Rosuvastatin Use Implicated in the Drug Reaction with Eosinophilia and Systemic Symptoms

Abstract

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a life-threatening druginduced hypersensitivity reaction that is most closely associated with antiepileptics and antibiotics. While cases of DRESS are rare, here we present a case of DRESS in an adult male following administration of rosuvastatin who presented with fevers, generalized rash, and facial fullness. Vitals on presentation were temperature 102 o F, pulse 95/min, blood pressure 95/47 mmHg, and respiratory rate of 14/min. His physical examination revealed scleral icterus, generalized blanching maculopapular rash, facial fullness, and right upper quadrant tenderness. Laboratory investigations found hemoglobin 10 gm/dl, white blood cell count 16.0 K/uL, peripheral eosinophil count 1,700 K/uL, alkaline phosphatase 2,501 U/L, aspartate transaminase 620 U/L, alanine transaminase 680 U/L, total bilirubin 13.2 mg/dl with a direct component of 9 mg/dl, blood urea nitrogen 66 mg/dl, creatinine 5.20 mg/dl, glomerular filtration rate 8 ml/min, and immunoglobulin E level 623 IU/mL. Serology for viral hepatitis, Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 was negative. Computed tomographic scan of chest, abdomen, and pelvis showed generalized lymphadenopathy. Over the next week, the patient deteriorated clinically with worsening transaminitis and oliguric acute renal failure requiring renal replacement therapy. As per the European Registry of Severe Cutaneous Adverse Reaction Criteria (RegiSCAR), the probability of rosuvastatin-induced DRESS syndrome was scored as "definite." He was treated with systemic and topical glucocorticoids leading to a gradual improvement in his symptoms. Skin biopsy was suggestive of DRESS syndrome as well. Since DRESS carries such a significant risk of mortality between 10% and 20%, DRESS must be recognized and treated as soon as symptoms present. Clinicians should also be aware that statins, one of the most commonly prescribed drugs, are also a potential cause DRESS.

Immunopathogenic Insights on Preferential Human Herpesvirus-6 Reactivation in Drug Rash With Eosinophilia and Systemic Symptoms: A Scoping Review

“… 45 As such, reports of negative HHV-6 assessed only once immediately or shortly after DRESS onset may have missed later reactivation. 8 , 11 , 44 , 46 - 50 While there are many reports of delayed seroconversion or reactivation, 9 , 15 , 33 , 37 , 51 - 54 sometimes with initially undetectable viral loads, 21 , 27 , 55 , 56 HHV-6 reactivation at the onset of DRESS is possible, as well. 8 , 28 , 32 , 57 , 58 It should be noted that HHV-6 reactivation has not been reported before DRESS onset, which suggests that HHV-6 reactivation likely does not cause DRESS.…”

Advances in Our Understanding of the Interaction of Drugs with T-cells: Implications for the Discovery of Biomarkers in Severe Cutaneous Drug Reactions

“…DRESS is an individual form of severe hypersensitivity reaction characterized not only by the presence of widespread skin inflammation but also by fever and abnormal hematological findings with multiorgan involvement. Commonly DRESS is associated viral reactivation including the human herpes virus family (HHV-6 and 7), Epstein–Barr virus (EBV), cytomegalovirus (CMV), and varicella zoster, which worsen the syndrome leading to poor prognosis. − As in seen with SJS/TEN, anticonvulsants and antibiotics are common therapeutic families associated with the disease, although more than 44 drugs have been associated with DRESS . Oddly, although DRESS is labeled as a severe cutaneous drug reaction, in some rare cases, skin damage is not seen …”

“…It is not surprising to see these overlapping features between severe cutaneous reactions, because as in SJS/TEN the number of infiltrating CD8 + cells is higher than CD4 + cells at the site of the skin reaction, and the presence of IL-17 secreting cells has been reported . Detailed sequencing studies have shown an oligoclonal response in CD8 + T-cells, and the increase of specific public TCR clones has not been reported .…”

Liver enzyme elevation and eosinophilia with atorvastatin: a case of probable DRESS without cutaneous symptoms

“…Many different medications are implicated in DRESS, however the most common causes are typically seen with anticonvulsants and antibiotics [1,4]. Statin class medications are not typically implicated or associated with DRESS [1].…”

“…Drug reaction with eosinophilia and systemic symptoms (DRESS) is a serious, potentially life threatening condition that typically presents with generalized skin rash, fevers, enlarged lymph nodes, hematological abnormalities in addition to eosinophilia and multiorgan dysfunction [1]. The diagnosis of DRESS is often challenging, with heterogeneity in clinical presentation, often initially misdiagnosed as infection [2].…”