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Revista do Instituto de Medicina Tropical de São Paulo

versão On-line ISSN 1678-9946

Rev. Inst. Med. trop. S. Paulo vol.54 no.4 São Paulo jul./ago. 2012 



Acute gouty arthritis as a manifestation of immune reconstitution inflammatory syndrome after initiation of antiretroviral therapy


Gota aguda como manifestação da síndrome inflamatória de reconstituição imune após início de terapia antirretroviral



Walter de Araujo Eyer-Silva; Maria Cecília da Fonseca Salgado; Jorge Francisco da Cunha Pinto; Fernando Raphael de Almeida Ferry; Rogério Neves-Motta; Marcelo Costa Velho Mendes de Azevedo; Carlos Alberto Morais-de-Sá

Clínica Médica B, 10ª Enfermaria, Hospital Universitário Gaffrée e Guinle, Departamento de Medicina Geral, Universidade Federal do Estado do Rio de Janeiro (UNI-RIO), Rio de Janeiro, Brazil

Correspondence to




Immune reconstitution inflammatory syndrome (IRIS) in HIV-infected subjects initiating antiretroviral therapy most commonly involves new or worsening manifestations of previously subclinical or overt infectious diseases. Reports of non-infectious IRIS are much less common but represent important diagnostic and treatment challenges. We report on a 34-year-old HIV-infected male patient with no history of gout who developed acute gouty arthritis in a single joint one month after initiating highly active antiretroviral therapy.

Keywords: Antiretroviral therapy; Gout; HIV infection; IRIS.


A síndrome inflamatória da reconstituição imune (IRIS) observada quando do início da terapia antirretroviral em indivíduos com infecção pelo HIV envolve mais comumente manifestações novas ou piora clínica de desordens infecciosas, previamente subclínicas ou não. Muito mais raras são as descrições de casos de IRIS de natureza não-infecciosa, embora representem importantes desafios ao diagnóstico e tratamento. Neste relato descrevemos um paciente HIV-positivo do sexo masculino, de 34 anos, sem antecedentes de gota e que desenvolveu monoartrite de gota um mês após início de terapia antirretroviral de alta atividade.




Reports of unusual symptoms and signs appearing in HIV-infected patients soon after initiation of antiretroviral therapy and associated with increasing CD4 cell counts have been reported since the advent of highly active antiretroviral therapy (HAART). This paradoxical clinical worsening, which has been termed immune reconstitution inflammatory syndrome (IRIS), most commonly involves new or worsening manifestations of previously subclinical or overt infectious diseases such as tuberculosis, Mycobacterium avium infections, cryptococcal meningitis, herpes zoster and cytomegalovirus disease5. Reports of non-infectious IRIS are much less common but represent important diagnostic and treatment challenges. We report on a patient who had no history of articular disease who developed gouty arthritis in a single joint after initiating HAART.



A previously asymptomatic, mildly overweight 34-year-old HIV infected male was started on a highly active antiretroviral regimen (lamivudine, tenofovir, atazanavir and ritonavir) due to a progressive decline of CD4 cell counts. At the time of HAART initiation his CD4 cell count was 166 cells/mm3 (a drop from 680 cells/mm3 to 166 cells/mm3 had been recorded in an 18-month period). Three weeks after initiation of HAART he presented with an abrupt onset of severe pain, redness and swelling in the area of the first right metatarsophalangeal joint. He complained of exquisite soft tissue tenderness to the point that he could not put on his right shoe. Laboratory evaluation was remarkable for mild hyperuricemia (7.7mg/dL; normal range 3.5-7.2mg/dL; uric acid urinary excretion was not measured). Serum uric acid had not been measured before the acute gout presentation. No abnormalities were found on plain radiology. The patient had no past history of gout or other rheumatological disorders, but informed that his father was a long-term gout sufferer. He also had no history of urolithiasis and was not under any other medication besides HAART and sulphametoxazole/trimethoprim thrice weekly. General measures of rest, a low-purine diet, and avoidance of alcohol intake were instituted. Colchicine and a nonsteroidal anti-inflammatory drug were started with slow resolution over the ensuing three months. During this period the patient experienced disabling, ongoing symptoms with intense inflammation, desquamation and a toothpaste-like, chalky discharge (Fig. 1). Despite the severity of the presentation and its temporal association with the initiation of the antiviral regimen, a decision was made not to interrupt HAART. Allopurinol was initiated one month after the acute presentation and a better clinical control was achieved. A progressive recovery of the CD4 cell count was recorded: 306 cells/mm3 and 459 cells/mm3 two and five months after initiation of HAART, respectively. The plasma HIV viral load dropped from 817.111 copies/mL to 57 copies/mL before and five months after HAART initiation, respectively. Six months after the acute presentation the patient still experienced gout flares associated with binge alcohol consumption (mainly beer) and non compliance with the prescribed diet. One year after presentation the patient was asymptomatic. No other joint has ever been affected. The serum uric acid returned to normal levels (7.2 mg/dL and 4.0 mg/dL, one and five months after acute gout presentation, respectively).






Non-infectious IRIS cases are being reported much less frequently than the clinical worsening or the unmasking of infectious disorders. One of the first such cases was reported in 19981 from a 36 year-old woman who developed systemic lupus erythematosus associated with rising antinuclear antibody titers after initiation of HAART. Since then, a variety of non-infectious IRIS cases have been reported, including sarcoidosis7, lymphoid pneumonitis7, cutaneous reaction to tattoo pigment11, alopecia universalis and Graves disease10, rheumatoid arthritis2, and Guillain-Barré syndrome8. SEBENY et al.9 have previously reported on a 53-year-old HIV-infected male patient with a history of intermittent attacks of gout who developed severe polyarticular gouty arthritis one week after initiation of a HAART regimen consisting of tenofovir, emtricitabine and efavirenz.

Gout has rarely been reported in association with HIV infection4. The present case shares resemblance to the previously reported patient who presented with polyarticular gouty arthritis as a manifestation of IRIS9. In contrast to the case reported by SEBENY et al.9, our patient had no prior history of gout and presented with monoarticular disease. Interestingly, he presented a relentless acute gout syndrome associated with exquisite pain that lasted three months and went on to develop signs of a draining tophus, which is uncommon in patients without prior signs and symptoms of gout. It has been suggested that improvements in neutrophil function and decreasing levels of the anti-inflammatory IL-10 cytokine after initiation of HAART may result in a restored ability to react against monosodium urate crystals9. The effect of individual antiretroviral agents on uric acid metabolism should also be considered. It is known that the nucleoside analogs stavudine and didanosine are associated with hyperuricemia, whereas the nucleotide analog tenofovir seems to lower serum uric acid12. It has also been suggested that ritonavir-including regimens may be associated with an increased risk of hyperuricemia and gout3,6.

Physicians caring for HIV-infected patients should be aware that severe acute gouty arthritis may emerge as a non-infectious manifestation of IRIS in HIV-infected patients initiating HAART.



The authors declare no conflict of interest.



There was no financial support.



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Correspondence to:
Prof. Walter A. Eyer-Silva
10ª Enfermaria, Hospital Universitário Gaffrée e Guinle
Rua Mariz e Barros 775, 20270-004 Rio de Janeiro, RJ, Brasil

Received: 8 February 2012
Accepted: 2 May 2012

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