Spectrum of Nail Sequelae in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Abstract

This case series documents the incidence of various nail changes as sequalae to Stevens-Johnson syndrome/toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) constitute a spectrum of severe cutaneous adverse drug reactions characterized by differing extents of cutaneous detachment. There is growing recognition that survivors experience various sequelae with long-term morbidity. Finger and toenail deformities have been observed in up to 50% of patients^1,2,3; however, the spectrum of these changes has yet to be clearly established. We seek to document the incidence of various nail changes as sequalae to SJS/TEN.

Methods

This case series study was conducted from January 1, 2014, through December 31, 2018, at the Singapore General Hospital. The study was approved by the SingHealth Centralised Institutional Review Board, and written informed consent was obtained from patients. Patients who were treated for SJS, SJS/TEN overlap, or TEN during the study period were included. Diagnosis and classification of epidermal necrolysis was based on established clinical criteria with supportive histologic evidence. Patients received supportive care and immunomodulatory therapy during the acute episode and were followed up at 6 weeks after discharge. Relevant clinical information and photographic documentation of cutaneous and nail involvement were collected throughout the acute course and follow-up.

Results

A total of 39 patients were included: 14 (36%) with SJS, 15 (38%) with SJS/TEN overlap, and 10 (26%) with TEN. Etiologic agents included allopurinol (n = 9, 23%), antiepileptics (n = 6, 15%), omeprazole (n = 6, 15%), antibiotics (n = 4, 10%), and sulfonamides (n = 4, 10%). There were 21 male (54%) and 18 female (46%) patients with a mean (SD) age of 50 (19) years.

At follow-up, 27 (69%) patients were found to have chronic nail changes not present during the acute phase. These appeared to correlate with disease classification: 5 (35%) with SJS, 12 (80%) with overlap, and 10 (100%) with TEN. The most common nail deformities were Beau lines (n = 14, 35%), onychomadesis (n = 11, 28%), and distal dyschromia of the nail plate (n = 7, 18%). Other findings included onycholysis, onychorrhexis, anonychia, erythronychia, onychoschizia, pterygium, koilonychia, and oil-drop sign (Table and Figure). During the acute phase of the disease, 10 patients (33%) developed periungual bullae, and 8 of them (80%) went on to develop permanent sequalae of onychomadesis/anonychia.

Table. Chronic Nail Sequelae in Patients.

Sequela	Frequency, No. (%)
	Total (n = 39)	SJS (n = 14)	SJS/TEN (n = 15)	TEN (n = 10)
Total No. with nail changes	27 (69)	5 (36)	12 (80)	10 (100)
Beau lines	14 (36)	3 (21)	6 (40)	5 (50)
Onychomadesis	11 (28)	2 (14)	5 (33)	4 (40)
Distal yellow dyschromia	7 (18)	2 (14)	4 (27)	1 (10)
Onychoschizia	5 (13)	0	3 (20)	2 (20)
Onycholysis	4 (10)	3 (21)	1 (7)	0
Permanent anonychia	3 (8)	0	2 (13)	1 (10)
Onychorrhexis	2 (5)	1 (7)	0	1 (10)
Erythronychia	2 (5)	0	2 (13)	0
Pterygium	2 (5)	0	1 (7)	1 (10)
Koilonychia	1 (3)	0	0	1 (10)
Oil-drop sign	1 (3)	0	1 (7)	0

Abbreviations: SJS, Stevens-Johnson syndrome, TEN, toxic epidermal necrolysis.

Figure. Chronic Nail Changes and Sequential Nail Changes.

A, Beau lines in the nail plates of both hands. B, Onychomadesis of the left second to fifth digits. Beau lines in the nail plates of the left thumb, right thumb, and right second to fifth digits. Distal yellow dyschromia is also seen on the right fourth digit. C, Onychoschizia, early pterygium formation, and erythronychia of the nail plate. D, Nailfold bullae with multiple vesicles during the acute phase. During follow-up of the patient pictured in panel D, nailfold hyperpigmentation with onychomadesis and anonychia (E) and anonychia of the fifth digit with gradual regrowth of dystrophic nail plate (F).

Discussion

These findings show that the burden of nail complications in SJS/TEN survivors may be significantly higher, affecting up to 70% of patients compared with prior studies with reported incidence of 10% to 50%.^2,3 These range from mild changes such as Beau lines to cosmetically disabling sequelae of onychomadesis and anonychia. We believe that the spectrum of nail complications is a representation of the varying extents and patterns of nail matrix damage that occurs during the acute phase of SJS/TEN. Beau lines arise from a partial arrest of the nail matrix⁴; onychomadesis arises from complete arrest⁴; erythronychia arises from focal loss of matrix function⁵; and onychoschizia and onychorrhexis arise from defective nail plate production with impairment of intercellular adhesions owing to nail matrix dysfunction.⁶

A novel observation was the presence of distal yellow dyschromia, which occurred in 18% of patients. We postulate that this distal dyschromia arises owing to the retardation of nail growth during the acute phase of the disease, analogous to yellow nail syndrome. We also observed that periungual bullae during the acute phase may predict for severe nail changes, such as onychomadesis and anonychia. There are limitations of the study—notably, the small sample size and the potential for referral bias.

In conclusion, our study adds to the growing literature on the burden of SJS/TEN and demonstrates the spectrum of its nail complications. This highlights the urgency to identify interventions to prevent such complications and/or treat them when they occur.