Bullous Pemphigoid

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Practice Essentials

Bullous pemphigoid is a chronic, autoimmune, subepidermal, blistering skin disease that rarely involves mucous membranes. Bullous pemphigoid is characterized by the presence of immunoglobulin G (IgG) autoantibodies specific for the hemidesmosomal bullous pemphigoid antigens (BPAgs) BP230 (BPAg1) and BP180 (BPAg2). Occasionally, sublamina densa deposits are noted, related to anti-p200 antibody. If untreated, bullous pemphigoid can persist for months or years, with periods of spontaneous remissions and exacerbations. It can be fatal, particularly in patients who are debilitated.

Signs and symptoms

Bullous pemphigoid may present with several distinct clinical presentations, as follows:

See Clinical Presentation for more detail.

Diagnosis

To establish a diagnosis of bullous pemphigoid, the following tests should be performed:



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Direct immunofluorescence study performed on perilesional skin biopsy specimen from patient with bullous pemphigoid detects linear band of IgG deposit....



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Indirect immunofluorescence study performed on salt-split normal human skin substrate with serum from patient with bullous pemphigoid detects IgG-clas....

DIF tests in patients with bullous pemphigoid usually demonstrate IgG and complement C3 deposition in a linear band at the dermal-epidermal junction, with IgG in salt-split skin found on the blister roof (epidermal side of split skin).

IDIF studies document the presence of circulating IgG autoantibodies in the patient's serum that target the skin basement membrane component. Seventy percent of patients with bullous pemphigoid have circulating autoantibodies that bind to split skin.

See Workup for more detail.

Management

As in other autoimmune bullous diseases, the goal of therapy in bullous pemphigoid is as follows:

The most commonly used medications for bullous pemphigoid are anti-inflammatory agents (eg, corticosteroids, tetracyclines, dapsone) and immunosuppressants (eg, azathioprine, methotrexate, mycophenolate mofetil, cyclophosphamide).[4, 5] Initial treatment with doxycycline was found to be effective and was associated with a lower incidence of adverse effects as compared with prednisone.[6, 7, 8]

Most patients affected with bullous pemphigoid require therapy for 6-60 months, after which many patients experience long-term remission of the disease. However, some patients have long-standing disease requiring treatment for years.

Most mortality associated with bullous pemphigoid occurs secondary to the effects of medications used in treatment. The population at risk for bullous pemphigoid is at an increased risk for comorbid conditions,[9] such as hypertension, diabetes mellitus,[10] and heart disease,[11] which treatment may exacerbate.

See Treatment and Medication for more detail.

Pathophysiology

In patients with bullous pemphigoid, immunoglobulin G (IgG) autoantibodies bind to the skin basement membrane. This binding activates complement and inflammatory mediators. Activation of the complement system is thought to play a critical role in attracting inflammatory cells to the basement membrane. These inflammatory cells are postulated to release proteases, which degrade hemidesmosomal proteins and lead to blister formation. On histopathologic analysis, eosinophils are characteristically present in human patients' blisters, though their presence is not an absolute diagnostic criterion.

The precise role of bullous pemphigoid antigens (BPAgs) in the pathogenesis of bullous pemphigoid is not completely clear. BPAg1 (BP230) is an intracellular component of the hemidesmosome; BPAg2 (BP180, type XVII collagen) is a transmembranous protein with a collagenous extracellular domain.[12] Passive transfer experiments in newborn mice demonstrated that rabbit antibodies against mouse BPAg2 can induce subepidermal blisters similar to those observed in patients with bullous pemphigoid. However, the eosinophil infiltration that is frequently observed in human bullous pemphigoid lesional skin was not detected in the passive transfer experimental model.[13]

Another study found that anti-BP180 NC16A domain autoantibodies purified from patients with bullous pemphigoid are capable of inducing dermal-epidermal separation in cryosections of normal human skin.[14]

Studies on autoreactive T and B cells from 35 patients with acute-onset bullous pemphigoid revealed that the percentage of T-cell and B-cell reactivity from these bullous pemphigoid patients against BPAg2 is much higher than that against BPAg1, further suggesting a more prominent role of BPAg2 in disease development.[15]

Serum levels of autoantibodies against BPAg2 have been correlated with disease activity in some studies.[16] Induction of antibodies against BPAg1 in rabbits does not induce primary blistering, but it can enhance the inflammatory response at the basement membrane. The role of autoantibodies specific for BPAgs in the initiation and the perpetuation of disease is unknown.

Although BPAg2 has been identified as the major antigen involved with bullous pemphigoid disease development, autoantibodies against alpha 6 integrin[17] and laminin-5,[18] two other components of skin basement membrane, have been identified in human patients affected by bullous pemphigoid.

No perfect active experimental model has been developed; however, an active animal model was generated in a 2010 study by transferring splenocytes from wild-type mice that had been immunized by grafting human BP180-transgenic mouse skin into Rag-2(–/–)/BP180-humanized mice.[19] The recipient immunodeficient mice developed antihuman BP180 antibodies, manifested with blisters that were consistent with the clinical, histologic, and immunopathologic features of human bullous pemphigoid, except eosinophil infiltration.

In addition, the autoantibody response can be induced in healthy BALB/c mice by immunizing the mice with synthetic peptides of the mouse type XVII collagen NC16A domain, the target region of autoantibodies in human patients affected with bullous pemphigoid.[20]

Eotaxin, an eosinophil-selective chemokine, is strongly expressed in the basal layer of the epidermis of lesional bullous pemphigoid skin and parallels the accumulation of eosinophils in the skin basement membrane zone area. It may play a role in the recruitment of eosinophils to the skin basement membrane area.

Other cytokines and chemokines have also been studied in bullous pemphigoid. In a 2004 study, interleukin (IL)-16, a major chemotactic factor responsible for recruiting CD4+ helper T cells to the skin and for inducing functional IL-2 receptors for cellular activation and proliferation, was found to be expressed strongly by epidermal cells and infiltrating CD4+ T cells in lesional bullous pemphigoid skin.[21] Significantly higher levels of IL-16 were detected in sera and blisters of bullous pemphigoid patients as compared with healthy subjects. These findings suggested a role for IL-16 in bullous pemphigoid development.

