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Chapter 39 Rheumatic Disease in Patients Infected with the Human Immunodeficiency Virus (AIDS)

Manual of Rheumatology and Outpatient Orthopedic Disorders

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Chapter 39 Rheumatic Disease in Patients Infected with the Human Immunodeficiency Virus (AIDS)

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Edward J. Parrish

General approach to the HIV-infected patient with rheumatic complaints
	Approach to diagnosis
	Suspicion of infection or neoplasia
	Complicating factors
	Interpretation of laboratory tests
	The social problems faced
Musculoskeletal disorders in human immunodeficiency virus infection
	Myopathy
	Human immunodeficiency virus-associated painful articular syndromes
	Human immunodeficiency virus-associated arthropathy
	Reactive arthropathy
	Sicca syndrome
	Autoimmune phenomena
	Lupuslike syndrome
	Vasculitis
Additional observations
	Cytomegalovirus
	Endocarditis
	Syphilis
	Interferon-Alfa
	Lymphoma
	Erythema nodosum
	Parvovirus infection
	Mycobacteria, tuberculous and atypical forms
	Lipodystrophy syndromes

It is not surprising that a number of musculoskeletal complaints and inflammatory phenomena develop in persons infected with the human immunodeficiency virus (HIV), given the fact that they are subject to a vast array of pathogens and have marked degrees of immune dysregulation, cytokine production, cell growth abnormalities, and a propensity to anaplasia. Although a clear picture of the epidemiology of rheumatic disease is not available, studies in small populations and anecdotal evidence persuade us not only that the occurrence of some of the following diseases is increased, but also that their manifestations (and therapies) may be altered by the presence of HIV and intercurrent HIV-related processes. Table 39-1 provides an overview of the range of rheumatic diseases reported in this population. What we cannot predict is the effect that aggressive antiretroviral therapy will have on these manifestations. At present, combination therapies are able to reduce dramatically the viral load in a sizable proportion of infected persons and to restore some immune capabilities in others. The rate of AIDS- related deaths and hospitalizations has declined throughout the United States, giving much hope. However, viral strains resistant to present drugs are emerging and spreading through the population. Further, impoverished countries lack the resources to provide effective therapies.

Table 39-1. Rheumatologic disease in HIV-infected persons

I. General approach to the HIV-infected patient with rheumatic complaints.

The principles of sound medical practice apply as much in the diagnosis and therapeutics of the HIV-infected population as in uninfected persons. However, a few important features are worth emphasizing with this patient group .

1. Approach to diagnosis. More often than not, the complaints of many patients are periarticular, enthesopathic, and myofascial rather than articular. The inability to define adequately the anatomic structures involved often frustrates the diagnostician. Therefore, a descriptive and generic approach to diagnosis is more helpful than are definitive classification systems until we learn more about the nature of these syndromes.
2. Suspicion of infection or neoplasia should be paramount. Many phenomena are the direct result of these two underlying processes or will be unmasked by their presence. The clinical expression of infectious agents can be decidedly different in the immunosuppressed patient.
3. Complicating factors. The incidence and array of neuropathies in particular are high. Neuropathy may coexist with or mimic a number of rheumatic diseases. Depression mimics and complicates rheumatic and neuropathic disease. Current drug regimens used to treat HIV-infected persons contain an impressive list of medications that cause both rheumatic and neurologic complaints. Likewise, the use of alcohol and illicit drugs notoriously produces a confounding range of pathology and should be thoroughly reviewed with all patients. Additionally, the use of alternative pharmaceuticals , megavitamins, herbs, and health foods by people with HIV is extensive . Like any ingested chemical, a number of these may cause or potentiate disease.
4. Interpretation of laboratory tests. The frequency of auto-antibodies is increased in this population, reflecting the presence of chronic infections, immune dysregulation, and medication use. The physician should be particularly discriminating in the use and interpretation of laboratory tests, therefore, to avoid complicating rather than clarifying a diagnostic dilemma.
5. The social problems faced by HIV-infected persons are often more debilitating than their physical problems. Ostracism from family and friends and loss of living quarters and jobs may make access to and compliance with medical care difficult. Even after all these years , prejudice and fear significantly challenge the medical community globally and personally .

