Pemphigoid Research Articles

The risk of Coronavirus disease 2019 (COVID-19) in patients with bullous pemphigoid and pemphigus: A population-based cohort study

The risk of Coronavirus disease 2019 (COVID-19) in patients with bullous pemphigoid and pemphigus: A population-based cohort study

The Value of Conjunctival Immunohistochemistry Analysis for the Diagnosis of Ocular Mucous Membrane Pemphigoid

Ocular Mucous Membrane Pemphigoid (OMMP), a subset of Mucous Membrane Pemphigoid (MMP) is an autoimmunemediated progressive cicatrizing conjunctivitis with the potential for corneal blindness. Direct Immunofluorescence (DIF) is considered the gold standard for the diagnostic confirmation of this condition; nevertheless, in many cases, this immunopathological technique is inconclusive. A 54 years old female presented to our service complaining of progressive diminished visual acuity, foreign body sensation, and photophobia in both eyes. The slit-lamp examination showed bulbar and palpebral conjunctival hyperaemia, as well as bilateral corneal scarring. During clinical follow-up, progressive conjunctival scarring with inferior fornix foreshortening, symblepharon formation, and significant corneal opacity dramatically diminished her visual acuity. A conjunctival biopsy was negative for DIF; therefore, Immunohistochemical analysis (IHCA) for IgG, IgA, and C3 immune reactants linear deposition on the conjunctival Basement-membrane zone (BMZ) was necessary for diagnosis confirmation. The present clinical case highlights the utility of paraffin-embedded conjunctival IHCA as an alternative immunohistopathology tool for the diagnosis of OMMP when DIF is non-conclusive.

Role of eosinophils in the pathogenesis of bullous pemphigoid

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering skin disease, and a large number of eosinophils (EOS) obviously infiltrate the dermis of BP lesions. Additionally, EOS and their activated cytokines and chemokines are abundantly present in blisters and peripheral blood of BP patients. It is also proved that EOS can induce the dermal-epidermal separation. The level of interleukin (IL) -5 is markedly increased in the sera and blister fluids of BP patients, and IL-5 secreted by Th2 cells and EOS can regulate the differentiation, activation and survival of EOS. All the above evidence indicates that EOS are associated with the occurrence of BP. Researches on EOS and their cytokines will develop a new field of targeted therapy for BP. Key words: Pemphigoid, bullous; Eosinophil; Pathogenesis; Dermal-epidermal separation

Diagnosis and treatment of skin diseases manifesting as desquamative gingivitis

Skin diseases manifesting as desquamative gingivitis (DG) can be divided into recurrent DG- and chronic DG-related skin diseases, including oral lichen planus, mucosal pemphigoid, pemphigus vulgaris and so on. A thorough medical history, detailed oral and histopathological examinations and serum immunological tests can be helpful for correct diagnosis of DG-related skin diseases. The treatment of DG-related skin diseases includes topical and systemic therapies. It is necessary to individualize treatment protocols due to treatment response. During the treatment of DG, oral hygiene should be strengthened, secondary fungal and bacterial infections should be avoided, and attention should be paid to the protection of oral cavity and periodontal tissues. Key words: Gingivitis; Lichen planus, oral; Pemphigus; Pemphigoid, benign mucous membrane; Epidermolysis bullosa acquisita

Evaluation of the value of indirect immunofluorescence on different substrates in the diagnosis of autoimmune subepidermal bullous diseases

