Photodistributed Toxic Epidermal Necrolysis

This case report describes a patient with photodistributed Stevens-Johnson syndrome and toxic epidermal necrolysis and highlights similarities to other cases reported in the literature.

Key Points

Question

What are the key characteristics of reported cases of photodistributed Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)?

Findings

Including the present case, a literature review found 9 reported cases of photodistributed SJS/TEN with known drug exposure followed by a substantial UV radiation (UVR) exposure event. Of these, the majority were reported in young women, and all but 1 case reported substantial UVR exposure 24 to 72 hours prior to onset of rash.

Meaning

The present case and cases in the literature reviewed herein suggest that UVR exposure may be associated with the development of SJS/TEN in a subset of young women.

Abstract

Importance

Cases of photodistributed Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been infrequently reported since the first documented case in 1989. This emerging clinical entity and its underlying mechanism have yet to be fully characterized.

Objective

To report a case of photodistributed SJS/TEN and highlight similarities to other cases reported in the literature.

Design, Setting, and Participants

Case report and literature review of published cases of photodistributed SJS/TEN. The case report describes a 29-year-old woman with recent lamotrigine and trimethoprim-sulfamethoxazole exposure who developed TEN in a photodistributed pattern 1 day after prolonged sun exposure. A search of PubMed using the keywords toxic epidermal necrolysis, Stevens-Johnson syndrome, photo-distributed, photo-induced, and sun-exposed was performed to identify other cases reported in the literature.

Results

Literature review revealed 8 previously reported cases of healthy individuals with known drug and UV radiation (UVR) exposures who subsequently developed SJS or TEN with photodistribution. Cases reviewed were skewed demographically to young women aged 19 to 48 years (8 of 9 patients) with all cases reporting UVR exposure 24 to 72 hours prior to the onset of symptoms.

Conclusions and Relevance

Photodistributed TEN has been increasingly described in the literature and may represent a distinct variant of SJS/TEN. While the pathogenesis remains unclear, the role of UVR as a “second hit” is suggested by the data presented in the cases documented thus far.

Introduction

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions characterized by painful skin detachment and mucosal erosions. Considered an extreme manifestation of a cytotoxic type IV delayed hypersensitivity, the majority of cases report a new drug exposure 1 to 8 weeks before the onset of the rash.¹ Cases of photodistributed TEN have been infrequently described.

Methods

We present a case of TEN with photodistribution in an otherwise healthy individual with known drug exposure. We also conducted a review of the current literature through PubMed using the keywords toxic epidermal necrolysis, Stevens-Johnson syndrome, photo-distributed, photo-induced, and sun-exposed.

Results

Report of a Case

A 29-year-old woman with history of bipolar 2 disorder who recently initiated treatment with lamotrigine (17 days prior) and trimethoprim-sulfamethoxazole (15 days prior) was admitted to the burn intensive care unit with 6 days of progressive rash, fever, dysuria, and dysphagia. The day before rash onset, she developed a sunburn on all sun-exposed skin after spending a day at the pool in a 2-piece bathing suit. She reported having no history of lupus erythematosus or manifestations of autoimmune disorders.

On admission, she presented with erythematous to dusky patches on her face, trunk, and extremities, with areas of confluent epidermal detachment and positive Nikolsky sign totaling 15% body surface area (BSA). There were sharply demarcated areas of sparing of her chest, back, buttocks, and pubic region in a 2-piece bathing suit distribution (Figure 1A and B). Further evaluation confirmed oral, esophageal, ocular, and vaginal mucosal involvement (Figure 1C). Laboratory evaluation revealed normal glucose level (117 mg/dL; to convert to mmol/L, multiply by 0.0555), normal blood urea nitrogen level (10 mg/dL; to convert to mmol/L, multiply by 0.357), normal bicarbonate level (25.0 mEq/L; to convert to mmol/L, multiply by 1.0), transaminitis (aspartate aminotransferase, 919 U/L; alanine aminotransferase, 1008 U/L; to convert to μkat/L, multiply by 0.0167), slight leukopenia (white blood cell count, 3400/μL; reference range: 4500-11 000/μL; to convert to ×10⁹/L, multiply by 0.001), and normal creatinine level (0.52 mg/dL; to convert to μmol/L, multiply by 76.25). A punch biopsy of her left thigh showed vacuolar interface with near–full-thickness epidermal necrosis and sparse inflammation, consistent with a diagnosis of TEN (Figure 2). She had a Severity-of-Illness Score for Toxic Epidermal Necrolysis of 1 on admission given BSA of greater than 10% involvement. During the course of the patient’s admission, detachment of skin progressed to 30% BSA, and she required intubation for airway protection. She received a 14-day course of cyclosporine (5 mg/kg/d for 7 days followed by 2.5 mg/kg/d for 7 days) as well as amniotic membrane grafting for significant ocular involvement. She was discharged on hospital day 21 with notable improvement at 2-week follow-up.

Figure 1. Photodistributed Toxic Epidermal Necrolysis.

Photodistributed toxic epidermal necrolysis with stark sparing of the bathing suit regions of the chest, back, buttocks, and pubis, and prominent mucositis with oral, esophageal, ocular, and vaginal mucosal involvement.

