Fixed drug eruption due to nabumetone in a patient with previous fixed drug eruptions due to naproxen.

Nabumetone is a nonacidic nonsteroidal anti-infl ammatory drug (NSAID) formulated as a pharmacologically inactive prodrug that becomes active only after absorption, predominantly in the small intestine, and through hepatic conversion to its active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA). This metabolite is structurally similar to naproxen, and is a potent inhibitor of prostaglandin synthesis, preferentially via the cyclooxygenase-2 (COX-2) pathway [1]. Nabumetone has been recommended as a safe alternative in most patients with hypersensitivity reactions to NSAIDs [2]. A 52-year-old woman complained of various episodes of itching, burning, and erythematous plaques—one on her forehead (1-2 cm diameter) and the other in the infraclavicular area (5 cm diameter)—in the previous 2 years. The plaques became red-brown and disappeared within 1 week without treatment. With time, the infraclavicular lesion persisted as brown pigmentation. After various episodes the patient noticed that the eruption might be related to the intake of naproxen tablets, but she was not sure. The last episode had occurred 1 year before consultation and she had subsequently tolerated oral acetylsalicylic acid, paracetamol, and ibuprofen. In order to confi rm the suspicion of fi xed drug eruption (FDE) due to naproxen, patch tests (30% in petrolatum) were carried out with this drug and other propionic acid derivatives (ibuprofen, dexibuprofen, ketoprofen, dexketoprofen, flurbiprofen, and ketorolac) and NSAIDs (diclofenac, indomethacin, benzydamine, bufexamac, phenylbutazone, piroxicam, and nabumetone). The tests were performed on previous lesions with naproxen and on the back (normal skin) with all the drugs mentioned. Readings at 48 and 96 hours were negative in all cases. An oral challenge test with naproxen was performed in the hospital after obtaining informed consent. Two hours later, lesions with the same characteristics as those described earlier reappeared at the same locations. With the purpose of identifying safe alternatives to naproxen, we performed oral challenge tests with dexketoprofen and nabumetone 6 weeks later. While dexketoprofen proved negative, nabumetone (1 g) produced an identical reaction to that induced by naproxen 2 hours after administration. The patient had not taken nabumetone previously. Nabumetone is generally a well-tolerated NSAID. The most frequent adverse effects are those commonly seen with COX inhibitors, namely diarrhea, dyspepsia, headache, abdominal pain, and nausea. Dermatological reactions such as pseudoporphyria have been associated with nabumetone, but systemic hypersensitivity reactions are not common [1]. To our knowledge, this is the fi rst report of FDE due to nabumetone and our case is particularly interesting because our patient had experienced previous FDE to naproxen. NSAIDs are common offending agents in FDE, and FDE to naproxen has been reported in single case reports and in some studies with a prevalence ranging from 3% [3] to 23% [4]. Lesions induced by naproxen frequently affect the lips, the face, and the neck [4]. False negative results are common when testing topical naproxen on both normal skin and previous FDE lesions, and oral provocation is still the most reliable method for the diagnosis of FDE [5,6]. Although cross-reactivity between drugs with similar molecular structures is possible, in a previous study, we did not fi nd cross-reactivity between naproxen and other propionic acid derivatives [6]. However, in the case reported here, the administration of nabumetone (a naphthylalkanone NSAID) was positive. In our opinion, the similarity of the chemical structure of naproxen and the active metabolite of nabumetone could be the reason for this reaction. Because there are no references in the literature to nabumetone intolerance in patients with FDE to naproxen, we believe that our case is interesting as it might help to prevent such reactions in the future.