Ulcerative colitis and bullous pemphigoid:Direct association or a medication side effect:A case report

BACKGROUND Bullous pemphigoid(BP)is an autoimmune blistering skin disorder.It is associated with other autoimmune disorders and the use of certain drugs.We describe a case of BP in a patient with ulcerative colitis(UC)treated with mesalamine.CASE SUMMARY A 38-year-old male patient with UC and a history of multiple flares was maintained on mesalamine with good clinical response.One year after starting mesalamine,he sought medical care following the onset of a severe itchy rash of several weeks’duration with a recent appearance of skin bullae.A biopsy of the skin revealed subepidermal blistering dermatitis with focal eosinophilic spongiosis.Direct immunofluorescence studies revealed linear IgG and C3 immune reactant deposits at the dermoepidermal junction,consistent with the diagnosis of BP.Prednisone therapy alleviated his symptoms.However,tapering prednisone led to re-eruption of the bullae.CONCLUSION BP should be considered when patients with UC develop skin manifestations.Although BP is not one of the extraintestinal manifestations of UC,there may be an association between these two conditions.Whether treatment with mesalamine or other therapeutic agents plays a role in the development of BP remains unclear.

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.

Ocular cicatricial pemphigoid:diagnosis and systemic management

Ocular cicatricial pemphigoid(OCP)is a subcategory of mucous membrane pemphigoid(MMP)where the conjunctiva is the main site of inflammation.It is a chronic and autoimmune disease characterized by acute and chronic conjunctivitis that can progress to severe conjunctival cicatrization,corneal opacification,ocular surface keratinization,and eyelid abnormalities.OCP can lead to structural damage that can result in visual impairment,visual loss,and blindness,and can have a significant impact in a patient’s quality of life.Patients may manifest with varying symptoms,degrees of severity and may have different rates of progression.Early diagnosis and appropriate systemic immunosuppression are of utmost importance for prompt and adequate disease control.Various systemic immunomodulatory therapies(IMTs),including anti-metabolites,alkylating,and biologic agents have been utilized to achieve inflammation control and remission.Careful monitoring of disease progression is important to assess response and to modify and escalate therapy if needed.Treatment to alleviate symptoms of dry eye disease and address trichiasis and other eyelid abnormalities is recommended as well.A multidisciplinary approach to optimize clinical care is recommended in the management of patients with OCP.This review will address the immunopathogenesis,clinical features,keys to diagnosis and staging of patients with OCP.It will highlight the current immunomodulators utilized for disease management and proposed stepladder strategies.This review will discuss the updated roles of combination therapy,novel use of biologics as well as the recent use of adrenocorticotropic hormone(ACTH)analog in severe recalcitrant cases.

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.

Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR) as Systemic Inflammatory Predictors in the Diagnosis of Bullous Pemphigoid and Pemphigus Vulgaris

Introduction: Autoimmune blistering skin disorders such as Bullous Pemphigoid and Pemphigus Vulgaris present diagnostic challenges. The Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR), are inflammatory markers used to assess the body’s immune-inflammatory response. Objectives: The study aims to evaluate the significance of hematologic markers, specifically the Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR), as diagnostic predictors of bullous pemphigoid (BP) and pemphigus vulgaris (PV). Methods: A retrospective study of 64 patients (36 with BP and 28 with PV). Patient clinical data: age, gender, complete blood count, autoimmune antibody levels (Dsg1, 3 and BP180, 230), IgE and C-reactive protein, and history of hypertension, diabetes, brain infarction, and coronary heart disease. The data was analyzed using SPSS. Results: The study involved 36 (56.3%) diagnosed with bullous pemphigoid (BP) and 28 (43.75%) with pemphigus vulgaris (PV). The average age in BP was 71 ± 8 and 52 ± 13 in PV. Laboratory findings showed high levels of Dsg1, Dsg3, neutrophil count, and lymphocyte count in PV, while high levels of eosinophils with a significant increase in C-reactive protein (CRP) in BP. Blood biomarkers, including NLR, PLR, SII, MPV, CRP, and IgE, proved an overall of 84.4% in disease prediction. Dsg1, Dsg3, BP180, and BP230 showed an overall of 88.1%. No significant relationship was noted between NLR, SII, and patients with comorbidities. Conclusion: The study highlights the diagnostic potential of SII and NLR in addition to hematologic markers in BP and PV, emphasizing their role in early diagnosis and therapeutic interventions, requiring further validation in larger patient cohorts.

