{"doi":"10.1002/ajh.26342","title":"First case of <scp>DRESS</scp> (drug reaction with eosinophilia and systemic symptoms) associated with voxelotor","abstract":"Sickle cell disease (SCD) is a group of inherited diseases that includes sickle cell anemia, an autosomal recessive disorder caused by a single amino acid substitution within the β-globin gene of hemoglobin (Hb). This mutation can result in polymerization of the Hb α2βs2 tetramer, causing red cell sickling, erythrocyte membrane damage and red cell destruction.1, 2 Until recently, there were few therapies which directly targeted red cell sickling. However, a novel agent, voxelotor, has demonstrated its ability to increase hemoglobin levels by bonding with the α chain of the α2βs2 tetramer and shifting the hemoglobin oxygenation dissociation curve to the left, which increases oxygen binding and decreases hemoglobin polymerization.3 Voxelotor was granted accelerated approval and breakthrough therapy designation by the FDA based on the HOPE trial (NCT 03036813) with the most common adverse reactions being headache, diarrhea, arthralgia, upper respiratory tract infection and rash.4 Studies examining new medications for rare diseases may be too small to demonstrate risk of rare adverse outcomes and so reports of any such outcomes post approval are critical for patient care. To our knowledge there have been no reported incidents of DRESS (drug rash with eosinophilia and systemic symptoms) due to voxelotor usage. We present here the first case of this. We report a 53-year-old African American woman with homozygous HbSS complicated by pulmonary hypertension and chronic kidney disease stage IV (baseline creatinine 2.5 mg/dl) with a baseline around Hb of 5.0 g/dl, on long-standing epoetin alfa since 2019 and requiring red cell transfusions approximately every 3 months for the treatment of symptomatic anemia. She had been hydroxyurea since 2017 but it had been held since March 2020 for reticulocytopenia and she was started on voxelotor 1500 mg once daily on October 10, 2020. On November 5, 2020, she developed acute kidney injury (AKI) with a creatine (Cr) of 5.32 mg/dl along with eosinophilia at an absolute count of 1.1 thousands per cubic milliliter (15% on complete blood count differential). Given concerns of a drug reaction voxelotor was held. It was restarted 2 weeks later on November 20 2020 at a reduced dose of 1000 mg daily after resolution of her AKI and decrease in eosinophilia to 0.9 thousands per cubic milliliter, and subsequently her hemoglobin improved to 10.4 g/dl. Five weeks later on December 30 she was admitted for fevers, fatigue, cough, facial swelling and a pruritic rash along her face, neck, chest, shoulders, back and lower extremities (Figure 1(A)) with no lymphadenopathy on physical exam. Her labs were significant for a drop in Hgb from 10.1 to 7.6 g/dl and an increase in white blood cell count of 13,900 per cubic milliliter with an absolute eosinophil count of 5200 per cubic milliliter, an AKI with Cr of 3.96 mg/dl and transaminitis with maximum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of 129 units per litre and 82 units per litre, respectively, along with alkaline phosphatase (ALP) of 243 units per litre and total bilirubin of 2.0 mg/dl. Infectious workup was negative and computed tomography (CT) of the chest revealed diffuse ground-glass opacities and mosaic attenuation without lymphadenopathy. The patient was evaluated by dermatology and underwent a punch biopsy of the left upper arm which revealed spongiosis and an interstitial, perivascular, and interface dermatitis with histiocytes, lymphocytes, and eosinophils. These histologic findings were felt to be compatible with a drug reaction (Figure 1(B)) and given the clinical picture, it was concluded this was an attenuated drug reaction with eosinophilia and systemic symptoms (DRESS) caused by voxeletor. The patient's skin findings resolved with emollients and high potency topical hydrocortisone 2.5% ointment and amlactin 12% lotion. Her liver and renal function tests improved and the patient was discharged 2 weeks later with stabilizati","journal":"American Journal of Hematology","year":2021,"id":203726,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":785044,"name":"Thomas Stringer","orcid":"0000-0002-5804-0801","position":1,"is_corresponding":false},{"id":781836,"name":"Jack Jacob","orcid":"0000-0002-6267-0806","position":2,"is_corresponding":false},{"id":785472,"name":"Elana M Friedman","orcid":null,"position":3,"is_corresponding":false},{"id":366913,"name":"Caterina P. Minniti","orcid":"0000-0002-7059-2959","position":4,"is_corresponding":false},{"id":785473,"name":"Henny H. Billett","orcid":null,"position":5,"is_corresponding":false},{"id":364947,"name":"Susanna A. Curtis","orcid":"0000-0002-2281-0843","position":6,"is_corresponding":false},{"id":759584,"name":"Matthew Lee","orcid":"0000-0001-7103-4660","position":0,"is_corresponding":true}],"reference_count":11,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:51:18.050175Z","pmid":"34478170","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}