In a 2006 study, serum levels of monokine induced by interferon gamma (MIG, a Th1-type chemokine) and serum levels of CCL17 and CCL22 (Th2-type chemokines) were significantly increased in bullous pemphigoid patients as compared with healthy subjects.[22]

In another 2006 study, matrix metalloproteinase (MMP)-2, MMP-9, and MMP-13 were found to be significantly increased in lesional bullous pemphigoid skin as compared with that of healthy skin, with T cells accounting for the majority of MMP cellular sources. These findings suggested a role for MMP in the blistering of bullous pemphigoid.[23]

In yet another 2006 study, the cytokine referred to as BAFF (B-cell activating factor, belonging to the tumor necrosis factor [TNF] family), which functions to regulate B-cell proliferation and survival, was found to be significantly increased in sera of bullous pemphigoid patients as compared with healthy subjects, though no significant association was noted between serum BAFF levels and anti-BPAg2 titers.[24]

A 2008 study established a role for the IgE class of autoantibodies, particularly those that target BP180; the higher level of IgE anti-BP180 was correlated with a more severe clinical phenotype.[25]

In a study that used an animal model in which C57BL/6 type of mice engrafted with syngeneic mouse skin transgenically expressed human BPAg2 in the epidermal basement membrane zone, antibodies against the human BPAg2 extracellular domain developed first, followed by antibodies to the intracellular domain of the same human BPAg2. It is noteworthy that the development of later antibodies was associated with the loss of the graft.[26]

IgG autoantibodies from bullous pemphigoid patients have been found to deplete cultured keratinocytes of the BPAg2 and weaken cell attachment in vitro; this further supports their pathogenic role.[27]

The coagulation cascade is activated in bullous pemphigoid patients, and such activation has been found to be correlated with disease severity and with eosinophilia, suggesting a role for eosinophils in this activation of coagulation, which may contribute to the potential thrombotic risk, as well as inflammation, tissue damage, and blister formation.[28]

A 2010 report that described finding anti-BP180 antibodies in unaffected subjects provided suggestive data for further study of the pathogenesis of bullous pemphigoid.[29]

A 2009 report of bullous pemphigoid that developed after adalimumab treatment for psoriasis raised questions about whether biologics can play a causative role in inducing the disease or whether this development simply reflected an association of bullous pemphigoid with psoriasis.[30]

Bullous pemphigoid has been associated with immune checkpoint inhibitors (eg, programmed cell death [PD]-1 inhibitors) used as targeted therapy for malignancy.[31] Some patients developed both pemphigoid and keratoacanthomas.[32, 33, 34]

Dipeptidyl peptidase 4 (DPP-4) inhibitors have been associated with a risk of developing bullous pemphigoid.[10, 35, 36, 37]

Environmental factors have been associated with bullous pemphigoid, including daily consumption of the following[38] :

Other triggers associated with bullous pemphigoid include use of lime-containg household cleaning products and high levels of mental stress.[38]

Epidemiology

United States and international statistics

Bullous pemphigoid is uncommon, and its precise frequency has not been definitively established.

Bullous pemphigoid has been reported to occur throughout the world. In Europe, bullous pemphigoid has been identified as the most common subepidermal autoimmune blistering disease. In France and Germany, the reported incidence is 6.6 cases per million people per year. In a population-based cohort study from the United Kingdom, the incidence of bullous pemphigoid was found to be 4.3 cases per 100,000 person-years.[39]

Age-, sex-, and race-related demographics

Bullous pemphigoid primarily affects elderly individuals in the fifth through seventh decades of life (average age at onset, 65 y). Bullous pemphigoid of childhood onset has been reported in the literature. It has been suggested that the childhood-onset form may be more self-limited.[40] One puzzling finding, however, is a report of rising incidence of infant-onset bullous pemphigoid.

The incidence of bullous pemphigoid appears to be equal in men and women.

No racial predilection is apparent.

Prognosis

Bullous pemphigoid is a chronic inflammatory disease. If untreated, bullous pemphigoid can persist for months or years, with periods of spontaneous remissions and exacerbations. Most patients affected with bullous pemphigoid require therapy for 6-60 months, after which many experience long-term remission of the disease. Some patients, however, have long-standing disease necessitating treatment for years. The lesions typically heal without scarring or milia formation.

Bullous pemphigoid involves the mucosa in 10-25% of patients. Patients who are affected may have limited oral intake secondary to dysphagia. Erosions secondary to rupture of the blisters may be painful and may limit patients' daily living activities. Blistering on the palms and the soles can severely interfere with patients' daily functions.

Bullous pemphigoid may be fatal, particularly in patients who are debilitated. The proximal causes of death are infection with sepsis and adverse events associated with treatment. Most of the mortality associated with bullous pemphigoid is secondary to the effects of the medications.

In a survey of patients conducted in a United States university medical center, no difference was noted in expected mortality in bullous pemphigoid patients as compared with the general population.[41] In a population-based cohort study in the United Kingdom, however, the risk of death for bullous pemphigoid patients was found to be twice as great as that for controls.[39] Furthermore, a Swiss prospective study confirmed a high case-fatality rate, with increased 1-year mortality compared with expected mortality for the age-adjusted and sex-adjusted general population.[42]

Patients with aggressive or widespread disease, those requiring high doses of corticosteroids and immunosuppressive agents, and those with underlying medical problems have increased morbidity (eg, peptic ulcer disease, gastrointestinal bleeding, agranulocytosis, and diabetes) and risk of death. Because the average age at the onset of disease is about 65 years, patients with bullous pemphigoid frequently have other comorbid conditions that are common in elderly persons and thus are more vulnerable to the adverse effects of corticosteroids and immunosuppressants.

The population at risk for bullous pemphigoid is at an increased risk for comorbid conditions such as hypertension, diabetes mellitus,[10] thromboembolism, and heart diseases, which treatment may exacerbate.[43] Bullous pemphigoid may be linked (directly or indirectly) to neurologic disorders.[9, 44, 45] An increase in the occurrence of neurologic disorders has been reported in patients affected by bullous pemphigoid, relative to the age-matched and sex-matched general population.[46] Further data from studies in different populations will be required to clarify this proposed relation.

