Hospital Consult

Outpatient Management and Follow-up Recommendations for Adverse Drug Reactions: Guidelines for Posthospitalization Care

Cutis. 2019 May;103(05):254-256, 258

References

Preventable adverse drug reactions: a focus on drug interactions. US Food and Drug Administration website. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm110632.htm. Updated March 6, 2018. Accessed April 12, 2019.
Thienvibul C, Vachiramon V, Chanprapaph K. Five-year retrospective review of acute generalized exanthematous pustulosis. Dermatol Res Pract. 2015;3:1-8.
Lee HY, Chou D, Pang SM, et al. Acute generalized exanthematous pustulosis: analysis of cases managed in a tertiary hospital in Singapore. Int J Dermatol. 2010;49:507-512.
Ropars N, Darrieux L, Tisseau L, et al. Acute generalized exanthematous pustulosis associated with primary Epstein-Barr virus infection. JAAD Case Rep. 2014;1:9-11.
Hattem S, Beerthuizen G, Kardaun S. Severe flucloxacillin‐induced acute generalized exanthematous pustulosis (AGEP), with toxic epidermal necrolysis (TEN)‐like features: does overlap between AGEP and TEN exist? clinical report and review of the literature. Br J Dermatol. 2014;171:1539-1545.
Tajmir-Riahi A, Wörl P, Harrer T, et al. Life-threatening atypical case of acute generalized exanthematous pustulosis. Int Arch Allergy Immunol. 2017;174:108-111.
Feldmeyer L, Heidemeyer K, Yawalkar N. Acute generalized exanthematous pustulosis: pathogenesis, genetic background, clinical variants and therapy. Int J Mol Sci. 2016;17:E1214.
Szatkowski J, Schwartz RA. Acute generalized exanthematous pustulosis (AGEP). a review and update. J Am Acad Dermatol. 2015;73:843-848.
Totonchy MB, McNiff JM, Bunick CG. Koebnerization of Hailey-Hailey disease into a cutaneous drug eruption of acute generalized exanthematous pustulosis associated with systemic symptoms. J Cutan Pathol. 2016;43:1031-1035.
Husain Z, Reddy BY, Schwartz RA. DRESS syndrome: part II. management and therapeutics. J Am Acad Dermatol. 2013;68:709.e1-e9; quiz 718-720.
Kano Y, Shiohara T. Long-term outcome of patients with severe cutaneous adverse reactions. Dermatologica Sinica. 2013;31:211-216.
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Ushigome Y, Kano Y, Ishida T, et al. Short- and long-term outcomes of 34 patients with drug-induced hypersensitivity syndrome in a single institution. J Am Acad Dermatol. 2013;68:721-728.
Ljungman P, Wang FZ, Clark DA, et al. High levels of human herpesvirus 6 DNA in peripheral blood leucocytes are correlated to platelet engraftment and disease in allogeneic stem cell transplant patients. Br J Haematol. 2000;111:774-781.
Asano Y, Kagawa H, Kano Y, et al. Cytomegalovirus disease during severe drug eruptions: report of 2 cases and retrospective study of 18 patients with drug-induced hypersensitivity syndrome. Arch Dermatol. 2009;145:1030-1036.
Kano Y , Tohyama M, Aihara M, et al. Sequelae in 145 patients with drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR). J Dermatol. 2015;42:276-282.
Morita C, Yanase T, Shiohara T, et al. Aggressive treatment in paediatric or young patients with drug-induced hypersensitivity syndrome (DiHS)/ drug reaction with eosinophilia and systemic symptoms (DRESS) is associated with future development of type III polyglandular autoimmune syndrome [published online October 27, 2018]. BMJ Case Rep. doi:10.1136/bcr-2018-225528.
Chiang A, Shiu J, Elsensohn AN, et al. Classic autoimmune type 1 diabetes mellitus after a case of drug reaction with eosinophilia and systemic symptoms (DRESS). JAAD Case Rep. 2018;4:295-297.
Lew TT, Creamer D, Mackenzie J, et al. Post-traumatic stress disorder following drug reaction with eosinophilia and systemic symptoms. Br J Dermatol. 2015;172:836-837.
Kumar R, Das A, Das S. Management of Stevens-Johnson syndrome-toxic epidermal necrolysis: looking beyond guidelines! Indian J Dermatol. 2018;63:117-124.
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Lee HY, Walsh SA, Creamer D. Long‐term complications of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN): the spectrum of chronic problems in patients who survive an episode of SJS/TEN necessitates multidisciplinary follow‐up. Br J Dermatol. 2017;177:924-935.
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Sant’ Anna AE, Hazarbassanov RM, de Freitas D, et al. Minor salivary glands and labial mucous membrane graft in the treatment of severe symblepharon and dry eye in patients with Stevens-Johnson syndrome. Br J Ophthalmol. 2012;96:234-239.
Hefez L, Zaghbib K, Sbidian E, et al. Post-traumatic stress disorder in Stevens-Johnson syndrome and toxic epidermal necrolysis: prevalence and risk factors. a prospective study of 31 patients [published online October 3, 2018]. Br J Dermatol. doi:10.1111/bjd.17267.
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Long-term Sequelae

