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Drug Rash, Eosinophilia, Systemic Symptoms (DRESS) in a Child With Acute Lymphoblastic Leukemia.

To the Editor: A 2-years-old-male child with precursor B-cell acute lymphoblastic leukemia (ALL) on consolidation phase chemotherapy as per BFM95 protocol was admitted with complaints of fever and macular rash over face, trunk, and limbs. He had recent history of admission for status epilepticus and posterior reversible encephalopathy syndrome postinduction chemotherapy, and hence was on multiple antihypertensives (amlodipine, enalapril and propranolol) and multiple anticonvulsants (levateracetam and phenytoin). With the background of ALL and secondary immune-suppression, a viral illness was on top of our differentials. His sepsis workup was negative and other laboratory parameters were normal (Table 1). He was managed with supportive care and intravenous immunoglobulin infusion. His fever subsided but rash persisted and he was discharged. He was readmitted 15 days later with fever, rash, mucositis, and decreased oral acceptance. On examination he had mucositis, aphthous ulcers, cheilitis and xerosis with crusting, waxing, and waning pruritic erythematous maculopapular rash over cheeks, neck, trunk, chest, and limbs. His hemogram showed eosinophilia. The details of the serial hemogram and other laboratory parameters are mentioned in Table 1. A possibility of the clinical and laboratory findings attributable to a drug was considered. A neurology and dermatology opinion was sought and phenytoin was withheld in view of diagnosis of drug rash, eosinophilia, systemic symptoms (DRESS) due to phenytoin. He was also started on oral prednisolone at 2 mg/kg/d for 3 weeks and then gradually tapered. His fever subsided, rash started to improve and eosinophilia resolved and was hence discharged after 6 days. DRESS has been well reported in association with several drugs in adults; however, this entity is relatively rare in children and its occurrence in a child with leukemia has rarely been reported.1,2 Aromatic antiepileptics are known to be associated with DRESS syndrome.3,4 DRESS is diagnosed based on the RegiSCAR criteria.3–5 The parameters favoring probable DRESS in our patient were: high grade fever, eosinophils > 20% with a leukocyte count of <4000/μL, absolute eosinophil count, 1399/μL, skin rash involving > 50% body surface area, facial puffiness, erythematous maculopapular rash with some purpuric changes over face and chest and blood culture was negative. Our patient did not have tender lymphadenopathy and other organ involvement (liver, kidney, heart, pancreas, etc.). He was also evaluated for antinuclear antibody, hepatitis A, B, and C, mycoplasma infection and none was detected. We intend to bring to attention the possible occurrence of this condition in pediatric oncology setting. Patients of leukemia may show various cutaneous manifestations at various timepoints of their disease such as leukemia cutis, septic/fungal eruptions, viral exanthemas, and drug eruptions. DRESS has rarely been reported among pediatric leukemia patients.2 Our case highlights the fact that it is important to pay heed to not just the total leukocyte count and neutrophil count, but also to the eosinophil count and in case of associated eosinophilia, this entity should be suspected. A delayed onset of symptoms 2 to 6 weeks after the initiation of causative drug is a feature of DRESS.2,5 The factors that help differentiate it from toxic epidermal necrolysis and Stevens-Johnson syndrome are delayed occurrence, paradoxical deterioration, possible flare ups, prolonged course, and slow resolution.2 The clinical picture may vary from mild to fatal illness.4,6 As DRESS can at times be life-threatening, a high index of suspicion should be kept. The pathogenesis is complex and partially understood. It is attributable to one or more of the following: detoxification defects leading to reactive metabolite formation and subsequent immunologic reactions, slow acetylation, and reactivation of human herpes, including Epstein-Barr virus and human herpesvirus (HHV)-6 and 7 and gradual dysfunction of regulatory