Data suggest that high serum levels of IgG1 and IgG4 targeting the noncollagenous 16A domain of BP180 correlate with more serious disease and a worse prognosis.[47] Age and the presence of circulating antibodies are also associated with poor outcome.[48]

In a multicenter, prospective cohort in France, a high titer of anti-BPAg2 autoantibodies by ELISA and a positive direct immunofluorescence (DIF) finding were found to be good indicators of further clinical relapse of bullous pemphigoid and may correlate with overall morbidity and mortality.[49, 50, 51]

Patient Education

Patients should avoid trauma to the skin. Their skin has been rendered fragile by the disease, as well as by the use of topical and systemic steroids. Patients should be educated about their disease and treatments, so that they can report adverse effects to their physicians.

History

The onset of bullous pemphigoid may be either subacute or acute, with widespread tense blisters. Significant pruritus is frequently present and may be the only manifestation of the disease, especially in older patients.[52] In some patients, the blisters arise after persistent urticarial lesions.

Bullous pemphigoid has been reported following several nonbullous chronic inflammatory skin diseases, such as lichen planus and psoriasis.

Bullous pemphigoid has been reported to be precipitated by ultraviolet (UV) light, radiation therapy, and exposure to some drugs.

Drugs associated with bullous pemphigoid include furosemide, ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs), captopril, penicillamine, and antibiotics.

Bullous pemphigoid has been reported to develop shortly after vaccination, particularly in children.[53]

Physical Examination

Bullous pemphigoid may present with several distinct clinical presentations, as follows:

Laboratory Studies

To establish a diagnosis of bullous pemphigoid, the following tests should be performed:

If the DIF result is positive, indirect immunofluorescence (IDIF) is performed with the patient's serum. The preferred substrate for IDIF is salt-split normal human skin substrate.

Direct immunofluorescence

DIF demonstrates in-vivo deposits of antibodies and other immunoreactants (eg, complement). Usually, immunoglobulin G (IgG; 70-90% of patients) and complement C3 deposition (90-100% of patients) can be seen in a linear band at the dermoepidermal junction (see the image below). This pattern of immunoreactants is not specific for bullous pemphigoid and may also be seen in cicatricial pemphigoid (CP) and epidermolysis bullosa acquisita (EBA).



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Direct immunofluorescence study performed on perilesional skin biopsy specimen from patient with bullous pemphigoid detects linear band of IgG deposit....

Bullous pemphigoid can be differentiated from CP and EBA by incubating the patient's skin biopsy sample in 1 mol/L salt before performing DIF. This process induces cleavage through the lamina lucida. DIF on salt-split skin reveals immunoglobulin G (IgG) on the blister roof (epidermal side of split skin) in patients with bullous pemphigoid, whereas in CP and EBA, IgG localizes to the blister floor (dermal side of split skin).

The optimal location for DIF testing is normal-appearing perilesional skin; false-positive results may occur when it is performed on lesional skin. There is a significant false-negative rate if the skin biopsy specimen is taken from skin of the legs.[3]  Rarely, skin biopsy samples placed in transport media may yield false-negative results. Thus, fresh tissue is the preferred substrate for DIF studies.

Indirect immunofluorescence

IDIF studies document the presence of IgG circulating autoantibodies in the patient's serum that target the skin basement membrane component. About 70% of patients with bullous pemphigoid have circulating autoantibodies that bind to split skin. The titer of circulating antibody is not correlated with the disease course. IDIF studies can be used to detect the patient's IgG circulating autoantibodies that bind to the epidermal roof (upper part) of the salt-split skin substrate (see the image below).



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Indirect immunofluorescence study performed on salt-split normal human skin substrate with serum from patient with bullous pemphigoid detects IgG-clas....

Other Tests

Tests available in research laboratories include direct and indirect immunoelectron microscopy (immunoEM), immunoblotting, immunoprecipitation, and enzyme-linked immunosorbent assay (ELISA), as follows.

Direct and indirect immunoelectron microscopy

Direct and indirect forms of immunoEM ultrastructurally localize in-vivo bound IgG autoantibodies (direct immunoEM) or the binding site of circulating IgG autoantibodies (indirect immunoEM) at the basement membrane. IgG autoantibodies are detected at the hemidesmosome/upper lamina lucida areas of the skin basement membrane.

Immunoblotting

Immunoblotting or Western blotting demonstrates reactivity of IgG in the sera of patients with proteins extracted from healthy human skin. Sensitivity varies: In 75% of patients, a reaction occurs with the BP230 antigen, whereas in 50%, a reaction occurs with the BP180 antigen.

Immunoprecipitation

Like immunoblotting, immunoprecipitation demonstrates reactivity with BP230 and BP180. Unlike immunoblotting, however, immunoprecipitation is performed with native rather than denatured protein; consequently, it is more sensitive. Immunoprecipitation is more difficult to perform than immunoblotting and is generally less available. In most cases, immunoprecipitation detects autoantibodies specific for BP230 and BP180.

Enzyme-linked immunosorbent assay

ELISA analyzes the bullous pemphigoid antigen (BPAg)-specific IgG autoantibodies in the patients' sera by using various lengths of recombinant proteins of the BPAg1 or BPAg2 antigens. It has been demonstrated to be highly sensitive and specific.[56] ELISA kits for testing BPAg-specific IgG autoantibodies are available commercially; however, relatively few centers offer this service. ELISAs based on recombinant proteins encoded by BP230 and BP180 have been developed[57] ; though not commercially available, these assays are promising as investigational tools. ELISA based on BP180 demonstrates sera reactivity with more than 90% of patients who have bullous pemphigoid.

Immunohistochemistry

If freshly frozen tissue is not available for DIF microscopy, formalin-fixed skin sections from patients with bullous pemphigoid may be used to examine the presence of C3 deposition along the epidermal basement membrane zone for confirmation of the diagnosis.[58]

Histologic Findings

The histopathologic examination demonstrates a subepidermal blister. The inflammatory infiltrate is typically polymorphous, with an eosinophil predominance. Mast cells and basophils may be prominent early in the disease course. Lesional skin biopsy specimens may reveal a predominantly neutrophilic infiltrate or minimal inflammation (pauci-inflammatory or cell-poor bullous pemphigoid).

Medical Care

As in other autoimmune bullous diseases, the general aims of therapy are to decrease blister formation, to promote healing of blisters and erosions, and to determine the minimal dose of medication necessary to control the disease process. Therapy must be individualized for each patient, keeping in mind preexisting conditions and other patient-specific factors.

