Treatment Of Bullous Pemphigoid Research Articles

18191 Experience of using rituximab and corticosteroid combination therapy for bullous pemphigoid: A 9-year case series analysis

Background: Bullous pemphigoid is the most common autoimmune bullous disease, with a mortality rate up to 13∼38% due to increased susceptibility in the aging population, high prevalence of comorbidities, and the use of immunosuppressants. In the recent years, a few case series, including one precedent case series from our facility, have demonstrated an increased rate of complete remission, steroid-sparing effect and a favorable safety profile of rituximab as a treatment for bullous pemphigoid.

Treatment of Bullous Pemphigoid in People Aged 80 Years and Older: A Systematic Review of the Literature

Bullous pemphigoid commonly affects older adults and has a detrimental effect on both quality of life and longevity. Systemic corticosteroids, the mainstay of therapy, may cause significant adverse effects, especially in older patients. Therefore, safer therapeutic options are being sought. The objective of this article was to systematically review the published evidence on the efficacy and safety of different treatment modalities for bullous pemphigoid in older patients. We performed a systematic review of all publications until May 2020 in PubMed, Google Scholar, and the ongoing trials registry of the US National Institutes of Health databases evaluating the efficacy and safety of bullous pemphigoid treatments in patients aged older than 80 years. The primary outcome was complete response. The secondary outcomes were partial response, complete remission on minimal therapy or during tapering, recurrence, adverse events, and mortality. Twenty-eight publications were included: 2 randomized controlled trials, 5 prospective cohort studies, 10 retrospective cohort studies, and 11 case series, with a total of 153 older patients. The overall complete response rate was 31%. Topical corticosteroids had the highest complete response rate (55%) with a low side-effect profile. Biologics (omalizumab and rituximab) were effective in achieving complete remission on minimal therapy (29%) without recurrence, although rituximab was associated with a relatively high mortality rate (29%). Current data suggest that topical corticosteroids are effective and safe and should remain the first line of treatment for bullous pemphigoid in older adults. However, their application is difficult and requires a high-functioning patient, third-party assistance, or a relatively mild disease. Biological agents are effective but warrant meticulous patient selection owing to the relatively high mortality rate associated with rituximab. PROSPERO registration number CRD42020186686.

Programmed Death-1 Inhibitors-induced Bullous Pemphigoid in 21 Cases

Objective To investigate the clinical features and treatments of programmed death-1(PD-1)inhibitors-induced bullous pemphigoid(BP).Methods The clinicopathological and immunohistological data of patients with PD-1 inhibitors-induced BP from Peking Union Medical Collage Hospital and reported in the literature were retrospectively analyzed.Results Totally 21 cases(15 males and 6 females)were enrolled.The average age was(70.9±9.7)years(56-86 years).The most common primary malignancies were melanoma(38.10%)and lung cancer(33.33%).The average duration from onset of PD-1 inhibitors treatment to diagnosis of BP was(49.1±23.7)weeks.Typical dermatopathological features were sub-epidermal blisters(76.19%)with infiltration of eosinophils(88.24%).Direct immunofluorescence features were linear deposition of complement C3(95%)and IgG(75%)in the basement membrane zone.Anti-BP180-NC16A antibodies were positive in most cases(84.21%).Patients were mainly treated with systemic corticosteroids,whereas biologics such as rituximab and omazumab were also effective.Conclusions The risk of PD-1 inhibitors-induced BP should be recognized by dermatologists and oncologists.Early diagnosis and timely treatment of BP induced by PD-1 inhibitors are important to improve the prognosis.

A Case Report on Idiopathic Severe Bullous Pemphigoid

Bullous Pemphigoid (BP) is an autoimmune disorder which exploits the immune system and affecting sub-epidermal region of skin causing mild itching to infection and blistering of sub-epidermal region. Clinical presentations are pruritis, urticarial, papular lesions. These later evolve to bullae in weeks to months and are typically present in the axillae, on the flexor surface of the forearms, medial thighs, trunk, and abdomen. The treatment for bullous pemphigoid is systemic corticosteroids, topical steroids in combination with nicotinamide plus tetracycline, minocycline or doxycycline have shown success in multiple cases. Immunosuppressive therapy is used when steroids do not control the disease or if patients have contraindications for systemic corticosteroid treatments. Patient was brought to emergency department with chief complaints itching, redness, bullous lesion all over the body for 2 months.Oral complaints including solitary erosion seen on right side of buccal mucosa, pharyngeal erythema. Laboratory investigations were carried out. Patient was diagnosed based on physical examination. Patient was provided with adequate treatment and counseling.
 Keywords: Bullous Pemphigoid, corticosteroid, Autoimmune disorder, sub-epidermal region.

