Treatment Of Bullous Pemphigoid Research Articles

Can Methotrexate Be Employed as Monotherapy for Bullous Pemphigoid? Analysis of Efficiency and Tolerance of Methotrexate Treatment in Patients with Bullous Pemphigoid.

The European Academy of Dermatology and Venerology (EADV) consensus states that the treatment of choice for bullous pemphigoid is systemic glucocorticosteroid therapy. Bearing in mind that long-term steroid therapy is associated with numerous side effects, an effective and safer treatment regimen for these patients is still being sought. A retrospective analysis was performed of the medical reports of patients with diagnosed bullous pemphigoid. The study included 40 patients with moderate or severe disease, and who had continued ambulatory treatment for at least six months. The patients were divided into two groups: one treated with methotrexate in monotherapy, or with combined methotrexate and systemic steroid therapy. A slightly better survival rate was noted in the methotrexate group. No significant differences were observed between the groups in time to achieve clinical remission. The combination therapy group demonstrated more frequent disease recurrence and exacerbations during treatment, and a higher mortality rate. None of the patients in either group presented with severe side effects related to methotrexate treatment. The treatment of bullous pemphigoid with methotrexate in monotherapy is an effective and safe therapeutic method for elderly patients.

Bullous pemphigoid: The role of type 2 inflammation in its pathogenesis and the prospect of targeted therapy.

Bullous pemphigoid (BP) is an autoimmune disease that mainly occurs in the elderly, severely affecting their health and life quality. Traditional therapy for BP is mainly based on the systemic use of corticosteroids, but long-term use of corticosteroids results in a series of side effects. Type 2 inflammation is an immune response largely mediated by group 2 innate lymphoid cells, type 2 T helper cells, eosinophils, and inflammatory cytokines, such as interleukin (IL)-4, IL-5 and IL-13. Among patients with BP, the levels of immunoglobulin E and eosinophils are significantly increased in the peripheral blood and skin lesions, suggesting that the pathogenesis is tightly related to type 2 inflammation. To date, various targeted drugs have been developed to treat type 2 inflammatory diseases. In this review, we summarize the general process of type 2 inflammation, its role in the pathogenesis of BP and potential therapeutic targets and medications related to type 2 inflammation. The content of this review may contribute to the development of more effective drugs with fewer side effects for the treatment of BP.

Successful pharmacological intervention at different levels of the complement system in an in vitro complement fixation model for bullous pemphigoid.

Bullous pemphigoid (BP) is characterized by deposition of immunoglobulins and complement along the epidermal basement membrane (BM). In humans, there is a lack of functional studies targeting the complement system (CS). This study investigates activation of all complement pathways in BP skin biopsies. Moreover, pharmacological inhibition at different levels of the CS was investigated using anti-complement compounds in a complement fixation BP assay. In this retrospective study, 21 frozen biopsies from BP patients were stained by direct immunofluorescence for C1q, MBL, ficolin-2, C4d, properdin, C3c and C5b-9. Sera from 10 patients were analysed in a complement fixation assay in the presence of C1 inhibitor, anti-factor B monoclonal antibody (mAb), anti-C3 mAb and anti-C5 mAb and compared with dexamethasone. The two readouts were the quantity of complement deposited along the BM and the release of sC5b-9 in the supernatant. Our results show classical and alternative complement pathway activation in BP skin biopsies, but could not demonstrate significant lectin pathway activation. In contrast to dexamethasone, complement deposition along the BM could be selectively inhibited by anti-C1 and anti- factor B. More downstream, selective intervention at the level of C3 and C5 could effectively reduce complement deposition along the BM and the release of sC5b-9 in the supernatant. This study shows that selective intervention in either the classical, alternative or terminal pathway prevented deposition of complement along the BM in an in vitro BP model. The results of our study greatly encourage the clinical development of complement inhibitors for the treatment of BP.

Clinical Efficacy of Dupilumab Injection in Combination with Systemic Low-Dose Hormones in the Treatment of Bullous Pemphigoid

Clinical Efficacy of Dupilumab Injection in Combination with Systemic Low-Dose Hormones in the Treatment of Bullous Pemphigoid

Effect of early initiation of steroid-sparing drugs in patients with bullous pemphigoid.