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.

Pseudopemphigoid as caused by topical drugs and pemphigus disease

Pseudopemphigoid can cause a chronic cicatricial conjunctivitis that is clinically identical to the manifestations seen in mucous membrane pemphigoid, a disorder with a common clinical phenotype and multiple autoimmune links. For the purpose of this review, we will describe pseudopemphigoid as caused by topical drugs, the most common etiology with ocular manifestations, and as caused by the pemphigus disease, a more rare etiology. Specifically, we will discuss the ophthalmological features of drug-induced cicatricial conjunctivitis, pemphigus vulgaris, and paraneoplastic pemphigus. Other etiologies of pseudopemphigoid exist that will not be described in this review including autoimmune or inflammatory conditions such as lichen planus, sarcoidosis, granulomatosis with polyangiitis(Wegener's granulomatosis), erythema multiforme(minor, major, and Stevens-Johnson syndrome), bullous pemphigoid, skin-dominated linear IgA bullous dermatosis, and skin-dominated epidermolysis bullosa acquisita. Prompt diagnosis of the underlying etiology in pseudopemphigoid is paramount to the patient's outcome as certain diseases are associated with a more severe clinical course, increased ocular involvement, and differential response to treatment. A completehistory and ocular examination may find early cicatricial changes in the conjunctiva that are important to note and evaluate to avoid progression to more severe disease manifestations. When such cicatricial changes are noted, proper diagnostic techniques are needed to help elucidate a diagnosis. Lastly, collaboration between ophthalmologists and subspecialists such as dermatologists, pathologists, immunologists, and others involved in the care of the patient is needed to ensure optimal management of disease.

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.

Clinical features and in vivo confocal microscopy assessment in 12 patients with ocular cicatricial pemphigoid

AIM： To describe the clinical features and microstructural characteristics assessed by in vivo confocal microscopy（IVCM） in patients with ocular cicatricial pemphigoid（OCP）.· METHODS： A descriptive, uncontrolled case series study. Patients diagnosed with OCP were examined by clinical history, slit-lamp biomicroscopy features and IVCM images. The results of direct immunofluorescence（DIF） biopsies and indirect immunofluorescence（IIF） were also recorded. Local and systemic immunosuppressive therapy were administered and adjusted according to response.·RESULTS： A total of 12 consecutive OCP patients（7male, 5 female; mean age 60.42 ±10.39y） were recruited.All patients exhibited bilateral progressive conjunctival scarring and recurrent chronic conjunctivitis was the most frequent clinical pattern. The mean duration of symptoms prior to diagnosis of OCP was 2.95 ±2.85y（range： 5mo to 10y）. The Foster classification varied from stage I to IV and 20 eyes（83%） were within or greater than Foster stage Ⅲ on presentation. Two of the 12patients（17%） demonstrated positive DIF; 3 of the 12（25%） patients reported positive IIF. The mean duration of the follow-up period was 20.17 ±11.88mo（range： 6 to48mo）. IVCM showed variable degrees of abnormality in the conjuctiva-cornea and conjuctival scarring was detected in all the involved eyes. Corneal stromal cell activation and dendritic cell infiltration presented asocular surface inflammation, ocular surface keratinization along with the destroyed Vogt palisades was noted in eyes with potential limbal stem cell deficiency. After treatment, remission of ocular surface inflammation was achieved in all the patients, 18 eyes（75%） remained stable, 6 eyes（25%） had recurrent conjunctivitis and cicatrization in 2 eyes（8%） was progressing.· CONCLUSION： As an autoimmune disease, OCP manifests as variable degrees of clinical and laboratory abnormalities with both local and systemic immunosuppressive treatment playing important roles in disease therapy. IVCM can be as a valuable non-invasive technique to assess ocular surface changes in a cellular level with a potential value for providing diagnostic evidence and monitoring therapeutic effects during follow-up.

