Drug-induced Bullous Pemphigoid Research Articles

The association between drugs and vaccines commonly prescribed to older people and bullous pemphigoid: a case-control study.

Bullous pemphigoid (BP) is an autoimmune skin disease that affects mainly older people. Numerous drugs have been previously associated with BP based on case series and small hospital-based studies. More reliable and precise estimates of associations between a broad selection of drugs/vaccines and BP will enable greater awareness of potential increased risk of BP following certain medicines and help identify clinical, histological and genomic characteristics of drug-induced BP for different types of culprit drugs. Greater awareness could lead to earlier recognition or suspicion of BP and referral to a dermatologist for diagnosis. Earlier diagnosis may lead to less aggressive treatment and improved well-being. To determine the association between drugs/vaccines commonly prescribed to older people and BP risk. We conducted a population-based nested case-control study between 1998-2021 using electronic primary care records from the Clinical Practice Research Datalink. We matched BP cases with up to 5 controls. Exposures were drugs/vaccines commonly prescribed to older people. We used multivariable conditional logistic regression adjusting for multiple drug use. For antibiotics, we considered prescriptions may be prescribed for undiagnosed symptoms of BP which resemble skin infection (protopathic bias) in a sensitivity analysis. Antibiotics were the therapeutic group associated with the highest risk of BP (OR: 4.60; 95%CI 4.40-4.80). However, after adjusting for protopathic bias, the OR reduced to 2.08 (95%CI 1.99-2.17). After adjusting for protopathic bias, of all antibiotic classes and subclasses, penicillins and penicillinase-resistant penicillins had the strongest associations with BP risk (OR: 3.44; 95%CI 3.29-3.60; sensitivity analysis OR; 1.74; 1.66-1.84 and OR: 7.56; 95%CI 7.15-8.00; sensitivity analysis OR: 2.64; 95%CI 2.45-2.85, respectively). Other drugs strongly associated with increased risk were gliptins (OR: 2.77; 95% CI 2.37-3.23), and second-generation antipsychotics (OR: 2.58; 95%CI 2.20-3.03). Healthcare professionals need to be aware of BP risk in older people particularly when prescribing penicillinase-resistant penicillins, gliptins, and second-generation antipsychotic drugs to recognise and manage BP early. Due to the low prevalence of disease, we do not suggest avoidance of drugs/vaccines to prevent BP. Further research should consider recency, dosage, and duration of antibiotic treatments.

Drug-induced Bullous Pemphigoid Secondary to Gliptin

Drug-induced Bullous Pemphigoid Secondary to Gliptin

A case of bullous pemphigoid in a psoriatic patient treated with etanercept

The prevalence of Bullous Pemphigoid (BP) as a most common autoimmune bullous skin disease has increased in recent years. Drug-induced BP is an uncommon form of BP. A 25-year-old psoriatic woman was admitted to Imam Khomeini hospital complex affiliated to the Tehran University of Medical Science with a chief complaint of generalized blistering lesions.

From Molecular Insights to Clinical Perspectives in Drug-Associated Bullous Pemphigoid

Bullous pemphigoid (BP), the most common autoimmune blistering disease, is characterized by the presence of autoantibodies targeting BP180 and BP230 in the basement membrane zone. This leads to the activation of complement-dependent and independent pathways, resulting in proteolytic cleavage at the dermoepidermal junction and an eosinophilic inflammatory response. While numerous drugs have been associated with BP in the literature, causality and pathogenic mechanisms remain elusive in most cases. Dipeptidyl peptidase 4 inhibitors (DPP4i), in particular, are the most frequently reported drugs related to BP and, therefore, have been extensively investigated. They can potentially trigger BP through the impaired proteolytic degradation of BP180, combined with immune dysregulation. DPP4i-associated BP can be categorized into true drug-induced BP and drug-triggered BP, with the latter resembling classic BP. Antineoplastic immunotherapy is increasingly associated with BP, with both B and T cells involved. Other drugs, including biologics, diuretics and cardiovascular and neuropsychiatric agents, present weaker evidence and poorly understood pathogenic mechanisms. Further research is needed due to the growing incidence of BP and the increasing identification of new potential triggers.