More specifically, treatment is directed at reducing inflammatory response and autoantibody production. Although target-specific therapy is the "Holy Grail" for immunodermatologists, nontargeted treatments are used at present. The medications most often given are anti-inflammatory agents (eg, corticosteroids, tetracyclines, and dapsone) and immunosuppressants (eg, azathioprine, methotrexate, mycophenolate mofetil, and cyclophosphamide). Strong topical corticosteroid treatment may achieve disease control while avoiding the adverse effects of systemic corticosteroids.[5, 4, 59, 60]  Omalizumab[61, 62] and dupilumab[63, 64] have been used as corticosteroid-sparing agents.

Several studies found initial treatment with doxycycline to be effective and to be associated with a lower incidence of adverse effects as compared with prednisolone.[6, 7, 8]

Proper treatment of bullous pemphigoid depends on the severity of the disease. For localized disease, a topical steroid plus a systemic anti-inflammatory (eg, tetracycline or nicotinamide) may be sufficient. The effects of monotherapy with nicotinamide are unknown. For more severe cases, systemic steroids along with immunosuppressants may be needed for control. If the disease proves difficult to control, it is worthwhile to consider treatment with the anti-CD20 antibody rituximab, which is relatively specific in targeting the antibody-producing B cells.[65, 66, 67, 68, 69, 70, 71, 72, 73]

Some case reports have suggested that Janus kinase (JAK) inhibitors (eg, tofacitinib, baricitinib, upadacitinib, and abrocitinib) may prove useful for treatment of bullous pemphigoid.[74]

Complications

Secondary infection may occur because of the presence of multiple erosions and immunosuppressants used to control the disease. These infections may be either systemic or localized to the skin. Cutaneous infection increases the risk of scarring and delays wound healing.

Malignancies due to immunosuppressants have been reported. Case-control series in patients with bullous pemphigoid have failed to detect an increased incidence of malignancy in patients with bullous pemphigoid when compared with age- and sex-matched controls

Bone marrow suppression may occur in patients receiving immunosuppressants.

Growth restriction may occur in children receiving systemic corticosteroids and immunosuppressants. Adrenal insufficiency may occur following prolonged use of glucocorticoids. Osteoporosis and bone fractures may result following the use of systemic corticosteroids.[75] Associated neurodegenerative disease may be antibody-mediated.[76]

There may be a higher incidence of squamous carcinoma and lymphoma in patients with pemphigoid.[77]

Diet

The lesions may flare in patients with oral disease after eating hard and crunchy foods, such as chips, raw fruits, and vegetables.

For patients treated with systemic corticosteroid for longer than 3 months, a combined supplement of calcium and vitamin D should be instituted to prevent osteoporosis; the dosage and the frequency are stated in the updated recommendations published by the American College of Rheumatology (ACR) in 2022.[75]

In addition to calcium and vitamin D supplementation, patients on long-term treatment with systemic corticosteroids should be taking a bisphosphonate (eg, alendronate), which specifically inhibits osteoclast-mediated bone resorption.

Activity

Patients should be instructed to avoid direct physical trauma to their skin surfaces. For example, localized bullous pemphigoid has rarely been described peristomally.

Consultations

Treatment of patients with bullous pemphigoid requires coordination of care between the dermatologist and the patient's primary care provider. Patients with oral disease may require an otolaryngologist and/or a dentist for evaluation and care. An ophthalmologist should evaluate patients with suspected ocular involvement and those requiring prolonged high-dose steroids.

Prednisone (Deltasone, Prednisone Intensol, Rayos)

Clinical Context: 

Prednisolone (FloPred, Millipred, Millipred DP)

Clinical Context: 

Clobetasol (Clobex, Clobex Spray, Cormax)

Clinical Context: 

Tetracycline

Clinical Context: 

Doxycycline (Acticlate, Adoxa, Atridox)

Clinical Context: 

Dapsone

Clinical Context: 

Azathioprine (Azasan, Imuran)

Clinical Context: 

Methotrexate (Jylamvo, Otrexup, Rasuvo)

Clinical Context: 

Mycophenolate (CellCept, MMF, Myfortic)

Clinical Context: 

Cyclophosphamide (Cytoxan)

Clinical Context: 

Rituximab (Riabni, Rituxan, Rituximab-abbs)

Clinical Context: 

Omalizumab (Xolair)

Clinical Context: 

Dupilumab (Dupixent)

Clinical Context: 

NADH (Nicotinamide adenine dinucleotide)

Clinical Context: 

What is bullous pemphigoid (BP)?What are the signs and symptoms of bullous pemphigoid (BP)?How is bullous pemphigoid (BP) diagnosed?What are the goals of bullous pemphigoid (BP) treatment?What are the most commonly used medications for treatment of bullous pemphigoid (BP)?What is the length of therapy for bullous pemphigoid (BP)?What is the most frequent cause of mortality in bullous pemphigoid (BP)?What is bullous pemphigoid (BP)?What is the role of IgG antibodies in the pathogenesis of bullous pemphigoid (BP)?What is the role of BP antigens in the pathogenesis of bullous pemphigoid?What is the role of BPAg2 in the pathogenesis of bullous pemphigoid (BP)?What is the role of cytokines and chemokines in the pathogenesis of bullous pemphigoid (BP)?What is the role of autoantibodies in the pathogenesis of bullous pemphigoid (BP)?What is the role of other therapies in the pathogenesis of bullous pemphigoid (BP)?How prevalent is bullous pemphigoid (BP) in the US?What is the global incidence of bullous pemphigoid (BP)?How does the prevalence of bullous pemphigoid (BP) vary by race?How does the prevalence of bullous pemphigoid (BP) vary by sex?How does the prevalence of bullous pemphigoid (BP) vary by age?What is the prognosis of bullous pemphigoid (BP)?What are the possible comorbidities of bullous pemphigoid (BP)?What are the indicators of relapse for bullous pemphigoid (BP)?What education about bullous pemphigoid (BP) should patients receive?Which factors increase the mortality risk of bullous pemphigoid (BP)?What are the possible sequelae of bullous pemphigoid (BP)?Which history findings suggest bullous pemphigoid (BP)?What are the signs and symptoms of bullous pemphigoid (BP)?Which conditions should be included in the differential diagnosis of bullous pemphigoid (BP)?What are the differential diagnoses for Bullous Pemphigoid?Which lab tests are used in the workup of bullous pemphigoid (BP)?What is the role of direct immunofluorescence (DIF) studies in the diagnosis of bullous pemphigoid (BP)?What is the role of indirect immunofluorescence (IDIF) in the diagnosis of bullous pemphigoid (BP)?Which tests are used in research labs to diagnosis bullous pemphigoid (BP)?Which histologic findings suggest bullous pemphigoid (BP) reveal?What is the goal of bullous pemphigoid (BP) therapy?What are possible complications of bullous pemphigoid (BP)?Which foods may trigger bullous pemphigoid (BP) lesions in patients with oral disease?What is the role of dietary supplements in the treatment of bullous pemphigoid (BP)?Which activity restrictions are helpful in the treatment of bullous pemphigoid (BP)?Which specialist consultations are helpful in the management of bullous pemphigoid (BP)?Which medications are used in the treatment of bullous pemphigoid (BP)?Which medications in the drug class Tetracyclines are used in the treatment of Bullous Pemphigoid?Which medications in the drug class Corticosteroids, Topical are used in the treatment of Bullous Pemphigoid?Which medications in the drug class Corticosteroids are used in the treatment of Bullous Pemphigoid?

