DRESS Syndrome with Cold Agglutinins: An Unusual Immune Response to Anticonvulsants.

Introduction: DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) is a rare adverse drug reaction characterized by cutaneous and systemic manifestations, with a mortality rate of up to 10%. In this study, we describe the case of a 77-year-old man who developed DRESS syndrome with cold agglutination.

Case presentation: A 77-year-old man prescribed phenytoin and carbamazepine for suspected cranial neuralgia after a tooth extraction developed high-grade fever and hemorrhagic crusting on the upper and lower lips and oral mucosa, morbilliform rashes over the chest, abdomen, and back along with facial edema, all occurring over 2 weeks. Clinically significant right-sided submandibular, cervical, and axillary lymphadenopathy was observed. Additional findings, including peripheral blood eosinophilia, hepatitis, and coagulopathy, helped us make a provisional diagnosis of DRESS syndrome. The peripheral blood smear showed an incidental finding of cold agglutination phenomenon at room temperature (16 °C; winter months in North India), which disappeared under warmer conditions. However, gross hemolysis was not confirmed. The patient showed significant response in both clinical and hematological parameters within 24 hours of initiating intravenous dexamethasone, which was continued and gradually tapered over 14 days. Follow-up at one month showed the disappearance of the cold agglutination phenomenon.

Conclusion: Cold agglutination in DRESS syndrome has not been documented in detail in the past. One hypothesis is the agglutination of red blood cells (RBCs) due to the effect of the pathogenetic antibodies in DRESS syndrome directed against RBC antigens. Further molecular research may elucidate the pathways of this rare clinical finding.