P0328DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS) SYNDROME: THE GREAT MIMICKER SECONDARY TO LENALIDOMIDE IN PERITONEAL DIALYSIS
Authors: Cazzato Silvia , Magistroni Riccardo , Ascione Elisabetta , Maccaferri Monica , Cappelli Gianni 
Published: June 2020

Abstract

Background and Aims
DRESS syndrome is a rare, idiosyncratic, potentially life-threatening adverse drug reaction, characterized by latent period after intake of the inciting drug (2-6 weeks), fever higher than 38.5°C, skin eruptions (usually pruritic maculopapular rash or diffuse erythematous eruption), eosinophilia (in 66-95% of patients), mononucleosis-like atypical lymphocytes (27-67% of pts), thrombocytopenia, lymphadenopathy (in 54% of pts) and multiple organ involvement. In 50-60% of patients, two or more organs are involved, most frequently liver (hepatomegaly, hepatitis with ALT&gt; 2 times and ALP&gt; 1,5 times the upper limit), kidney (acute interstitial nephritis, most often induced by allopurinol) and lung (interstitial pneumonia). Cardiovascular involvement occurs lately (up to four months after recovery) with myocarditis, decreased LV function and elevated troponin. Different mechanisms have been involved in the pathogenesis of DRESS syndrome, including detoxification defects leading to reactive metabolite formation and subsequent immunological reactions, slow acetylation and reactivation of human herpes, including Epstein-Barr virus and HHV-6. Cacoub et al reported 172 cases of DRESS: the most frequently reported “trigger-drugs” were carbamazepine, allopurinol, sulfasalazine, phenobarbital, nevirapine and HHV-6 infections were positive in 80% of cases. Interestingly, the culprit drug could be able to trigger viral reactivation, inducing a pathogenic anti-viral CD8+ response. According to available literature, the drug should be withdrawn and, in cases of visceral involvement, systemic steroids are indicated (1 mg/kg orally with slow taper over 3-6 months). In severe cases, other therapies include IVIG, plasmapheresis and immunosuppressant drugs.
CASE REPORT A 72-year-old male, affected by ESKD in peritoneal dialysis and hypokinetic heart disease, started lenalidomide for multiple myeloma with bone involvement. After 18 days he presented a violet maculopapular rash involving &gt;50% of his body, fever (38,5 °C), leukopenia with CRP &lt;0,8 mg/dl. Lenalidomide was withdrawn and started oral steroid, anti-histamine and levofloxacin. One week later he was admitted for a syncopal episode. Laboratory tests revealed leukocytosis (12.250/mm), eosinophilia (until 56%, 4.550/mm) and cholestatic-cellular liver damage (ALT 1448 U/l, ALP 308 U/l) requiring albumin infusion.
Extensive infectious and autoimmune workup was negative, including ANA test, immunological liver diseases tests, blood cultures, viral/bacterial tests, except for HHV6 reactivation (420 copies/ml). US abdominal study was negative, while DLCO test showed an important diffusive deficit. ECHO showed a reduced LV ejection.
Skin biopsy demonstrated sparse vacuolization of epidermis and dermal-epidermal inflammation with some eosinophils and CD8+ T cells, suggesting a drug reaction.
For clinic and laboratory features RegiSCAR score system and Japanese consensus group categorized this case as “definite DRESS” respectively with score 6 and 7. So we started IVIG (1 gr/Kg for 2 days) and prednisone with reduced dose for comorbidities (0,8 mg/Kg daily, tapered to 0,6 mg/Kg after 1 week); the patient gradually improved but after 1 week, DRESS syndrome relapsed with rash, elevated GOT and GPT and troponin until 330 ng/l with normal ECG; he has just started steroid bolus and IVIG.

Conclusion
The variety of drugs, the clinical course with slow resolution and relapse and HHV-6 reactivation suggest that drugs cannot be the sole etiology of DRESS. Precise mechanism of lenalidomide in DRESS syndrome is not clear and its immunomodulatory activity could contribute in the hypersensivity reaction. Only few cases are reported in literature, but with the increasing use of lenalidomide a broad workup and a careful approach are important for a fast diagnosis