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 Table of Contents  
Year : 2018  |  Volume : 30  |  Issue : 4  |  Page : 427-431

Drug-induced bullous pemphigoid – a case report with review

1 Department of Oral Medicine and Radiology, Mar Baselios Dental College, Kothamangalam, Ernakulam, Kerala, India
2 Department of Oral and Maxillofacial Surgery, Mar Baselios Dental College, Kothamangalam, Ernakulam, Kerala, India
3 Department of Oral and Maxillofacial Pathology, Mar Baselios Dental College, Kothamangalam, Ernakulam, Kerala, India

Date of Submission30-Jun-2018
Date of Acceptance20-Nov-2018
Date of Web Publication17-Jan-2019

Correspondence Address:
Dr. Kamala Rawson
Department of Oral Medicine and Radiology, Mar Baselios Dental College, Kothamangalam, Ernakulam, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiaomr.jiaomr_126_18

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

Keywords: Autoimmune disease, bullous pemphigoid, corticosteroids

How to cite this article:
Rawson K, Vinod S, Sreenivasan B, Roy G. Drug-induced bullous pemphigoid – a case report with review. J Indian Acad Oral Med Radiol 2018;30:427-31

How to cite this URL:
Rawson K, Vinod S, Sreenivasan B, Roy G. Drug-induced bullous pemphigoid – a case report with review. J Indian Acad Oral Med Radiol [serial online] 2018 [cited 2019 Jun 26];30:427-31. Available from: http://www.jiaomr.in/text.asp?2018/30/4/427/250247

   Introduction Top

Bullous pemphigoid (BP) is an acquired autoimmune disease that affects mainly the elderly people and is characterized by subepidermal blistering.[1] The incidence is between 0.2 and 3 per 100,000 person years. Pemphigus vulgaris (PV) is more commonly encountered than BP in India. It affects elderly individuals in the fifth to seventh decade of life, with an average age of onset being 65 years. BP in childhood has been reported from various countries including India. There is no known ethnic, racial, or sexual predilection.[2]

Although in most cases the causative agent remains unidentified, certain medications have been implicated in the pathogenesis of the disease. The drug-induced variant of BP follows the oral or (sometimes) topical administration of specific drugs. It is difficult to differentiate clinically from classic BP and must always be considered as a possible diagnosis in elderly patients who have recently changed or added a new drug in their normal medication regimen.[1]

A wide range of drugs especially furosemide, nonsteroidal anti-inflammatory drugs (NSAIDs; ibuprofen), captopril, phenacetin, penicillamine, etarnacept, and systemic antibiotics have been associated with BP.[1],[2]

   Case Report Top

A 63-year-old female patient reported to the Department of Oral Medicine and Radiology, with chief complaint of pain and bleeding gums since 5 months. She also complained of burning sensation to hot and spicy food. She had noticed blisters on mouth, scalp, face, shoulder, hands, and feet which were ruptured and formed ulcers since 5 days. Medical history revealed that she is a known diabetic for which she is taking a drug (vildagliptin) since 5 months along with insulin. Personal history and family history were noncontributory. On general physical examination, all vital signs were within the normal limits.

Extraoral examination of the head and neck revealed erythematous areas on the right and left shoulder, preauricular area, flexor surface of legs, arms, and on the scalp [Figure 1]. Ruptured blister with alopecia was noted on the scalp [Figure 2]. Multiple ulcers were present on trunk back [Figure 3], shoulder, arms, and legs. Recently, ruptured vesicles on back and extremities showed serum discharge. Intraoral examination revealed fluid-filled blisters and desquamation of gingiva with erosive areas involving interdental papilla, marginal gingiva, and attached gingiva [Figure 4]. Bleeding from marginal gingiva was noted [Figure 5]. In upper gingiva, linear erythematous area with superficial necrotic slough and in lower gingiva diffuse swollen erythematous area with central ulceration were noted. Other parts of oral cavity were free from ulceration. Hence, on the basis of history and clinical examination, a provisional diagnosis of PV was given with a differential diagnosis of drug-induced BP, erosive lichen planus, chronic desquamative gingivitis, and cicatricial pemphigoid.
Figure 1: Blister in the pretragal area with multiple papular eruptions on face

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Figure 2: Ruptured blister with alopecia noted on scalp

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Figure 3: Ruptured eroded area noted on trunk back

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Figure 4: Desquamation of gingiva with erosive areas involving interdental papilla, marginal gingiva and attached gingiva

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Figure 5: Bleeding from marginal gingiva irt 44