Author

Lawrence S Chan, MD, Dr Orville J Stone Professor of Dermatology, Head, Department of Dermatology, University of Illinois College of Medicine

Disclosure: Nothing to disclose.

Specialty Editors

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Disclosure: Nothing to disclose.

Julia R Nunley, MD, Professor, Department of Dermatology, Virginia Commonwealth University Medical Center

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Board of Dermatology<br/>Author for: Up-to-date.

Chief Editor

Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Russell Hall, MD, J Lamar Callaway Professor And Chair, Department of Dermatology, Duke University Medical Center, Duke University School of Medicine

Disclosure: Received consulting fee from Novan for consulting; Received consulting fee from Stieffel, a GSK company for consulting; Received salary from Society for Investigative Dermatology for board membership.

References

  1. Waisbourd-Zinman O, Ben-Amitai D, Cohen AD, Feinmesser M, Mimouni D, Adir-Shani A, et al. Bullous pemphigoid in infancy: Clinical and epidemiologic characteristics. J Am Acad Dermatol. 2008 Jan. 58 (1):41-8. [View Abstract]
  2. Diercks GF, Pas HH, Jonkman MF. Immunofluorescence of Autoimmune Bullous Diseases. Surg Pathol Clin. 2017 Jun. 10 (2):505-512. [View Abstract]
  3. Perry DM, Wilson A, Self S, Maize JC. False-Negative Rate of Direct Immunofluorescence on Lower Extremities in Bullous Pemphigoid. Am J Dermatopathol. 2021 Jan 1. 43 (1):42-44. [View Abstract]
  4. Terra JB, Potze WJ, Jonkman MF. Whole body application of a potent topical corticosteroid for bullous pemphigoid. J Eur Acad Dermatol Venereol. 2014 Jun. 28 (6):712-8. [View Abstract]
  5. Gual A, Iranzo P, Mascaró JM Jr. Treatment of bullous pemphigoid with low-dose oral cyclophosphamide: a case series of 20 patients. J Eur Acad Dermatol Venereol. 2014 Jun. 28 (6):814-8. [View Abstract]
  6. Chalmers JR, Wojnarowska F, Kirtschig G, Mason J, Childs M, Whitham D, et al. A randomised controlled trial to compare the safety, effectiveness and cost-effectiveness of doxycycline (200 mg/day) with that of oral prednisolone (0.5 mg/kg/day) for initial treatment of bullous pemphigoid: the Bullous Pemphigoid Steroids and Tetracyclines (BLISTER) trial. Health Technol Assess. 2017 Mar. 21 (10):1-90. [View Abstract]
  7. Williams HC, Wojnarowska F, Kirtschig G, Mason J, Godec TR, Schmidt E, et al. Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial. Lancet. 2017 Apr 22. 389 (10079):1630-1638. [View Abstract]
  8. Grantham HJ, Stocken DD, Reynolds NJ. Doxycycline: a first-line treatment for bullous pemphigoid?. Lancet. 2017 Apr 22. 389 (10079):1586-1588. [View Abstract]
  9. Kim BR, Lee KH, Paik K, Kim M, Bae JM, Choi CW, et al. Comorbid diseases in bullous pemphigoid: A population-based case-control study. J Dermatol. 2024 Dec 13. [View Abstract]
  10. Li JH, Zuo YG. The "entanglement" between bullous pemphigoid and diabetes mellitus: a comprehensive review and expert recommendations. Expert Rev Clin Immunol. 2024 Nov 13. 1-14. [View Abstract]
  11. Mashima E, Saito-Sasaki N, Sawada Y. Systemic Implications of Bullous Pemphigoid: Bridging Dermatology and Internal Medicine. Diagnostics (Basel). 2024 Oct 12. 14 (20):[View Abstract]
  12. Xu L, Robinson N, Miller SD, Chan LS. Characterization of BALB/c mice B lymphocyte autoimmune responses to skin basement membrane component type XVII collagen, the target antigen of autoimmune skin disease bullous pemphigoid. Immunol Lett. 2001 Jun 1. 77 (2):105-11. [View Abstract]
  13. Liu Z, Diaz LA, Troy JL, Taylor AF, Emery DJ, Fairley JA, et al. A passive transfer model of the organ-specific autoimmune disease, bullous pemphigoid, using antibodies generated against the hemidesmosomal antigen, BP180. J Clin Invest. 1993 Nov. 92 (5):2480-8. [View Abstract]
  14. Sitaru C, Schmidt E, Petermann S, Munteanu LS, Bröcker EB, Zillikens D. Autoantibodies to bullous pemphigoid antigen 180 induce dermal-epidermal separation in cryosections of human skin. J Invest Dermatol. 2002 Apr. 118 (4):664-71. [View Abstract]
  15. Thoma-Uszynski S, Uter W, Schwietzke S, Schuler G, Borradori L, Hertl M. Autoreactive T and B cells from bullous pemphigoid (BP) patients recognize epitopes clustered in distinct regions of BP180 and BP230. J Immunol. 2006 Feb 1. 176 (3):2015-23. [View Abstract]
  16. Schmidt E, Obe K, Bröcker EB, Zillikens D. Serum levels of autoantibodies to BP180 correlate with disease activity in patients with bullous pemphigoid. Arch Dermatol. 2000 Feb. 136 (2):174-8. [View Abstract]
  17. Kiss M, Perényi A, Marczinovits I, Molnár J, Dobozy A, Kemény L, et al. Autoantibodies to human alpha6 integrin in patients with bullous pemphigoid. Ann N Y Acad Sci. 2005 Jun. 1051:104-10. [View Abstract]
  18. Bekou V, Thoma-Uszynski S, Wendler O, Uter W, Schwietzke S, Hunziker T, et al. Detection of laminin 5-specific auto-antibodies in mucous membrane and bullous pemphigoid sera by ELISA. J Invest Dermatol. 2005 Apr. 124 (4):732-40. [View Abstract]