II. Musculoskeletal disorders in human immunodeficiency virus infection

1. Myopathy
   1. Clinical spectrum. The occurrence of myopathy is one of the most striking features of HIV disease. It is likely the most common rheumatologic problem encountered , yet it is often overlooked because of its highly variable expression. The majority of cases are silent and found incidentally as transient increases in muscle enzymes. Typically, symptoms and findings will wax and wane with little persistent clinical consequence. Pain is often absent, or the patient will complain of achiness. Rarely, the pain may be debilitating. Although the distribution is usually proximal, as in idiopathic polymyositis, it can be distal and in this form is frequently confused with neuropathy. Indeed, superimposed neurogenic complaints and findings are common. Sometimes, atrophy will gradually develop in the muscle groups involved. Dysfunction may lead to falling or inability to ambulate.
   2. Prevalence. Myalgia has been reported in 10% to 35% of patients, and the incidence of muscle atrophy was 6% in one cohort.
   3. Pathology. The range of histologic findings in muscle from HIV-infected patients is broad. Of note, most biopsy specimens have features indistinguishable from those of idiopathic autoimmune polymyositisthat is, variation in fiber size , often with an inflammatory mononuclear cell infiltrate. Frank necrosis may be present and associated with polymorphonuclear cell infiltration. Nemaline rods may be present, usually without inflammation . Red ragged fibers were found only in patients treated with azidothymidine (AZT). These have been seen in other diseases also, especially thyroid -associated myopathy, and are therefore not specific for drug-induced disease. Pyomyositis, a disorder often caused by Staphylococcus aureus and previously limited to the tropics, is increased in the HIV population. Nonpyogenic infectious agents may infiltrate muscle locally or diffusely. Neoplastic infiltration, especially with lymphoma, is not uncommon.
   4. Etiology . The waxing and waning nature of the complaints and findings of muscle disease in the HIV-infected population suggests that underlying low-grade myopathy may be quite common but of little consequence. This implies that for clinically significant disease to develop, additional insults are likely. Inciting factors may include drugs, intercurrent infection, or fever .
      1. Drug toxicity
         1. Azidothymidine has been shown to cause an inflammatory myositis in humans . The defect appears at the mitochondrial level and is manifested by the appearance of red ragged fibers and loss of specific mitochondrial peptides.
         2. Other therapeutic agents. Sulfonamides, penicillin, rifampin, phenytoin, cimetidine, and chloroquine are just a few of the medications that have been associated with myopathy. Although these drugs rarely cause muscle disease, they should be considered especially when significant muscle impairment develops with a temporal relationship to the use of new medications.
         3. Alcohol and illicit drugs. In the rush to look for other causes of myopathy, one must remember that the use of recreational drugs is common in many persons infected with HIV. Besides ethanol, the most common offenders are cocaine, crack, and mixtures of heroin. The extent to which these drugs, even in small quantities , contribute to significant myopathy is not fully appreciated.
      2. Infectious causes. Besides HIV itself, a number of infectious agents appear frequently in HIV-infected persons, in particular mycobacteria, Microsporidia, Toxoplasma, hepatitis B virus, hepatitis C virus, and human T-cell lymphotropic virus type I (HTLV-I).
   5. Differential diagnosis. It is important to differentiate myopathic processes from a number of conditions that may mimic or exacerbate their manifestations. Above all, consider infection. Although the incidence of direct infection is not common, it is sufficient to require diligence. Most importantly, neuropathy may cause concomitant atrophy and weakness in addition to associated pain; these findings can be virtually indistinguishable on clinical grounds from those of a primary myopathic process. Enthesopathy and periostitis, especially in the distal femur, can produce a confusing picture. Bursitis and arthritis, especially of the shoulder and pelvic girdle, can mimic muscle disease. Rarely, soft- tissue processes such as erythema nodosum or phlegmon may lead some to consider a localized infectious myositis. Underlying osteomyelitis could be difficult to distinguish from primary muscle disease. Adrenal insufficiency is common in HIV-infected persons. Although it does not cause muscle disease itself, one of the most common complaints of the steroid- deficient person is myalgia.
   6. History and physical examination. The clinician will most often be rewarded by focusing on the temporal relationship between the onset of muscle disease and the introduction of new medications or other clinical changes. When this is not fruitful and especially when the onset is abrupt, a strong suspicion for occult infection or malignancy should be pursued, whether or not fever is present. Virtually any such process can be local or diffuse. Tenderness is more indicative of an inflammatory process, although hyperesthesia from a neuropathy can occur.