Bullous pemphigoid (BP) can be treated using systemic and topical glucocorticoids and/or other immunomodulatory agents. However, the long-term use of systemic glucocorticoids causes severe adverse side effects. This study was aimed at investigating whether the early initiation of corticosteroid-sparing therapy (CST) in BP patients results in better outcomes than late or no CST. We retrospectively identified all BP patients referred to the tertiary center, of the Department of Dermatology and Venerology, Aarhus University Hospital, Denmark, from 2015 to 2021. Patients' demographics, comorbidities, treatment, remission of BP, length of admission, relapse, and 1-year mortality were recorded. All patients who received CST were dichotomised into two groups: initiated with CST <28 or >28 days. The groups were compared using t-tests. Additionally, all patients who received CST were compared with those who received systemic glucocorticoids alone. Our cohort was compared with that of a previous study (2006-2013) performed in our department. In 2015, we revised our BP treatment guidelines to include the early initiation of CST. On comparing the group of patients initiated with CST <28 versus >28 days, we found no significant differences in the complications or mortality between the groups (p = 0.63 and p=0.79, respectively). The <28 days group had a lower rate of relapse (p < 0.05). On comparing data from this study with those from the previous study, conducted before we revised our treatment guideline, we found a reduced initial dose of prednisolone and reduced admission time in this study. No significant differences were found between patients treated with CST and those treated with systemic glucocorticoids alone. The rate of complications and 1-year mortality did not differ significantly between the two subgroups in this study. The relapse rate was lower in the CST <28 days group than in the CST >28 days group. The initial dose of prednisolone and admission time were reduced in this study compared with those in the previous study performed before the implementation of a local treatment guideline recommending the early initiation of CST.

Intravenous immunoglobulin in patients with bullous pemphigoid insufficient response to corticosteroids: Nationwide post-marketing surveillance in Japan

BackgroundIn Japan, intravenous immunoglobulin (IVIG) has been approved for corticosteroid-unresponsive bullous pemphigoid (BP); however, its usage, efficacy, and safety in clinical settings remain unclear. ObjectiveTo elucidate IVIG efficacy, we examined the improvement in disease severity based on the Bullous Pemphigoid Disease Area Index (BPDAI). MethodsIn this 3-year (April 2016–March 2019), prospective, post-marketing, observational surveillance study, we enrolled 379 patients (51.3 % men; mean age, 74.5 years) with corticosteroid-unresponsive BP treated with IVIG from 143 institutions in Japan (720 treatment cycles). The percentage of patients who improved by at least one severity stage or whose symptoms completely resolved based on the BPDAI score was evaluated at 15, 30, and 60–90 days. ResultsThe improvement rates at 15, 30, and 60–90 days after initial treatment in the 328 IVIG-naïve patients were 70.7 %, 83.5 %, and 84.3 %, respectively. The BPDAI score decreased rapidly and significantly by 15 days compared with that observed during pre-treatment. Further improvement was observed at 30 and 60–90 days. The corticosteroid dose and anti-BP180 antibody titers decreased significantly post-treatment (both, p < .001). Approximately 25 % of IVIG-naïve patients underwent multiple treatment cycles. The improvement rate at 30 days after the final dose was 88 %, and the symptoms completely resolved in 44 % of patients. The incidence of adverse drug reactions per cycle was 8.34 %; the most common reaction was transient thrombocytopenia. ConclusionMost patients showed improvement in severity and decrease in corticosteroid dose and anti-BP180 antibody levels post-treatment, indicating that IVIG is useful for corticosteroid-unresponsive BP treatment.

Bullous pemphigoid in 65 years old female: a case report

Introduction: Bullous pemphigoid is an autoimmune disorder. The incidence of bullous pemphigoid has increased over time, current understanding regarding treatment and complication is an important issue considering the disease often occur in elderly resulting in high rates of morbidity to the patients.&#x0D; Objective: Aim of the current case report is to describe the clinical relevance regarding symptom and treatment of bullous pemphigoid.&#x0D; Case report: A 65 years old female patient, came with chief complaints of bullae in the abdominal region with itching and burning sensation in the ruptured bullae. Over time bullae spread in the lower and upper extremity. The patient was admitted for four days with therapy intravenous steroids, an oral antihistamine, and potent topical steroids. The patient was discharged from hospital in good condition.&#x0D; Conclusion: Bullous pemphigoid is an inflammatory autoimmune skin disease and usually result in good prognosis with adequate management.