Figure 2. Punch Biopsy of Left Thigh .

Punch biopsy of left thigh with hematoxylin-eosin staining. A, Detached necrotic epidermis with vacuolar interface changes extending down a hair follicle with comparatively sparse inflammation. B, Detached epidermis with numerous necrotic keratinocytes with overlying basket weave orthokeratosis reflecting rapid onset of this process. C, Vacuolar interface changes with sparse inflammation are easily observed in the follicular epithelium.

Review of Literature

Review of the literature revealed 8 cases of photodistributed SJS and/or TEN in patients with a reported significant UV radiation (UVR) exposure event from 1989 to 2021 (Table^{2,3,4,5,6,7,8,9}). We found in the literature review that, when combined with the present case, 8 of 9 cases occurred in women aged 19 to 48 years. The time elapsed between UVR exposure and rash onset ranged from 24 to 72 hours, and all had known drug exposures within 1 to 8 weeks of rash onset. Histopathology patterns varied but consistently demonstrated epidermal necrosis at the basal layer with minimal inflammation and lack of mucin deposition.

Table. Clinical Characteristics of Previously Reported Cases of Photo-Induced Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN).

Source	Age/race/sex	Offending drug(s)	Time from drug exposure to rash onset	UVR exposure typea	Time from sun exposure to rash onset	SJS/TEN	Mucosal involvement	Treatment
Ortel et al,2 1989	12-y-old White male	Chloroquine, sulfadoxine-pyrimethamine	4 wk	Sun	72 h	SJS	Oral, ocular, genital	Dexamethasone, unspecified course
Moghaddam and Connolly,3 2014	19-y-old Female	Ciprofloxacin (C) and fluconazole (F)	11 d (C), 1 d (F)	Sun	48 h	SJS	Oral, genital	Prednisone, 60 mg × 7 d, no taper
Gatson et al,4 2011	22-y-old White female	Ibuprofen	5 d	Tanning bed	24 h	TEN	Ocular, genital	Cyclosporine × 2 d, IVIG × 3 d
Russomanno et al,5 2021	22-y-old White female	Lamotrigine	2 wk	Tanning bed	72 hb	TEN	Oral, ocular	Cyclosporine × 5 d
Redondo et al,6 1996	23-y-old White female	Clobazam	12 d	Sun	36 h	TEN	Oral, genital	Pentoxifylline, 900 mg/d
Callaly et al,7 2008	29-y-old White female	Hydroxychloroquine	Chronic use	Sun	72 h	TEN	Oral, ocular, genital	Supportive care only
Borrás-Blasco et al,8 2003	34-y-old White male	Sulfasalazine	2 mo	Sun	72 h	SJS	Oral, genital	Prednisone, 60 mg × 7 d, no taper
Eloranta et al,9 2016	48-y-old White female	Itraconazole	4 d	Sun	24 hc	SJS	Oral, ocular	Oral steroids (NOS) × 21 d
Current case	29-y-old White female	Lamotrigine (L) and TMP-SMX	17 d (L), 15 d (TMP-SMX)	Sun exposure	24 h	TEN	Oral, ocular, esophageal, genital	Cyclosporine × 14 d

Abbreviations: IVIG, intravenous immunoglobulin; NOS, not otherwise specified; TMP-SMX, trimethoprim-sulfamethoxazole; UVR, UV radiation.

^a As reported by patient.

^b Patient had used tanning beds daily and stopped 3 days before rash onset.

^c Patient had exposure for 3 days in a row and on the fourth day developed a rash.

Discussion

The consistent timing (24-72 hours) between UVR exposure and onset of rash supports its role as a trigger or potentiator of TEN in sun-exposed areas; however, the precise mechanism of this phenomenon is elusive. Similar but distinct eruptions that could be considered in the differential diagnosis include phototoxic drug eruption and recall reaction. Although a purely phototoxic drug reaction could present similarly in the initial stages, the subsequent extensive mucositis seen in the present patient and similar cases would argue strongly against this as a primary mechanism. A drug-induced sunburn recall phenomenon is also an unlikely mechanism because the patients in this series had a preceding UVR exposure in close temporal relationship (24-72 hours) to the rash onset.

Some authors have proposed that UVR may act as an accelerator, or “second hit,” for patients whose keratinocytes have previously been primed by an offending drug leading to an elaboration of inflammatory cytokines from exposed cells.^4,5,6 It is possible that this initial robust local reaction evolves into a systemic response leading to more classic TEN manifestations, particularly mucositis. However, this mechanism does not explain why photoprotected skin so often remains unaffected. Previous studies have highlighted the potential pathogenic role of tumor necrosis factor-α in both TEN and sunburn as a common pathway for photodistributed TEN^4,5,6,10; however, such a link remains speculative, particularly as the exact pathogenesis of TEN has not been well substantiated.

Limitations

The generalizability of these findings is limited by the small number of cases reported. The lack of standardization of reported variables among published cases makes it challenging to draw conclusions about the pathogenesis of this condition.

Conclusions

Photodistributed TEN has been increasingly described in the literature and may represent a growing variant of SJS/TEN. While the pathogenesis for photodistributed TEN is unclear, the role of UVR as a “second hit” is suggested by the data presented in the cases documented thus far.