Treatment of bullous pemphigoid in Chinese patients with Tripterygium wilfordii Hook F.

Tripterygium wilfordii Hook F (TwHF) is a traditional Chinese herb used in many medicinal applications, but the treatment of bullous pemphigoid (BP) with TwHF has never been reported. The aim of this study was to evaluate the efficacy and safety of TwHF in BP patients. A retrospective study was performed from January 2015 to September 2019 in the Department of Dermatology, Peking Union Medical College Hospital. A total of 10 patients with mild to moderate BP and treated with TwHF were enrolled in the study with 10 mild or moderate BP patients treated with systemic glucocorticoid randomly selected as controls. In the TwHF group, a major response was seen in seven patients, a minor response in one and no response was seen in two patients. In the glucocorticoid group, a major response was seen in nine patients and a minor response in one patient. Two patients experienced treatment failure. The time to disease control in the TwHF group (34 ± 11 days) was longer as compared to the glucocorticoid group (18 ± 8 days, P < .05). Ten patients relapsed during the follow-up period. The adverse events in the TwHF group were lower than those in the glucocorticoid group (13 vs 19). Low-dose TwHF may be effective and safe for treating mild and moderate BP.

Pemphigus Vulgaris and Bullous Pemphigoid: Update on Diagnosis and Treatment.

Autoimmune bullous disorders are a heterogeneous spectrum of skin disorders characterized by the production of autoantibodies against adhesion molecules of the skin. The 2 major groups of diseases are "pemphigus diseases" and "autoimmune bullous diseases of the pemphigoid type." Pemphigus diseases are a group of autoimmune blistering diseases of the skin and mucous membranes characterized by intraepithelial cleft and acantholysis. The main subtypes of pemphigus include pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus. Diagnosis is based on clinical manifestations and confirmed with histological, immunofluorescence, and serological testing. Recently multivariant enzyme-linked immunosorbent assay systems have been developed as practical screening tools for patients with suspected autoimmune bullous dermatoses. The current first-line treatment of pemphigus is based on systemic corticosteroids that are often combined with immunosuppressive adjuvants, such as azathioprine, mycophenolate mofetil, and the anti-CD20 monoclonal antibody rituximab, usually at initiation of treatment. Rituximab efficacy is higher when it is administered early in the course of the disease. Therefore, it should be used as first-line treatment to improve efficacy and reduce cumulative doses of corticosteroids and their side effects. Treatment of bullous pemphigoid is based on disease extension. Localized and mild forms can be treated with superpotent topical corticosteroids or with nonimmunosuppressive agents. In patients with generalized disease or whose disease is resistant to the treatments described above, systemic corticosteroids are preferred and effective. Adjuvant immunosuppressants are often combined with steroids for their steroid-sparing effect.

Management of immune checkpoint inhibitor–induced bullous pemphigoid

Management of immune checkpoint inhibitor–induced bullous pemphigoid

Association Between Bullous Pemphigoid and Dipeptidyl Peptidase 4 Inhibitors: A Retrospective Cohort Study

BackgroundThe association between dipeptidyl peptidase 4 inhibitors (DPP-4i) and bullous pemphigoid (BP) has been demonstrated in several studies. The main aim of this study was to estimate the use of DPP-4i treatment in patients diagnosed with BP in our setting. MethodsWe selected patients histologically diagnosed with BP in our department between October 2015 and October 2018 and performed a retrospective chart review to assess clinical and epidemiological data and direct immunofluorescence (DIF) patterns. ResultsOf the 70 patients diagnosed with BP during the study period, 50% were diabetic and 88.57% of these were being treated with a DPP-4i when diagnosed with BP. The most common DPP-4i was linagliptin (used in 18.6% of patients), followed by vildagliptin (17.1%). The median latency period between initiation of DPP-4i treatment and diagnosis of BP was 27.5 months for all treatments, 16 months for linagliptin, and 39 months for vildagliptin (log rank < 0.01). A negative DIF result was significantly more common in patients not being treated with a DPP-4i. The DIF pattern most strongly (and significantly) associated with DPP-4i treatment was linear immunoglobulin G deposits along the dermal-epidermal junction. DPP-4i treatment was withdrawn in 87% of patients and 96% of these achieved a complete response. ConclusionsDPP-4i treatment is very common in patients with BP in our setting. The latency period between start of treatment and onset of BP seems to be shorter with linagliptin than with other types of gliptins. Patients receiving DPP-4i treatment may show different DIF patterns to those not receiving treatment.

