Hanyang Med Rev.  2016 Aug;36(3):174-181. 10.7599/hmr.2016.36.3.174.

Ocular Manifestations of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

• Kang MH

• KMID: 2350368
• DOI: http://doi.org/10.7599/hmr.2016.36.3.174

Abstract

Steven-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and sometimes life-threatening hypersensitivity mucocutaneous disease triggered mostly by medication and infections Major involving tissues are the mucous membranes of oral, gastrointestinal, respiratory, integument, and gynecologic tissues. Even after recovering from skin problems without sequelae, survivors can have serious ocular complications leading to blindness despite local and systemic therapy. There is no definite effective systemic and local treatment for SJS/TEN. Early detection and aggressive treatment are important for the long-term prognosis of the eye. Eyelid margin and palpebral conjunctiva and fornix should be checked thoroughly to detect the cicatrical changes that make chronic ocular surface failure such as limbal cell deficiency and complete ocular surface keratinization. Amniotic membrane transplantation and cultivated oral mucosal graft are beneficial to reduce the risk of ocular surface failure.

Keyword

Stevens-Johnson Syndrome; Toxic Epidermal Necrolysis; Limbal Cell Deficiency, Cicatrical Keratinization; Amniotic Membrane Transplantation

MeSH Terms

Amnion
Blindness
Conjunctiva
Eyelids
Humans
Hypersensitivity
Mucous Membrane
Prognosis
Skin
Stevens-Johnson Syndrome*
Survivors
Transplants

Figure

• 

  Fig. 1 Subacute/chronic phase Steven-Johnson syndrome. Both eyes show the superficial punctate erosion of more than half of the ocular surface. Lid margins show the irregularity of the mucocutaneous junction and keratin deposition (A, C: right eye, B, D: left eye).

• 

  Fig. 2 Infrared photography of the meibomian gland. In the chronic phase of Steven-Johnson syndrome, both eyelid show diffuse shortening and total loss of meibomian gland acinus and atrophy of ductal opening (White dot lines show the borderlines of meibomian gland, A, C: right eye, B, D: left eye).

Reference

1. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007; 5:75–92.

2. Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, Wolkenstein P. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol. 2000; 115:149–153.

3. Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau J. CLinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol. 1993; 129:92–96.

4. Nickoloff BJ. Saving the skin from drug-induced detachment. Nat Med. 2008; 14:1311–1313.

5. Hsu DY, Brieva J, Silverberg NB, Silverberg JI. Morbidity and mortality of Stevens-Johnson syndrome and toxic epidermal necrolysis in united states adults. J Invest Dermatol. 2016.

6. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature. 2004; 486.

7. Halevy S, Ghislain PD, Mockenhaupt M, Fagot JP, Bouwes Bavinck JN, Sidoroff A, et al. Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel. J Am Acad Dermatol. 2008; 58:25–32.

8. Lee HS, Ueta M, Kim MK, Seo KY, Sotozono C, Kinoshita S, et al. Analysis of ocular manifestation and genetic association of allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in South Korea. Cornea. 2016; 35:199–204.

9. Miliszewski MA, Kirchhof MG, Sikora S, Papp A, Dutz JP. Stevens-Johnson syndrome and toxic epidermal necrolysis: an analysis of triggers and implications for improving prevention. Am J Med. 2016.

10. Ueta M, Kaniwa N, Sotozono C, Tokunaga K, Saito Y, Sawai H, et al. Independent strong association of HLA-A^*02:06 and HLA-B^*44:03 with cold medicine-related Stevens-Johnson syndrome with severe mucosal involvement. Sci Rep. 2014; 4:4862.

11. Kohanim S, Palioura S, Saeed HN, Akpek EK, Amescua G, Basu S. Stevens-Johnson syndrome/toxic epidermal necrolysis--a comprehensive review and guide to therapy. I. Systemic Disease. Ocul Surf. 2016; 14:2–19.

12. Friedmann PS, Strickland I, Pirmohamed M, Park B. INvestigation of mechanisms in toxic epidermal necrolysis induced by carbamazepine. Arch Dermatol. 1994; 130:598–604.

13. Saeed HN, Chodosh J. Immunologic mediators in Stevens-Johnson syndrome and toxic epidermal necrolysis. Semin Ophthalmol. 2016; 31:85–90.

14. French LE, Tschopp J. Protein-based therapeutic approaches targeting death receptors. Cell Death Differ. 2003; 10:117–123.

15. Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D, et al. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science. 1998; 282:490–493.

16. Chang HY, Cooper ZA, Swetter SM, Marinkovich MP. Kinetics and Specificity of fas ligand induction in toxic epidermal necrolysis. Arch Dermatol. 2004; 140:242–244.

17. Gaultier F, Ejeil AL, Igondjo-Tchen S, Dohan D, Dridi SM, Maman L, et al. Possible involvement of gelatinase A (MMP2) and gelatinase B (MMP9) in toxic epidermal necrolysis or Stevens-Johnson syndrome. Arch Dermatol Research. 2004; 296:220–225.