  19. Ujiie H, Shibaki A, Nishie W, Sawamura D, Wang G, Tateishi Y, et al. A novel active mouse model for bullous pemphigoid targeting humanized pathogenic antigen. J Immunol. 2010 Feb 15. 184 (4):2166-74. [View Abstract]
  20. Schachter M, Brieva JC, Jones JC, Zillikens D, Skrobek C, Chan LS. Pemphigoid nodularis associated with autoantibodies to the NC16A domain of BP180 and a hyperproliferative integrin profile. J Am Acad Dermatol. 2001 Nov. 45 (5):747-54. [View Abstract]
  21. Frezzolini A, Cianchini G, Ruffelli M, Cadoni S, Puddu P, De Pità O. Interleukin-16 expression and release in bullous pemphigoid. Clin Exp Immunol. 2004 Sep. 137 (3):595-600. [View Abstract]
  22. Echigo T, Hasegawa M, Shimada Y, Inaoki M, Takehara K, Sato S. Both Th1 and Th2 chemokines are elevated in sera of patients with autoimmune blistering diseases. Arch Dermatol Res. 2006 Jun. 298 (1):38-45. [View Abstract]
  23. Niimi Y, Pawankar R, Kawana S. Increased expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and matrix metalloproteinase-13 in lesional skin of bullous pemphigoid. Int Arch Allergy Immunol. 2006. 139 (2):104-13. [View Abstract]
  24. Asashima N, Fujimoto M, Watanabe R, Nakashima H, Yazawa N, Okochi H, et al. Serum levels of BAFF are increased in bullous pemphigoid but not in pemphigus vulgaris. Br J Dermatol. 2006 Aug. 155 (2):330-6. [View Abstract]
  25. Iwata Y, Komura K, Kodera M, Usuda T, Yokoyama Y, Hara T, et al. Correlation of IgE autoantibody to BP180 with a severe form of bullous pemphigoid. Arch Dermatol. 2008 Jan. 144 (1):41-8. [View Abstract]
  26. Di Zenzo G, Calabresi V, Olasz EB, Zambruno G, Yancey KB. Sequential intramolecular epitope spreading of humoral responses to human BPAG2 in a transgenic model. J Invest Dermatol. 2010 Apr. 130 (4):1040-7. [View Abstract]
  27. Iwata H, Kamio N, Aoyama Y, Yamamoto Y, Hirako Y, Owaribe K, et al. IgG from patients with bullous pemphigoid depletes cultured keratinocytes of the 180-kDa bullous pemphigoid antigen (type XVII collagen) and weakens cell attachment. J Invest Dermatol. 2009 Apr. 129 (4):919-26. [View Abstract]
  28. Marzano AV, Tedeschi A, Fanoni D, Bonanni E, Venegoni L, Berti E, et al. Activation of blood coagulation in bullous pemphigoid: role of eosinophils, and local and systemic implications. Br J Dermatol. 2009 Feb. 160 (2):266-72. [View Abstract]
  29. Wieland CN, Comfere NI, Gibson LE, Weaver AL, Krause PK, Murray JA. Anti-bullous pemphigoid 180 and 230 antibodies in a sample of unaffected subjects. Arch Dermatol. 2010 Jan. 146 (1):21-5. [View Abstract]
  30. Stausbøl-Grøn B, Deleuran M, Sommer Hansen E, Kragballe K. Development of bullous pemphigoid during treatment of psoriasis with adalimumab. Clin Exp Dermatol. 2009 Oct. 34 (7):e285-6. [View Abstract]
  31. Tan H, Chen X, Chen Y, Ou X, Yang T, Yan X. Immune checkpoint inhibitor-associated bullous pemphigoid: A retrospective and real-world study based on the United States Food and Drug Administration adverse event reporting system. J Dermatol. 2024 Oct 26. [View Abstract]
  32. Sowerby L, Dewan AK, Granter S, Gandhi L, LeBoeuf NR. Rituximab Treatment of Nivolumab-Induced Bullous Pemphigoid. JAMA Dermatol. 2017 Jun 1. 153 (6):603-605. [View Abstract]
  33. Rofe O, Bar-Sela G, Keidar Z, Sezin T, Sadik CD, Bergman R. Severe bullous pemphigoid associated with pembrolizumab therapy for metastatic melanoma with complete regression. Clin Exp Dermatol. 2017 Apr. 42 (3):309-312. [View Abstract]
  34. Lopez AT, Khanna T, Antonov N, Audrey-Bayan C, Geskin L. A review of bullous pemphigoid associated with PD-1 and PD-L1 inhibitors. Int J Dermatol. 2018 Jun. 57 (6):664-669. [View Abstract]
  35. Kridin K, Bergman R. Association of Bullous Pemphigoid With Dipeptidyl-Peptidase 4 Inhibitors in Patients With Diabetes: Estimating the Risk of the New Agents and Characterizing the Patients. JAMA Dermatol. 2018 Oct 1. 154 (10):1152-1158. [View Abstract]
  36. Muramatsu K, Zheng M, Yoshimoto N, Ito T, Ujiie I, Iwata H, et al. Regulatory T cell subsets in bullous pemphigoid and dipeptidyl peptidase-4 inhibitor-associated bullous pemphigoid. J Dermatol Sci. 2020 Oct. 100 (1):23-30. [View Abstract]
  37. Yang W, Cai X, Zhang S, Han X, Ji L. Dipeptidyl peptidase-4 inhibitor treatment and the risk of bullous pemphigoid and skin-related adverse events: A systematic review and meta-analysis of randomized controlled trials. Diabetes Metab Res Rev. 2021 Mar. 37 (3):e3391. [View Abstract]
  38. Stone C, Bak G, Oh D, Zhao C, Venugopal S, Kumar K, et al. Environmental triggers of pemphigus vulgaris and bullous pemphigoid: a case control study. Front Med (Lausanne). 2024. 11:1441369. [View Abstract]
  39. Langan SM, Smeeth L, Hubbard R, Fleming KM, Smith CJ, West J. Bullous pemphigoid and pemphigus vulgaris--incidence and mortality in the UK: population based cohort study. BMJ. 2008 Jul 9. 337 (7662):a180. [View Abstract]
