Bullous pemphigoid associated with acquired hemophilia A: A case report

BACKGROUND Acquired hemophilia A (AHA) is a rare and potentially severe bleeding disordercaused by circulating autoantibodies against factor Ⅷ (FⅧ). In approximately50% of the patients, the condition is associated with autoimmune diseases,cancers, medication use, pregnancy, and the post-partum period. Bullous pemphigoid(BP) is a chronic autoimmune subepidermal blistering disease associatedwith tissue-bound and circulating autoantibodies against BP antigens 180 (BP180)and 230 (BP230). AHA-associated BP has a high mortality rate;hence, the understandingof this disease must improve.CASE SUMMARY A 69-year-old man presented with erythema, blisters, blood blisters, and crustsaccompanied by severe pruritus for more than 20 days, and ecchymosis andswelling on his left upper arm for 3 days. Pathological examination revealed asubepidermal blister that contained eosinophils. Laboratory tests showed that theBP180 autoantibody levels had increased, isolated activated partial thromboplastintime was notably prolonged (115.6 s), and coagulation FⅧ activity wasextremely low (< 1.0%). Furthermore, the FⅧ inhibitor titer had greatlyincreased (59.2 Bethesda units). Therefore, the patient was diagnosed as having BP associated with AHA, prescribed 0.05% topical halometasone cream, and transferred to a higher-level hospitalfor effective treatment;however, he died after 2 days.CONCLUSION AHA associated BP is rare, dangerous, and has a high mortality rate. Therefore, its timely diagnosis and effectivetreatment are necessary.

Bullous Pemphigoid Induced by Doxycycline: Case Report and Literature Review

Bullous pemphigoid (BP) is the most prevalent autoimmune sub-epidermal blistering disease that affects mainly the elderly and could lead to serious morbidity. It has numerous risk factors and triggers, including an aging population with several comorbidities and drug exposure. In the published paper, we reported a case about a 32 years old male patient with unknown medical conditions who presented with erythematous patches and plaques on the scalp, face, and trunk with scattered blisters two weeks after initiating doxycycline treatment for folliculitis. The exact pathogenesis of the drug-reaction in drug- associated bullous pemphigoid (DABP) remains controversial. In conclusion, it is crucial for clinicians to be aware of DABP when prescribing doxycycline. The purpose of this case report is to raise awareness of the possible association between bullous pemphigoid and doxycycline.

Urticarial Bullous Pemphigoid: A New Case Report

Background: Bullous pemphigoid (BP) is the most common autoimmune bullous disease and it primarily affects the elderly population. It typically presents with tense bullae and severe pruritus. Non-bullous pemphigoid is a subtype of BP characterized by lacking the typical bullae formation with different presentations including erythematous, eczematous, urticarial, polycyclic, targetoid, nodular, lichenoid, vesicular and erythrodermic. Aim: to document a new case presentation of urticarial BP who was treated for several years as chronic urticarial and chronic eczema. Case Report: A 56-year-old male patient presented with a history of recurrent severely pruritic urticarial wheals for 4 years duration involving the lower abdomen, lower back, upper and lower extremities associated with excoriations, keratosis, and post-inflammatory hyperpigmentations on resolved sites, diagnosed as urticarial BP on histopathology & direct immunofluorescence study (DIF) and was improved on systemic doxycycline therapy. Conclusion: BP can be presented with atypical manifestation. Urticarial BP is a rare variant of non-bullous pemphigoid that should be taken into consideration in the differential diagnosis of an atypical urticarial wheal not responding to conventional therapy.