Dupilumab as a novel therapy for bullous pemphigoid: A multicenter case series

Bullous pemphigoid (BP) is an autoimmune blistering disorder occurring mostly in the elderly that lacks adequate treatments. To describe our experience using dupilumab in a series of patients with BP. This is a case series of patients from 5 academic centers receiving dupilumab for BP. Patients were eligible if they had a clinical diagnosis of BP confirmed by lesional skin biopsy evaluated by one of more of the following: hematoxylin and eosin staining, direct immunofluorescence, or enzyme-linked immunosorbent assay for BP180 or BP230, or both. We identified 13 patients. Patients were an average age of 76.8years, and the average duration of BP before dupilumab initiation was 28.8months (range, 1-60months). Disease clearance or satisfactory response was achieved in 92.3% (12 of 13) of the patients. Satisfactory response was defined as clinician documentation of disease improvement and patient desire to stay on the medication without documentation of disease clearance. Total clearance of the BP was achieved in 53.8% (7of 13) of patients No adverse events were reported. Include small sample size, lack of a control group, lack of a standardized assessment tool, and lack of standardized safety monitoring. Dupilumab may be an additional treatment for BP, leading to disease clearance or satisfactory response in 92.3% of patients, including in those in whomprevious conventional therapy had failed.

Orphan designation: dimethyl fumarate, Treatment of bullous pemphigoid

Orphan designation: dimethyl fumarate, Treatment of bullous pemphigoid

Use of Immunosuppressants/Immunomodulators in Autoimmune/Inflammatory Dermatologic Diseases during COVID-19 Pandemic-General Recommendation Based on Available Evidence.

Use of Immunosuppressants/Immunomodulators in Autoimmune/Inflammatory Dermatologic Diseases during COVID-19 Pandemic-General Recommendation Based on Available Evidence.

Asociación entre penfigoide ampolloso e inhibidores de la dipeptidilpeptidasa-4: estudio de cohortes retrospectivo

BackgroundThe association between dipeptidyl peptidase 4 inhibitors (DPP-4i) and bullous pemphigoid (BP) has been demonstrated in several studies. The main aim of this study was to estimate the use of DPP-4i treatment in patients diagnosed with BP in our setting. MethodsWe selected patients histologically diagnosed with BP in our department between October 2015 and October 2018 and performed a retrospective chart review to assess clinical and epidemiological data and direct immunofluorescence (DIF) patterns. ResultsOf the 70 patients diagnosed with BP during the study period, 50% were diabetic and 88.57% of these were being treated with a DPP-4i when diagnosed with BP. The most common DPP-4i was linagliptin (used in 18.6% of patients), followed by vildagliptin (17.1%). The median latency period between initiation of DPP-4i treatment and diagnosis of BP was 27.5 months for all treatments, 16 months for linagliptin, and 39 months for vildagliptin (log rank < 0.01). A negative DIF result was significantly more common in patients not being treated with a DPP-4i. The DIF pattern most strongly (and significantly) associated with DPP-4i treatment was linear immunoglobulin G deposits along the dermal-epidermal junction. DPP-4i treatment was withdrawn in 87% of patients and 96% of these achieved a complete response. ConclusionsDPP-4i treatment is very common in patients with BP in our setting. The latency period between start of treatment and onset of BP seems to be shorter with linagliptin than with other types of gliptins. Patients receiving DPP-4i treatment may show different DIF patterns to those not receiving treatment.

Association of pemphigus and pemphigoid with osteoporosis and pathological fractures.

