An 84-year-old man with a personal history of prostate cancer with no other underlying medical conditions, underwent a CT scan with ICM ioversol in January 2021. No other suspected drugs were involved. He had no history of drug allergy and previously tolerated ICM.

Seven days later, he developed fever (temperature 38.7 °C) and an itchy erythematous, blanching morbilliform exanthema on the trunk that spread to the abdomen and upper limbs. Forty-eight hours later he went to the Emergency Department for persistent fever and skin worsening with facial edema and generalized maculopapular rash with intense erythematous-violaceous lesions on the face, trunk, back, chest and abdomen covering more than 60% of his body surface, without mucosal involvement or lymphadenopathy.

Blood test revealed an elevated cardiac enzyme level (troponin 41 ng/l), mild acute kidney injury (creatinine 1.29 mg/dl) and abnormal liver profile (GPT 108 U/L) that he did not have previously. He developed peripheral eosinophilia on the 4th day of admission, with peak eosinophil count of 2000 eos/uL.

Blood cultures were negative, and the C-reactive protein and antinuclear antibodies levels were within normal limits. Serologies were negative for HIV, HBV, HCV, EBV, CMV, syphilis and parvovirus.

The patient was admitted to the hospital and, after treatment with intravenous methylprednisolone, he had significant clinical and biochemical improvement.

Fever and rash were completely resolved whitin 15 days. On discharge, he had normalization of creatinine level (0.89 mg/dl), liver function (GPT 60 U/L), cardiac enzyme level (troponin 5.1 ng/l) and eosinophilia count (300 eos /uL).

On discharge, 5 more days of systemic corticosteroids were prescribed to complete the tapering.

Our patient’s clinical manifestations included an extensive dermatosis, fever, elevated cardiac enzyme levels, eosinophilia, acute renal and liver injury, without lymphadenopathy or mucosal involvement. Application of the RegiSCAR DRESS criteria in this case yielded a score of 7 (definitive) (skin involvement (≥ 50%) + 2, organ involvement + 2, eosinophilia: 2000 eos/uL. + 2, evaluation of other potential causes + 1) [1].

Intradermal testing (IDT) with ioversol, and other ICM (diluted 1/10): iopamidol, iopramide, iobitridol, iodixanol, iomeprol were performed for etiologic diagnosis and possible cross-reactivity between ICM. Ioversol and iomeprol were positive at 24 h in late readings, and negative to the remaining ICM tested (Fig. 1).

Intradermal test with contrast media. Image shows significant positivity to the culprit drug (ioversol) with cross-reactivity with iomeprol

A punch biopsy was performed on the ioversol-positive IDT (Fig. 2) with dermatopathologic features suggestive of a drug reaction. Histology of the skin biopsy revealed a skin layer lined by epidermis of usual thickness and an orthokeratotic chorneal layer, without apoptotic keratinocytes or lichenoid inflammatory infiltrates. The underlying dermis showed a moderate superficial perivascular inflammatory infiltrate with lymphocytes and eosinophils, and epidermal involvement without microabscesses, micropustules or vesicles.

Histology of a skin biopsy performed on the positive intradermal test with the culprit drug (ioversol)