Discussion:
The diagnosis of DRESS syndrome was made in this patient based on the criteria adopted by the European group RegiSCAR [3]. In our case, the score was four(probable case) because of: skin rash over 50% of body surface area (1 point), facial edema and infiltrated skin lesions (1 point), generalized lymphadenopathy (1 point) and eosinophilia at 14.9% (1 points). The responsibility of allopurinol in inducing DRESS syndrome was evaluated as I3 (C2S2) according to the updated French method of imputability because of the compatible delay (22 months after dug intake) and the favorable outcome after the medication withdrawal [4,5].
Despite that currently the pathogenesis of allopurinol-induced DRESS syndrome is only partially understood, it is thought to be multi-factorial and implicate at least three components[6]: first, the accumulation of allopurinol’s metabolite which may directly cause cell damage. Second, genetic predisposition through specific human leukocyte antigen (HLA) allele’s subtype. The third possible component is that DRESS syndrome, as a delayed hypersensitivity reaction, may induce the reactivation of viruses of the Herpes group by the activation of T lymphocytes. In fact, it has demonstrated that the TH1-type cytotoxic T cell response was directed against viral antigens and not against drugs. In this situation the drug promote the passage from a latent stage of infection to a viral reactivation, by increasing the viral replication either by a direct action on the virus itself, or by creating a state of immunosuppression[7]. This cascade reaction is thought to be accelerated by community-acquired bacterial and viral infections and can be observed in other stressful situations of immunosuppression such as hospitalizations in intensive care units [8].
The clinical presentation of DRESS syndrome is variable and occurs in response to a range of drugs, usually 3 weeks to 3 months after initiation. In the present case, allopurinol was being used over 22 months, but the clinical manifestations appeared, six weeks after the first urinary tract infection and 15 days after the second one, which is a suggestive delay.
Hence, we believe that these two infectious episodes, with the hospital stay, might have contributed to accelerate the cascade reaction by creating a state of immunosuppression and inducing a viral reactivation. This hypothesis might explain the longer delay, than generally accepted, between initiating allopurinol and the occurrence of DRESS syndrome. However, we could not determine the HHV-6, HHV-7, CMV and EBV reactivation, due to lack of the measurement kits at our laboratory. To the best of our knowledge, there has only been one patient diagnosed with DRESS syndrome after a long drug exposure. In that case, the patient had been treated for 12 months with sulphasalazine, and had undergone H1N1 vaccination 4 days prior to the symptoms. HHV 6 reactivation had been confirmed with a serological test [9].