Patients with pemphigus and bullous pemphigoid (BP) have potential risk factors for osteoporosis and/or fractures. To determine whether pemphigus and BP are associated with osteoporosis and fractures in the US, across-sectional study of 198,102,435 adultswas performed, including 4506 with pemphigus and 8864 with BP from the 2006-2012 National Emergency Department Sample, a 20% sample of emergency care visits throughout the US. Pemphigus was associated with higher odds (multivariate logistic regression; adjusted odds ratio [95% confidence intervals]) of osteopenia (2.20 [1.59-3.05]), osteoporosis (2.54 [2.16-2.98]), osteomalacia (29.70 [4.05-217.83]), and pathological fractures (2.04 [1.42-2.91]). BP was associated with osteoporosis (1.55 [1.39-1.73]) and pathological fractures (1.52 [1.22-1.88]). When compared to BP, pemphigus was associated with higher odds of osteopenia (1.59 [1.06-2.41]), osteoporosis (1.38 [1.18-1.63]), and fractures (1.26 [1.04-1.53]), particularly of the ulna and radius (3.17 [1.23-8.17]). Patients with pemphigus or BP as well as long-term systemic corticosteroid use had highest odds of osteoporosis and fractures. No data were available on treatments for pemphigus or BP. Pemphigus and BP were associated with osteopenia, osteoporosis, and pathologic fractures. Patients with PEM and BP may benefit from increased screening for osteoporosis and interventions to prevent fractures.

Diabetes mellitus and hyperglycemic complications in bullous pemphigoid

Diabetes mellitus and hyperglycemic complications in bullous pemphigoid

Clinical characteristics of bullous pemphigoid in elderly patients with type 2 diabetes mellitus: The association with the use of dipeptidyl peptidase-4 inhibitors

Bullous pemphigoid (BP) is an autoimmune skin disorder characterized by the production of autoantibodies. Several recent reports have described the occurrence of BP in diabetic patients treated with dipeptidyl peptidase-4 (DPP-4) inhibitors. However, the clinical features of BP in diabetic patients, particularly in those treated with DPP-4 inhibitors, have not yet been examined. The aim of this study was to clarify clinical characteristics of BP in elderly type 2 diabetic patients. We found cases of BP in 15 elderly type 2 diabetic patients (11 men, 4 women) and 20 non-diabetic patients (8 men, 12 women) from September, 2012 to September, 2016. These patients had all been treated with corticosteroid therapy. We investigated the participants' basic clinical characteristics and the course of BP treatment. The differences in variables between the two groups were analyzed using Wilcoxon's test and the chi-square test. The mean age of type 2 diabetes patients with BP was 81.1±5.5 years. The mean HbA1c was 7.3±1.6%. A total of 87% of diabetic patients had been treated with DPP-4 inhibitors for 11.7 months prior to the BP onset. The diabetic patients had a lower prevalence of neurogenerative disease, severe ADL disabilities, and dementia than the non-diabetic patients. Furthermore, the diabetic patients with BP tended to be younger and more frequently male than those without diabetes. After stopping the DPP-4 inhibitors, the skin lesions were successfully treated with systemic corticosteroid therapy, and glycemic control was achieved using intensive insulin therapy. DPP-4 inhibitors were used in all cases where the aniti-BP180NC16a antibody showed negative conversion. BP in patients with type 2 diabetes had different clinical features from that in non-diabetic patients, suggesting an association between BP and the use of DPP-4 inhibitors.

Human Herpesvirus-6 corneal Endotheliitis after intravitreal injection of Ranibizumab

BackgroundTo report the first case of human herpesvirus-6 (HHV-6) corneal endotheliitis that developed after intravitreal ranibizumab injections.Case presentationA 63-year-old man with a medical history of diabetes and systemic steroid treatment for bullous pemphigoid had been receiving intravitreal injections of ranibizumab in the left eye for 2 years according to a Pro Re Nata treatment regimen for macular edema associated with branch retinal vein occlusion. Twenty days after the last injection, the patient presented with pain and decreased visual acuity in his left eye. His best corrected visual acuity in the left eye was 2/200, and intraocular pressure was 45 mmHg with edema of the central stromal cornea, mild conjunctival injection, intermediate keratic precipitates, and mild anterior chamber reaction. HHV-6 DNA was detected in the aqueous humor using multiplex strip polymerase chain reaction, and it was identified as variant A, HHV-6A. A diagnosis of HHV-6A-associated corneal endotheliitis was made. Oral valganciclovir and topical ganciclovir therapy was initiated with good resolution of all symptoms and signs.ConclusionsHHV-6A can be a possible complication of intravitreal ranibizumab therapy. To the best of our knowledge, this is the first reported case of HHV-6A corneal endotheliitis following intravitreal ranibizumab injection.

