D2.415 - DRESS Syndrome induced by Lenalidomide

Lenalidomide is an oral analogue of thalidomide used in relapsed or refractory multiple myeloma (MM).

It activates T lymphocytes and inhibits interleukin-6, stimulating pro-apoptotic signals and thereby conferring its antitumor activity.

A 59-year-old woman was diagnosed with IgA-K MM with a personal history of vertebral fractures and breast carcinoma in remission. She started treatment with lenalidomide, acyclovir, bortezomib, and dexamethasone 40 mg.

Sixteen days later, she developed dyspnea on minimal exertion, chills, diffuse pruritic erythroderma, lip and tongue edema, pitting edema, and petechiae on the legs. Nikolsky's sign was negative. There was no mucosal involvement. She was admitted to the Emergency Department.

Laboratory tests: renal profile, procalcitonin, CK, and TnT were normal; CRP was 79.47 mg/L (0.00-5.00 mg/L), BNP was 2068 pg/mL, ALT was elevated 71 U/L (0-40 U/L), and LDH was elevated at 270 U/L (10-250 U/L), with normal AST, total bilirubin, and coagulation, except for D-dimer, which was elevated at 2.04 µg/mL (0.00-0.50 µg/mL). Lymphopenia was present (740), eosinophils were 430. 

TTE: good biventricular function. 

Chest CT: pulmonary embolism ruled out; signs of fluid overload were present.

Furosemide was administered iv, and home treatment was prescribed. Lenalidomide was discontinued.

Upon evaluation, we initiated treatment with prednisone and discontinued allopurinol.

Expanded blood tests and a skin biopsy were performed.

Liver function tests BNP, IgG, IgA, and IgM, amylase, and lipase levels normalised; ANAs and viral and bacterial serologies were negative. Blood count: lymphopenia (1330) and eosinophilia (4210). 

Skin biopsy: interstitial granulomatous dermatitis, vacuolar interface damage, and foci of spongiosis.

We diagnosed the patient with DRESS syndrome due to lenalidomide (RegiSCAR score: 6). Clinical and blood count improvement followed treatment with prednisone; the patient continued treatment exclusively with bortezomib.

DRESS syndrome is a rare adverse reaction with a 10% mortality rate, characterized by acute skin rash, fever, lymphadenopathy, eosinophilia, and systemic symptoms due to internal organ involvement. The pathogenesis involves: virus-drug interactions with viral reactivation (HHV-6, EBV, CMV, and HHV-6), genetic associations between HLA and drug structure, and accumulation of drug metabolites due to genetic enzyme deficiencies.