Objective To evaluate the value of indirect immunofluorescence (IIF) on three different substrates including normal human skin (NS) , monkey esophagus (ME) and salt-split human skin (SS) in the diagnosis of autoimmune subepidermal bullous diseases. Methods A total of 56 patients with autoimmune subepidermal bullous diseases, including 47 with bullous pemphigoid (BP) , 6 with epidermolysis bullosa acquisita (EBA) , 2 with linear IgA bullous dermatosis, and 1 with anti-P200 pemphigoid, were diagnosed in and enrolled from Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Sciences between January 2015 and December 2016. Seventy patients with pemphigus, 15 patients with chronic eczema and 15 healthy adults served as controls. Blood samples collected from these patients and controls were subjected to IIF on three different substrates including NS, ME and SS, and the fluorescence deposition was observed. The sensitivities and specificities of IIF in the diagnosis of different subepidermal bullous diseases were compared. Statistical analysis was carried out with SPSS 13.0 software by using chi-square test for the comparison of enumeration data. Results IIF on NS or ME in the serum of patients with BP showed linear deposition of fluorescent material along the basement membrane zone. IIF on SS showed linear deposition of fluorescent material in the epidermis in the patients with BP, but in the dermis in the patients with EBA and anti-P200 pemphigoid. The sensitivities of IIF on NS, ME or SS in the diagnosis of subepidermal bullous diseases were 73.2%, 60.7% and 94.6% respectively, and the specificities were 98.0%, 100% and 97.1% respectively. There were significant differences among the sensitivities (χ2 = 18.2, P 0.05) . The diagnostic sensitivity of IIF on SS was significantly higher than that of IIF on NS or ME (χ2 = 8.0, 16.7, both P < 0.05) . Conclusion In the diagnosis of autoimmune subepidermal bullous diseases, IIF on SS is superior to IIF on ME or NS. Key words: Fluorescent antibody technique, indirect; Pemphigoid, bullous; Autoimmune subepidermal bullous disease; Diagnosis; Sensitivity; Specificity

BP180-related autoimmune blistering diseases

BP180-related autoimmune blistering diseases include bullous pemphigoid, lichen planus pemphigoides, linear IgA bullous dermatosis, pemphigoid gestationis and cicatricial pemphigoid. There are multiple autoantibody-reactive sites on the extracellular region of BP180. Current studies show that there is heterogeneity in the autoimmune blistering disease-related target sites on BP180, and different clinical manifestations of the same disease are related to the heterogeneity of target sites. However, further studies and analysis are still needed for the mechanism of the heterogeneity. Key words: Pemphigoid, bullous; Pemphigoid gestationis; Pemphigoid, benign mucous membrane; Linear IgA bullous dermatosis; BP180

Efficacy of combined lymphoplasma exchange for the treatment of severe refractory immune-related skin diseases: a clinical observation

Objective To evaluate the clinical efficacy of lymphoplasma exchange (LPE) for the treatment of severe refractory immune-related skin diseases. Methods From May 2013 to October 2015, 8 patients with toxic epidermal necrolysis, drug-induced hypersensitivity syndrome (DIHS) , pemphigus vulgaris, pemphigoid or paraneoplastic pemphigus were enrolled from Department of Dermatology, Xiangya Hospital, Central South University, who showed no response to conventional therapy or presented with multiple organ dysfunction. After the treatment with LPE, the efficacy was evaluated, and adverse reactions were observed. Results After one session of LPE therapy, 6 patients received marked improvement, and were cured at last. In 1 patient with pemphigus vulgaris who was resistant to the treatment with high doses of glucocorticoids and immunosuppressive agents, the rashes regressed during the treatment with LPE, but recurred after the end of treatment. One patient with bullous pemphigoid presented with eruptive blisters on the next day after the treatment with LPE, which were considered as allergic reactions to allogeneic plasma. There were no obvious differences in white blood cell count, lymphocyte count, neutrophil count and blood platelet count in the peripheral blood of 8 patients before and after the treatment with LPE. During the follow-up of 3-5 years, all of the patients were recovered without recurrence, except 1 patient with bullous pemphigoid who died of disseminated tuberculosis after 1 year. Conclusion LPE is effective for the treatment of severe immune-related skin diseases, but attention should be paid to potential transfusion reaction and allergic reactions. Key words: Plasma exchange; Epidermal necrolysis, toxic; Pemphigus; Pemphigoid, bullous; Drug reaction with eosinophilia and systemic symptoms; Paraneoplastic pemphigus

Expression of BP180 antibody in sera of patients with bullous pemphigoid and nervous system diseases