Endocrine
Thyroid gland abnormalities secondary to DRESS syndrome include Graves disease and Hashimoto disease as well as variations in biomarkers including elevated free thyroxine and low and elevated thyroid-stimulating hormone levels.^16,17 Type 1 diabetes mellitus also has been seen after DRESS syndrome, developing within the first 10 months after onset with unknown pathogenesis.¹⁸

Autoimmune
Other reported sequelae of DRESS syndrome include elevated antinuclear antibodies with possible development into systemic lupus erythematosus, autoimmune hemolytic anemia, vitiligo, and rheumatoid arthritis.^11,16 Symptoms may be exacerbated in patients with preexisting autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, and patients with preexisting renal disease are at an increased risk for requiring lifelong hemodialysis after DRESS syndrome.¹⁶

Other
Studies have demonstrated that pneumonia, thrombosis, and alopecia can be complications of DRESS syndrome.^11,16 Psychiatric disturbances including fear of taking new medications, anxiety, and depression also have been reported.¹⁹ Children with DRESS syndrome may develop vitiligo, alopecia, sclerodermatous lesions, photophobia, uveitis, and Vogt-Koyanagi-Harada disease.¹⁷

Follow-up Recommendations

It is important to inform patients of both the potential short-term and long-term sequelae of DRESS syndrome, including those associated with treatment. A thorough review of systems should be performed at each visit, along with laboratory evaluation including a complete blood cell count with differential and liver function testing every 1 to 2 weeks after discharge until normalized, with monthly monitoring of glucose, thyroid-stimulating hormone, and free thyroxine levels for 3 months after discharge.

STEVENS-JOHNSON SYNDROME/TOXIC EPIDERMAL NECROLYSIS

Stevens-Johnson syndrome/toxic epidermal necrolysis are severe ADRs that present with dusky violaceous macules. Inciting medications include nonsteroidal anti-inflammatory drugs, allopurinol, antibiotics, and anticonvulsants, and symptoms begin 1 to 3 weeks after medication exposure.¹² Initially, the lesions often begin on the trunk and can progress to full-body erythema and exfoliation with a necrotic epidermis and mucosal involvement.^12,20

Notable Sequelae

Cutaneous
Chronic eczema can present at any time and can vary in severity in SJS/TEN patients.²¹ Xerosis and pruritus can be treated with emollients.¹¹ Dyschromia is common. Hypertrophic and keloidal scarring can result from surgical debridement and are best prevented with the use of nonadherent dressings.²² Nail changes such as anonychia, dystrophy, longitudinal ridges, and pterygium also are seen, and topical steroids can be helpful. Other reported dermatologic sequelae include dyschromia and eruption of ectopic sebaceous glands.^21,22

Ocular
Ocular sequelae include dry eyes, photophobia, symblepharon, corneal scarring, corneal neovascularization, corneal xerosis, trichiasis, reduced visual acuity, blindness, and subconjunctival fibrosis. The most common sequelae are bilateral conjunctivitis and corneal ulcerations.^22,23 Early and regular ophthalmologic follow-up is recommended, as SJS/TEN-induced blindness can result from delayed therapy, destroying corneal stem cells.²¹ Amniotic membrane transplantation replaces the damaged corneal membrane, which may reduce corneal inflammation.²⁴

Chronic dry eye syndrome can recur for years after SJS/TEN resolves and progresses over time.²² Frequent use of nonpreserved artificial tears and salivary gland transplantation can be helpful.²⁴ Unfortunately, ocular disease may develop months after discharge; therefore, it is recommended that dermatologists ask all SJS/TEN patients about ocular symptoms in follow-up visits. If ocular involvement was present initially, patients should be followed by ophthalmology for at least 1 year after discharge.²³