   7. Laboratory studies
      1. Electrolyte abnormalities. Weakness or frank myonecrosis can occur from alterations in potassium, phosphorus, calcium, or magnesium levels. Patients with metabolic abnormalities or those with nutritional deficiencies may demonstrate such findings.
      2. Muscle enzymes. Creatine kinase (CK) and aldolase are the most common and sensitive indicators of muscle damage. Either may be elevated exclusively. In general, the CK level should be checked first and aldolase measured as needed if the CK level is not elevated and clinical suspicion is high. In the face of intercurrent infection, trauma, fever, or use of cocaine or alcohol, the CK level may become dramatically elevated. Typically, after the insult has been eliminated, CK will return to the normal range within a few days.
      3. Biopsy and imaging. Biopsy should be considered whenever infection is suspected or when clinical deterioration continues in the face of therapy. Additionally, muscle biopsy should be considered before the patient is committed to long- term immunosuppressive medications. As in idiopathic autoimmune polymyositis, biopsy may miss the areas of involvement. The probability of a diagnostic biopsy may be enhanced by the use of imaging techniques. Magnetic resonance imaging (MRI) has been shown to be particularly sensitive in the definition of inflammatory and infiltrative muscle disease. Additionally, ultrasonography and radionuclide techniques with gallium or technetium pyrophosphate can be helpful.
   8. Treatment
      1. What to treat. Because of the multiplicity of causes and the waxing and waning nature of muscle disease in this population, the fortuitous finding of myopathy by laboratory criteria does not in itself require intervention. CK elevations in particular often do not correlate with complaints or physical findings and may persist at even high levels without clinical significance. Pain and weakness are the main reasons for initiating therapy.
      2. Modalities
         1. The patient should discontinue any offending agents, particularly alcohol, illicit drugs, and any medications that are not absolutely necessary.
         2. Treatment of infection. Any direct infection of muscle or any intercurrent infection should be treated.
         3. Antiretroviral therapy is indicated for those patients with HIV-related myositis who are not presently on a medication regimen.
         4. Pain relief. Symptomatic relief of pain is often required. This is particularly true in muscle disease, in which pain leads to disuse and disuse leads to atrophy. Mild analgesics may be sufficient, but often nonsteroidal antiinflammatory drugs (NSAIDs) are necessary to resolve the symptoms.
         5. Physical and occupational therapy should be started early to prevent wasting and contractures.
         6. Intravenous immune globulin works quickly and may be administered at necessary intervals, with months between treatments often possible in some patients.
         7. Steroid therapy. When the above measures have failed or when complaints and dysfunction progressively worsen, steroid therapy at low dose appears to have dramatic results and is well tolerated. Prednisone (30 mg daily tapered to 10 mg daily during a 10-day period) is satisfactory for most patients. One may then switch to an alternate-day therapeutic schedule with further tapering as the patient can tolerate . The toxicity of low-level steroid maintenance therapy for several months is not yet known. Within days of initiation of steroid therapy, however, exacerbation of mucocutaneous candidiasis and reactivation of herpes simplex are seen. Usually, these abate with steroid taper and antifungal or antiherpes regimens, respectively. There is presently no role for cytotoxic drug therapy.
      3. When to stop azidothymidine. AZT is being used less and less in antiretroviral cocktails. However, in those who presently have good retroviral suppression on AZT, discontinuation of the drug must be weighed against the benefit it confers. Cessation for even brief periods has been shown to lead to overgrowth of resistant virus that cannot be suppressed by reinstitution of AZT. Discontinuing AZT is helpful in resolving myopathy in only 50% of the cases in which it is suspected of being a factor. AZT-induced cardiomyopathy is the most serious consequence and demands discontinuation of the drug.
2. Human immunodeficiency virus-associated painful articular syndromes
   1. Definition and differentiation. These syndromes are unique to HIV-infected persons. They are among the most common musculoskeletal manifestations but because of the paucity of anatomic findings are the most difficult to delineate. It is convenient to distinguish them arbitrarily from HIV-associated arthropathy by the absence of joint effusions. The clinical presentations require differentiation from enthesopathy, periostitis, myositis, and neuropathy, although these may coexist. One may discern two types on clinical grounds:
