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Successful desensitization to mycophenolate mofetil: a case report.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disorder with a wide range of clinical features. Diagnosis is based on clinical assessment supported by investigations, including autoantibody determinations [1]. In a significant number of patients, SLE can cause nephritis, which can result in renal failure, with significant morbidity and mortality [2]. The immunosuppressive agents commonly used to treat SLE (eg, corticosteroids, cyclophosphamide, azathioprine, and ciclosporin) have a high incidence of severe side effects [3]. Consequently, mycophenolate mofetil (MMF) was used to treat lupus nephritis, initially in uncontrolled cohort studies and then in randomized controlled trials [2]. Hypersensitivity to MMF in SLE and successful desensitization to MMF were first reported by SzyperKravitz et al in 2005 [4]. The clinical picture comprised a maculopapular rash that was suggestive of type IV hypersensitivity reaction. We report the case of a patient with SLE that was refractory to standard immunosuppressive regimens who developed a hypersensitivity reaction to MMF and underwent successful desensitization. The patient experienced maculopapular rash with the first dose and anaphylaxis with the second, thus indicating both type I and type IV hypersensitivity reaction. No reactions occurred during the desensitization procedure, and the final total dose of 2000 mg was successfully administered. A 24-year-old woman diagnosed with SLE at the age of 19 was referred to our allergy outpatient clinic because of previous hypersensitivity reactions to MMF. The patient had been receiving corticosteroids for 5 years. Azathioprine was included in the treatment schedule to control SLE but was suspended because of its side effects. Since the disease remained uncontrolled with conventional therapy, MMF was started at a daily dose of 2000 mg. A maculopapular rash developed during the first 2 weeks, and treatment was stopped. The reaction was successfully managed with methylprednisone and pheniramine, and the rash resolved within 3 days. Three weeks later her doctors decided to reintroduce MMF to the treatment schedule. Thirty minutes after taking 1000 mg of MMF orally, she experienced an anaphylactic reaction, which manifested as dyspnea, palpitations, and hypotension, and was immediately given 0.3 mg of epinephrine, 45 mg of pheniramine, and 40 mg of methylprednisolone. The reaction resolved within 2 hours. A skin test with the culprit drug was performed to investigate drug hypersensitivity. This test was conducted 4 weeks after the last reaction to minimize the likelihood of a false-negative result. A skin prick test was performed on the volar forearm with the drug crushed and diluted in 1 mL of 0.9% saline solution according to a method described elsewhere [5]. The result was negative after 15 minutes. Since intradermal skin testing was unviable because a parenteral form of the drug does not exist, a patch test was performed with the drug crushed and diluted in petrolatum (30% drug + 70% petrolatum) [5]. This test revealed a positive reaction (++) in the first hour. Vesicles and papules appeared at the patch test site on the second day. The positivity in the first hour was considered an irritant reaction, but the positivity on the second day was considered a delayed-type reaction. Skin testing in 10 healthy volunteers did not reveal a positive reaction, thus confirming the positivity of the patch test result. As alternative immunosuppressive treatment was not recommended, a desensitization protocol with MMF was planned. After the patient gave her informed consent, desensitization was carried out in an intensive care setting with oral doses of MMF that increased according to the schedule presented in the Table; 40 mg methylprednisone and 45.5 mg pheniramine were administered intravenously 30 minutes before initiation of the protocol. No adverse reactions were observed during the desensitization procedure, and the patient eventually tolerated a total dose of 2000 mg. We report the case of a patient with a history of anaphylaxis and maculopapular rash due to MMF to treat SLE. The patient successfully completed a desensitization protocol for MMF. The literature contains only 1 report of a patient with SLE who experienced a maculopapular rash due to MMF and was successfully desensitized [4]. Szyper-Kravitz et al [4] administered the desensitization protocol based on gradual