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.