18. Chave TA, Mortimer NJ, Sladden MJ, Hall AP, Hutchinson PE. Toxic epidermal necrolysis: current evidence, practical management and future directions. Br J Dermatol. 2005; 153:241–253.

19. Nassif A, Moslehi H, Le Gouvello S, Bagot M, Lyonnet L, Michel L, et al. Evaluation of the potential role of cytokines in toxic epidermal necrolysis. J Invest Dermatol. 2004; 123:850–855.

20. Posadas SJ, Padial A, Torres MJ, Mayorga C, Leyva L, Sanchez E, et al. Delayed reactions to drugs show levels of perforin, granzyme B, and Fas-L to be related to disease severity. J Allergy Clin Immunol. 2002; 109:155–161.

21. Patz A. Ocular involvement in erythema multiforme. Arch Ophthal. 1950; 43:244–256.

22. Howard GM. The Stevens-Johnson syndrome. Ocular prognosis and treatment. Am J Ophthalmol. 1963; 55:893–900.

23. Lopez-Garcia JS, Rivas Jara L, Garcia-Lozano CI, Conesa E, de Juan IE, Murube del Castillo J. Ocular features and histopathologic changes during follow-up of toxic epidermal necrolysis. Ophthalmology. 2011; 118:265–271.

24. Power WJ, Ghoraishi M, Merayo-Lloves J, Neves RA, Foster CS. Analysis of the acute ophthalmic manifestations of the erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease spectrum. Ophthalmology. 1995; 102:1669–1676.

25. Basu S, Pillai VS, Sangwan VS. Mucosal complications of modified osteo-odonto keratoprosthesis in chronic Stevens-Johnson syndrome. Am J Ophthalmol. 2013; 156:867–873.e2.

26. Isawi H, Dhaliwal DK. Corneal melting and perforation in Stevens Johnson syndrome following topical bromfenac use. J Cataract Refract Surg. 2007; 33:1644–1646.

27. Sachdev R, Bansal S, Sinha R, Sharma N, Titiyal JS. Bilateral microbial keratitis in highly active antiretroviral therapy-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: a case series. Ocul Immunol Inflamm. 2011; 19:343–345.

28. Di Pascuale MA, Espana EM, Liu DT-S, Kawakita T, Li W, Gao YY, et al. Correlation of corneal complications with eyelid cicatricial pathologies in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis syndrome. Ophthalmology. 2005; 112:904–912.

29. Iyer G, Pillai VS, Srinivasan B, Guruswami S, Padmanabhan P. Mucous membrane grafting for lid margin keratinization in Stevens-Johnson syndrome: results. Cornea. 2010; 29:146–151.

30. Sotozono C, Ang LP, Koizumi N, Higashihara H, Ueta M, Inatomi T, et al. New grading system for the evaluation of chronic ocular manifestations in patients with Stevens-Johnson syndrome. Ophthalmology. 2007; 114:1294–1302.

31. Sotozono C, Ueta M, Koizumi N, Inatomi T, Shirakata Y, Ikezawa Z, et al. Diagnosis and treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis with ocular complications. Ophthalmology. 2009; 116:685–690.

32. Jain R, Sharma N, Basu S, Iyer G, Ueta M, Sotozono C, et al. Stevens-Johnson syndrome: the role of an ophthalmologist. Surv Ophthalmol. 2016.

33. Tseng SC, Di Pascuale MA, Liu DT, Gao YY, Baradaran-Rafii A. Intraoperative mitomycin C and amniotic membrane transplantation for fornix reconstruction in severe cicatricial ocular surface diseases. Ophthalmology. 2005; 112:896–903.

34. Shay E, Kheirkhah A, Liang L, Sheha H, Gregory DG, Tseng SC. Amniotic membrane transplantation as a new therapy for the acute ocular manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis. Surv Ophthalmol. 2009; 54:686–696.

35. Wall V, Yen MT, Yang MC, Huang AJ, Pflugfelder SC. Management of the late ocular sequelae of Stevens-Johnson syndrome. Ocul Surf. 2003; 1:192–201.

36. Chang YS, Huang FC, Tseng SH, Hsu CK, Ho CL, Sheu HM. Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis: acute ocular manifestations, causes, and management. Cornea. 2007; 26:123–129.

37. Kaido M, Yamada M, Sotozono C, Kinoshita S, Shimazaki J, Tagawa Y, et al. The relation between visual performance and clinical ocular manifestations in Stevens-Johnson syndrome. Am J Ophthalmol. 2012; 154:499–511.e1.

38. Sotozono C, Ueta M, Nakatani E, Kitami A, Watanabe H, Sueki H, et al. Predictive factors associated with acute ocular involvement in Stevens-Johnson syndrome and toxic epidermal necrolysis. Am J Ophthalmol. 2015; 160:228–237.e2.

39. Catt CJ, Hamilton GM, Fish J, Mireskandari K, Ali A. Ocular manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis in children. Am J Ophthalmol. 2016.

40. Kim DH, Yoon KC, Seo KY, Lee HS, Yoon SC, Sotozono C, et al. The role of systemic immunomodulatory treatment and prognostic factors on chronic ocular complications in Stevens-Johnson syndrome. Ophthalmology. 2015; 122:254–264.