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Incisional biopsy was done including perilesional area from gingiva. Histopathological report came as BP. The given hematoxylin and eosin–stained soft tissue section showed parakeratinized stratified squamous epithelium with subepithelial split. Basal cells were intact with surface epithelium. Areas of subepithelial inflammatory cell infiltrate were seen particularly lymphocytes. Connective tissue showed bundles of collagen fibers with vascular channels and areas of extravasated RBCs [Figure 6]. Direct immunofluorescence (DIF) was done for a confirmatory diagnosis. DIF features were favoring BP.
Figure 6: The given H/E stained soft tissue section shows parakeratinised stratified squamous epithelium with subepithelial split

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Management was done by giving 20 mg of tab prednisolone twice daily for 1 week, and subsequently the dose was reduced to 10 mg twice daily for the next 2 weeks. Oral lesion was managed with tab betamethasone 0.5 mg for swish and spit once daily. For dermal lesions, we prescribed ointment Clonate-F cream (clobetasol and fusidic acid topical) to be applied twice daily along with discontinuation of vildagliptin. Her blood sugar level was under normal range which was managed by insulin. Systemic steroids were tapered and discontinued after 3 weeks. For oral and dermal lesion, tab betamethasone and Clonate-F cream were continued. After 1 month of medication, the extraoral lesions were healed and intraoral ulcerations subsided [Figure 7], [Figure 8], [Figure 9], [Figure 10].
Figure 7: Post medication after 1 month- Partial healing of oral lesions

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Figure 8: Post medication after 1 month- Bleeding subsided

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Figure 9: Post medication after 1 month- Healing lesions on trunk back

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Figure 10: Post medication after 1 month- Partial healing lesion on scalp

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   Discussion Top

BP, which is the most common of the subepithelial blistering diseases, occurs chiefly in adults older than 60 years of age. It is self-limited and may last from a few months to 5 years. BP may be a cause of death in older debilitated individuals.[3]


BP is an autoimmune disease caused by the binding of autoantibodies to specific antigens found in the lamina lucida region of the basement membrane on the hemidesmosomes of epithelial basal cells. These antigens are glycoproteins referred to as BP antigens, BP 230 (BPAg1) and BP 180 (BPAg2, COL17). Binding of antibody to antigen activates both leukocytes and complement, causing localized damage to the basement membrane, resulting in vesicle formation in the subepithelial region. BPAg1 is a cytoplasmic protein involved in the anchorage of intermediate filaments to the cytoskeleton. BPAg2 is a transmembrane adhesion molecule with several collagenous extracellular domains. Antibodies to BPAg2 appear to be important in subepidermal blister formation. BPAg1 may have a secondary role, and its exact function in the pathogenesis is not fully defined. Autoantibodies against alpha 6 integrin and laminin-5, two other skin basement membrane components, have also been identified in BP.[2],[3]

Precipitating factors

The precipitating factors include ultraviolet (UV) light, either UVB or psoralen with ultraviolet A (PUVA), radiation therapy, percutaneous endoscopic gastrostomy, thermal burn, amputation stump, incisional hernia scar, injection, or an adhesive dressing. BP has also been reported in association with other autoimmune diseases such as diabetes mellitus and pernicious anemia, chronic inflammatory skin diseases such as lichen planus and psoriasis, and various malignancies.[4]

Drugs associated with bullous pemphigoid

Since drug-induced BP was first reported in 1970 in an 11-year-old boy receiving salicylazosulphapyridine,[5] multiple drugs have been implicated in the pathogenesis of the disease[6]. Medications that have been associated with BP-like disease include furosemide, NSAIDs (ibuprofen), antidiabetics like vildagliptin, sitagliptin, and tolbutamide, captopril, phenacetin, penicillamine, etarnacept, and systemic antibiotics. Tibolone (a selective tissue estrogenic activity regulator that has progestogenic, some androgenic and estrogenic effects) induced BP.[2]

Clinical manifestations

Lesions usually appear as tense bullae on normally appearing skin, or (more uncommonly) on an erythematous or even urticarial base. They may be accompanied by erythema multiforme type of lesions such as target lesions on palms and soles.[1] Nikolsky sign can be positive in some cases.[1],[4] It chiefly involves the scalp, abdomen, extremities, axilla, and groin. Patients with BP may experience one episode or recurrent bouts of lesions.[3] The bullae are usually filled with clear fluid but may be hemorrhagic. There is rarely oral and ocular mucosal involvement. The bullae usually heal with postinflammatory pigmentary changes, and there is no scarring or milia formation.[2]

BP of childhood is rare. The age of onset in childhood BP varied from 2.5 months to 14 years. Childhood BP often follows a benign course, with disease duration of <1 year.[2]

Oral findings

Oral involvement can be seen in 10%–20% of patients with BP. The oral lesions of BP are smaller, form more slowly, and are less painful than those seen in PV; the often extensive labial involvement seen in PV is not present. Desquamative gingivitis has also been reported as the most common oral manifestation of BP, and the gingival lesions may be the only site of oral involvement. The gingival lesions consist of generalized edema, inflammation, and desquamation with localized areas of discrete vesicle formation.[3]

