Rare Side Effects of Subcutaneous Methotrexate Therapy

To the Editor:

I read with great interest the recent report by Hassanzadeh, et al¹. Subcutaneous methotrexate (MTX) may rarely be associated with a number of unique side effects.

Pulmonary complications such as pneumonitis have been reported following the use of subcutaneous MTX². Similarly, the uses of subcutaneous MTX may be associated with the development of tumors such as pylomatrixomas³. Cutaneous B cell lymphomas may develop at the subcutaneous injection site. For instance, Giard, et al have reported the development of Epstein-Barr virus-associated B cell lymphomas at the subcutaneous injection site⁴.

Semicircular atrophy is another rare dermatological complication. It is especially seen in children who are administered subcutaneous MTX⁵. It is more common when the MTX is administered in the anterior thigh region. Rarely, the neurological system may also be involved. Neurological symptoms may include weakness and dysmetria². Dysarthria has also been reported following subcutaneous MTX administration. Neurological findings such as hyporeflexia and magnetic gait may be seen.

The above examples highlight the rare complications of subcutaneous MTX and the need to monitor these patients for the development of these side effects.