  40. Gajic-Veljic M, Nikolic M, Medenica L. Juvenile bullous pemphigoid: the presentation and follow-up of six cases. J Eur Acad Dermatol Venereol. 2010 Jan. 24 (1):69-72. [View Abstract]
  41. Parker SR, Dyson S, Brisman S, Pennie M, Swerlick RA, Khan R, et al. Mortality of bullous pemphigoid: an evaluation of 223 patients and comparison with the mortality in the general population in the United States. J Am Acad Dermatol. 2008 Oct. 59 (4):582-8. [View Abstract]
  42. Cortés B, Marazza G, Naldi L, Combescure C, Borradori L, Autoimmune Bullous Disease Swiss Study Group. Mortality of bullous pemphigoid in Switzerland: a prospective study. Br J Dermatol. 2011 Aug. 165 (2):368-74. [View Abstract]
  43. Cugno M, Marzano AV, Bucciarelli P, Balice Y, Cianchini G, Quaglino P, et al. Increased risk of venous thromboembolism in patients with bullous pemphigoid. The INVENTEP (INcidence of VENous ThromboEmbolism in bullous Pemphigoid) study. Thromb Haemost. 2015 Aug 6. 114 (6):[View Abstract]
  44. Langan SM, Groves RW, West J. The relationship between neurological disease and bullous pemphigoid: a population-based case-control study. J Invest Dermatol. 2011 Mar. 131 (3):631-6. [View Abstract]
  45. Taghipour K, Chi CC, Bhogal B, Groves RW, Venning V, Wojnarowska F. Immunopathological characteristics of patients with bullous pemphigoid and neurological disease. J Eur Acad Dermatol Venereol. 2014 May. 28 (5):569-73. [View Abstract]
  46. Jedlickova H, Hlubinka M, Pavlik T, Semradova V, Budinska E, Vlasin Z. Bullous pemphigoid and internal diseases - A case-control study. Eur J Dermatol. 2010 Jan-Feb. 20 (1):96-101. [View Abstract]
  47. Zhou XP, Liu B, Xu Q, Yang Y, He CX, Zuo YG, et al. Serum levels of immunoglobulins G1 and G4 targeting the non-collagenous 16A domain of BP180 reflect bullous pemphigoid activity and predict bad prognosis. J Dermatol. 2016 Feb. 43 (2):141-8. [View Abstract]
  48. Liu YD, Wang YH, Ye YC, Zhao WL, Li L. Prognostic factors for mortality in patients with bullous pemphigoid: a meta-analysis. Arch Dermatol Res. 2017 Jul. 309 (5):335-347. [View Abstract]
  49. Bernard P, Reguiai Z, Tancrède-Bohin E, Cordel N, Plantin P, Pauwels C, et al. Risk factors for relapse in patients with bullous pemphigoid in clinical remission: a multicenter, prospective, cohort study. Arch Dermatol. 2009 May. 145 (5):537-42. [View Abstract]
  50. Koga H, Teye K, Ishii N, Ohata C, Nakama T. High Index Values of Enzyme-Linked Immunosorbent Assay for BP180 at Baseline Predict Relapse in Patients With Bullous Pemphigoid. Front Med (Lausanne). 2018. 5:139. [View Abstract]
  51. Holtsche MM, Goletz S, van Beek N, Zillikens D, Benoit S, Harman K, et al. Prospective study in bullous pemphigoid: association of high serum anti-BP180 IgG levels with increased mortality and reduced Karnofsky score. Br J Dermatol. 2018 Oct. 179 (4):918-924. [View Abstract]
  52. Bakker CV, Terra JB, Pas HH, Jonkman MF. Bullous pemphigoid as pruritus in the elderly: a common presentation. JAMA Dermatol. 2013 Aug. 149 (8):950-3. [View Abstract]
  53. Baykal C, Okan G, Sarica R. Childhood bullous pemphigoid developed after the first vaccination. J Am Acad Dermatol. 2001 Feb. 44 (2 Suppl):348-50. [View Abstract]
  54. Sun C, Chang B, Gu H. Non-bullous lesions as the first manifestation of bullous pemphigoid: a retrospective analysis of 24 cases. J Dermatolog Treat. 2009. 20 (4):233-7. [View Abstract]
  55. Chan LS, Dorman MA, Agha A, Suzuki T, Cooper KD, Hashimoto K. Pemphigoid vegetans represents a bullous pemphigoid variant. Patient's IgG autoantibodies identify the major bullous pemphigoid antigen. J Am Acad Dermatol. 1993 Feb. 28 (2 Pt 2):331-5. [View Abstract]
  56. Roussel A, Benichou J, Randriamanantany ZA, Gilbert D, Drenovska K, Houivet E, et al. Enzyme-linked immunosorbent assay for the combination of bullous pemphigoid antigens 1 and 2 in the diagnosis of bullous pemphigoid. Arch Dermatol. 2011 Mar. 147 (3):293-8. [View Abstract]
  57. Charneux J, Lorin J, Vitry F, Antonicelli F, Reguiai Z, Barbe C, et al. Usefulness of BP230 and BP180-NC16a enzyme-linked immunosorbent assays in the initial diagnosis of bullous pemphigoid: a retrospective study of 138 patients. Arch Dermatol. 2011 Mar. 147 (3):286-91. [View Abstract]
  58. Pfaltz K, Mertz K, Rose C, Scheidegger P, Pfaltz M, Kempf W. C3d immunohistochemistry on formalin-fixed tissue is a valuable tool in the diagnosis of bullous pemphigoid of the skin. J Cutan Pathol. 2010 Jun. 37 (6):654-8. [View Abstract]
  59. Joly P, Roujeau JC, Benichou J, Picard C, Dreno B, Delaporte E, et al. A comparison of oral and topical corticosteroids in patients with bullous pemphigoid. N Engl J Med. 2002 Jan 31. 346 (5):321-7. [View Abstract]
  60. Spivey J, Nye AM. Bullous pemphigoid: corticosteroid treatment and adverse effects in long-term care patients. Consult Pharm. 2013 Jul. 28 (7):455-62. [View Abstract]