Objective To measure the expression of BP180 antibody in sera of patients with bullous pemphigoid (BP) and/or nervous system diseases (ND) , and to explore the relationship between BP and ND. Methods Clinical data were collected from some inpatients and outpatients with BP in Department of Dermatology, as well as some inpatients with ND in Department of Neurology, the Second Hospital of Jilin University between March 2012 and September 2013. Peripheral blood samples were obtained from 20 BP patients without a medical history of ND (BP group) , 20 patients with ND alone (ND group) , 20 BP patients with a medical history of ND (BP + ND group) , and 20 healthy controls (healthy control group) separately. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum level of BP180 antibody in the above groups. Statistical analysis was carried out with SPSS17.0 software by using chi-square test for comparing enumeration data, analysis of variance for comparing the anti-BP180 antibody titer or ages among the above 4 groups, and Games-Howell test for multiple comparisons. Results No anti-BP180 antibody was detected in any of the 20 subjects in the healthy control group. All of the patients in the BP group and BP + ND group were positive for anti-BP180 antibody, and the antibody titers were 128.347 ± 54.678 and 143.482 ± 72.568 respectively. Of the 20 patients in the ND group, 7 were positive for anti-BP180 antibody, including 4 with cerebral hemorrhage and 3 with cerebral thrombosis, and the highest anti-BP180 antibody titer of 39.638 was recorded in 1 patient with cerebral infarction. There was a significant difference in the anti-BP180 antibody titer among the 4 groups (F = 55.624, P < 0.05) . In addition, there was no significant difference in the anti-BP180 antibody titer between the BP group and BP + ND group (P = 0.878) , while the anti-BP180 antibody titers significantly differed between the BP group and ND group, between the BP group and healthy control group, between the BP + ND group and ND group, between the BP + ND group and healthy control group, and between the ND group and healthy control group (P < 0.05) . Conclusion BP may occur in ND patients with an increased anti-BP180 antibody titer. Key words: Pemphigoid, bullous; Nervous system diseases; Autoantibodies; BP180

Evaluation of the value of Western blot analysis based on human epidermal extracts prepared by thermal separation in the diagnosis of bullous pemphigoid

Objective To prepare human epidermal extracts by thermal separation, and to evaluate the value of epidermal extract-based Western blot analysis in the diagnosis of bullous pemphigoid (BP) . Methods Human epidermal extracts were prepared by thermal separation from circumcised foreskins of healthy males. Serum samples were obtained from 22 inpatients with BP and 25 inpatients without BP in Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 and August 2017. These serum samples were subjected to Western blot analysis with epidermal extracts as substrates, as well as to BP180-NC16A enzyme-linked immunosorbent assay (ELISA) . Statistical analysis was carried out using chi-square test and Fisher′s exact test with the SPSS22.0 software. Results The sensitivities of epidermal extract-based Western blot analysis and BP180-NC16A ELISA in the diagnosis of BP were 86.36% (95%CI: 64.03%-96.41%) and 95.45% (95%CI: 75.11%-99.76%) respectively (χ2= 1.10, P= 0.294) , and the specificities were 100% (95% CI: 83.42%-100%) and 92% (95% CI: 75.11%-99.76%) respectively (χ2 = 20.8, P = 0.149) . Epidermal extract-based Western blot analysis in the 22 patients with BP showed a protein band with relative molecular mass (RMM) of 230 000 in 4 patients, a protein band with RMM of 180 000 in 18, a protein band with RMM of 120 000 in 1, and a protein band with RMM of 97 000 in 1. The BP180-NC16A ELISA showed that the antibody titers were more than 50 U/ml in the BP patients with protein bands of RMM of 180 000. Conclusions The epidermal extract-based Western blot analysis mainly showed the protein band with RMM of 180 000 in the patients with BP. The sensitivity of the epidermal extract-based Western blot analysis was lower than that of the BP180-NC16A ELISA, and the epidermal extract-based Western blot analysis tends to be negative when the titer of the autoantibody is low. Key words: Pemphigoid, bullous; Blotting, Western; Epidermis; Autoantigens; Enzyme-linked immunosorbent assay; Thermal separation; Human epidermal extract

Appearance of prominent milia as secondary lesions during recovery of refractory bullous pemphigoid: a case report

Appearance of prominent milia as secondary lesions during recovery of refractory bullous pemphigoid: a case report