Drug-Induced Bullous Pemphigoid Associated with the Severe Acute Respiratory Syndrome-Coronavirus Disease 2019 Vaccine: Case Report

Drug-Induced Bullous Pemphigoid Associated with the Severe Acute Respiratory Syndrome-Coronavirus Disease 2019 Vaccine: Case Report

Evaluation of Dupilumab in Patients With Bullous Pemphigoid

Dupilumab is a theoretically novel therapy for bullous pemphigoid (BP). However, its effectiveness and safety have yet to be confirmed in a large-scale study. To assess the efficacy and safety of dupilumab in patients with BP and evaluate factors that potentially affect short-term and long-term outcomes. A retrospective cohort study was conducted from January 1, 2021, to July 31, 2022. The median (IQR) follow-up period was 24.6 (11.5-38.4) weeks. This multicenter study was performed in 6 dermatology departments of the National Autoimmune Bullous Diseases Cooperative Group of China. Adult patients with BP that received 300 mg of dupilumab every 2 weeks following an initial dose of 600 mg were included. Patients were eligible if they had a clinical presentation of BP combined with immunological or pathological evidence. Patients with drug-induced BP, with less than 4 weeks of follow-up, and who received dupilumab or any other biologics within 6 months were excluded. The primary outcome was the proportion of patients who achieved disease control within 4 weeks. Disease control was defined as the absence of new lesions and pruritus, combined with the healing of existing lesions. Complete remission rates, relapse rates, changes in Bullous Pemphigoid Disease Area Index (BPDAI) scores, itching numerical rating scale (NRS) scores, laboratory results within 64 weeks, and adverse events (AEs) were also assessed. Among 146 patients (median [IQR] age, 73 [64-85] years; 86 [58.9%] male patients) included in the study, 127 (87.0%) patients achieved disease control within 4 weeks, with a median (IQR) time of 14 (7-14) days. A total of 52 (35.6%) patients achieved complete remission, and 13 (8.9%) patients relapsed during the observation period. The complete remission rate and cumulative relapse rate at week 64 were 62.5% (5 of 8) and 30.9%, respectively. There was rapid and sustained improvement in clinical indicators and laboratory examination results after dupilumab treatment, including BPDAI scores, itching NRS scores, serum anti-BP180 and anti-BP230 antibodies, total IgE levels, and eosinophil count. Of these 146 patients, 107 (73.3%) did not report any AEs. The most common AEs were infections and eosinophilia. Serum anti-BP180 antibody levels of greater than 50 relative units (RU)/mL (OR, 3.63; 95% CI, 0.97-12.61; P = .045) were associated with 4-week disease control, and male patients were more likely to relapse (HR, 10.97; 95% CI, 1.42-84.92; P = .02). In this retrospective cohort study, dupilumab treatment was associated with improved clinical symptoms in patients with BP. The safety profile was favorable, although concurrent infection and eosinophilia might pose potential concerns. This study suggests that patients with anti-BP180 antibody levels of at least 50 RU/mL and female sex may respond better.

Lisinopril prevents bullous pemphigoid induced by dipeptidyl peptidase 4 inhibitors via the Mas receptor pathway.

Recent studies have suggested that dipeptidyl peptidase 4 (DPP4) inhibitors increase the risk of development of bullous pemphigoid (BP), which is the most common autoimmune blistering skin disease; however, the associated mechanisms remain unclear, and thus far, no therapeutic targets responsible for drug-induced BP have been identified. Therefore, we used clinical data mining to identify candidate drugs that can suppress DPP4 inhibitor-associated BP, and we experimentally examined the underlying molecular mechanisms using human peripheral blood mononuclear cells (hPBMCs). A search of the US Food and Drug Administration Adverse Event Reporting System and the IBM® MarketScan® Research databases indicated that DPP4 inhibitors increased the risk of BP, and that the concomitant use of lisinopril, an angiotensin-converting enzyme inhibitor, significantly decreased the incidence of BP in patients receiving DPP4 inhibitors. Additionally, in vitro experiments with hPBMCs showed that DPP4 inhibitors upregulated mRNA expression of MMP9 and ACE2, which are responsible for the pathophysiology of BP in monocytes/macrophages. Furthermore, lisinopril and Mas receptor (MasR) inhibitors suppressed DPP4 inhibitor-induced upregulation of MMP9. These findings suggest that the modulation of the renin-angiotensin system, especially the angiotensin1-7/MasR axis, is a therapeutic target in DPP4 inhibitor-associated BP.