Bullous dermatoses secondary to anti-PD-L1 agents: a case report and review of the literature

Immune checkpoint inhibitors are used to treat numerous malignancies but may be associated with severe adverse events. Bullous dermatoses, chiefly bullous pemphigoid (BP), are potentially progressive adverse events that cause blistering skin lesions and may involve a significant body surface area. Herein, we report an 87-year-old man with urothelial cell carcinoma undergoing atezolizumab treatment who presented with an acute-onset blistering eruption. Biopsy revealed a subepidermal bulla, direct immunofluorescence revealed linear IgG and C3 deposits at the dermal-epidermal junction, and serum studies revealed elevated levels of antibodies to BP180 and BP230. Anti-PD-L1-induced BP was diagnosed, immunotherapy was withheld, and he was treated with oral doxycycline with niacinamide and clobetasol ointment. He restarted atezolizumab and has successfully received four cycles (every 3 weeks) while continuing this BP treatment regimen. A literature review revealed eight other cases of anti-PD-L1-induced bullous disorders. The incidence of bullous dermatoses with anti-PD-1/anti-PD-L1 agents combined is 1%, whereas the reported incidence for anti-PD-L1 agents alone ranges from 1.3-5%, raising concerns for a higher overall risk. In addition to our case, only one other case reported successful resumption of immunotherapy. Early control and management of immunotherapy-induced BP may reduce complications and prevent treatment discontinuation.

IgE blockade in autoimmunity: Omalizumab induced remission of bullous pemphigoid

Bullous pemphigoid (BP) is a blistering dermopathy and a prototypic antibody-mediated autoimmune disease. Detection of IgG autoantibodies against hemidesmosomal proteins BP180 and/or BP230 are diagnostic and levels can correlate with disease activity. Therapies include corticosteroids and oral immunosuppressants, while intravenous immunoglobulin and rituximab are reserved for treatment resistant cases. Here we describe a patient with severe BP which was refractory to standard first line therapy, intravenous immunoglobulin and rituximab induced depletion of peripheral B cells. Use of the monoclonal anti-IgE antibody omalizumab resulted in rapid resolution of blistering despite ongoing high levels of anti-skin IgG antibodies. To our knowledge this is the first case of BP responsive to omalizumab after failure of rituximab to be reported. This case adds to emerging data on omalizumab as a novel BP treatment as well as providing new evidence of an independent role for autoreactive IgE-mediated inflammation in the formation of BP skin lesions.

P68: THE PATHOGENIC ROLE OF AUTOREACTIVE IGE IN BULLOUS PEMPHIGOID: A UNIQUE CASE SUPPORTING CONCLUSIONS FROM EXPERIMENTAL DATA

Bullous pemphigoid (BP), a blistering dermopathy, is a prototypic antibody‐mediated disease. Detection of IgG autoantibodies against hemidesmosomal proteins BP180 and/or BP230 are diagnostic and levels correlate with disease activity. Therapies include corticosteroids and oral immunosuppressants, while intravenous immunoglobulin (IVIG) and rituximab are reserved for resistant cases. These observations together support a central role for B cells and autoreactive IgG in BP pathogenesis. We describe a patient with persistent biopsy‐proven severe BP on a background of stable HIV infection with long‐term viral suppression and normal CD4 T cell counts, type 2 diabetes and chronic renal failure. The disease was widespread and refractory to standard first line therapy, IVIG and also rituximab, despite peripheral B cell depletion. Use of the monoclonal anti‐IgE antibody omalizumab resulted in a rapid resolution, within days, of pruritis and bullae formation. Disease remission has been maintained with ongoing Omalizumab therapy despite persistent high level junctional anti‐skin IgG antibodies. To our knowledge this is the first case of BP responsive to omalizumab after failure of rituximab to be described in the literature. Omalizumab does not currently have an established role in treatment of BP, although this case adds to previous case reports suggesting a role for omalizumab as a novel BP treatment. This is also supported by recent experimental data demonstrating a role for autoreactive IgE in bullous formation and correlation with disease activity. Selection of patients with BP who would benefit from anti‐IgE therapy remains to be defined, although given the speed of response and the low risk associated with its use, a therapeutic trial may be warranted in severe and/or resistant cases, particularly to reduce the side‐effects of standard therapies.

Doxycycline, a Well-Tolerated, Economic, and Effective Alternative for the First-Line Treatment of Bullous Pemphigoid

Doxycycline, a Well-Tolerated, Economic, and Effective Alternative for the First-Line Treatment of Bullous Pemphigoid