      1. Acute. The acute painful articular syndrome is dramatic. Typically, the patient is carried by friends into the emergency department and complains of the rapid onset of pain in the knees or ankles. It is frequently symmetric. The physical findings are unimpressive except that the patient may not be able to stand. Response to NSAIDs is poor. Often, narcotics are required for pain control. The symptoms abate within 2 to 24 hours, although they may last for a few days. The recovery is with minimal residuum.
      2. Subacute. Typically, this syndrome has a gradual onset during a period of a few weeks. It too has a predilection for knees and ankles. At times, it appears as a classic patellofemoral syndrome and may be accompanied by some degree of quadriceps femoris atrophy. Often, direct palpation in the area of complaint will elicit diffuse tenderness of muscle, tendons, and bone, suggesting myositis, enthesitis, or periostitis. Most cases gradually resolve during weeks or months and require minimal intervention. Some are progressive and lead to significant debility.
   2. Pathology. Little is known about the etiology of these syndromes, but recurrent ischemia may be an underlying factor. This is supported by the following evidence:
      1. The acute form is most reminiscent of the musculoskeletal pain of a sickle cell crisis in its rapidity of onset and resolution, and in the poor correlation between the severity of complaints and the physical findings.
      2. Necropsy specimens of knee synovium show effacement consistent with recurrent ischemic insult.
      3. Some have suggested a predilection toward osteonecrosis in HIV-infected patients. Although no studies have been performed to support this claim, anecdotes of extensive aseptic necrosis in persons without other known predisposing factors tend to support this possibility.
   3. Treatment
      1. Acute. Response to NSAIDs is poor as a rule, although the use of IM ketorolac may hold promise. Otherwise , narcotic analgesia usually suffices until the episode abates.
      2. Subacute. NSAIDS are variably helpful; usually indomethacin is required for sufficient control. At times, the level of disability is so severe that a trial of systemic steroid is warranted. Usually, this produces dramatic relief. Steroids often may be tapered rapidly to minimal dosage and discontinued during 1 week.
3. Human immunodeficiency virus-associated arthropathy
   1. Clinical presentation. This resembles the subacute form of the painful articular syndrome, but joint effusion is present. Indeed, it may likely be a continuum of the same process. Symptoms develop during a period of weeks and abate, usually within a month. There is a predilection for the lower extremities, and the pain may be quite severe, with direct distal femur tenderness. The joint fluid is typically not inflammatory (<10 ³ cells per milliliter), although the patient may respond dramatically to intraarticular steroid. As an important distinction from classic presentations of reactive arthritis, these patients do not possess the HLA-B27 major histocompatibility complex (MHC) class I phenotype and do not demonstrate the extraarticular manifestations of Reiter's syndrome (i.e., conjunctivitis, urethritis).
   2. Pathology. Although the joint fluid is not inflammatory, synovial biopsy in these patients usually shows some degree of mononuclear and plasma cell infiltrate. This is usually mild and seldom of the severity seen in other forms of inflammatory arthropathy. Periosteal reaction may be found on radiographs, and these patients may have hypertrophic osteoarthropathy. For this reason, it is prudent to exclude intercurrent infection, especially of a pulmonic source, in these patients. It is tempting to view this syndrome as part of a continuum of periarticular ischemia that produces the acute painful articular syndromes.
4. Reactive arthropathy
   1. Clinical syndromes. Since the first description by Winchester and co-workers in 1987, no group of rheumatic syndromes has been the topic of so much discussion as the reactive arthritides in patients infected with HIV. The central issue has been whether HIV contributes to reactive arthritis. The arguments obviously hinge on the question of whether there is indeed an increased incidence of reactive arthritis in the HIV-infected population. The difficulty of comparing equivalent populations, the lack of adequate diagnostic criteria for some disease states, and the incomplete manifestation of some syndromes have hampered the resolution of this question. The best study, which prospectively evaluated all patients in an infectious disease clinic, concluded that incomplete Reiter's syndrome and enthesopathy were increased in frequency in HIV-infected patients. This does not, however, imply a direct causal role for HIV in the arthropathy. The advent of highly effective antiretroviral therapies has not resolved the question. One might explain an increased incidence on the basis of exposure to or persistence of the same pathogens ( Chlamydia and enteric pathogens) known to elicit reactive arthritis in nonHIV-infected persons.