Leukocytoclastic vasculitis in association with linear epidermal basement membrane zone immunoglobulin deposition: Linear vasculitis.

Cutaneous leukocytoclastic vasculitis (LCV) has a distinctive clinical and light microscopic presentation; however, the etiologic basis of LCV is varied. Most cases are attributable to immune complex deposition within a vessel wall and represent an Arthus type III immune complex reaction. The prototypic immunoreactant profile is characterized by granular deposits of components of complement activation in concert with immunoglobulin within the cutaneous vasculature. We encountered nine patients with vasculitic and/or vesiculobullous clinical presentations exhibiting an LCV in association with an immunoreactant profile characterized by homogeneous linear deposits of immunoglobulin along the dermal epidermal junction in a fashion resembling an autoimmune vesiculobullous disease. Among the clinical presentations were palpable purpura, urticarial vasculitis, and vesiculobullous eruptions with supervening purpura. Two patients with Crohn disease presented with classic palpable purpura with biopsy-proven LCV, and direct immunofluorescence (DIF) studies demonstrated linear immunoglobulin G (IgG) with floor localization on the salt-split skin assay. Four patients with systemic lupus erythematosus (SLE) showed purpuric vesiculobullous lesions, with evidence of a neutrophilic interface dermatitis and LCV in three of the four. The remaining patient had urticarial nonbullous lesions showing small-vessel vasculitiswith a neutrophilic interface dermatitis. In all of the patients with SLE, DIF studies showed linear immunoglobulin deposits within the basement membrane zone (BMZ). These constellation of findings clinically, light microscopically, and by immunofluorescence were those of a vasculitic presentation of bullous systemic lupus erythematosus. Two patients had linear IgA disease, which was drug induced in one and paraneoplastic in the other, and the dominant morphology on biopsy in both cases was an LCV. One patient microscopically demonstrated drug-associated and eosinophilic enriched LCV with DIF studies showing striking linear deposits of IgG suggestive of bullous pemphigoid, which was consistent with a vasculitic presentation of drug-induced bullous pemphigoid. In all cases, typical granular vascular immunoglobulin and complement deposition compatible with immune complex mediated vasculitis was observed. It is likely that local immune complexes derived from BMZ antigen bound to antibody are pathogenically relevant. We propose the designation of linear vasculitis for this unique scenario of LCV and linear immunoglobulin epidermal BMZ staining, which in some cases represents a vasculitic presentation of conventional autoimmune vesiculobullous disease.

Bullous pemphigoid in a patient with a neuropsychological disorder and a possible novel drug trigger: A case report and review of the literature.

A 59-year-old woman with schizoaffective disorder presented with an itchy, blistering generalised rash. One month prior, she had started empagliflozin, a sodium glucose transporter-2 (SGLT-2) inhibitor, used in type-2-diabetes. She was already established on paliperidone, an atypical antipsychotic, for 1year. Serology at presentation was positive for anti-pemphigoid antibodies. Histology demonstrated subepidermal blistering, perivascular inflammation and eosinophils. Direct immunofluorescence was characteristic of bullous pemphigoid (BP), with linear IgG and C3 at the basement membrane. Both empagliflozin and paliperidone were discontinued. However, the blisters persisted. Treatment included: topical Dermovate and Eumovate ointment for the body and face respectively, alongside oral doxycycline 200mg and prednisolone 40mg for a week (reducing by 5mg/week over 8weeks). Nevertheless, new blisters continued developing, hence dapsone 50mg was introduced, with significant improvement. Increasingly, several neurological and psychiatric disorders have been linked with BP, complicating aetiology and management. The underlying mechanism for these associations is not fully understood. Bullous pemphigoid autoantigens BP180 and BP230 are expressed in the central nervous system and it is thought that neurodegeneration may expose antigens to the immune system, generating a cross-reactive immune response. However, there also appears to be bidirectional causality between BP and neuropsychological conditions. Furthermore, as there was an association of empagliflozin initiation and BP onset, this further complicates the aetiology and presents a potential novel drug cause of BP. This case emphasises the neuropsychological issues associated with managing complex BP cases, a possible novel cause of drug-induced BP and highlights the likelihood of these issues becoming increasingly prevalent for the future.

