Imatinib-Induced Erythema Nodosum : A Case Report and Literature Review

The list of drugs inducing an erythema nodosum is long and is extending. Their accountability is difficult to ascertain; rare observations relate positive drug provocation tests. Observation: We report a case of subintrant push of erythema nodosum caused by the Imatinib (Glivec) administration in a patient aged of 34 years old and followed for chronic myeloid leukemia. The drug provocation test was positive. In front of the recurrent, the painful character, the significant functional deficiency caused by the lesions and the positive drug provocation test, the imatinib was finally stopped. The evolution was characterized by the absence of recurrence 2 years after stopping the treatment. Conclusion: Even if it is exceptional, the Imatinib may induce severe erythema nodosum imposing its stopping. Such side effects should be reported to improve their monitoring and treatment.


Introduction
The list of drugs inducing erythema nodosum (EN) is long and extending.Their accountability is difficult to ascertain, rare observations relate positive provocation tests.The Imatinib is a chemotherapeutic means used to treat many diseases, including chronic myelogenous leukemia.Many skin reactions to this drug have been described in the literature, however, the EN caused by its use is rare.We report a case of EN induced by the Imatinib with a positive drug provocation test.

Case Report
Ms. N.B, 34 years old, followed because of chronic myeloid leukemia, takes Imatinib (Glivec) 400 mg / day with a good clinical and hematologic reaction.The patient presented, one month after the start of the treatment with Imatinib, several erythematous and painful nodules, associated with arthralgia, in the upper and lower limbs,.The symptoms evolved by subintrant pushes that last 2 to 4 weeks without leaving any residual pigmentation.Her clinical examination at the admission showed various erythematous nodules embedded in the dermis, with variable size, from 1 to 3 cm, well limited, hot and painful spontaneously and on palpation, located in the upper limbs (Figure 1) and lower limbs (Figure 2).The skin biopsy revealed a mostly septal

Discussion
The EN is the most frequent and the best individualized among the panniculitides.The pathogenesis of EN is not fully elucidated.It is likely a delayed hypersensitivity reaction, which can be triggered by a variety of infectious and non-infectious antigenic stimuli including drugs like it would be the case with your patient [1].
The EN is clinically translated by the unexpected appearance of painful, warm, erythematous, slightly raised nodules, measuring one to five centimeters in diameter and may coalesce to form plaques. Usually, these lesions undergo a bruise-like transformation and disappear after two to eight weeks without leaving scars [2,3].
Habitually, the lesions reach bilaterally and symmetrically the extension faces of the lower limbs.However, all body parts can be affected as the ankles, the thighs, the forearms, the face, the neck and the trunk [4,5].
Nevertheless the etiology, the nonspecific symptoms may occur.They include: malaise, low-grade fever, and arthralgia with or without arthritis [6].
The diagnosis of the EN is usually clinical.The skin biopsy is not required in typical forms; when we performed it, it objectives, habitually, septal panniculitis without vasculitis [7,8].
The etiologies of the EN are numerous including: infections, malignancies, autoimmune diseases, systemic illnesses, drugs, and pregnancy [9].Our patient had two conditions that can induce the EN: the leukemia and taking the Imatinib, but she had not made any push to the EN before the taking of this drug and the provocation test was positive which advocates its accountability.
The Imatinib is an oral inhibitor of the tyrosine kinase BCR-Abl, c-KIT and platelet-derived growth factor receptor, successfully used in the treatment of several diseases such as chronic lymphocytic leukemia, gastrointestinal stromal tumor, hypereosinophilic syndrome, chronic myelomonocytic leukemia, systemic mastocytosis, dermatofibrosarcoma protuberans and melanoma.
Despite its enormous therapeutic effects, the Imatinib has very frequent side effects including digestive disorders (nausea, vomiting, diarrhea), asthenia, myalgia, cramps, fluid retention and lowered resistance to infection (due to neutropenia) [10].
Only one case of Imatinib-induced EN has-been described in the literature by Drummond et al.This was a patient with tender subcutaneous nodules that were clinically and histologically consistent with EN, not controlled with oral prednisilone and azathioprine, ultimately required stop of the therapy [12].
Our patient had a severe form of E.N, recurrent and moderately relieved by symptomatic treatment, hence, the decision to substitute the Imatinib by another treatment, considered as effective but less provider of severe adverse effects.

Conclusion
Even if it is exceptional, the Imatinib may induce severe EN imposing its stopping and its substitution by another therapeutic alternative.
stopping of the Imatinib and its substitution by Nilotinib were decided.The evolution was marked by the absence of recurrence 2 years after stopping the Imatinib.

Figure 1 :
Figure 1: Painful erythematous nodules of the upper limbs.

Figure 2 :
Figure 2: Painful erythematous nodules of the lower limbs.