41. Morales ME, Purdue GF, Verity SM, Arnoldo BD, Blomquist PH. Ophthalmic manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis and relation to SCORTEN. Am J Ophthalmol. 2010; 150:505–510.e1.

42. Yip LW, Thong BY, Lim J, Tan AW, Wong HB, Handa S, et al. Ocular manifestations and complications of Stevens-Johnson syndrome and toxic epidermal necrolysis: an Asian series. Allergy. 2007; 62:527–531.

43. Saeed H, Mantagos IS, Chodosh J. Complications of Stevens-Johnson syndrome beyond the eye and skin. Burns. 2016; 42:20–27.

44. De Rojas MV, Dart JK, Saw VP. The natural history of Stevens Johnson syndrome: patterns of chronic ocular disease and the role of systemic immunosuppressive therapy. Br J Ophthalmol. 2007; 91:1048–1053.

45. Dodiuk-Gad RP, Chung WH, Valeyrie-Allanore L, Shear NH. Stevens-Johnson syndrome and toxic epidermal necrolysis: an update. Am J Clin Dermatol. 2015; 16:475–493.

46. Yamane Y, Matsukura S, Watanabe Y, Yamaguchi Y, Nakamura K, Kambara T, et al. Retrospective analysis of Stevens-Johnson syndrome and toxic epidermal necrolysis in 87 Japanese patients--Treatment and outcome. Allergol Int. 2016; 65:74–81.

47. Shay E, Khadem JJ, Tseng SC. Efficacy and limitation of sutureless amniotic membrane transplantation for acute toxic epidermal necrolysis. Cornea. 2010; 29:359–361.

48. Iyer G, Srinivasan B, Agarwal S, Pillai VS, Ahuja A. Treatment modalities and clinical outcomes in ocular sequelae of Stevens-Johnson syndrome over 25 years--a paradigm shift. Cornea. 2016; 35:46–50.

49. Kohanim S, Palioura S, Saeed HN, Akpek EK, Amescua G, Basu S. Acute and chronic ophthalmic involvement in Stevens-Johnson syndrome/toxic epidermal necrolysis - a comprehensive review and guide to therapy. II. Ophthalmic Disease. Ocul Surf. 2016; 14:168–188.

50. Weber SL, de Souza RB, Gomes JA, Hofling-Lima AL. The use of the esclera scleral contact lens in the treatment of moderate to severe dry eye disease. Am J Ophthalmol. 2016; 163:167–173.e1.

51. Sindt CW, Longmuir RA. Contact lens strategies for the patient with dry eye. Ocul Surf. 2007; 5:294–307.

52. McCord CD Jr, Chen WP. Tarsal polishing and mucous membrane grafting for cicatricial entropion, trichiasis and epidermalization. Ophthalmic Surg. 1983; 14:1021–1025.

53. Nakamura T, Inatomi T, Sotozono C, Amemiya T, Kanamura N, Kinoshita S. Transplantation of cultivated autologous oral mucosal epithelial cells in patients with severe ocular surface disorders. Br J Ophthalmol. 2004; 88:1280–1284.

54. Nakamura T, Koizumi N, Tsuzuki M, Inoki K, Sano Y, Sotozono C, et al. Successful regrafting of cultivated corneal epithelium using amniotic membrane as a carrier in severe ocular surface disease. Cornea. 2003; 22:70–71.

55. Shimazaki J, Maruyama F, Shimmura S, Fujishima H, Tsubota K. Immunologic rejection of the central graft after limbal allograft transplantation combined with penetrating keratoplasty. Cornea. 2001; 20:149–152.

56. Tseng SG, Prabhasawat P, Barton K, Gray T, Meller D. AMniotic membrane transplantation with or without limbal allografts for corneal surface reconstruction in patients with limbal stem cell deficiency. Arch Ophthalmol. 1998; 116:431–441.

57. Venugopal R, Satpathy G, Sangwan S, Kapil A, Aron N, Agarwal T, et al. Conjunctival microbial flora in ocular Stevens-Johnson syndrome sequelae patients at a tertiary eye care center. Cornea. 2016.

58. Utheim TP. Concise review: transplantation of cultured oral mucosal epithelial cells for treating limbal stem cell deficiency—current status and future perspectives. Stem Cells. 2015; 33:1685–1695.

59. Sayegh RR, Ang LPK, Foster CS, Dohlman CH. The boston keratoprosthesis in Stevens-Johnson syndrome. Am J Ophthalmol. 2008; 145:438–444.

60. Strampelli B, Valvo A, Tusa E. Osteo-odonto-keratoprosthesis in a case treated for anchylobepharon and total simbleraphon. Annali di Ottalmologia e Clinica Oculistica. 1965; 91:462–479.

61. Strampelli B. Technical improvements in osteo-odonto-keratoprothesis. Annali di Ottalmologia e Clinica Oculistica. 1966; 92:155–178.

62. Strampelli B. Osteo-chondro-keratoprosthesis in substitution of the osteo-odonto-keratoprosthesis in edentulous patients. Annali di Ottalmologia e Clinica Oculistica. 1967; 93:975–978.