      The spectrum of reactive arthropathy or spondyloarthropathy is impressive. Findings range from frank synovitis to enthesitis and axial skeleton involvement. Extraarticular manifestations include dermal (psoriasiform, keratoderma blennorrhagicum, circinate balanitis), ocular (conjunctivitis, uveitis), mucosal (palatine and buccal ulcerations), genital (urethritis, cervicitis, prostatitis), and intestinal involvement. Any combination of findings may coexist. In the HIV-infected patient, two categories are frequently foundthe post-infectious and psoriasis-related reactive type of arthritides.

      1. Post-infectious
         1. Enteric pathogens. Infection with an array of enteric pathogens is common in HIV disease. Chronic or recurrent diarrhea is virtually the norm, and the causes are legion. There appears to be an increased frequency of salmonellosis. Small-bowel biopsy in some patients reveals lesions similar to those found in Whipple's disease, raising the question of whether other bowel flora such as mycobacteria may result in systemic disease.
         2. Venereal infection. The high incidence of sexually transmitted diseases in the HIV-infected population is mirrored in the increased frequency of gonococcal and chlamydial infection. There is evidence that gonococcal and chlamydial products may persist in joint fluids in persons with arthritis. Some have suggested that inadequate therapy and other host factors lead to incomplete eradication. It is unclear whether HIV infection is associated with persistence of these agents or their products.
      2. Psoriatic. There is an increase in both the frequency and severity of all forms of psoriasis in HIV-infected patients. This includes the vulgaris, pustular, and erythroderma forms. There is also an increase in the extra-dermatologic manifestations of the disease, including arthritis. Interestingly, the extra-dermatologic disease tends to follow patterns more commonly associated with variants of Reiter's syndrome, including an increased incidence of conjunctivitis, urethritis, and enthesopathy. No excess of HLA antigens associated with classic psoriasis has been found in this group; indeed there was an increase in HLA-B27. Thus, the line between psoriatic and reactive arthropathy is indistinct in the HIV-infected population.
   2. Treatment
      1. Nonsteroidal antiinflammatory drugs are often sufficient to control both joint and extraarticular manifestations of the disease. Long-term use is usually required. Many cases will respond only to indomethacin, as has been found in nonHIV-infected persons with similar complaints. Cyclooxygenase-2 (COX-2) inhibitors may show promise in this population.
      2. Sulfasalazine, increasingly used to treat Reiter's syndrome in the non-HIV population, has been shown anecdotally to be helpful in achieving disease control in patients unresponsive to NSAID therapy alone. Dosages of 1 to 2 g/d are often adequate.
      3. Etretinate. This medication was incidentally found to relieve joint symptoms in patients with psoriasis. It appears to be helpful in those without overt skin disease but with enthesopathy. Its use must be weighed against possible hepatic and hematologic toxicity.
      4. Gold. Parenteral gold was reported to be effective in one patient with Reiter's arthropathy and another with the psoriatic form. Although studies have suggested its utility in psoriatic arthropathy in nonHIV-infected persons, it does not appear to have a role in Reiter's syndrome.
      5. Immunosuppressive and cytotoxic therapy. Anecdotes reporting the onset of AIDS, opportunistic infection, Kaposi's sarcoma, and death in some patients soon after the institution of methotrexate or azathioprine has led to the widespread notion that these agents are contraindicated in HIV-infected patients. Prudence would require exhaustion of other modalities and the presence of significant debility before a course of therapy with either agent was undertaken.
      6. Antibiotics. Recent studies suggest that efforts to eradicate gonococci and Chlamydia with long-term (3 months) antibiotic therapy appear to resolve or relieve reactive arthritis. Most studies have chosen tetracycline derivatives, which incidentally have antiphlogistic properties. It would be reasonable, after thorough culture and use of DNA probes, to consider doxycycline in persons with persistent joint disease. Doxycycline is known to inhibit certain matrix metallo protease (MMP) enzyme systems.
5. Sicca syndrome
   1. Clinical presentation. Xerostomia and xerophthalmia are common in HIV-infected patients and can be quite severe. This can further compromise their otherwise tenuous nutritional state by causing a decrease in caloric intake. Often, the causes are multifactorial, including an array of medications (neuroleptic agents, NSAIDs, antibiotics) and infection ( Candida ). In a number of HIV-infected patients, however, features consistent with Sjgren's syndrome develop, including parotitis with an inflammatory cell infiltrate within salivary glands. The infiltrating mononuclear cells are CD8+ lymphocytes rather than the CD4+ cells of classic autoimmune Sjgren's syndrome. Further, there is a notable absence of the auto-antibodies (anti-Ro, anti-La) classically found in the idiopathic syndrome. A subset of patients manifests far more extensive visceral involvement by CD8+ lymphocytes, especially of the lungs, gastrointestinal system, and central nervous system. This has been designated diffuse infiltrative lymphocytosis syndrome.
   2. Treatment. Avoidance of medications that exacerbate xerostomia and xerophthalmia is important. In particular, the physician should find substitutes for, or eliminate, antihistamines, decongestants, NSAIDs, antihypertensives, tricyclic antidepressants, and other anticholinergic agents. Aggressive treatment of candidiasis is important. Instructing the patient to use dietetic gelatin lozenges and increase fluid intake with meals may help. Use of topical methylcellulose lacrimal substitutes will often prevent corneal abrasion.
6. Autoimmune phenomena. Much interest has been generated by the finding of auto-antibodies and immune complexes in patients with HIV. Antinuclear antibodies, rheumatoid factor, anti- platelet antibodies, and direct anti-globulin (Coombs') antibodies are examples. A few have clinical significance, including those associated with the development of anemia and thrombocytopenia. Anti-phospholipid antibodies occur in 85% of HIV-infected persons; however, they do not appear to be associated with as high a frequency of thrombotic events as in nonHIV-infected patients with the anti-phospholipid syndrome.
7. Lupuslike syndrome. The plethora of autoimmune laboratory findings coupled with an array of cutaneous, articular, central nervous system, and visceral inflammatory disease has, at times, produced some diagnostic uncertainty. Often, particularly when HIV infects young women, the clinical and laboratory manifestations may be virtually indistinguishable from those of systemic lupus erythematosus. Fortunately, in the majority of HIV-infected persons who are positive for antinuclear antibodies, they are present in very low titers, and rarely, if ever, is antids-DNA antibody demonstrated. Patients with collagen vascular disease often have cross- reacting antibodies against constituents of the HIV or cells infected with HIV, which leads to false-positive results of assays for HIV antibodies. Typically, however, they demonstrate antibodies to only one or two proteins of HIV on Western blot, not to products of all three major retroviral genes (gag, pol, and env) simultaneously . Therefore, in patients in whom such a question arises, it is important to inform the laboratory technologist and define the actual Western blot pattern.
8. Vasculitis. Vasculitides of various sorts have been documented in patients with HIV. The presence of necrotizing vasculitides such as polyarteritis nodosa is often a harbinger of rapid demise. Leukocytoclastic angiitis and eosinophilic vasculitides of small and medium vessels are seen more frequently. Isolated angiitis of the central nervous system may play a role in the development of stroke or dementia in these patients. Hepatitis B and C viruses have been implicated in the development of necrotizing and cryoglobulinemic vasculitides, respectively. Modalities directed at control of viral replication in both of these entities have met with disappointing results to date.