Incidence, prevalence, and demographic characteristics of ocular cicatricial pemphigoid in Colombia: data from the National Health Registry 2009-2019

AIM:To provide an epidemiological characterization of ocular cicatricial pemphigoid(OCP)in Colombia.METHODS:We conducted a cross-sectional study using SISPRO.We applied the specific code of the International Classification of Diseases for Ocular Pemphigoid,from 2009-2019 to estimate prevalence,incidence,and the demographic status of the disease in Colombia.RESULTS:The estimated average prevalence was 0.22 per 1000000 inhabitants,and the estimated average incidence was 0.24 per 1000000 inhabitants.With a female predominance of 62.5%,and a male/female ratio of 1:1.6.The group of patients diagnosed with the disease after the age of 80 presented the highest prevalence.The departments with the highest prevalence were Antioquia,Bogotá,and Santander.CONCLUSION:There are important differences between worldwide and Colombian prevalence and incidence data,which may be related to genetic and epigenetic factors,and the possible underdiagnosis of the disease.According to the results,OCP is an extremely rare disease in Colombia.Nevertheless,it is important to encourage awareness of the disease due to its devastating consequences.

Cicatricial Pemphigoid in Accompany with Rheumatoid Arthritis:a Case Report

CICATRICIAL pemphigoid （CP, also known as benign mucous membrane pemphigoid） is a rare chronic autoimmune subepithelial blister- ing disease, with an incidence of 1 per million,characterized by erosive lesions of mucous membranes and skin that result in scarring. Rheumatoid arthritis （RA） is a symmetric inflammatory arthritis that mainly affects the small joints of hands and feet, with a prevalence of 0.3% in China.3 In this case report we described the diagnosis of and treatment for a patient developing CP 18 years after the onset of RA, a combination rarely encountered or reported so far.

Diagnosis,fetal risk and treatment of pemphigoid gestationis in pregnancy:A case report

BACKGROUND Pemphigoid gestationis(PG)is a rare autoimmune blistering disease that usually presents in the second or third trimester,with an incidence of 1 per 50000 pregnancies.PG tends to recur with an earlier onset and a more severe course in subsequent pregnancies.Skin biopsy markers can be confirmed by direct immunofluorescence staining.CASE SUMMARY Our patient was diagnosed with PG at 8 mo of gestation with fresh bullous lesion marks on the abdomen and limbs.Termination of the pregnancy was performed by cesarean section at 37+4 wk of gestation.The patient delivered an infant weighing 3620 gm.The infant had urticaria-like and vesicular skin lesions and was diagnosed with PG.The patient was discharged on prednisolone and in a satisfactory condition.The infant was discharged after anti-inflammatory therapy for one week.CONCLUSION PG is a rarely reported disease,and 10%of newborns develop mild clinical symptoms consisting of urticaria-like or vesicular skin lesions.We intend to remind clinicians to consider this condition when a patient presents with such lesions so that treatment can be started early and neonatal morbidity can be taken into account.

Coexistence of ocular cicatricial pemphigoid with Stevens Johnson syndrome

Dear Sir, I am Dr. Hande Taylan Sekeroglu, from the Ophthalmology Department of Cukurova University Faculty of Medicine. I want to present a case of recalcitrant ocular cicatricial pemphigoid (OCP) which was coincidently diagnosed with Stevens

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.

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.

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.

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.