Successful treatment of CINCA syndrome with a combination of etanercept and methotrexate in a Greek child

A 15 years old girl of Greek descent was admitted to our hospital for experimental treatment. The patient had been previously treated within the first 3 years of her life with azathioprine and ASS due to a diagnosis of Still's disease. At age 7 years CINCA syndrome (CINCA stands for Chronic Infantile Neurological Cutaneous and Articular) was suspected. In the following years different immunosuppressive therapy approaches were performed, none of which led to remission of the disease. Before admission to our hospital in May 2003, the patient suffered continuously from arthralgia, urticaria, as well as recurrent episodes of fever. On clinical examination, opticus atrophy, mild hemiplegia, arthritis and retardation of growth were found. Laboratory investigation showed significant elevation of several indicators of inflammation such as ESR, C-reactive protein, leukocyte count and TNF-α. Treatment was initiated with the TNF-α-inhibitor etanercept (Enbrel) in combination with methotrexate long-term therapy. This combined immunosuppressive therapy led to significant improvement of several clinical parameters including (i) general condition (ii) walking impairment (increase in walking distance from 20 m up to 500 m) and (iii) extent of urticarious exanthema. As inflammation parameters were still elevated under this treatment methotrexate dosage was increased, resulting in a decrease of these parameters. No side effects of the immunosuppressive therapy, particularly etanercept, were observed in the first weeks of treatment. Final dosage of etanercept was 2.5mg/kg s.c. twice weekly and methotrexate 20mg/sqm p.o. once weekly.

Conclusion: This is the first report of a combined application of etanercept and methotrexate in the treatment of CINCA syndrome. The described combination resulted in a significant improvement of the clinical outcome as well as inflammatory parameters in our patient. However, long-term observation of the patient under immunosuppressive therapy is necessary to support these preliminary observations.