Are there any reports of pachymeningitis as an adverse drug reaction to hydroxycarbamid?/nA middle-

Fråga: Are there any reports of pachymeningitis as an adverse drug reaction to hydroxycarbamid?

A middle-aged woman has essential thrombocytosis that has been treated with hydroxycarbamid (Hydrea) for more than ten years. Since seven years she has suffered from pachymeningitis, a rare autoimmune, granulomatous, vasculitis-induced meningitis that involves inflammation of the Dura mater.

Sammanfattning: We found no reports of pachymeningitis or other vasculitis involving the meninges as an adverse drug reaction after hydroxycarbamid treatment. Hydroxycarbamid use has in rare cases been associated with small vessel vasculitis, presented as cutaneous ulcerations on the lower limbs.

Svar: Hydroxycarbamid is a chemotherapeutic agent used for myeloproliferative diseases such as chronic myeloic leukaemia, polycytaemia vera and essential thrombocytosis. The mechanism of action is largely unknown but is thought to involve the inhibition of DNA synthesis (1).

In the Swedish adverse drug reaction database SWEDIS there are 76 reports for hydroxycarbamid but no reports dealing with pachymeningitis or other vasculitis disorders (2).

No relevant reports of pachymeningitis or other autoimmune disorders associated with hydroxycarbamid treatment were found in a literature review. Vasculitis causing cutaneous ulcerations is a rare side effect to hydroxycarbamid according to FASS but has been reported when hydroxycarbamid is concomitantly used together with interferons (1).

In Pubmed we found a few case-reports (N= 4 patients) of small vessel vasculitis, presented as cutaneus ulcerations localised to the legs, as a possible adverse drug reaction to hydroxycarbamid (3,4). No reports of vasculitis involving the meningies were found.

According to our literature review there is no evidence for pachymeningitis to be an adverse drug reaction to hydroxycarbamid. If the hydroxicarbamid treatment is stopped and the patient then recover from the pachymeningitis we recommend the questioner to report the case to the regional adverse drug reaction monitoring centre (Biverkningsenheten). FASS 2010 SWEDIS 2010-01-20 Stahl RL, Silber R. Vasculitic leg ulcers in chronic myelogenous leukemia. Am J Med. 1985 May;78(5):869-72 Tomiyama J, Yano K, Uchino S, Ito T, Kudo H, Irimajiri J, Ohkubo H, Kanazawa A, Kawahara Y. Bilateral leg ulcers with pathologic evidence of small vessel vasculitis by skin biopsy during hydroxyurea therapy of chronic myelogenous leukemia] [Article in Japanese] Rinsho Ketsueki. 1997 Mar;38(3):231-3. (Abstract)