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].