Omalizumab as a corticosteroid-sparing agent in the treatment of bullous pemphigoid.

Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease, characterized by the development of autoantibodies against hemidesmosomal components BP180 and BP230. The mainstay of therapy is topical and systemic corticosteroids (CS) and immunosuppressors. As this pathology mainly involves the elderly, subjects often have numerous comorbidities that influence the clinical management. Omalizumab is a recombinant humanized monoclonal anti-IgE antibody which has recently emerged as a promising treatment for BP in patients for whom CS are contraindicated or conventional treatments have failed to control the disease. For this study, we selected five patients who presented with corticosteroid-dependent BP with a contraindication to the use of other immunosuppressive treatments. The objectives of our study were to evaluate the effectiveness of omalizumab in controlling BP and allowing to decrease the dosage of systemic CS, assessing the effects of omalizumab on the clinical manifestations and the titers of circulating anti-BP180 and BP230 antibodies, IgE and eosinophils. A reduction in the dose of systemic CS was possible in 100% of the patients and complete resolution of the clinical picture was seen in 100% for skin lesions and in 40% for pruritus. A reduction of circulating IgE was found in 40%, anti-BP180 and BP230 IgGs were decreased in 60% and eosinophils in 80%.

A Review of the Immunologic Pathways Involved in Bullous Pemphigoid and Novel Therapeutic Targets.

Bullous pemphigoid (BP) is a rare, chronic antibody-mediated autoimmune blistering disease primarily affecting the elderly, with an age of onset over 60. Current treatment options are limited and involve the use of corticosteroids and immunosuppressants, but their long-term use is associated with significant morbidity and mortality. In Japan, human intravenous immunoglobin is approved for the treatment of corticosteroid-refractory BP. However, no treatment option is approved by the Food and Drug Administration for the management of BP. Therefore, developing effective therapies free of debilitating side effects is imperative. In this review, we summarize the main immunologic pathways involved in the pathogenesis of BP, with an emphasis on the role of eosinophils, immunoglobulins, cytokines such as the interleukin (IL)-4 and IL-5, and complements. We further discuss the latest advances with novel therapeutic targets tested for the management of BP. Ongoing efforts are needed to run well-designed controlled trials and test the efficacy and safety of investigational drugs while providing much-needed access to these medications for refractory patients who will not otherwise be able to afford them as off-label prescriptions.

How Do Experts Treat Patients with Bullous Pemphigoid around the World? An International Survey

Many treatments are currently proposed for treating patients with bullous pemphigoid (BP). We assessed treatment modalities of BP depending on the different countries, BP extent, and patients’ comorbidities. We surveyed worldwide experts about how they treat patients with BP. A total of 61 experts from 27 countries completed the survey. Severe and moderate BP were treated with oral prednisone (61.4 and 53.7%, respectively) or superpotent topical corticosteroids (CSs) (38.6 and 46.3%, respectively). Conventional immunosuppressants were more frequently combined with oral prednisone (74.5%) than with superpotent topical CS (37.5%) in severe BP. Topical CSs were mainly used in Europe in mild (81.1%), moderate (55.3%), and severe (54.3%) BP. In the United States of America and Asia, systemic CSs were mainly proposed for treating severe (77.8 and 100%, respectively), moderate (70 and 77.8%, respectively), and also mild (47.1 and 33.3%, respectively) BP. Most experts reduced the initial dose of oral CS in patients with diabetes mellitus (48.1%) or cardiac insufficiency (40.2%) but rarely changed BP treatment in patients with neurological disorders or neoplasia. This survey showed major differences in the way patients with BP are treated between AmeriPac countries (United State of America, Latin America, and Australia) and Asia on the one hand and Europe and the Middle East on the other hand.

