Pirfenidone induced Steven-Johnson syndrome/Toxic epidermal necrolysis: 1st case report

Pirfenidone is a novel orally administered drug used for idiopathic pulmonary fibrosis (IPF) and recently in systemic sclerosis associated lung disease.² It has antifibrotic, anti-inflammatory and antioxidant actions by inhibition of TGF-β and TNF-α. It is known to cause photosensitivity and cutaneous rash as side effects but this was the 1^st case report of Steven-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN) due to the drug reported in IJDVL.

A 78-year-old woman presented with a 24 hour history of a pruriginous cutaneous rash with odynophagia and photophobia. She was started on pirfenidone two weeks ago for IPF. On cutaneous examination there were multiple erythematous macules, papules with few vesicles distributed over the trunk and proximal extremities. Mucosal examination revealed intense conjunctival hyperemia with pseudomembranes and extensive erosions on the buccal and palatal surfaces. Histopathology revealed full-thickness epidermal necrosis with a minimal lymphocytic infiltrate in the dermis consistent with the diagnosis of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) related to pirfenidone.

Patient was managed in a burns centre with contact isolation and topical antibiotic to avoid superinfection. Pirfenidone was stopped and subcutaneous etanercept 25 mg twice a week was initiated. The patient required a three-month stay in the ICU until complete resolution of both cutaneous and mucosal lesions. Etanercept administration was maintained until the end of therapy.

In conclusion a serious possibility of SJS/TEN due to pirfenidone should be kept in mind as its use has been increasing in the recent times. Also though there is less evidence etanercept could be an effective treatment for SJS/TEN.³

Source-

1. de Perosanz-Lobo D, Fernández-Nieto D, Burgos-Blasco P, Aroca-Ruiz M, Fernández-Guarino M. Stevens-Johnson syndrome/toxic epidermal necrolysis induced by pirfenidone. Indian J Dermatol Venereol Leprol 2021;87:542-4.
2. Acharya N, Sharma SK, Mishra D, Dhooria S, Dhir V, Jain S. Efficacy and safety of pirfenidone in systemic sclerosis-related interstitial lung disease-a randomised controlled trial. Rheumatol Int. 2020 May;40(5):703-710. doi: 10.1007/s00296-020-04565-w. Epub 2020 Apr 1. PMID: 32239322.
3. Creamer D, Walsh SA, Dziewulski P, Exton LS, Lee HY, Dart JKG, Setterfield J, Bunker CB, Ardern-Jones MR, Watson KMT, Wong GAE, Philippidou M, Vercueil A, Martin RV, Williams G, Shah M, Brown D, Williams P, Mohd Mustapa MF, Smith CH. UK guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016. J Plast Reconstr Aesthet Surg. 2016 Jun;69(6):e119-e153. doi: 10.1016/j.bjps.2016.01.034. PMID: 27287213.