Antituberculous Therapy-Induced Rare Skin Toxicity: Bullous Pemphigoid

Abstract

Bullous pemphigoid (BP) is an autoimmune blistering disorder rarely triggered by antituberculous therapy (ATT). A 56-year-old diabetic female developed extensive fluid-filled blisters 72 h after initiating first-line ATT. Skin biopsy and immunofluorescence confirmed BP. ATT was stopped, and treatment with systemic and topical steroids resulted in clinical improvement. Although ATT is known for a wide range of adverse effects, BP is an extremely rare but serious dermatologic toxicity. Early identification and withdrawal of the offending drug are crucial.

INTRODUCTION

Bullous pemphigoid (BP) is the most frequently encountered autoimmune subepidermal blistering disorder, typically affecting elderly individuals. It presents with intensely pruritic urticarial plaques that evolve into tense bullae, primarily over the trunk and extremities.[1] The disease is characterized histologically by subepidermal blister formation with an eosinophil-rich infiltrate, and direct immunofluorescence revealing linear deposits of Immunoglobulin G (IgG) and complement component 3 (C3) along the basement membrane zone.[2]

While most cases of BP are idiopathic, a growing number of medications have been implicated as potential triggers. Drugs such as dipeptidyl peptidase-4 inhibitors, aldosterone antagonists, neuroleptics, and certain antibiotics have been associated with the onset of drug-induced BP.[3] Among these, first-line antituberculous therapy (ATT)—particularly isoniazid and rifampicin—has been rarely linked to BP, with only a limited number of cases reported in the literature.[4]

Early identification of drug-induced BP is critical, especially in patients on polypharmacy or those receiving long-term antimicrobial therapy. The condition can be challenging to differentiate from idiopathic BP due to overlapping clinical and histopathological features.[5] This case highlights a rare instance of BP induced by first-line ATT, underscoring the need for heightened clinical suspicion and prompt intervention.

CASE HISTORY

A 56-year-old diabetic woman presented with fever and cough for one month. While the sputum cartridge-based nucleic acid amplification test (CBNAAT) was negative for Mycobacterium tuberculosis, high-resolution computed tomography (HRCT) showed findings suggestive of pulmonary tuberculosis. She was started on first-line ATT (isoniazid, rifampicin, pyrazinamide, ethambutol).

Within 72 h, the patient developed multiple tense, fluid-filled blisters over the body, leading to ATT discontinuation. Despite stopping therapy, the lesions worsened, prompting hospital referral. Examination showed extensive blistering over the neck, back, arms, and legs [Figure 1]. Oral mucosa was spared, Nikolsky’s sign was negative, and the Bulla spread sign was positive.

Figure 1.

Clinical presentation

INVESTIGATIONS

• Blood Work: Leukocytosis (13,070 cells/mm³), eosinophilia (13.3%), thrombocytosis (5.07 lakh/mm³), normal renal and hepatic functions.

• Skin Biopsy: Subepidermal blistering with eosinophil-rich infiltrate [Figure 2 up].

• Direct Immunofluorescence: Linear deposition of IgG and C3 on basement membrane [Figure 2 down].

• Imaging: HRCT—tree-in-bud opacities, bilateral consolidation suggesting endobronchial spread.

• Bronchoscopy and bronchoalveolar lavage (BAL): Negative for M. tuberculosis, sterile cultures.

Figure 2.

Investigations

DIAGNOSIS

Antituberculous therapy-induced bullous pemphigoid

Treatment

The patient was managed with intravenous (IV) antibiotics, IV antihistamines, and topical corticosteroids, followed by systemic steroids. Skin lesions improved significantly during the hospital stay.

Outcome and follow-up

The patient was discharged on systemic steroids with outpatient follow-up advice but was subsequently lost to follow-up.

DISCUSSION

BP is a chronic autoimmune blistering disorder that may occasionally present as a drug-induced reaction. While numerous medications such as diuretics, antipsychotics, and dipeptidyl peptidase-4 (DPP-4) inhibitors have been implicated, antitubercular drugs like isoniazid and rifampicin are rarely reported as causative agents.[6] In drug-induced BP, the clinical presentation closely mimics idiopathic BP, and diagnosis often requires correlating the timing of drug exposure with symptom onset.[7]

The pathogenesis involves autoantibody formation against hemidesmosomal proteins, leading to complement activation and dermoepidermal separation. In the context of ATT, these immunologic responses may be triggered by drug metabolites acting as haptens.[8] Early recognition and discontinuation of the offending agent are essential to prevent disease progression. In many cases, as observed here, withdrawal of the suspected drug combined with systemic or topical corticosteroids results in favorable outcomes.[9]

Our case also met the criteria for a probable adverse drug reaction using both the Naranjo and World Health Organization (WHO) – Uppsala Monitoring Centre (UMC) scales, supporting a causal link with ATT.[10] Given the widespread use of ATT in tuberculosis-endemic regions, clinicians should maintain a high index of suspicion for rare but serious cutaneous adverse effects such as BP to ensure timely diagnosis and management.

Learning points

• BP may be a rare but serious adverse reaction to first-line ATT.

• Prompt recognition and drug withdrawal can prevent complications.

• Physicians should consider drug-induced causes in sudden blistering eruptions post-ATT initiation.

Patient perspective

“This illness was one of the most disabling experiences of my life. I looked at myself in disbelief. Due to the blisters, I felt stigmatized and avoided public interactions. With my doctors’ help, I’m recovering and feel hopeful again.”

Key message

Clinicians must be aware of rare dermatologic toxicities, such as bullous pemphigoid (BP), associated with first-line ATT to ensure early diagnosis and prevent progression.

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.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.