Rituximab Therapy for Persistent, Severe and Extensive Idiopathic Bullous Pemphigoid

Background: Idiopathic Bullous Pemphigoid (IBP) is a rare blistering autoimmune disease. Its morbidity and mortality have remained high owing to complications of extensive skin involvement as well as its conventional steroid therapy. We reviewed the medical literature and found indicators of an autoimmune etiology for its pathogenesis triggering genetically predisposed patients. Objective: to evaluate, prospectively, the role of Rituximab (R) therapy in its persistent, severe and extensive form. Patients and methods: A total of 12 patients, with disease duration of 6 ± 1 months, were treated with yearly R infusions (1 g followed by 1 g 2 weeks later). Results: Significant clinical improvement was achieved as documented by decrease in total score of Bullous Pemphigoid Disease Area Index from 60 ± 3 to 6 ± 2 that persisted for 26 ± 11 months of follow up. Moreover, IBP autoantibodies (anti-BP 180 and anti-320 IgG) levels fell from to 91 ± 3 and 81 ± 2 to 8 ± 2 and 9 ± 2, respectively. Conclusions: R is a safe and effective treatment for severe IBP and such response further confirms its autoimmune pathogenesis.

Topical use of ozone effectively alleviates the acute symptoms and quality of life of patients with moderate to severe bullous pemphigoid: a randomized controlled trial

Objective:To evaluate the adjuvant treatment of acute stage symptoms and quality of life of patients with bullous pemphigoid(BP)with ozone.Methods:We included 74 patients with moderate and severe BP hospitalized from July 2018 to December 2020.The participants were randomly divided into the control group and the ozone group,with 37 patients in each group(n=37).The control group used tap water to wash the whole body,and mupirocin ointment was used for the erosions.The ozone group used ozone water to wash the whole body,and the erosion place was coated with ozone oil.The bullous pemphigoid disease area index(BPDAI)score of BP disease was used to observe the clinical symptoms and skin lesions of the two groups before and on day 3,7,and 14 after treatment.Pruritus and sleep were observed before and on day 3,7,and 14 after treatment.The Dermatology Life Quality Index(DLQI)was used to observe the quality of life before and after treatment and the adverse reactions were recorded.Results:The total BPDAI score and erythema score in the ozone group were significantly different from those in the control group on day 3,7,and 14 after treatment(P<0.050).The scab drying time and erosion drying time of ozone group were shorter than that of control group(P<0.001).There were statistically significant differences between the ozone group and the control group in pruritus score and sleep score on day 3,7,and 14 after treatment(P<0.001).There was statistically significant difference in skin disease quality of life between the two groups 14 days after treatment(P<0.001).No significant adverse reactions and complications were observed in both groups.Conclusions:Ozone external use can rapidly improve the acute stage of edema erythema,erosion,and itching of BP,improve the quality of life of patients,is an effective treatment method,and wor thy of clinical promotion.

Expression of MMP-2 and MMP-13 in Bullous Pemphigoid

Objective:To investigate the expression and significance of matrix metalloproteinase-2(MMP-2)and matrix metalloproteinase-13(MMP-13)in bullous pemphigoid(BP)skin lesions.Methods:Immunohistochemical SP method was used to detect the expression of MMP-2 and MMP-13 in 32 BP skin lesions,and compared with 15 normal skin tissues.Results:The expression of MMP-2 in the case group was significantly increased(38.56±10.06)compared to the normal control group(21.20±5.98);the expression of MMP-13 in the case group was significantly augmented(18.62±5.90)compared to the normal control group(11.47±8.484).The expressions of MMP-2 and MMP-13 in the skin lesions of patients with bullous pemphigoid were statistically different from those of normal people(both P<0.05).Compared with the expression of MMP-2 and MMP-13 in bullous pemphigoid,the expression of MMP-2 and MMP-13 was moderately correlated(correlation coefficient was 0.523).Conclusion:The expression of MMP-2 and MMP-13 is significantly increased in bullous pemphigoid skin lesions,suggesting that they may play an important role in the pathogenesis of BP.There is a certain correlation between the expression of MMP-2 and MMP-13,suggesting that the high expression of MMP-13 may play a role in the mechanism that further leads to the high expression of MMP-2.

