DISCUSSION:
The mechanism underlying SJS still remains unknown in patients
administered with combination chemotherapy. In our case, we believed
that the patient’s problem was related to one of the four chemotherapy
drugs since the syndrome was not present before the initiation of
chemotherapy, suggesting that it was not part of the presenting features
of his disease.
Although SJS occurs in a very small percentage of patients who use
chemotherapy drugs, there are several reports reporting a potential
association of anticancer drugs with SJS and TEN, including conventional
cytotoxic and novel targeted agents. [6] In our case, the last
administered drug to the patient was Daunorubicin which according to
FAERS (Food and Drug Administration Adverse Effect Reporting System) has
very few reported cases of SJS. [6] We believe Daunorubicin to be
the culprit for SJS in our patient as the immediate withdrawal of
Daunorubicin led to improvement in signs and symptoms.
Daunorubicin forms the cornerstone of treatment in the remission
induction of both adult and childhhod acute leukaemia. A liposomal
formulation of daunorubicin is available as a first line therapy for
advanced HIV related Kaposi sarcoma. It is a cytotoxic antibiotic which
acts by intercalating between DNA base pairs and uncoiling the DNA
helix, which results in inhibition of DNA synthesis and apoptosis of
rapidly dividing cells. Common side-effects of Daunorubicine include
myelosuppression, nausea, vomiting, mucositis, diarrhea, alopecia, red
urine and cardiotoxicity. Cutaneous side effects are very rare and
include reversible alopecia, rash, contact dermatitis and urticaria.
[7] The possible association of Daunorubicin with SJS has not been
well-established and inconsistently reported.
The main difficulty in attempting to identify an offending agent in
chemotherapy that may potentially serve as triggers stems from the
frequent co-administration of not only multiple anticancer agents but
also drugs that are known to have strong associations with these
cutaneous reactions (e.g. sulfonamide antibiotics, corticosteroids,
allopurinol). [1-4] In the majority of published case reports
patients were exposed to multiple agents.
In our case, the patient was also co-administered corticosteroids as
part of the remission induction chemotherapy. Although, there are few
reports suggesting corticosteroids as an offending agent of SJS/TEN,
their role as triggers is not clearly defined and there is a high
potential for confounding by several factors, including the use of
anti-infective and anticonvulsant agents, a history of radiotherapy, and
a history of collagen vascular disease. [8,9]
The mucocutaneous complications of anti-cancer drugs are widely observed
in oncology and hematology departments, but clinicians/oncologists may
overlook these reactions because of the severity of the underlying
primary disorder itself. In conclusion, it is very critical but
complicated to identify the offending agents when oncologic patients
develop SJS during chemotherapyIt is crucial to be able to differentiate
life-threatening cutaneous adverse reaction that require immediate
management from more benign manifestations of chemotherapy and treat the
same as an oncologic emergency. The potential association of
Daunorubicin with SJS should be considered and administered with
caution. As soon as the first suspicious sign of SJS/TEN is observed,
the offending drug must be discontinued immediately, aggressive medical
management must be started or the patient must be referred to
appropriate centers promptly.
Early recognition and intervention can significantly alter the course of
the disease and improve the outcome. Identification and prompt removal
of precipitating factors are the most pivotal steps for the lifesaving
management of SJS.