Pyrazinamide-induced Toxic Epidermal Necrolysis

Abstract

The antitubercular drugs are associated with different cutaneous adverse drug reactions. Toxic epidermal necrolysis (TEN) is a severe form of cutaneous reaction. Although it is rare, it carries a high mortality rate. We report a case of a 75-year-old man with abdominal tuberculosis, who developed pyrazinamide-induced TEN.

CASE REPORT

A 75-year-old man presented with complaints of painful oral ulcers and multiple skin lesions for 6 days. There was no history of fever or joint pain. He has been taking antitubercular therapy consisting of rifampicin, isoniazid, ethambutol, and pyrazinamide for 3 weeks since he was diagnosed with abdominal tuberculosis. On physical examination, he had tachycardia with a heart rate of 126 beats/min. He had multiple erosive lesions in the buccal mucosa. The cutaneous lesions included multiple erythematous purpuric macules which coalesced to form sheets of erythematous patches over the trunk, upper limbs, and lower limbs. There was also the formation of bullae, some of which had excoriated [Figure 1]. The scrotal skin was also eroded. Other systemic examinations were unremarkable. The laboratory investigations, including complete hemogram, liver function tests, and kidney function tests were within normal limits except for a hemoglobin level of 10 g/dl and a serum sodium level of 128 meq/L. Wound culture did not grow any pathogenic organisms. Histopathological examination of the skin biopsy specimen showed subepidermal splitting and full-thickness epidermal necrosis with perivascular lymphocytic infiltration. A diagnosis of toxic epidermal necrolysis (TEN) was made. All antitubercular drugs (ATDs) were withheld. He was treated with supportive management such as intravenous fluids, cutaneous wound care, ocular care, and pain management. He responded well to the ongoing management and the lesions started to heal within 10 days. To identify the culprit agent, oral provocation was done with sequential reintroduction of ATDs. In this case, pyrazinamide was found to be the inciting agent. Hence, the antitubercular therapy was modified replacing pyrazinamide with levofloxacin.

Figure 1.

The photograph showing the presence of multiple erythematous purpuric macules on the back (a), the macules coalesced to form sheets of erythematous patches on the lower limbs. There is also the presence of excoriated bullae (b)

DISCUSSION

ATDs can cause a diverse variety of cutaneous adverse reactions ranging from mild pruritus to severe forms like drug reaction with eosinophilia and systemic symptoms, Stevens–Johnson syndrome, TEN, bullous fixed drug eruption, lichenoid drug eruption, and acute generalized exanthematous pustulosis.[1] TEN is a severe form of epidermolytic reaction that results in the separation of the skin at the dermo-epidermal junction leading to the formation of bullae and subsequent sloughing out of the affected skin area. It is a rare and potentially life-threatening dermatologic emergency with a mortality of up to 48%.[2] TEN has been associated with all the first-line ATDs such as rifampicin, isoniazid, ethambutol, and pyrazinamide as well as various second-line ATDs such as fluoroquinolone, aminoglycosides, linezolid, and cycloserine. Oral drug provocation test remains the gold standard in the establishment of causal relationships. Temporary suspension of all potentially culprit ATDs followed by sequential oral rechallenge of the drugs helps to identify the drug of concern.[3]

Declaration of patient consent

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

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.