Long-term sequelae from Stevens-Johnson syndrome/toxic epidermal necrolysis in a large retrospective cohort

To the Editor: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare, severe drug reaction associated with significant mortality.1Hsu D.Y. Brieva J. Silverberg N.B. Silverberg J.I. Morbidity and mortality of Stevens-Johnson syndrome and toxic epidermal necrolysis in United States adults.J Invest Dermatol. 2016; 136: 1387-1397Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar Although the reaction itself is self-limited, associated morbidity may last well beyond the initial hospitalization. However, little is known about the frequency and risk factors associated with long-term SJS/TEN-related sequelae.2Yang C. Cho Y. Chen K. Chen Y. Song H. Chu C. Long-term sequelae of Stevens-Johnson syndrome/toxic epidermal necrolysis.Acta Derm Venereol. 2016; 96: 525-529Crossref PubMed Scopus (53) Google Scholar,3Gueudry J. Roujeau J.-C. Binaghi M. Soubrane G. Muraine M. Risk factors for the development of ocular complications of Stevens-Johnson Syndrome and toxic epidermal necrolysis.Arch Dermatol. 2009; 145: 157-162Crossref PubMed Scopus (123) Google Scholar We analyzed a large, multicenter, retrospective cohort of 368 adult patients with SJS/TEN from the United States.4Micheletti R.G. Chiesa-Fuxench Z. Noe M.H. et al.Stevens-Johnson syndrome/toxic epidermal necrolysis: a multicenter retrospective study of 377 adult patients from the United States.J Invest Dermatol. 2018; 138: 2315-2321Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar Of 314 patients known to survive to hospital discharge, 150 (47.8%) had information available regarding postdischarge follow-up. Of these, there was no mention of SJS/TEN-related sequelae in 54.7% (82/150), and long-term sequelae were noted in the remaining 45.3% (68/150), characterized as ocular, cutaneous, gastrointestinal, genital, renal, pulmonary, or other. Sequelae were reported to be severe in 15.3% (23/150) of patients (Table I). Ocular sequelae were most common (20.6%, 31/150), followed by cutaneous (19.3%, 29/150), genital (5.3%, 8/150), oral (4.0%, 6/150), renal (2.0%, 3/150), and gastrointestinal (0.67%, 1/150). Other sequelae not fitting into these categories included depression, anxiety, chronic pain, tinnitus, and limb amputations.Table IFrequency of long-term sequelae among survivors of SJS/TENCharacteristicsData available (N = 150)Any sequelae (n = 68, 45.3%)No sequelae (n = 82, 54.7%)P valueSevere sequelae∗Severe sequelae: presence of severe sequelae involving any individual body surface/organ system. Severe ocular sequelae: symblepharon, scarring, blindness; Severe oral sequelae: gingival inflammation, oral pain. Severe genital sequelae: dyspareunia, adhesions, stenosis. Severe cutaneous sequelae: severe dyspigmentation or scarring. Severe renal sequelae: end-stage renal disease, ongoing dialysis. Severe gastrointestinal sequelae: esophageal strictures. (n = 23, 15.3%)Mild sequelae†Mild sequelae: presence of sequelae other than severe. (n = 45, 30.0%)No sequelae (n = 82, 54.7%)P valueAge, years, median (IQR)42.5 (26.0-56.9)39.6 (26.7-57.1)43.6 (25.4-56.6).6438.56 (22.6-46.6)43.26 (28.3-57.40)43.6 (25.4-56.6).28Female sex, n/total (%)82/150 (54.7)42/68 (61.8)40/82 (48.7).1114/23 (60.9)28/45 (62.2)40/82 (48.7).28White, n/total (%)71/150 (47.3)28/68 (41.1)43/82 (52.4).177/23 (30.4)21/45 (46.7)43/82 (52.4).17Black, n/total (%)46/150 (30.7)23/68 (33.8)23/82 (28.0).4511/23 (47.8)12/45 (26.7)23/82 (28.0).80Asian, n/total (%)21/150 (14.0)10/68 (14.7)11/82 (13.4).823/23 (13.0)7/45 (15.6)11/82 (13.4).94Hispanic, n/total (%)6/150 (4.0)2/68 (2.94)4/82 (4.87).550/23 (0.0)2/25 (8.0)4/82 (4.89).41Median % BSA, admission (IQR)10 (5-30)20 (10-30)9 (5-20)<.0130 (13-30)20 (10, 30)9 (5-20)<.01Median % BSA, maximum (IQR)19 (7.5-30)30 (15-60)9.5 (5-25)<.0150 (30-75)20 (10-40)9.5 (5-25)<.01Median SCORTEN (IQR)1 (1-2)2 (1-3)1 (1-2).042 (1-2)2 (1-3)1 (1-2).09Severe ocular involvement, n/total (%)‡Severe ocular involvement: presence of adhesions, synechiae, need for active ophthalmologic management such as lysis of synechiae, placement of amniotic membranes.19/150 (12.7)17/68 (25.0)2/82 (2.44)<.0112/23 (52.2)5/45 (11.1)2/82 (2.44)<.01Severe oral involvement, n/total (%)§Severe oral involvement: presence of severe oral erosions, need for nasogastric tube, intubation for airway management.51/150 (34.0)32/68 (47.1)19/82 (23.2)<.0118/23 (78.3)14/45 (31.1)19/82 (23.2)<.01Severe genitourinary involvement, n/total (%)ǁSevere genitourinary involvement: presence of severe erosions, adhesions, need for active genitourinary management such as lysis of adhesions, vaginal dilator, catheter placement.19/150 (12.7)11/68 (16.2)8/82 (9.76).247/23 (30.4)4/45 (8.89)8/82 (9.76).02Drug cause, n/total (%)136/150 (90.7)63/68 (92.6)73/82 (89.0).4523/23 (100.0)40/45 (91.1)73/82 (89.0).25Infection cause, n/total (%)14/150 (9.33)4/68 (5.88)10/82 (12.2).190/23 (0.0)4/45 (8.89)10/82 (12.2).20Days from symptom onset to admission, mean (95% CI)3.8 (2.7-4.9)3.7 (2.9-4.5)3.9 (2.1-5.8).962.3 (1.7-3.0)4.4 (3.2-5.6)3.9 (2.1-5.8).03Days from symptom onset to dermatology consult, mean (95% CI)4.8 (3.9-5.7)4.4 (3.5-5.2)5.2 (3.6-6.7).503.0 (2.2-3.9)5.0 (3.8-6.2)5.2 (3.6-6.7).04Days from symptom onset to diagnosis, mean (95% CI)4.7 (4.0-5.3)4.5 (3.6,-5.3)4.8 (3.8-5.9).653.0 (2.2-3.9)5.2 (4.1-6.4)4.8 (3.8-5.9)<.01Days from symptom onset to drug d/c, mean (95% CI)0.8 (07-0.8)0.8 (0.7-0.9)0.8 (0.7-0.9).350.9 (0.7-1.0)0.8 (0.6-0.9)0.8 (0.7-0.9).63BSA, Body surface area; CI, confidence interval; d/c, discontinuation; IQR, interquartile range; SCORTEN, Score of Toxic Epidermal Necrosis; SJS/TEN, Stevens-Johnson syndrome/toxic epidermal necrolysis.∗ Severe sequelae: presence of severe sequelae involving any individual body surface/organ system. Severe ocular sequelae: symblepharon, scarring, blindness; Severe oral sequelae: gingival inflammation, oral pain. Severe genital sequelae: dyspareunia, adhesions, stenosis. Severe cutaneous sequelae: severe dyspigmentation or scarring. Severe renal sequelae: end-stage renal disease, ongoing dialysis. Severe gastrointestinal sequelae: esophageal strictures.† Mild sequelae: presence of sequelae other than severe.‡ Severe ocular involvement: presence of adhesions, synechiae, need for active ophthalmologic management such as lysis of synechiae, placement of amniotic membranes.§ Severe oral involvement: presence of severe oral erosions, need for nasogastric tube, intubation for airway management.ǁ Severe genitourinary involvement: presence of severe erosions, adhesions, need for active genitourinary management such as lysis of adhesions, vaginal dilator, catheter placement. Open table in a new tab BSA, Body surface area; CI, confidence interval; d/c, discontinuation; IQR, interquartile range; SCORTEN, Score of Toxic Epidermal Necrosis; SJS/TEN, Stevens-Johnson syndrome/toxic epidermal necrolysis. At the time of initial hospitalization, 12.7% (19/150) of patients had severe ocular SJS/TEN, and 34.0% (51/150) had severe oral SJS/TEN. Such patients, as well as those with higher median body surface area involvement, were at increased risk of long-term sequelae, including sequelae characterized as severe (all P < .01). Patients with severe genitourinary SJS/TEN (12.7%, 19/150) were also at risk of severe long-term sequelae (P = .02) (Table I). There was no association between age, sex, or race and the risk of long-term sequelae in this cohort. SJS/TEN cause/trigger and days from symptom onset to hospital admission, dermatology consultation, diagnosis, and drug discontinuation also were not associated with development of SJS/TEN-related sequelae. These data suggest that long-term SJS/TEN-related sequelae are relatively common and frequently severe, corroborating rates of previously reported sequelae in SJS/TEN. Higher acuity of SJS/TEN at the time of initial presentation—specifically, the presence of severe mucosal disease and higher total body surface area involvement—predicts the development of long-term SJS/TEN-related sequelae. This study is limited by its retrospective nature, which obscures a detailed accounting of the specific features of patient sequelae and almost certainly underestimates their prevalence, because information on sequelae was determined via retrospective chart review rather than prospective systematic evaluation and was not available for all patients. Because all patients were managed by dermatology hospitalists at academic referral centers, results may not be fully generalizable. Future studies should prospectively evaluate the long-term sequelae of patients with SJS/TEN as an important marker of disease outcome and treatment efficacy. Clinicians should be aware of the potential for long-term complications among SJS/TEN survivors.