Large lymphadenopathies complicating the abacavir hypersensitivity reaction

Abstract

Abacavir is a nucleoside analogue approved for the treatment of HIV infection, which may cause hypersensitivity reactions within the first 4–6 weeks of therapy in approximately 5% of cases [1]. Typically, clinical manifestations include fever, rash, malaise, respiratory and gastrointestinal symptoms. Herein, we report three individuals who developed large lymphadenopathies after the initiation of abacavir-containing regimens, mimicking immune reconstitution inflammatory syndrome (IRIS). Three Caucasian men infected with HIV were admitted to two hospitals located in Madrid complaining of painful neck enlargement, along with fever, rash and severe malaise. The CD4 cell counts were below 350 cells/μl in two of them and all had plasma HIV-RNA levels above 1000 copies/μl (Table 1). All but one had started their first antiretroviral therapy 6–7 days earlier with distinct abacavir-containing antiretroviral regimens. The third patient had already been on antiretroviral therapy and had experienced a doubtful abacavir hypersensitivity reaction with fever and malaise 12 months earlier in another hospital after exposure for only 3 days to abacavir, which was discontinued. Currently, he had begun a regimen with abacavir, lamivudine and atazanavir/ritonavir before presenting 5 days later with a large neck and axilar lymphadenopathies.Table 1: Main characteristics of the study population.Although painful lymph node enlargement was the main reason for complaining in all three patients, mimicking IRIS, all patients presented with fever and rash. Although they had been advised to stop abacavir in case these symptoms developed, they continued on the drug until painful lymphadenopathies appeared. Physical examination revealed large cervical and axilar lymphadenopathies in all cases. Laboratory values showed liver enzyme elevations and leukocytosis. All antiretroviral agents were discontinued and intravenous fluids and corticosteroids were given. The first two patients completely recovered after 3–5 days. The patient who had been rechallenged with abacavir recovered from lymphadenopathies within 5 days but developed multiorgan failure that required admission to the intensive care unit. Eventually he completely recovered over the next 3 weeks. All patients were retrospectively tested for HLA-B*5701 and were found to be positive. Drug hypersensitivity is the major limiting side effect of abacavir therapy. It must be considered in all HIV-infected individuals presenting with suggestive clinical signs or symptoms within the first 4–6 weeks of abacavir therapy. Resolution is the rule within 72 h after drug withdrawal. Characteristic manifestations include fever, rash, fatigue, respiratory or gastrointestinal symptoms. The persistent use of abacavir despite initial manifestations or unrecognized hypersensitivity reactions may result in the development of severe clinical illness comprising lethargy, generalized oedemas and respiratory insufficiency. Anaphylaxis will evolve to hepatic and renal failure, hypotension, and eventually death [2]. Laboratory abnormalities may include changes in liver function tests, and increases in creatine phosphokinase, lactate dehydrogenase and creatinine. Drug hypersensitivity reactions accompanied by lymph node enlargements have already been reported in association with allergic reactions to penicillin, cephalosporines, sulfonamides, carbamazepine and phenytoin [3]. To the best of our knowledge, this is the first report of lymphadenopathies as part of the abacavir-associated hypersensitivity reaction, probably because patients are generally advised to stop the medication as soon as the first hypersensitivity reaction manifestations appear. The suspicion of IRIS may challenge the recognition of abacavir-associated hypersensitivity reaction when lymph node enlargement is the main clinical manifestation, as it was in our cases. Large lymphadenopathies and dermatological manifestations may be recognised in up to one third of IRIS after the initiation of potent antiretroviral therapy [4]. The presence of severe immune deficiency and high viral load along with rapid CD4 cell gains after HAART initiation favours the diagnosis of IRIS. Corticoids may help to manage IRIS even without stopping HAART. In contrast, abacavir-associated hypersensitivity reaction may evolve to fatality if antiretroviral therapy is continued. The removal of abacavir and the positive testing for HLA-B*5701 clearly confirmed the diagnosis in our patients. The strong positive predictive value of abacavir-associated hypersensitivity reaction of the HLA-B*5701 allele has been well established in Caucasian and Hispanic individuals [5–9]. In conclusion, large lymphadenopathies mimicking an immune inflammatory reaction may develop in patients who start an abacavir-containing regimen and continue to receive the drug despite initial manifestations of hypersensitivity reaction. HLA-B*5701 testing may help to make the appropriate diagnosis. Conflicts of interest: None.