Rare bullous pemphigoid during PD-1 inhibitor therapy:a case report

Immunotherapy is an important treatment modality in cancer,but it can also cause adverse reactions,with skin toxicity being the most common.The increasing number of immune checkpoint inhibitors being used in the clinic will inevitably cause an increase in the rate of adverse skin reactions that markedly affect the patient's quality of life.A 58-year-old patient with intrahepatic cholangiocareinoma developed bullous pemphigoid(BP)nearly a year after using immune checkpoint inhibitors,which is different from what has been reported inthe literature within two weeks of treatment.Pathologically,the skin biopsy diagnosis was epidermal hyperplasia and focal sub-epidermal pustule formation,consistent with drug-induced dermatitis.The patient was treated with methylprednisolone,minocyeline,colchicine,nicotinamide,triamcinolone,and traditional Chinese medicine decoction.No new blisters developed after 1 week of treatment.The medication was gradually discontinued,and BP did not recur.Clinicians should carefully consider the risk-benefit ratio when using PD-1 inhibitors,particularly concerning rash severity.Further studies are needed to investigate the relationship between adverse skin reactions and drug efficacy.

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

Introduction Bullous pemphigoid (BP) is an autoimmune blistering disease that affects patients of advanced age. BP is characterized clinically by tense bullae on the extremities and trunk, histopathologically by subepi-dermal blisters with eosinophilic infiltration, and immunologically by autoantibodies to BP180 and BP230. Direct immunofluorescence of perilesional skin shows depositions of IgG and C3 in the basement membrane zone(1)BP rarely shows prominent milia formation, which is a hallmark of epidermolysis bullosa acquisita. We herein describe a 53-year-old man with refractory BP showing numerous milia during recovery.

Preliminary Application of High-Frequency Ultrasound in the Differentiation of Pemphigus and Bullous Pemphigoid:An Observational Study

Objective:Ultrasonography is a diagnostic imaging technique used to visualize subcutaneous body structures for identification of possible pathologies.In this study,we aimed to explore the clinical significance of high-frequency ultrasound in differentiating the location of blisters between pemphigus and bullous pemphigoid.Methods:Eighteen patients were recruited in Department of Dermatology,Zhongda Hospital from 2020 to 2021 and divided into a pemphigus group(n=8)and a bullous pemphigoid group(n=10)according to the diagnostic criteria for each.Ultrasonographic images were collected using a 50-MHz high-frequency ultrasound system.The indexes of ultrasonic evaluation were the layer(epidermis or dermis),size,shape,internal echo,and boundary of the blister.Categorical variables are expressed as n(%),and differences were compared using Fisher’s exact test.Results:The ultrasonographic images in the pemphigus group showed an intraepidermal semi-arc or irregular anechoic or hypoechoic areas.The inferior borders were situated above the characteristic thin linear hyperechoic bands of the epidermis.A linear hypoechoic band was present at the dermoepidermal junction in some cases.In the ultrasonographic images of the bullous pemphigoid group,the linear hyperechoic bands of the epidermis were continuous and intact.An oval fluid anechoic area(subepidermal blister)was present immediately below the bands.The location of the blisters in the ultrasonographic images was significantly different between the 2 groups(P<0.001).Conclusion:High-frequency ultrasound can be used as an auxiliary means to differentiate the location of blisters between pemphigus and bullous pemphigoid.

Nivolumab-induced severe bullous pemphigoid in a patient with renal cancer:a case report and literature review

With the widespread use of immunotherapy in numerous solid tumours,immunotherapy-related adverse events(irAEs)have started to emerge and bring new challenges for clinicians to manage.Among established irAEs,dermatologic toxicity is one of the most common toxicities;it is often mild but can be severe and potentially life-threatening,such as bullous pemphigoid.Here,we report a case of nivolumab-mediated severe,extensive,refractory bullous pemphigoid involving both skin and oral mucosa in a patient with metastatic renal cancer.We also summarise a list of selected case reports of immunotherapy-induced bullous pemphigoid by literature review.We highlight various presentations,investigations and managements of this type of skin irAEs.Meantime,we would like to discuss the correlation of skin irAEs incidence rate with immunotherapy drug benefit and resistance.

Esophagitis dissecans superficialis and autoimmune bullous dermatoses: A review

Esophagitis dissecans superficialis(EDS)is a rare and severe endoscopic finding characterized by sloughing of large fragments of esophageal mucosal lining.Although EDS has been reported in association with serious illnesses and certain medications,the pathophysiological association of autoimmune bullous dermatoses with EDS has gained remarkable attention.Among these dermatoses,pemphigus vulgaris and pemphigoid frequently present with various types of esophageal involvement including EDS.We review the pathophysiology and clinical features of this involvement with the presentation of our experiences.The importance of endoscopic evaluation of this entity is discussed.

