D3.377 - Causes of a morbilliform rash: when the most frequent answer is not

In the assessment of drug hypersensitivity reactions, distinguishing between immediate and delayed reactions is required, followed by a detailed description of clinical features, which in this case involves the skin, as it a SCAR (severe cutaneous adverse reaction).

This is a case of a 77-year-old woman who presented with alarm symptoms in the context of recent drug exposure, presenting high fever (39 °C), malaise, and a pruritic rash.

An erythematous-violaceous maculopapular rash spread during its evolution, with lesions tending to coalesce, without delayed desquamation or positive Nikolsky sign. Facial and auricular edema were present, with mild palmar involvement. Mucous membranes were spared.

Regarding recent medications, the patient had started apixaban three days earlier for an incidental asymptomatic thrombosis of the left superior lobar vein. Ten days before admission, she had completed a one-week course of amoxicillin-clavulanate for pharyngotonsillitis. Her medical history included active renal cancer and stage IV lung cancer, treated with Nivolumab, last administered 20 days prior. A drug-induced toxicoderma was therefore suspected.

Serial laboratory tests revealed no hepatic involvement and only mild transient renal impairment, attributed to prerenal dehydration. Acute-phase reactants were elevated, with a CRP of 88 mg/dL on admission, followed by a progressive decrease. There was no eosinophilia.

A skin biopsy performed during the acute phase confirmed toxicoderma.

All suspected drugs were discontinued and she was treated with corticosteroids, with a good response.

Three months later, a lymphocyte transformation (LTT) test was performed.

The TTL was positive for apixaban and negative for amoxicillin-clavulanate and Nivolumab. 

According to the complementary tests, we can resume that it was a morbilliform rash, more probably due to apixaban. This case highlights the importance of a comprehensive diagnostic evaluation, utilizing all available tools adapted to the patient’s condition. The LTT results provide the possibility of safely assessing exposure to other drugs involved, if necessary, and contribute to the documentation of data for potential future cases.