Coexistence of chronic actinic dermatitis with bullous pemphigoid: a rare case report

Coexistence of chronic actinic dermatitis with bullous pemphigoid: a rare case report

Association of Pemphigus and Pemphigoid with Osteoporosis and Pathological Fractures

Abstract not available. Disclosures: None. Copyright 2018 SKIN

Advance of rituximab in the treatment of ocular inflammatory diseases

Rituximab (RTX) is a monoclonal antibody directed against the CD20 antigen expressed on B cells. It has been successfully employed in the treatment of non-Hodgkin's lymphoma and varied systemic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and granulomatosis with polyangiitis. Recently its efficacy in the treatment of ocular inflammatory diseases (OID), including refractory scleritis, peripheral ulcerative keratitis, uveitis, and ocular cicatricial pemphigoid, has aroused more concerns. The literature suggests that RTX may be useful for controlling the inflammation and decreasing or stopping the use of corticosteroids and other immunosuppressants in OID, which may contribute a new treatment alternative in patients with the recalcitrant and sight-threatening forms of OID. This article reviews the clinical application status of RTX in the treatment of OID. Key words: Rituximab; Ocular inflammatory disease; Treatment; Review

There is no correlation between the serum level of interleukin-21 and bullous pemphigoid

Objective To investigate the correlations of the serum level of interleukin-21 (IL-21) with anti-BP180 antibodies, peripheral eosinophil level, bullous pemphigoid disease area index (BPDAI) in patients with bullous pemphigoid (BP) . Methods A total of 31 patients with bullous pemphigoid and 31 healthy controls were enrolled into this study. Blood samples were collected from all the subjects, and enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum level of IL-21 and serum titer of anti-BP180 antibodies. BPDAI was assessed among 13 patients, and the correlation of the IL-21 level with anti-BP180 antibody titers, eosinophil count and BPDAI were analyzed. Results No significant difference in the serum level of IL-21 was observed between the patients (M[P25 - P75]: 255.28 [156.19 - 361.59] ng/L) and healthy controls (150.47 [72.4 - 268.73] ng/L, P = 0.14) . There was no correlation between the serum level of IL-21 and serum titer of anti-BP180 antibodies (82.98 [26.82 - 132.92]U/ml, rs = 0.18, P = 0.332) . Among the 27 BP patients who underwent blood cell count, no correlation was found between the serum levels of IL-21 and whole-blood eosinophil counts (rs = 0.104, P = 0.606) . Among the 13 BP patients who underwent assessment of BPDAI, there was no correlation between the serum levels of IL-21 and BPDAI scores (rs = 0.233, P = 0.464) . Conclusion The IL-21 level is uncorrelated with anti-BP180 antibody level, peripheral eosinophil level or BPDAI in patients with BP. Key words: Pemphigoid, bullous; Eosinophils; Interleukin-21; Anti-BP180 antibody

Cutaneous adverse events caused byimmune checkpoint inhibitors: classification and management

Immune checkpoint inhibitors (ICPIs) have been successfully used in the treatment of multiple malignancies. However, immune-related adverse events (irAEs) may occur during treatment. Cutaneous adverse event (CAE) is acommon type of irAE. Mild CAEs include maculopapule, lichenoid reaction, bullous pemphigoid, vitiligo, psoriasis, and scleroderma. Severe and even life-threatening CAEs include Steven-Johnson syndromeand toxic epidermal necrolysis. Other CAEs include drug reactionwith eosinophiliaand systemic symptoms, Sweet′s syndrome, alopecia, Grover′s disease, and paraneoplastic syndrome. This paper reviews the treatment of cutaneous adverse events associated with ICPIs. Key words: immune checkpoint inhibitors; immune-related adverse events; cutaneous adverse events

Indirect immunofluorescence on salt-split skin and bullous pemphigoid 180 NC16a enzyme-linked immunosorbent assay in the diagnosis of bullous pemphigoid