Identification of human herpesvirus-8 in Kaposi＆#39;s sarcoma with bullous pemphigoid

Kaposi＆#39;s sarcoma （KS） is a rare,malignant vascular.tumor of the skin,mucosa,and viscera with an increased incidence in human immunodeficiency virus （HIV）-positive patients.According to the clinical characteristics and the affected population,four clinical types of KS have been described successively：classic,endemic to Africa,acquired immunodeficiency syndrome （AIDS）-associated,and immunosuppression associated type.Bullous pemphigoid （BP） is an acquired autoimmune bullous skin disease that frequently occurs in the elderly and is characterized by intraepidermal blisters and immunoglobulin G （IgG） deposits on the basement membrane.A few cases of KS have occurred in immunosuppressed patients with BP.Here,we report a Chinese female patient diagnosed with immunosuppression associated KS that was induced by the short-term use of immunosuppressive agents for BP.We also present a review of the literature on immunosuppressed KS with BP and discuss the potential role of human herpesvirus-8 （HHV-8） in the pathogenic mechanism.

Oral Manifestations, Gingival Index and Dental State of Vesiculobullous Diseases

Objective: To determine the occurrence of oral manifestations, gingival index, dental state and associated therapeutic aspects in patients with vesiculobullous diseases. Study design: Prospective and observational study conducted with 69 patients from May 2013 to May 2014 at the Dermatology Outpatient Clinic of the Clinical Hospital, University of S&atilde;o Paulo Medical School, Brazil. Data were analyzed for frequency in absolute values, percentage and correlation using the Chi-square test. Results: 84.1% of the patients had oral manifestations of vesiculobullous diseases (p = 0.001);25% had gingival lesions;18.2% had lesions in the buccal mucosa, and 17.6% in the lips, with no correlation between the location and the type of disease (p = 0.990). Among all patients with bullous pemphigoid, linear IgA dermatosis, and mucous membrane pemphigoid, 59 (93.6%) patients had gingival inflammation of dental origin but without significant correlation (p = 0.42). There was correlation between pemphigus vulgaris and periodontal disease (p = 0.05). Conclusion: Gingival inflammation seems to interfere negatively with the clinical course of these diseases. Further studies should be conducted to better clarify the interrelations between dental and gingival state, and between vesiculobullous diseases and oral involvement.

Bullous Pemphigoid With Nail Damage Associated With Kaposi Sarcoma:A Case Report

Introduction:Bullous pemphigoid is an acquired autoimmune bullous skin disease that occurs in the elderly,and nail involvement is relatively rare.Kaposi sarcoma(KS) is a rare opportunistic tumor in patients with iatrogenic immunosuppression and is rarely associated with autoimmune bullotic disease.Case presentation:The patient was diagnosed with bullous pemphigoid based on her history,bullous pemphigoid antibody,and skin pathological examination.And nail involvement occurred 20 days prior to the recurrence of the disease.Moreover,KS occurred during high-dose glucocorticoid therapy in this patient.Discussion:The patient was admitted to hospital because of a five-month history of erythema and blisters and a one-month history of nodules and plaques.The diagnosis of bullous pemphigoid was followed by treatment with glucocorticoids and intravenous gamma globulin.During treatment,the disease recurred due to discontinuation of glucocorticoids.There were erythema and blisters all over the body,and purple nodules,plaques appeared in the base of some blisters.Pathological examination of nodules was consistent with KS.In addition,nail involvement occurred 20 days before recurrence.The particularity of this case lies in the simultaneous occurrence of nail involvement,bullous pemphigoid,and KS.Conclusion:Patients with autoimmune bullous skin disease may suddenly develop abnormal nails,and such patients should be vigilant about recurrence of the disease.Doctors should be aware of the possibility of KS when rapidly progressing purplish red plaques or nodules appear in patients receiving high doses of corticosteroids or immunosuppressants.

