“DRESS syndrome with AGEP features” Adrian Tinajero, DO, Sadaf Sheikh, MD St. John’s Episcopal Hospital, Far Rockaway, NY, Department of Dermatology Albert Strojan DO, Chief Academic Officer; Suzanne Sirota Rozenberg DO, Dermatology Program Director

Abstract Images Discussion Conclusion

Severe cutaneous adverse reaction to drugs Drug reaction with eosinophilia and systemic Severe cutaneous adverse drug reactions (SCARs) affect approximately 2% of hospitalized symptoms (DRESS), usually begins 2-6 weeks after (SCARs) in hospitalized patients carry increase patients and are associated with morbidity, mortality, exposure to certain drugs. DRESS has a complex morbidity, mortality and health-care cost. SJS/TEN are health-care cost, and drug and diagnosis challenges. natural course and very diverse clinical considered the most severe types of SCARs; 1 Diagnosis criteria has been established for each of presentation. Anticonvulsant medications tend the however, DRESS syndrome carries up to 20% these entities; however, there are overlapping features be the most common triggers, however, other drugs mortality. Patients with DRESS syndrome can have which pose a diagnosis challenge. For example, AGEP including antibiotics, osteoporosis medications, and multiple organ involvement including cardiac 2 may present with facial edema and present with blisters kinase inhibitors have been reported. Dermatologic involvement which can be fatal. Additionally, patients or even mucosal involvement. DRESS may have findings include facial edema, exanthematous with DRESS syndrome carry a higher risk of pustules and even have a TEN-like presentation. It is morbiliform eruption, pustules and sometimes autoimmune thyroiditis.5 important for health care providers to be aware of these mucosal involvement. Systemic involvement is Here we presented a case of DRESS overlapping features in order to avoid pitfalls in thought to result from organ infiltration of eosinophils syndrome associated with use of phenytoin. Our case diagnosis and treatment.5 or lymphocytes. The organs typically involved include was interesting because this case also showed AGEP Dress syndrome has up to 20% mortality and liver presenting as hepatic cytolysis to fulminant features including multiple tiny non-follicular pustules hepatitis; kidney, lung and heart involvement. carries a risk of autoimmune conditions including auto b on an erythematous base involving the trunk and face. immune thyroiditis, while AGEP tends to be benign and Cardiac involvement leading to myocarditis or This case shows that SCARs have overlapping carries no sequela. pericarditis with elevation of cardiac enzymes can be features and therefore, practitioners must be aware of 3 fatal. such features as to avoid delay in diagnosis and treatment. Dress syndrome carrier a much higher Acute generalized exanthematous pustulosis mortality than AGEP and there is increased risk of Case (AGEP) is an adverse drug reaction which typically autoimmune thyroiditis and therefore close follow up is begin within 48 hours of drug exposure but can be as required. long as 11 days post exposure.3 Most common A 37-year-old male with history of seizure associated medications include aminopenicillins, disorder on Levetiracetam for several years presented quinolones, hydroxychloroquine, sulfonamides, References to the ED with an itchy rash for 4 days. Phenytoin was terbinafine, diltiazem, ketoconazole, and fluconazole; added to his seizure treatment 4 weeks prior. Initial Histology however, viral infections, dietary supplements, and 1. Tennis, P, Stern, R. Risk of serious cutaneous disorders after initiation of use work up demonstrated leukocytosis with elevated hypersensitivity to mercury, radiation and spider bites of phenytoin, carbamazepine, or sodium valproate: a record linkage study. eosinophils, and elevated liver enzymes. Patient had H&E 4x subcorneal have been reported as triggers for AGEP.4 Neurology. 1997; 49(2): 542 confluent erythema involving trunk, upper extremities, pustule with mixed 2. Bouvresse, S, Valeyrie-Allanore, L, Ortonne, N, Konstantinou, M, Kardaun, S, infiltrate. Superficial and Dermatologic features of AGEP include hundreds of Bagot, M, Wolkenstein, P, Roujeau, J. Toxic epidermal necrolysis, DRESS, thighs and face. There were hundreds of tiny non- deep dermal infiltrate of nonfollicular sterile tiny pustules on an erythematous AGEP: Do overlap cases exist? Orphanet Journal of rare diseases. 2012 (7):72. Kardaun, S, Sekula, P, Valeryrie-Allanore, L, Liss, Y, Chu, C, Creamer, D, follicular sterile pustules on the upper chest and face. lymphocytes, base. It favors intertriginous region and often begins Sidorff, A, Naldi, L, Mockenhaupt, M, Roujeau, J, RegiSCAR study group. Drug He had facial edema and desquamation of the upper eosinophils and on the trunk and it can be pruritic.3 reaction with eosinophilia and systemic symptoms (DRESS): an original neutrophils. multisystem adverse drug reaction. Results from the prospective RegiSCAR chest and neck. Punch skin biopsy showed study. Br J Dermatology. 2013; 169(5): 1071 perivascular dermatitis with eosinophils. Patient met There has been randomized controlled studies 3. Duong, T, Valeyrie-Allanore, L, Wolkenstein P, Chosidow, O. Severe cutaneous adverse reaction to drugs. Lancet. 2017 May 02; (390):1996-2011 the diagnosis of DRESS under the RegiSCAR and looking into management of DRESS and AGEP. Choudhary, S, McLeod, M, Torchia, D, Romanelli, P. Drug reaction with Japanese’s group criteria. He also has a possible Systemic corticosteroids have been used for the eosinophilia and systemic symptoms (DRESS) syndrome. J Clin Aesthet Dermatol. 2013 June; (6):31-37 diagnosis of AGEP under the EuroSCAR study. He H&E 40x Interphase management of DRESS but there is no standardized 4. Lee, Y, Chung, W. Acute generalized exanthematous pustulosis: A was treated with systemic methylprednisolone 60 mg dermatitis with assessment of outcomes. Retrospective studies have retrospective study of 51 cases in Taiwan. Dermatologica Sinica. 2014; (32): 137- 140 intravenously every 6 hours and triamcinolone acetate infiltrate of shown the use of potent topical corticosteroids to be lymphocytes, 5. Rosen, A, Paggio, J, Chan, B, Abu-Abed, S, Rawls, M, Ellis, A. Acute 0.1% ointment topically. Within the next 5 days, his helpful in mild to moderate DRESS with less side generalized exanthematous pustulosis with multisystem manifestations. Letters / histiocytes and Ann Allergy Astham Immunol 2018; (120):90-106 laboratory abnormalities improved. Patient was eosinophils. effects that systemic corticosteroids. Prompt 6. Szatkowski, J, Schwartz, R. Acute generalized exanthematous pustulosis discharged home with a slow oral steroid taper and withdrawal of the offending drug for AGEP my be (AGEP): A review and update. J American Academy of Dermatology. 2015 Sep 06; (73):843-848 was followed up for recurrence. Within one month his adequate with topical corticosteroids as adjunctive 7. Bolognia JL, Lorizzo JL, Schaffer JV. Dermatology. 4rd rev. ed. London: liver enzymes normalized completely. therapy.3 Saunders; 2018. 8. Patterson JW. Weedon’s skin pathology. 4th ed. Hosler GA, contributor. London: Churchil Livingstone; 2016.