Objective To evaluate the value of indirect immunofluorescence on salt-split skin (IIF-SSS) and bullous pemphigoid 180 NC16a enzyme-linked immunosorbent assay (BP180 NC16a-ELISA) in the diagnosis of bullous pemphigoid (BP) . Methods Serum samples were collected from 174 BP patients and 129 controls, who were enrolled from Institute of Dermatology of Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 and August 2017, and subjected to IIF-SSS and BP180 NC16a-ELISA. Direct immunofluorescence (DIF) test was performed in 25 cases of BP, and its sensitivity for the diagnosis of BP was compared with that of IIF-SSS and BP180 NC16a-ELISA. Results The sensitivities for IIF-SSS and BP180 NC16a-ELISA were 93.67% and 96.55% respectively, and the specificities for IIF-SSS and BP180 NC16a-ELISA were 100% and 96.12% respectively. IIF-SSS was weakly correlated with BP180 NC16a-ELISA with a correlation coefficient of 0.147. There was no significant difference in the sensitivity between the serological diagnostic methods (IIF-SSS and BP180 NC16a-ELISA) and DIF. Conclusion Serological diagnostic methods show high specificity and sensitivity in the diagnosis of BP, and are worthy of clinical promotion and application. Key words: Pemphigoid, bullous; Diagnosis; Fluorescent antibody technique, indirect; Skin; Enzyme-linked immunosorbent assay

A case of psoriasis complicated by bullous pemphigoid with secondary Kaposi sarcoma

A case of psoriasis complicated by bullous pemphigoid with secondary Kaposi sarcoma

A case of widespread eruptive milia after the cure of bullous pemphigoid

A case of widespread eruptive milia after the cure of bullous pemphigoid

Three cases of trauma-triggered autoimmune bullous skin diseases

Objective To summarize clinical and histopathological features of trauma-triggered autoimmune bullous skin diseases, and to explore its possible pathogenesis. Methods Clinical manifestations, histopathological features and treatment of 3 cases of trauma-triggered pemphigus or pemphigoid were analyzed, and summarized according to related domestic and overseas literature. Results Of the 3 cases, 1 was a female aged 62 years, and 2 were males aged 60 and 71 years respectively. They all had a history of skin trauma or surgery before the onset of the diseases, and time intervals from trauma to diseases were 5, 5 weeks and 3 days respectively. The 3 cases were diagnosed as bullous pemphigoid (anti-BP180 antibody 109 U/ml, anti-BP230 antibody negative) , pemphigus vulgaris (anti-Dsg1 antibody 68.8 U/ml, anti-Dsg3 antibody 219 U/ml) and pemphigus foliaceus (anti-Dsg1 antibody 143 U/ml, anti-Dsg3 antibody negative) respectively. Their lesions were relieved dramatically after oral and (or) topical glucocorticoid treatment. Conclusions Trauma may be a triggering factor for autoimmune bullous skin diseases. For patients with post-traumatic poor wound healing or skin erythema, blisters and erosion, which can hardly be attributed to trauma or surgery itself, autoimmune bullous skin diseases should be considered, and histopathological or immunopathological examinations should be performed timely. Key words: Pemphigus; Pemphigoid, bullous; Wounds and injuries

Role of cytotechnique in evaluation of non infectious vesiculobullous lesions of skin

Aim: To evaluate the efficacy and diagnostic accuracy of cytological techniques in evaluation of noninfectious vesiculobulloous lesions of skin. Materials and methods: Tzanck smear prepared from vesiculobullous lesions. Giemsa stainining of cytology smears. Biopsy of lesions where possible. Result: 22 patients (indoor/outdoor) with vesiculobullous skin lesions were subjected to cytological examination and biopsy. Twenty two cases of vesiculobullous lesions were comprised of 12 cases (54.54%) of bullous pemphigoid, 7 cases (12.96%) of pemphigus vulgaris, two cases of linear IgA bullous dermatosis (9.09%) and one case of pemphigus foliaceus (1.85%). Sensitivity, specificity and diagnostic accuracy of tzanck smear for diagnosing vesiculobullous lesions were 100%, 100% and 100% respectively Conclusion: Cytological examination is a very simple and useful modality, requires minimum equipments and can be performed in outpatient clinic. The procedure is safe, free from complications and is well tolerated by patients.