Omalizumab for the Treatment of Bullous Pemphigoid: A Systematic Review of Efficacy and Safety.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease. Current treatment strategies are limited by their efficacy and/or side effect profile and the need for safer and effective alternatives is undeniable. We aimed to conduct a systematic review focusing on the efficacy and safety of omalizumab in BP patients. Embase, PubMed, Cochrane, and clinicaltrials.gov were searched for English and French articles published from inception to July 1, 2021, using search terms "omalizumab" OR "Xolair" OR "IGE025" OR "olizumab" AND "bullous pemphigoid." Screening and data extraction was performed by two raters independently. The primary outcome was complete response (CR), and secondary outcomes were partial response (PR), flare-ups, adverse events/vital status. In total, 22 articles were included, with a total of 56 patients. All patients had a refractory BP with mean disease duration of 13.5 ± 20.2 months (Standard Deviation (SD)) and failed 3.1 ± 1.6 therapies and many remained corticosteroids dependent. Overall, 87.5% of patients responded to treatment (55.4% CR and 32.1% PR), 7.1% discontinued the protocol and only 5.4% were non responders. A third of patients were able to discontinue all other therapies and most others were able to discontinue or taper systemic corticosteroids to <10 mg daily. Flare-ups occurred in 57.7% of patients upon discontinuation of omalizumab and/or steroid tapering, most patients recaptured response thereafter. Omalizumab was well tolerated by most patients. Omalizumab appears to be a promising treatment for BP with a good response rate and safety profile. However, several limitations were identified in current literature, and highlight the need for randomized controlled trials of omalizumab in BP.

Strategies to Improve Outcomes of Bullous Pemphigoid: A Comprehensive Review of Clinical Presentations, Diagnosis, and Patients' Assessment.

Bullous pemphigoid (BP) is the most frequent autoimmune bullous disease mainly affecting elderlies. Diagnosis usually results from clinical features, histological examination, and the quantification of circulating typical autoantibodies, due to its higher incidence in elderly patients, bullous pemphigoid treatment and management still represents a challenge due to the higher frequency of several comorbidities in this group of patients, which may also be linked to a reduced tolerance to BP treatments. Hence, an early diagnosis and a prompt correct treatment are mandatory to reach better clinical outcomes and improve as much as possible BP outcomes. Herein, we carried out a comprehensive literature review about the known clinical presentations, diagnosis, assessment and monitoring procedures used in daily clinical practice in patients with BP, to better define strategies to improve as much as possible BP clinical outcomes.

The Use of Mycophenolate Mofetil in the Treatment of Bullous Pemphigoid.

The first-line treatment for patients with bullous pemphigoid (BP), the most common autoimmune blistering disease, is systemic glucocorticoids, which are associated with numerous side effects. Mycophenolate mofetil (MMF) may be beneficial in BP as a steroid-sparing alternative; however, evidence is limited. To evaluate the efficacy and safety of MMF in patients with BP. In this retrospective chart review, records of patients with BP treated with MMF alone or in combination with prednisone, who presented between 2013 and 2017, were analyzed. Twenty-six patients were included. Twelve patients were treated with MMF alone (monotherapy) and fourteen were treated with MMF and prednisone concomitantly at some point during their treatment course (dual therapy). Improvement in BP was observed in 26 (100%) patients with MMF therapy. Mean time to improvement was 0.8 months. Twenty-five (96.2%) patients [11/12 (91.7%) on monotherapy and 14/14 (100%) on dual therapy] achieved complete control of their disease. Mean time to complete control amongst all patients was 5.6 months. Twelve (46.2%) patients [4/12 (33.3%) on monotherapy and 8/14 (57.1%) on dual therapy] experienced disease remission with no subsequent flares for up to 15 months after MMF was discontinued. Twelve mild adverse effects were reported with one individual discontinuing therapy due to gastrointestinal symptoms. No serious adverse effects were reported. MMF is a safe and effective therapy for BP and can yield improvement and complete response in most patients and remission in some. J Drugs Dermatol. 2022;21(2):151-155. doi:10.36849/JDD.6042.

