Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the elderly, mediated by autoantibodies against BP180 and BP230 hemidesmosomal proteins (1, 2). The resulting complement activation and inflammatory cascade lead to dermal–epidermal separation and tense bulla formation.

Several drugs have been linked to BP (diuretics, antibiotics, neuroleptics), but DPP-4 inhibitors used in Type 2 Diabetes Mellitus (T2DM) have emerged as important offenders (3–5). DPP-4 inhibition disturbs immune homeostasis and eosinophilic activity, precipitating autoantibody formation (4).

This case series describes eight patients from R.G. Kar Medical College and Hospital, Kolkata, who developed BP after gliptin use, adding to limited Indian pharmacovigilance data.

OBJECTIVES

• To report eight cases of drug-induced Bullous Pemphigoid associated with gliptin therapy.
  • To highlight vildagliptin and teneligliptin use in T2DM patients as emerging offenders in Indian patients.

METHODS

Eight T2DM patients who developed BP during gliptin therapy were referred from the Department of Endocrinology to the Clinical Pharmacology and Therapeutics OPD and evaluated in the Department of Pharmacology, R.G. Kar Medical College and Hospital.

Diagnosis was confirmed by clinical features, histopathology, and direct immunofluorescence (DIF). All cases were reported to the Adverse Drug Reaction Monitoring Centre (AMC) under PvPI before causality assessment using the WHO–UMC and Naranjo scales (6, 7).

RESULTS

Eight patients (4 males, 4 females; mean age 63 years) presented with bullous lesions during gliptin-based dual oral antidiabetic therapy. Six were on vildagliptin, two on teneligliptin. Lesions involved the trunk and limbs, sparing mucosa. Mean HbA1c 7.7%. Histopathology showed subepidermal blisters with eosinophilic infiltrates; DIF demonstrated linear IgG and C3 deposits. Withdrawal of gliptin with systemic corticosteroids (Prednisolone 30-40 mg/day), topical steroids and antihistamines resulted in remission within 1-3 weeks. No relapses occurred over 3months follow-up. All cases were rated “probable.”

Table 1. Clinical Profile of Gliptin-Associated Drug-Induced Bullous Pemphigoid (n = 8)

DISCUSSION

DPP-4 inhibitors have been increasingly implicated in drug-induced Bullous Pemphigoid (1–5). The consistent latency, typical histopathology, and recovery after gliptin withdrawal support causality. All the cases were treated with Systemic & topical Corticosteroids and anti-histamines.

Pharmacovigilance context: Global databases, including WHO–UMC and EudraVigilance, contain >1,000 ICSRs linking vildagliptin and ~400 ICSRs implicating teneligliptin (3, 5). Our eight cases reported through AMC–PvPI align with these signals and strengthen regional evidence.

Pathophysiology: DPP-4 (CD26) modulates immune regulation and cytokine balance; its inhibition disrupts T-cell function and promotes eosinophil-mediated inflammation and autoantibody generation (4). Vildagliptin’s lipophilicity may enhance this effect (5).

Clinical relevance: Given the extensive use of gliptins in India, clinicians should maintain a high index of suspicion for Bullous Pemphigoid in diabetic patients presenting with new bullous eruptions. Prompt discontinuation of the suspected gliptin generally leads to remission.

Limitations and Future Directions

Small sample size and absence of BP180/BP230 antibody testing were limitations. Larger, multicentric studies with genetic profiling are needed to define risk factors for gliptin-induced BP in Indian patients.

CONCLUSION

Vildagliptin and Teneligliptin, though effective for T2DM management, can act as offenders causing drug-induced Bullous Pemphigoid. Early recognition, drug withdrawal, and systemic and topical corticosteroid therapy ensure recovery. Pharmacovigilance reporting via AMC–PvPI is vital for signal detection and safe drug use.

Declarations

Funding: None
Conflict of Interest: None declared
Ethical Approval: Institutional Ethics Committee approval obtained
Patient Consent: Written informed consent obtained

Acknowledgements

The authors sincerely acknowledge the Departments of Dermatology and Endocrinology, R.G. Kar Medical College and Hospital, Kolkata, for their support in diagnosis and management. The authors also thank Mr. Abhik Saha, Pharmacovigilance Associate, Adverse Drug Reaction Monitoring Centre (AMC–PvPI), R.G. Kar Medical College and Hospital, for assistance in ADR reporting and data compilation and acknowledge NCC, PvPI.

REFERENCES

1. Pasmatzi E, Monastirli A, Habeos J, Georgiou S, Tsambaos D. DPP-4 inhibitors cause bullous pemphigoid. Diabetes Care. 2011;34(8):e133.
2. Saha M, Bandyopadhyay M, Mandal A, et al. Bullous pemphigoid associated with DPP-4 inhibitors. Natl J Physiol Pharm Pharmacol. 2024;14(9):249–53.
3. Varpuluoma O, Försti AK, Jokelainen J, et al. Vildagliptin increases risk of bullous pemphigoid. J Invest Dermatol. 2018;138(7):1659–61.
4. Tasanen K, Varpuluoma O, Nishie W. DPP-4 inhibitor-associated bullous pemphigoid: mechanisms and clinical features. Front Immunol. 2019;10:1238.
5. Plaquevent M, Tétart F, Ingen-Housz-Oro S, et al. Association between DPP-4 inhibitors and bullous pemphigoid: a pharmacovigilance study. Br J Dermatol. 2019;180(5):1099–1100.
6. World Health Organization. The use of the WHO–UMC system for standardized case causality assessment. Uppsala Monitoring Centre; 2018.
7. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239–45.