Differential diagnosis

Differential diagnosis includes erosive form of lichen planus, PV, and other subepithelial bullous dermatoses. The erosive and ulcerative forms of lichen planus frequently exhibit white Wickham striae at the periphery along with ulcerations and erosions. PV usually has more extensive erosion of mucosa and skin involvement. The other subepithelial bullous dermatoses appear clinically similar to BP and can only be distinguished by immunofluorescent and molecular techniques.[3]

Laboratory investigations

Routine histology of a biopsy specimen demonstrates separation of the epithelium from the connective tissue at the basement membrane zone and an inflammatory infiltrate that is usually rich in eosinophils, particularly in skin biopsies.

DIF study of a biopsy specimen taken from perilesional inflamed tissue demonstrates deposition of IgG and C3 bound in a linear band to the basement membrane[3] [Figure 11]. Indirect immunoflourescence study of serum obtained from patients with BP demonstrates IgG antibodies bound to the epidermal aspect using the salt-split skin technique. The salt-split skin test is particularly useful in distinguishing BP from cicatricial pemphigoid and epidermolysis bullosa acquisita that has IgG antibodies localized to the dermal side of the salt-split skin (floor of the blister)[3] [Figure 12].
Figure 11: Direct immunofluorescence analysis of lesional skin, showing linear deposition of immunoglobulinG at the dermal–epidermal junction

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Figure 12: Immunofluorescence analysis using 1 mol/L sodium chloride split skin as a substrate, showing linear deposition of immunoglobulin G on the roof side of the separation at the dermal–epidermal junction

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Direct and indirect immunoelectron microscopy ultrastructurally localizes in vivo-bound IgG autoantibodies to the binding site at the basement membrane.[2] Immunoblotting or Western blotting demonstrates reactivity of IgG in the sera of patients with BP, with proteins extracted from healthy human skin. The sensitivity of immunoblotting varies.[2] Immunoprecipitation also demonstrates reactivity with BP230 and BP180. Unlike immunoblotting, immunoprecipitation is performed with native rather than denatured protein and is more sensitive.[2] Enzyme-linked immunosorbent assay analyzes the BP antigen-specific IgG autoantibodies in the patients' sera using various lengths of recombinant proteins of the BPAg1 or BPAg2 antigens.[2]


Patients with localized oral lesions of BP may be treated with high-potency topical steroids, such as clobetasol or betamethasone.[3],[7],[8] Patients with more extensive disease require use of systemic corticosteroids alone or combined with immunosuppressive drugs such as azathioprine, cyclophosphamide, mycophenolate, or rituximab.[3],[7],[8] Patients with moderate levels of disease may minimize the use of systemic steroids by the use of dapsone or tetracycline, doxycycline, or minocycline, which may be combined with niacinamide.[3],[7],[8]

   Conclusion Top

In everyday clinical practice, the differential diagnosis of drug-induced BP can prove to be quite difficult. The recent history of received medications and the histopathological picture of the disease can set a possible diagnosis. After withdrawal of a suspect medication, most patients respond rapidly to treatment and do not experience relapses of the condition. In the future, as new therapies emerge, the number of drugs thought to cause BP will probably increase. Therefore, more studies are needed to identify those regimens that are more commonly associated with drug-induced BP and those patients who are more prone to develop the condition.[1]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

StavropoulosPG, Soura E, Antoniou C. Drug-induced pemphigoid: A review of the literature. J Eur Acad Dermatol Venereol 2014;28:1133-40.  Back to cited text no. 1
Khandpur S, Verma P. Bullous pemphigoid. Indian J Dermatol Venereol Leprol 2011;77:450-5.  Back to cited text no. 2
[PUBMED]  [Full text]  
Glick M. Burket's Oral Medicine. 12th ed; 2015. p. 82-3.  Back to cited text no. 3
Bean SF, Good RA, Windhorst DB. Bullous pemphigoid in an 11-year old boy. Arch Dermatol 1970;102:205-8.  Back to cited text no. 4
Vassileva S. Drug-induced pemphigoid: Bullous and cicatricial. Clin Dermatol 1998;16:379-87.  Back to cited text no. 5
Soni AG. Nikolsky's sign – A clinical method to evaluate damage at epidermal-dermal junction. J Indian Acad Oral Med Radiol 2018;30:68-72.  Back to cited text no. 6
  [Full text]  
Fontaine J. Treatment of bullous pemphigoid. J Dermatol 2003;30:83-90.  Back to cited text no. 7
Wojnarowska F. Guidelines for the management of bullous pemphigoid. Br J Dermatol 2002;147:214-21.  Back to cited text no. 8


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12]


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