Risk of All-Cause Mortality, Cardiovascular Disease Mortality, and Cancer Mortality in Patients With Bullous Pemphigoid

The role of bullous pemphigoid (BP) in cardiovascular disease (CVD) mortality remains controversial, and analyses of causes of death among patients with BP based on individual data remain lacking. To evaluate the risk of all-cause mortality, CVD mortality, and cancer mortality in patients with BP. This cohort study identified patients who received a diagnosis of and treatment for BP during their dermatology clinic visits at a tertiary medical center in central Taiwan between January 1, 2007, and December 31, 2017. Controls were patients without BP and were individually matched to cases (4:1) according to age, sex, and date of the dermatology clinic visit. Data were analyzed from March 6, 2019, to April 2, 2021. Bullous pemphigoid was confirmed pathologically with typical direct immunofluorescence findings or clinically with typical clinical presentation, positive findings of an anti-basement membrane zone antibody test, and corticosteroid use for at least 28 cumulative days. Mortality outcomes confirmed by the National Death Registry. Of 252 patients with BP and 1008 matched control patients (N = 1260), 685 (54.4%) were men and the median age was 78.0 (IQR, 70.3-84.8) years. Patients with BP had higher CVD mortality at 1 year (20 [7.9%] vs 13 [1.3%]), 3 years (28 [11.1%] vs 24 [2.4%]), and 5 years (31 [12.3%] vs 39 [3.9%]) compared with matched control patients. After adjusting for potential confounding variables, patients with BP had a 5-fold higher risk of CVD mortality at 1 year (hazard ratio [HR], 5.29 [95% CI, 2.40-11.68]), 3 years (HR, 5.79 [95% CI, 3.11-10.78]), and 5 years (HR, 4.95 [95% CI, 2.88-8.51]). Subgroup analyses revealed that the CVD mortality risk associated with BP was higher in patients without a history of hypertension (HR, 7.28 [95% CI, 3.87-13.69]) or CVD (HR, 6.59 [95% CI, 3.40-12.79]) and in patients without prior diuretic use (HR, 5.75 [95% CI, 3.15-10.50]) compared with matched control patients. In addition, all-cause mortality associated with BP was higher in patients without prior corticosteroid use than in control patients (HR 5.65 [95% CI, 4.19-7.61]). The findings of this cohort study suggest that BP was associated with a 5-fold higher risk of CVD mortality, particularly in patients without underlying hypertension or CVD or those without prior corticosteroid or diuretic use. Future studies should investigate the benefits of routine monitoring and timely management of CVD symptoms and signs in patients with BP.

Successful induction treatment of bullous pemphigoid using reslizumab: a case report

BackgroundBullous pemphigoid (BP) is a potentially life-threatening autoimmune blistering disease which is characterized by autoantibodies against hemidesmosomal proteins of the skin and mucous membranes. In recent years, the role of eosinophil and immunoglobulin E autoantibodies have been further elucidated in BP, and have been considered potential therapeutic targets.Case presentationsA 67-year-old male presented with erythematous bullous eruption. The skin eruption was located on whole body, and suggested BP. Peripheral blood eosinophil count and total immunoglobulin E markedly elevated in initial laboratory findings. Topical and systemic steroid (methylprednisolone 2 mg/kg/day) treatment was started, and his skin symptoms worsened repeatedly, whenever systemic steroid were reduced. On admission day 29, reslizumab (anti-interleukin-5) 3.5 mg/kg was administered intravenously to the patients. The bullous skin lesion began to improve rapidly, and methylprednisolone (8 mg/day) was reduced without any worsening of symptoms during two doses of reslizumab.ConclusionsWe report a case of successful treatment response to reslizumab administration in a patient with BP. Further studies are needed to confirm the role of anti-interleukin-5 as a treatment for BP in the future.

Interventions for bullous pemphigoid: An updated systematic review of randomized clinical trials.

