Rheumatologic manifestations of HIV disease are being recognized with increased frequency. Musculoskeletal complaints are reported in 33 to 75% of HIV-infected patients and may present as a variety of rheumatologic disorders (
Table 417-3) . The severity of disease ranges from intermittent arthralgias to debilitating arthritis and vasculitis. An array of autoimmune antibodies, including antinuclear, antiplatelet, antilymphocyte, antigranulocyte, and antiphospholipid (anticardiolipin and lupus anticoagulant) antibodies are associated with HIV infection along with circulating immune complexes, rheumatoid factor, and cryoglobulins. Despite the presence of these antibodies in some patients, the precise mechanisms by which the rheumatologic abnormalities develop have not been elucidated and most likely are different for each particular disorder.
Arthralgia is a common manifestation of acute HIV seroconversion, in addition to fever, myalgia, headache, sore throat, abdominal cramps, and lymphadenopathy. Generalized arthralgias are reported in up to one third of HIV-infected patients with minimally symptomatic disease. Some patients develop arthralgias and myalgias when zidovudine therapy is initiated; however, these symptoms are usually self-limited and abate within 4 to 6 weeks after starting treatment.
The “painful articular syndrome” is characterized by severe articular pain of 2 to 24 hours’ duration. Although uncommon, this disorder is quite incapacitating and usually unresponsive to oral nonsteroidal anti-inflammatory agents (NSAIDs) or narcotic analgesics. Its etiology remains unknown. With the exception of the painful articular syndrome, most of the arthralgias associated with HIV disease are treated with nonsteroidal agents.
Polymyositis-like illnesses, characterized by myalgias, proximal muscle weakness, and wasting, have been reported in several HIV-infected patients and have been the initial HIV-defining presentation in a few. The findings of creatinine phosphokinase (CPK) elevation (>5 times normal) and abnormal electromyography are indistinguishable from idiopathic polymyositis. Muscle biopsies reveal necrosis, fibrosis, and inflammation, but usually to a lesser extent than is noted in non-HIV-infected individuals. The presence of nemaline rods, often noted in muscle biopsies of older adults with myositis, suggests the likelihood of underlying HIV infection when noted in biopsy specimens obtained from younger adults, especially in the absence of inflammation.
Although virus-like particles have been demonstrated rarely in synovial tissue and HIV p24 antigen has been noted in the cytoplasm of degenerating muscle cells, no specific viral etiology has been determined. All attempts to culture HIV-1 from muscle tissue of patients with myositis have been unsuccessful.
Patients receiving long-term zidovudine therapy may develop myositis characterized by muscle weakness, elevated CPK levels, myalgias, and evidence of myopathy with a paucity of inflammatory cells on biopsy. Zidovudine-associated myositis usually responds to drug discontinuation and may recur on rechallenge. No definitive therapy exists for HIV-associated polymyositis, although corticosteroid therapy has been successful in reversing symptoms in some patients. If corticosteroid therapy is contemplated, the potential risks of superimposing immunosuppressive therapy on an immunocompromised host must be considered.
Reiter’s syndrome is noted in up to 10% of HIV-infected patients who develop arthritis, and an additional 10 to 20% of patients are classified as having “reactive arthritis” because they lack the nonarticular features of Reiter’s. Severe, persistent oligoarticular arthritis associated with urethritis, conjunctivitis, painless oral ulcerations, keratoderma blennorrhagicum, or circinate balanitis are the hallmarks of Reiter’s disease in both HIV-infected and noninfected individuals. Clinical manifestations of Reiter’s syndrome may precede or occur at the time of the initial diagnosis of HIV infection but most often follow the onset of immunodeficiency. HLA-B27 positivity is noted in 65 to 75% of HIV-infected patients with Reiter’s syndrome.
However, studies of African HIV patients with Reiter’s disease or reactive arthritis revealed no increased incidence of HLA-B27, suggesting involvement of other gene markers in this group. Shigella, Campylobacter, Ureaplasma, and other bacterial species associated with the development of reactive arthropathies are rarely described in HIV patients with Reiter’s syndrome. However, underlying concomitant sexually transmitted disease(s) may prove to be an important etiologic factor.