Case of Linagliptin-Induced Bullous Pemphigoid

Bullous pemphigoid is an autoimmune subepidermal blistering condition in which autoantibodies target components of the hemidesmosomal proteins. It typically presents as pruritic bullous lesions in a generalized distribution. Certain drugs such as diuretics, NSAIDs, antibiotics, and ACE inhibitors have been implicated in the development of bullous pemphigoid. Recently, a class of medications for type II diabetes, dipeptidyl peptidase-4 (DPP-4) inhibitors (commonly called gliptins) have been implicated in drug-induced bullous pemphigoid. We report a case of a 73-year-old female with type II diabetes mellitus who presented with biopsy-proven bullous pemphigoid after being treated with linagliptin. After discontinuing linagliptin and receiving first-line treatment, the patient achieved remission by her five-week follow-up. It is imperative that dermatologists and primary care physicians remain aware of this association when diagnosing and treating bullous pemphigoid, particularly in diabetic patients.

Gliptin-Induced Bullous Pemphigoid: Canadian Case Series of 10 Patients.

Bullous pemphigoid (BP) is a chronic immune-mediated vesiculobullous disorder. Recently, several reports have described dipeptidyl peptidase-4 inhibitors, also known as gliptins, as causative agents for drug-induced BP. To report and describe clinical and histologic characteristics of 10 cases of gliptin-induced BP. We identified 10 patients with gliptin-induced BP. Nine were secondary to linagliptin, and 1 case was attributed to sitagliptin. All patients showed significant improvement after withdrawal of gliptin medications and proper medical treatment. There has been no evidence of relapse after 4 months of follow-up. This report supports the proposed association between gliptins and BP. Physicians should be aware of this potential adverse effect, as gliptin-induced BP can be reversible once identified and the responsible medication is stopped. Early withdrawal of the offending drug and proper treatment can lead to rapid improvement and reduced morbidity.

Missed drug-induced bullous pemphigoid leads to longer immunosuppression than recognized cases: A 9-year retrospective review

Missed drug-induced bullous pemphigoid leads to longer immunosuppression than recognized cases: A 9-year retrospective review

药物诱发大疱性类天疱疮的研究进展

药物诱发大疱性类天疱疮的研究进展

Linagliptin-Associated Alopecia and Bullous Pemphigoid.

Bullous pemphigoid is a chronic autoimmune blistering disease. Recently, several reports suggested dipeptidyl peptidase 4 (DPP-4) inhibitors, also known as gliptins, were a potential cause of drug-induced bullous pemphigoid but not of both bullous pemphigoid and alopecia areata together. Here we describe the case of a 68-year-old man with type 2 diabetes mellitus who developed new onset diffuse alopecia on the scalp with diffuse tense bullae over his body a few months after linagliptin was introduced for better control of his diabetes.DPP-4 inhibitors are not known to increase the risk of alopecia. To the best of our knowledge, this is the first report of linagliptin-associated alopecia areata and bullous pemphigoid, which may help demonstrate if there are any links between DPP-4 inhibitors and alopecia.LEARNING POINTSThis is the first report of linagliptin-associated alopecia areata and bullous pemphigoid (BP), which may help demonstrate a link between DPP-4 inhibitors and alopecia.Since the time of onset of BP after initiation of a DPP-4 inhibitor varies, a high index of suspicion is needed for diagnosis.Early diagnosis is essential as DPP-4 inhibitor withdrawal has a significant effect on disease remission.