A Case Report of Pemphigoid Nodularis as Masquerader of Neurotic Excoriations

Introduction:Pemphigoid nodularis is a rare clinical variant of bullous pemphigoid characterized by both prurigo nodularis-like lesions and pemphigoid-like blisters.Case presentation:A 72-year-old Chinese man has been on follow-up at an outpatient Dermatology unit for extensive prurigo nodularis for past 4 to 5 years until an inpatient stay when he was admitted for labile mood and erratic behavior due to the intense pruritus and skin lesions.During the admission,the inpatient team noticed tense hemorrhagic blisters on his right thigh for which histological examination confirmed the diagnosis of bullous pemphigoid.He was treated with oral prednisolone,doxycycline,and nicotinamide,which led to clinical improvement.Discussion:Pemphigoid nodularis can be easily misdiagnosed as prurigo nodularis.We discuss clinical clues that can raise the suspicion of an underlying immunobullous disorder,including erythematous nodules with a much larger surface area affected by central erosions and ulceration.Pruritus associated with larger areas of erosions and ulceration is clues that lesions can be more than mere excoriations.Conclusion:It is important for clinicians to be aware of the presentation of prurigo nodularis in association with bullous pemphigoid such that effective treatment can be promptly instituted.This is especially illustrated in this case,as the treatment of bullous pemphigoid not only improved his skin condition but it also improved his psychological health and behavior with the resolution of itch.

寻常性银屑病合并自身免疫性大疱性皮肤病13例临床分析

目的:分析寻常性银屑病合并自身免疫性大疱性皮肤病患者的临床特点、诊断及治疗。方法:回顾性分析2008—2021年西京医院皮肤科确诊寻常性银屑病合并自身免疫性大疱性皮肤病住院患者的临床资料。结果:收集13例寻常性银屑病合并自身免疫性大疱性皮肤病患者,其中男8例,女5例,平均年龄(44.69±8.02)岁。所有患者于银屑病发生后平均(14.85±7.54)年合并自身免疫性大疱性皮肤病。所有患者中7例合并天疱疮(其中1例伴有汞中毒),5例合并大疱性类天疱疮(1例确诊肺腺癌),1例合并成人型线状Ig A大疱性皮病。7例患者采用糖皮质激素和(或)免疫抑制剂治疗,6例予单用免疫抑制剂治疗。出院后随访2个月~13年,10例患者治愈或病情稳定,3例失访。结论:寻常性银屑病可合并多种自身免疫性大疱性皮肤病,临床较为少见。患者多为银屑病病程中出现水疱、大疱性皮损,明确诊断需结合皮损组织病理表现、免疫荧光、疱病自身抗体等检查结果综合判断。提示临床上需警惕合并汞中毒可能,并重视对肿瘤的筛查和随访,根据疱病严重程度制定合理的治疗方案。

临床药师参与1例大疱性类天疱疮、肺曲霉病合并播散性皮疽诺卡菌感染治疗的药学实践

目的为大疱性类天疱疮、肺曲霉病合并播散性皮疽诺卡菌感染患者的抗菌药物方案调整、不良反应识别和个体化药学监护提供参考。方法临床药师参与1例大疱性类天疱疮、肺曲霉病合并播散性皮疽诺卡菌感染患者的治疗全过程,结合循证证据协助临床遴选初期抗皮疽诺卡菌感染的联合治疗方案,并及时沟通微生物室以提供早期药敏数据;在患者出现癫痫时甄别可疑药物,并提醒临床亚胺培南西司他丁钠会影响丙戊酸钠疗效,建议将丙戊酸钠换为左乙拉西坦抗癫痫治疗,并停用亚胺培南西司他丁钠;治疗期间,建议临床对伏立康唑、利奈唑胺进行血药浓度监测,并根据监测结果协助临床及时调整用药剂量。结果医生采纳临床药师建议。患者病情好转,带药出院。结论临床药师基于循证医学证据、药敏试验结果和血药浓度监测数据,协助临床为患者选择敏感的抗感染方案;及时识别不良反应并调整治疗方案,并为患者提供全程用药监护,保证了临床药物治疗的安全性和有效性。

