 is expressed throughout the gastrointestinal epithelia and its activation induces adenosine triphosphate (ATP) exocytosis that is involved in visceral hypersensitivity. As an ATP transporter, vesicular nucleotide transporter (VNUT) mediates ATP storage in secretory vesicles and ATP release via exocytosis upon stimulation. SUMMARY: TRPV4 is sensitized under inflammatory conditions by a variety of factors, including proteases and serotonin, whereas methylation-dependent silencing of TRPV4 expression is associated with various pathophysiological conditions. Gastrointestinal epithelia also release ATP in response to hypo-osmolality or acid through molecular mechanisms that remain unclear. These synergistically released ATP could be involved in visceral hypersensitivity. Low concentrations of the first generation bisphosphate, clodronate, were recently reported to inhibit VNUT activity and thus clodronate may be a safe and potent therapeutic option to treat visceral pain. Key Messages: This review focuses on: (1) ATP and TRPV4 activities in gastrointestinal epithelia; (2) factors that could modulate TRPV4 activity in gastrointestinal epithelia; and (3) the inhibition of VNUT as a potential novel therapeutic strategy for functional gastrointestinal disorders.

Mucosal wave measurements in the diagnosis of functional dysphonia.

ntroduction: The publication describes the characteristics of the glottis in FDs objectified by OQ, measured with VSK and EGG. AIM: The aim of the study was to objectify glottal function in different types of FDs. The scope was to use open quotients gained from various mucosal wave imaging techniques for differential diagnosis of FDs. MATERIAL AND METHOD: The study included 204 individuals. In the study, each patient underwent otolaryngological and phoniatric examination. LVS, EGG and VSK were conducted, their results were recorded and stored using an EndoSTROB-DX- -Xion GmbH (Berlin) device with DIVAS software. RESULTS: All patients with FDs had abnormalities in LVS. A statistical analysis showed differences in LVS characteristics according to the type of FD. The mean value of OQVSK was 0.521 in the control group and 0.565 in the study group (P < 0.05). Significant differences were found between patients with hypofunctional - 0.584 and hyperfunctional dysphonia - 0.55. The QOQEGG mean value in patients with FDs was 0.581 and in the control group 0.549 (P < 0.01). There were statistically significant differences between groups of patients with hyper- and hypofunctional dysphonias. Medians amounted to 0.574 and 0.604, respectively. Authors observed different relations of OQ with the type of FD. They decided to introduce a new parameter, illustrating the proportion of QOQEGG/OQVSK. CONCLUSIONS: Videostrobokymographic and electroglottographic open quotients differentiate euphony from dysphony. The value of OQVSK and QOQEGG and their proportion varies depending on different types of functional dysphonias. The OQVSK and QOQEGG should be included in the diagnostic algorithm of voice.

Intestinal Injury in Heat Stroke.

BACKGROUND: Heat stroke is a life-threatening syndrome that is characterized by its severe clinical symptoms, rapid progression, and high rate of mortality. Recently, research has indicated that a dysfunctional intestinal epithelia barrier plays an important role in the pathophysiology of heat stroke. Protecting the intestines from heat stress had been identified as a potentially effective treatment for patients with heat stroke and may reduce the innate immune response caused by endotoxins in circulation. OBJECTIVES: The aim of this review is to discuss this key event in heat stroke and to describe the mechanism during progression. DISCUSSION: Direct injuries and secondary impairments of the intestine induced by heat stress are discussed; recent studies that refer to intestine-specific prevention and treatment in heat stroke and heat stress-induced injuries are also summarized. CONCLUSIONS: A more detailed pathogenesis of heat stroke needs to be elucidated so that potentially effective means of treatment and prevention of heat stroke can be developed and studied.

Scattering properties and femtosecond laser ablation thresholds of human and canine vocal folds at 776-nm wavelength.