Background: Bullous pemphigoid (BP) is a widely recognized autoimmune blistering disease (AIBD) linked with a high incidence of morbidity and mortality. The aim of this study was to evaluate the available findings of randomized clinical trial studies to update interventions for Bullous pemphigoid. Methods: This article provides an updated overview of interventions for BP. A literature search was performed using Cochrane Central Register of Clinical Trials, MEDLINE, Scopus, and Web of Science from August 2010 to December 2020. All randomized clinical trials (RCTs) were done on adults and investigated the effectiveness of administered topical or systemic medications versus placebos or controls included in the current systematic review. Three RCTs comprising 363 patients were included in the systematic review. One of the eligible studies was placebo-controlled. All of the included studies used various interventions including, methylprednisolone plus azathioprine versus methylprednisolone plus dapsone, doxycycline versus prednisolone, and intravenous immunoglobulin (IVIG). Results: Following their potentials in disease control, no difference was observed between dapsone and azathioprine; although, dapsone had a higher corticosteroid-sparing potential. The evaluation of the effect of doxycycline in short-term blister control in comparison to corticosteroids showed that the medication was not inferior to prednisolone, although it had a higher long-term safety. Conclusion: Therapeutic outcome of IVIG for steroid-resistant patients was satisfactory. Moreover, the effectiveness and reliability of various immunosuppressive drugs and tetracyclines are investigated by blinded RCTs for the treatment of BP.

Neutrophil extracellular traps contribute to immune dysregulation in bullous pemphigoid via inducing B-cell differentiation and antibody production.

Bullous pemphigoid (BP), an autoimmune skin disease, is characterized by autoantibodies against hemidesmosomal proteins in the skin and mucous membranes. Neutrophils infiltrate BP skin lesions, however, their role in immune dysregulation remains unclear. We investigated whether BP involves aberrant neutrophil extracellular traps (NETs) formation in skin lesions and circulation; and examined the triggers and deleterious immuno-inflammatory consequences. In the present study, we found that circulating NET-related biomarker levels increased in serum and blister fluid of BP patients and significantly correlated with disease severity. Additionally, circulating neutrophils from BP patients displayed enhanced spontaneous NETs formation than healthy controls. In vitro, BP180-NC16A immune complexes-induced NETosis in neutrophils from BP patients, which was abrogated by Fcγ receptor and/or NADPH pathway blockade. Furthermore, the elevated levels of NETs from BP patients boosted autoantibody production by inducing B-cell differentiation into plasma cells, mediated by MAPK P38 cascade activation. Together, our findings provide strong evidence that NETs are involved in a pathogenic loop, causing excessive differentiation of B cells and promotion of autoantibody production. Hence, targeting aberrant neutrophil responses will provide novel potential targets for the treatment of BP.

The association between statins and subsequent risk of bullous pemphigoid: A population-based cohort study

The association between statins and subsequent risk of bullous pemphigoid: A population-based cohort study

Diagnosis and treatment of bullous pemphigoid that developed twice after total knee replacement arthroplasty: a case report

BackgroundTotal knee replacement arthroplasty (TKA) is frequently performed in South Korea. Simple swelling-associated blistering around the periphery of the operative wound is a well-known adverse effect. However, in rare cases, the blisters are bullous pemphigoid (BP).Case presentationA 75-year-old male presented with knee pain that had not improved despite 5 years of medication. We performed TKA of the left knee, placing a Stryker posteriorly stabilized prosthesis. Three days later, blisters developed near the buttocks and thighs and, on day 10 after surgery, around the operative site. A skin biopsy revealed BP. Commencing on day 14 after surgery, prednisolone 10 mg was administered twice daily. The symptoms improved by 3 weeks after surgery and were healed at 4 months. After 1 year, we performed TKA of the right knee. On day 2 after surgery, as formerly, blisters developed on the buttocks and an immediate biopsy revealed BP. Commencing on day 3 after surgery, prednisolone 10 mg was administered twice daily. On day 10 after surgery, the blisters on the buttocks had improved and no blisters were observed at the surgical site. All symptoms had resolved by 2.5 months after surgery.ConclusionsAfter TKA surgery, generalized BP may develop, diagnosed via skin biopsy. A quick diagnosis is important because early treatment can prevent symptom progression and shorten treatment.

A Case Report of Pemphigoid Nodularis as Masquerader of Neurotic Excoriations

Abstract Introduction: Pemphigoid nodularis is a rare clinical variant of bullous pemphigoid characterized by both prurigo nodularis-like lesions and pemphigoid-like blisters. Herein, we report a case of pemphigoid nodularis in a cognitively-impaired patient who has been managed as extensive prurigo nodularis with neurotic exocriations for many years. 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.