白细胞介素-17和白细胞介素-22在大疱性类天疱疮患者皮损及血清中的表达与意义

目的检测分析大疱性类天疱疮(BP)患者皮损及血清中白细胞介素(IL)-17和IL-22的表达情况,并探讨其在BP发病机制中的意义。方法选取41例BP患者皮损组织(BP组)及25名健康人正常皮肤组织(对照组),用免疫组化方法检测IL-17和IL-22的表达情况。采用酶联免疫吸附试验(ELISA)检测27例BP患者血清中IL-17和IL-22的水平,并以25名健康人作为对照。结果BP组患者皮损中IL-17和IL-22的表达均明显高于对照组,差异有统计学意义(均P<0.01)。且BP组患者皮损组织中IL-17与IL-22的表达呈正相关性。BP组患者血清中IL-17和IL-22的表达水平均高于对照组,差异有统计学意义(均P<0.01)。BP组患者血清中IL-17与IL-22的表达呈正相关性。结论BP患者血清及皮损IL-17和IL-22的表达水平上调,可能参与BP的发病,且两者可能起协同作用。提示3型固有淋巴细胞(ILC3)可能参与BP的致病过程。

抗桥粒芯蛋白1、3抗体及大疱性类天疱疮180、230抗体联合检测诊断大疱性皮肤病的应用价值

目的 探讨抗桥粒芯蛋白1、3(Dsg1、3)抗体及大疱性类天疱疮180、230(BP180、230)抗体联合检测在大疱性皮肤病临床诊断中的应用价值。方法 自2020年3月至2023年1月,纳入郑州大学第一附属医院收治的经组织病理结果、直接免疫荧光检测确诊的大疱性皮肤病患者88例为观察组,选取本院同期健康体检者76名为对照组。分析两组Dsg1、Dsg3、BP180、BP230抗体的阳性检出情况;分析观察组血清Dsg1、Dsg3、BP180、BP230抗体标本诊断类型占比及观察组不同年龄组大疱性皮肤病疾病类型阳性率占比;绘制ROC曲线分析Dsg1、Dsg3、BP180、BP230抗体单一及联合检测对大疱性皮肤病的诊断价值。结果 两组血清Dsg1、Dsg3、BP180、BP230抗体阳性率比较差异具有统计学意义(P<0.05)。据Dsg1、Dsg3、BP180、BP230抗体检测结果,诊断类型:BP、PV、PF、PF+BP、PV+BP阳性率分别为32.95%、20.45%、11.36%、7.95%、3.41%。其中BP阳性率占比最高,PV+BP阳性率占比最低,两者比较差异具有统计学意义(P<0.05)。>60岁组BP阳性率高于≤60岁组,PV及PF阳性率低于≤60岁组,差异有统计学意义(P<0.05)。Dsg1、Dsg3、BP180、BP230抗体联合检测对大疱性皮肤病灵敏度、特异度分别为91.02%、88.66%,AUC(95%CI)为0.821(0.745~0.911),均高于上述抗体单一检测(P<0.05)。结论 Dsg1、Dsg3、BP180、BP230抗体在大疱性皮肤病诊断中具有重要参考价值,且联合检测可提高诊断的准确性;大疱性皮肤病患者年龄和抗体类型之间也存在一定的关联,联合检测Dsg1、Dsg3、BP180、BP230抗体有助于大疱性皮肤病进行更精细的诊断和治疗。

度普利尤单抗治疗老年难治性大疱性类天疱疮5例

度普利尤单抗治疗5例老年难治性大疱性类天疱疮(BP)患者。5例患者平均年龄为78.2岁,合并多种基础疾病。明确诊断后,给予其度普利尤单抗规律治疗3~5次,BP患者皮损得到控制,瘙痒明显缓解,定期随访中。度普利尤单抗是一种全人类IgG4单克隆抗体,通过与IL-4R和IL-13R-亚基的共同链结合,阻断IL-4/13信号传导途径,从而打断了BP发病的炎症通路,其还可通过对IL-4和IL-13的直接作用和对嗜酸性粒细胞的作用导致IL-31分泌减少,从而减少外周瘙痒感觉神经元的信号传递,因此可缓解老年BP的瘙痒问题。