Ultrafast laser ablation may provide a treatment for vocal fold (VF) scarring. Optical properties of VFs must be known prior to clinical implementation to select appropriate laser surgery conditions. We present scattering lengths of epithelium ℓs , ep, superficial lamina propria ℓs , SLP, and ablation thresholds Fth of human and canine VF tissues. Our experimental approach involves an image-guided, laser-ablation-based method that allows for simultaneous determination of ℓs and Fth in these multilayered tissues. Studying eight canine samples, we found ℓs , ep = 75.3 ± 5.7 µm, ℓs , SLP = 26.1 ± 1.2 µm, Fth , ep = 1.58 ± 0.06 J / cm2, and Fth , SLP = 1.55 ± 0.17 J / cm2. Studying five human samples, we found ℓs , ep = 42.8 ± 3.3 µm and Fth , ep = 1.66 ± 0.10 J / cm2. We studied the effects of cumulative pulse overlap on ablation threshold and found no significant variations beyond 12 overlapping pulses. Interestingly, our studies about the effect of sample storage on the scattering properties of porcine VF show a 60% increase in ℓs , ep for fresh porcine VF when compared to the same sample stored in isotonic solution. These results provide guidelines for clinical implementation by enabling selection of optimal laser surgery parameters for subsurface ablation of VF tissues.

Zinc deficits, mucositis, and mucosal macrophage perturbation: is there a relationship?

PURPOSE OF REVIEW: Mucositis is a common and therapy-limiting adverse effect of cancer treatments including radiotherapy, chemotherapy, and immunotherapy. The optimal zinc formulation, dosage, and timing of administration warrant further research as does the efficacious prevention of febrile mucositis that predisposes to febrile neutropenia. RECENT FINDINGS: Metaanalyses concluded that zinc sulfate failed to significantly reduce the incidence or severity of chemotherapy-induced oral mucositis, whereas polaprezinc was associated with a significant reduction. Three new trials were published in 2018. The first trial found that zinc sulfate reduced the incidence and severity of chemotherapy-induced oral mucositis. The second reported that polaprezinc reduced oral mucositis in pediatric patients receiving high-dose chemotherapy for hematopoietic stem cell transplantation. The third trial demonstrated efficacy for a zinc lozenge for postoperative sore throat induced by an endotracheal intubation. SUMMARY: Zinc deficits, dietary or induced by cancer, are common in patients with cancer. Febrile mucositis may better describe the condition linking mucositis with febrile neutropenia. Febrile mucositis disrupts treatment and may be life-threatening. A paradigm shift is needed for a more comprehensive understanding of febrile mucositis. Zinc effects on the thymic immunological network and T lymphocytes during chemoradiotherapy regimens also warrant further investigation.

Multi-scale modeling of an upper respiratory airway: Effect of mucosal adhesion on Eustachian tube function in young children.

BACKGROUND: The Eustachian tube is a collapsible upper respiratory airway that is periodically opened to maintain a healthy middle ear. Young children, <10 years old, exhibit reduced Eustachian tube opening efficiency and are at risk for developing middle ear infections. Although these infections increase mucosal adhesion, it is not known how adhesion forces alters the biomechanics of Eustachian tube opening in young children. This study uses computational techniques to investigate how increased mucosal adhesion alters Eustachian tube function in young children. METHODS: Multi-scale finite element models were used to simulate the muscle-assisted opening of the Eustachian tube in healthy adults and young children. Airflow during opening was quantified as a function of adhesion strength, muscle forces and tissue mechanics. FINDINGS: Although Eustachian tube function was sensitive to increased mucosal adhesion in both adults and children, young children developed Eustachian tube dysfunction at significantly lower values of mucosal adhesion. Specifically, the critical adhesion value was 2 orders of magnitude lower in young children as compared to healthy adults. Although increased adhesion did not alter the sensitivity of Eustachian tube function to tensor and levator veli palatini muscles forces, increased adhesion in young children did reduced the sensitivity of Eustachian tube function to changes in cartilage and mucosal tissue stiffness. INTERPRETATIONS: These results indicate that increased mucosal adhesion can significantly alter the biomechanical mechanisms of Eustachian tube function in young children and that clinical assessment of adhesion levels may be important in therapy selection.

Current view on the structure and function of the frontal sinus: literature review.

OBJECTIVE: Introduction: Chronic inflammatory diseases of the mucous membranes of the nose, paranasal sinuses, and pharynx are the most common pathology of the upper airways. Pathological processes develop more often in the maxillary and ethmoidal sinuses than in the frontal ones; however, the clinical course of frontitis is more severe. Fundamental understanding of the specific structure of frontal sinuses is crucial in the awareness of the precursors of the onset and development of its pathology, the choice of methods of diagnostics and treatment. The aim: The paper was aimed at the analysis of the publications on current data related to the structure and functions of the human frontal sinus and its structural components. Materials and methods: The bibliosemantic method has been used during the study. Findings of the current research works on the study of the human frontal sinus have been analyzed. RESULTS: Review: The resulting analysis shows that despite the significant amount of research works devoted to the study of the structure and functions of the frontal sinus, the morphofunctional features of its mucosa and the state of local immune protection remained unknown for a long time. CONCLUSION: Conclusions: The resulting literature review showed that the study of the morphofunctional properties of the frontal sinus is relevant to date that is reflected in the number of research works, elucidating its topographoanatomical, histological, physiological and immunohistochemical features.