Furosemide induced bullous pemphigoid: a case report

Bullous pemphigoid is an acquired autoimmune disease characterized by subepidermal vesicles and bullae. The etiology is mostly idiopathic with the highest occurrence in elderly patients. However, it is now well-accepted that bp has been triggered by or associated with drug therapy. Over 50 agents have been implicated as a cause of Drug-induced bullous pemphigoid, including diuretics, ace inhibitors, and antibiotics. We present a case of Bullous pemphigoid in a 75 year old male probably induced by furosemide. A 75 year old male was admitted to the dermatology department of KIMS hospital, Bengaluru. Presented with multiple tense bullae and vesicles over both upper limbs, forearm and few collapsed bullae and vesicles over the extensor aspect of forearm. Patient had a past history of myocardial infarction and undergone coronary artery bypass grafting for the same and treated with multiple medications. Among the treatment given injection furosemide was the one of the drug, after which he developed lesions and also presented with fluid filled bullae. A diagnosis of bullous pemphigoid was made based on clinical history and was treated with prednisolone, halobetasol and antibiotics. The lesions improved significantly with the above management and patient recovered enough to be discharged from the hospital after 5 days. Severe and serious reactions such as bullous pemphigoid can be caused by used drugs like furosemide.

Drug-induced bullous pemphigoid – a case report with review

Bullous pemphigoid (BP) is an acquired autoimmune disease that affects mainly the elderly and is characterized by subepidermal blistering. The drug-induced variant of BP follows the oral or (sometimes) topical administration of specific drugs. More than 50 different drugs have been associated with the appearance of BP, and as new therapies emerge, this number is very likely to increase. Drug-induced BP is difficult to differentially diagnose from its idiopathic counterpart, as the clinical picture and histopathological findings in both conditions may have only subtle differences. After withdrawal of the suspect medication, most patients respond rapidly to treatment and do not experience relapses. We report a case of BP following administration of certain medication.

Drug-induced bullous pemphigoid.

Drug-induced bullous pemphigoid.

Persistency of Bullous Pemphigoid Lesions on a Burn Scar: A Clinically Proven Locoregional Immune Dysregulation

A case of a 75 year old woman with drug-induced bullous pemphigoid is reported. Lesions also involved the site of a burn scar. Systemic steroid therapy proved to be effective on all lesions except for the ones located on the burn scar. In this patient the scarred area acted as a ‘vulnerable’ site, not only facilitating the localization of bullae on the scar (Koebner phenomenon), but also rendering these lesions resistant to the steroid treatment that proved to be effective elsewhere. The persistency of bullae precisely and solely on the burn scar features another facet of the immunocompromised district.

Drug‐induced pemphigoid: a review of the literature

Bullous pemphigoid is an acquired autoimmune disease that is characterized by subepidermal blistering and affects mainly the elderly. The pathogenesis of the condition has not yet been fully elucidated, but it is widely accepted that a strong correlation with various medications may exist. In reality, more than 50 different drugs have been associated with the appearance of bullous pemphigoid and as new therapies emerge, this number is very likely to increase. A number of pathogenetic mechanisms have been proposed in the past. It is true that a delicate immunological balance is disturbed in all patients with the disease. The variable effects that may be exhibited by the use of biological drugs could shed some light in this complex immunological behaviour. At the same time, drug-induced bullous pemphigoid is difficult to differentially diagnose from its idiopathic counterpart, as the clinical picture and histopathological findings in both conditions may only have subtle differences. Patients who present with bullous pemphigoid and receive multiple regimens should always be suspected of suffering from the drug-induced variant of the condition. This possibility must be considered, as after the withdrawal of the suspect medication most patients respond rapidly to treatment and do not experience relapses.

Drug-induced bullous pemphigoid

Drug-induced bullous pemphigoid (DIBP) is a kind of autoimmune bullous disease caused by systemic or local use of drugs and characterized by vesicles and bullae.The causative drugs are various,including antibiotics,diureticum and angiotensin converting enzyme inhibitors,etc.The pathogenesis is unclear at present,but is considered to be different from that of idiopathic bullous pemphigoid (BP),and varies among DIBP induced by different drugs.DIBP is somewhat different from idiopathic BP in clinical manifestations,but similar to idiopathic BP in clinical laboratory findings.Therefore,clinicians should pay attention to potential causative drugs in patients with DIBP,and stop the use of suspected drugs when necessary. Key words: Pemphigoid ,bullous; Pharmaceutical preparations