  61. Balakirski G, Alkhateeb A, Merk HF, Leverkus M, Megahed M. Successful treatment of bullous pemphigoid with omalizumab as corticosteroid-sparing agent: report of two cases and review of literature. J Eur Acad Dermatol Venereol. 2016 Oct. 30 (10):1778-1782. [View Abstract]
  62. Sinha S, Agrawal D, Sardana K, Kulhari A, Malhotra P. Complete Remission in a Patient with Treatment Refractory Bullous Pemphigoid after a Single Dose of Omalizumab. Indian Dermatol Online J. 2020 Jul-Aug. 11 (4):607-611. [View Abstract]
  63. Abdat R, Waldman RA, de Bedout V, Czernik A, Mcleod M, King B, et al. Dupilumab as a novel therapy for bullous pemphigoid: A multicenter case series. J Am Acad Dermatol. 2020 Jul. 83 (1):46-52. [View Abstract]
  64. Planella-Fontanillas N, Bosch-Amate X, Jiménez Antón A, Moreno-Vílchez C, Guerrero MG, Del Mar Blanes Martínez M, et al. Real-World Evaluation of the Effectiveness and Safety of Dupilumab in Bullous Pemphigoid: An Ambispective Multicenter Case Series. Br J Dermatol. 2024 Oct 17. [View Abstract]
  65. Ahmed AR, Spigelman Z, Cavacini LA, Posner MR. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med. 2006 Oct 26. 355 (17):1772-9. [View Abstract]
  66. Dupuy A, Viguier M, Bédane C, Cordoliani F, Blaise S, Aucouturier F, et al. Treatment of refractory pemphigus vulgaris with rituximab (anti-CD20 monoclonal antibody). Arch Dermatol. 2004 Jan. 140 (1):91-6. [View Abstract]
  67. Morrison LH. Therapy of refractory pemphigus vulgaris with monoclonal anti-CD20 antibody (rituximab). J Am Acad Dermatol. 2004 Nov. 51 (5):817-9. [View Abstract]
  68. Reguiaï Z, Tchen T, Perceau G, Bernard P. [Efficacy of rituximab in a case of refractory bullous pemphigoid]. Ann Dermatol Venereol. 2009 May. 136 (5):431-4. [View Abstract]
  69. Peterson JD, Chan LS. Effectiveness and side effects of anti-CD20 therapy for autoantibody-mediated blistering skin diseases: A comprehensive survey of 71 consecutive patients from the Initial use to 2007. Ther Clin Risk Manag. 2009 Feb. 5 (1):1-7. [View Abstract]
  70. Schmidt E, Seitz CS, Benoit S, Bröcker EB, Goebeler M. Rituximab in autoimmune bullous diseases: mixed responses and adverse effects. Br J Dermatol. 2007 Feb. 156 (2):352-6. [View Abstract]
  71. Schulze J, Bader P, Henke U, Rose MA, Zielen S. Severe bullous pemphigoid in an infant--successful treatment with rituximab. Pediatr Dermatol. 2008 Jul-Aug. 25 (4):462-5. [View Abstract]
  72. Shetty S, Ahmed AR. Treatment of bullous pemphigoid with rituximab: critical analysis of the current literature. J Drugs Dermatol. 2013 Jun 1. 12 (6):672-7. [View Abstract]
  73. Lamberts A, Euverman HI, Terra JB, Jonkman MF, Horváth B. Effectiveness and Safety of Rituximab in Recalcitrant Pemphigoid Diseases. Front Immunol. 2018. 9:248. [View Abstract]
  74. Li X, Zhang L, Gu H, He W, Zhai Z, Zhang M. Treatment and molecular analysis of bullous pemphigoid with tofacitinib: a case report and review of current literature. Front Immunol. 2024. 15:1464474. [View Abstract]
  75. [Guideline] Humphrey MB, Russell L, Danila MI, Fink HA, Guyatt G, Cannon M, et al. 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Rheumatol. 2023 Dec. 75 (12):2088-2102. [View Abstract]
  76. Barrick BJ, Ida CM, Laniosz V, Jentoft ME, Sominidi-Damodaran S, Wieland CN, et al. Bullous Pemphigoid, Neurodegenerative Disease, and Hippocampal BP180 Expression: A Retrospective Postmortem Neuropathologic Study. J Invest Dermatol. 2016 Oct. 136 (10):2090-2092. [View Abstract]
  77. Albadri Z, Thorslund K, Häbel H, Seifert O, Grönhagen C. Increased Risk of Squamous Cell Carcinoma of the Skin and Lymphoma Among 5,739 Patients with Bullous Pemphigoid: A Swedish Nationwide Cohort Study. Acta Derm Venereol. 2020 Oct 14. 100 (17):adv00289. [View Abstract]

Direct immunofluorescence study performed on perilesional skin biopsy specimen from patient with bullous pemphigoid detects linear band of IgG deposit along dermoepidermal junction.

Indirect immunofluorescence study performed on salt-split normal human skin substrate with serum from patient with bullous pemphigoid detects IgG-class circulating autoantibodies binding to epidermal (roof) side of skin basement membrane.

Direct immunofluorescence study performed on perilesional skin biopsy specimen from patient with bullous pemphigoid detects linear band of IgG deposit along dermoepidermal junction.

Indirect immunofluorescence study performed on salt-split normal human skin substrate with serum from patient with bullous pemphigoid detects IgG-class circulating autoantibodies binding to epidermal (roof) side of skin basement membrane.

Direct immunofluorescence study performed on perilesional skin biopsy specimen from patient with bullous pemphigoid detects linear band of IgG deposit along dermoepidermal junction.

Indirect immunofluorescence study performed on salt-split normal human skin substrate with serum from patient with bullous pemphigoid detects IgG-class circulating autoantibodies binding to epidermal (roof) side of skin basement membrane.