Mucosal Impedance: a New Approach to Diagnosing Gastroesophageal Reflux Disease and Eosinophilic Esophagitis.

PURPOSE OF REVIEW: In this review, we discuss current diagnostic testing modalities for both gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) and then introduce mucosal impedance (MI), a novel technology that measures epithelial integrity in real time during endoscopy. We describe the advantages and disadvantages of MI as compared with traditional diagnostic testing. RECENT FINDINGS: We review studies that demonstrate that GERD and EoE have distinct MI patterns, and that physicians can accurately diagnose and distinguish the two during endoscopy with minimal time added to the procedure. We also review studies showing that MI has the capability to assess treatment response in both GERD and EoE and that it can be used to diagnose GERD in patients with extraesophageal reflux symptoms. Mucosal impedance testing is a major advancement in the diagnosis of GERD and EoE. Future studies are planned to assess whether MI can be used as a treatment endpoint in EoE and whether it can be used to predict response to anti-reflux surgery.

Metric substage according to micro and extensive lamina propria invasion improves prognostics in T1 bladder cancer.

BACKGROUND: Reliable prognosticators for T1 bladder cancer (T1BC) are urgently needed. OBJECTIVE: To compare the prognostic value of 2 substage systems for T1BC in patients treated by transurethral resection (TUR) and adjuvant bacillus Calmette-Guérin therapy. DESIGN, SETTING, AND PARTICIPANTS: The slides of 601 primary T1BCs from four institutes were reviewed by 2 uropathologists and substaged according to 2 classifications: metric substage according to T1 microinvasive (T1m-lamina propria invasion <0.5mm) and T1 extensive invasive (pT1e-invasion ≥ 0.5mm), and according to invasion of the muscularis mucosae (MM) (T1a-invasion above or into MM/T1b). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable analyses for progression-free (PFS) and cancer-specific survival (CSS) were performed including substage, size, multiplicity, carcinoma in situ, sex, age, WHO-grade 1973, and WHO-grade 2004 as variables. RESULTS: Median follow-up was 5.9 years (interquartile range: 3.3-9.0). Progression to T2BC was observed in 148 (25%) patients and 94 (16%) died of BC. The MM was not present at the invasion front in 135 (22%) of tumors. Slides were substaged as follows: 213 T1m and 388 T1e and 281 T1a and 320 T1b. On multivariable analysis, T1m/e substage and WHO 1973 grade were the strongest prognosticators for PFS (hazard ratio [HR] = 3.8 and HR = 1.8) and CSS (HR = 2.7 and HR = 2.6), respectively. Other prognostic factors for CSS were age (HR = 1.03), and tumor size (HR = 1.8). Substage according to MM-invasion was not significant. Our study was limited by its retrospective design and that standard re-TUR was not performed if TUR was macroscopically complete and muscularis propria was present in resected specimens. CONCLUSIONS: Metric substaging of T1BC was possible in all cases of 601 T1BC patients and it was a strong independent prognosticator of both PFS and CSS.

Vegetating erosive cutaneous lesions and pyogenic granuloma in the course of mucous membrane pemphigoid: a case report and review of literature.

Mucous membrane pemphigoid (MMP) is a group of chronic autoimmune sub-epithelial blistering disorders, which mostly affect the oral mucosa and the conjunctiva. MMP is very diverse in terms of both the clinical and immunological features (IgG and IgA autoantibodies may react with different antigens). MMP can be induced by infections and medication, including ophthalmologic medication, which may lead to the development of eye lesions. In contrast, a vegetating variant of MMP is extremely rare. Here, we report an MMP case that demonstrated unusual clinical features, that is, pyogenic granulomas on the conjunctivae and extensive vegetating erosions on the skin of intertriginous regions. All these lesions were considered to be induced by unconventional medication containing arsenic.