Rheumatic Complications of Human Immunodeficiency Virus Infection in the Era of Highly Active Antiretroviral Therapy: Emergence of a New Syndrome of Immune Reconstitution and Changing Patterns of Disease

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Objective

To describe the impact of the introduction of highly active antiretroviral therapy (HAART) on the nature and frequency of rheumatic complications in human immunodeficiency virus (HIV)-infected patients.

Methods

Case report and systematic review of a newly described syndrome of rheumatic immune reconstitution syndrome and prospective longitudinal cohort study analyzing the frequency and nature of rheumatic complications in the setting of HIV infection from 1989 through 2000.

Results

A newly described syndrome of either the de novo appearance or the exacerbation of clinically occult autoimmunity following immune reconstitution from HAART is described. Including the present case report, 32 cases have been individually described with sarcoidosis and autoimmune thyroid disease being most common with arthritis and various forms of connective tissue disease making up the rest. The mean onset to their appearance following HAART was nearly 9 months and most resolved with little or no therapy. In addition, a longitudinal analysis of 395 HIV-infected patients from 1989 to 2000 designed to detect the appearance of rheumatic complications has revealed a dramatic decline in certain problems such as reactive arthritis, psoriatic arthritis, and various forms of connective tissue disease. New rheumatic complications possibly due to the effects of longer survival and metabolic derangements associated with this form of therapy are now being described and may become more formidable problems in this population in the future.

Conclusions

HAART has had a profound beneficial effect on survival in HIV-infected patients but has also contributed to both an altered frequency and a different nature of rheumatic complications now being observed in this population. Rheumatologists need to be aware of these changes to provide optimal diagnosis and treatment for this group.

Section snippets

Part 1. Case Report

A 39-year-old homosexual man was diagnosed with HIV in March 2003 after 2 months of generalized weakness and vertigo culminating in cranial nerve VII and VIII shingles (Ramsey–Hunt syndrome) and resulting in right peripheral cranial nerve VII palsy. His past medical history was remarkable only for migratory superficial thrombophlebitis in the remote past. There was no family history of connective tissue disease; however, he has a twin sister with ulcerative colitis. At the time of HIV diagnosis

Methods

We performed a computer-based search from 1996 to 2004 (MEDLINE, National Library of Medicine, Bethesda, MD). Keywords used in the search were as follows: HAART, antiretroviral therapy (highly active), autoimmunity, lupus, arthritis (rheumatoid), arthritis (psoriatic), arthritis (reactive), systemic lupus erythematosus, connective tissue disease, vasculitis, sarcoidosis, prednisone, HIV-1, HIV infections, anti-HIV agents, immune reconstitution, acquired immunodeficiency syndrome,

Results

Table 1 describes all cases of noninfectious autoimmune complications to have presumably occurred as a consequence of immune reconstitution as a result of HAART (10, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39). Of the 31 cases reported, sarcoidosis appears to be the most common, followed by autoimmune thyroid disease, and then various forms of inflammatory arthritis and connective tissue disease. Given that this entity has not been clinically described in any

Patients and Methods

Beginning in September 1989, all HIV-infected patients seen in the Clinical Immunology Department of the Cleveland Clinic Foundation were enrolled in a prospective study of potential manifestations of rheumatic disease. Each patient underwent a baseline history and physical examination and a detailed rheumatologic evaluation by a rheumatologist (L.H.C.). Only patients seen and evaluated for primary treatment of their underlying HIV disease were enlisted; all patients referred for the expressed

Results

The demographics of the overall study group, including age, sex, and HIV risk behaviors, are stated in Table 2. Among the 395 HIV-infected subjects enrolled in the study, 57 were already receiving follow-up care at the time the prospective study was initiated in 1987 (follow-up 0 to 61 months); thus these patients were studied both retrospectively and prospectively. The remaining 338 patients were studied only during the prospective phase of the study. The mean duration of known HIV infection

Discussion

Since the beginning of the epidemic of HIV/AIDS in the early 1980s much has been written about rheumatic complications. Numerous case reports and clinical series from both Western industrial as well as underdeveloped countries have helped define a spectrum of disease that while clinically uncommon often displays distinctive features. The vast majority of these reports arose in the era before HAART became the standard of care (ie, before late 1995). Differentiating infectious and autoimmune

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