Treatment options for HIV patients with Reiter’s disease are quite limited. Responses to NSAIDs are minimal, and more potent immunosuppressive agents, such as methotrexate and azathioprine, frequently lead to opportunistic diseases and Kaposi’s sarcoma shortly after initiation of therapy.
Xerophthalmia and xerostomia, the characteristic symptoms of Sjogren’s syndrome (SS), have been reported with increasing frequency in AIDS patients. Features that closely resemble idiopathic SS, including sicca symptoms, a positive Schirmer test, abnormal salivary gland emptying, and abnormal salivary gland biopsies, have been reported in HIV-infected patients. As a result, it has been suggested that AIDS be an exclusionary disease for the diagnosis of idiopathic SS. The predominance of male patients, the absence of anti-Ro/SS-A and anti-La/SS-B antibodies, the absence of a well-defined connective tissue disease, the presence of HLA-DR52 and DR5 alleles instead of the characteristic A1, B8, DR3, DR2, and DQ1/DQ2 antigens, and a predominance of CD8+ lymphocytes instead of CD4+ cells infiltrating salivary tissue are the characteristic features of AIDS-associated SS, which differs from classic idiopathic SS. Treatment is primarily symptomatic.
Joint space infection is remarkably uncommon in HIV-infected patients. Sporadic case reports have been published of septic arthritis due to fungal pathogens, such as C. neoformans, H. capsulatum, and S. schenkii, mycobacteria, and routine pyogenic organisms. The approach to diagnosis and treatment of septic arthritis is the same for HIV-infected patients as non-HIV-infected individuals.
A relatively uncommon arthritis has been described in patients with moderately advanced HIV disease who demonstrate no other signs of any recognizable rheumatologic disease. The so-called HIV-associated arthropathy (HIVAA) presents as a mono- of pauciarticular arthritis. The arthritis is usually severe, affects primarily the knees and ankles, and lasts from 1 week to 6 months. No extra-articular manifestations have been noted. The synovial fluid is noninflammatory in nature, although a mild synovitis consisting of a chronic mononuclear cell infiltrate is noted on biopsy. Rheumatoid factor, antinuclear antibodies, anti-DNA antibodies, and antibodies against RNP, Sm, Ro/SS-A, and La/SS-B are negative. No predominant HLA pattern has been described. NSAIDs are of some benefit, but some patients require intra-articular steroid injections.
Several varieties of vasculitis have been reported in association with HIV infection. Necrotizing vasculitis of the polyarteritis nodosa type is reported most commonly and presents as a peripheral sensory or sensorimotor neuropathy. The vasculitis involves the medium-sized vessels of the nerves, skin, and muscle. None of the reported patients with HIV-related PAN were hepatitis B surface antigen positive. Primary angiitis of the CNS has been noted in two patients, one of whom had persistent varicella-zoster virus infection. Lymphomatoid granulomatosis has also been reported in HIV-infected patients. Henoch-Schonlein purpura has been reported rarely; however, no distinct etiology has been elucidated. Drug-induced hypersensitivity vasculitis, usually presenting as cutaneous disease, has been reported associated with penicillin, trimethoprim-sulfamethoxazole, amitriptyline, and griseofulvin. Recently, several cases of uveitis have been reported with rifabutin therapy, especially when this drug is administered with fluconazole and clarithromycin.
It is unclear whether HIV-associated vasculitis is the result of direct HIV invasion of the vessels, an immunologic reaction to an underlying viral infection, or a response to an opportunistic viral pathogen that invades vascular tissue. As with other serious rheumatologic manifestations of HIV disease, treatment options are limited by the underlying immunodeficiency of the host.
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Rao TKS: Human immunodeficiency virus (HIV) associated nephropathy. Annu Rev Med 42:391, 1991. Succinct review of the renal complications of HIV disease, with special focus on the HIV-associated nephropathy.
Smith MC, Austen JT, Casey JT, et al: Prednisone improves renal function and preteinuria in HIV associated nephropathy. Am J Med 101:41, 1996. A case series of successful outcomes using steroid therapy for HIVAN.
Revision date: June 20, 2011
Last revised: by Amalia K. Gagarina, M.S., R.D.