III. Additional observations

1. Cytomegalovirus produces a vasculitis by direct infection and necrosis of the vascular endothelium. This may mimic noninfectious vasculitis.
2. Endocarditis is well-known for its array of immune clinical syndromes, including arthritis, leukocytoclastic vasculitis, stroke, and glomerulonephritis. Certainly, in the population using IV drugs, it remains a common cause of morbidity and mortality.
3. Syphilis continues to live up to its accolade as the great imitator. In the presence of HIV, reactivation can occur and the clinical presentation may be quite atypical. Lues, especially in the secondary stages, may have an associated arthropathy.
4. The use of interferon-alfa appears to predispose to autoimmune disease and serologic phenomena, particularly thyroid abnormalities. With its use in the treatment of Kaposi's sarcoma and as an antiretroviral agent, we might expect an increase in these features as patients live longer.
5. Lymphoma often takes atypical forms in patients with HIV infection. In particular, destructive bony or joint lesions often mimic infectious or inflammatory lesions. Localized infiltration of muscle may cause a mass lesion, pain, or weakness. Paraneoplastic syndromes include arthropathy, myopathy, vasculitis, and neuropathy.
6. Erythema nodosum may be confused with a phlegmon, infiltrative mass lesions, or arthritis, depending on its location and appearance. Post-infectious, intercurrent mycobacterial or paraneoplastic stimuli for erythema nodosum are common in the HIV-infected population.
7. Parvovirus infection is associated with a rheumatoidlike polyarticular arthritis in nonHIV-infected adults. Some observers feel that it may play a role in bone marrow suppression during HIV infection.
8. Mycobacteria, tuberculous and atypical forms, may cause joint infection by direct extension or hematogenous spread. Atypical forms may be isolated from blood or joint fluid. Tubercle bacilli are somewhat more difficult to isolate; if they are strongly suspected, synovial membrane biopsy with tissue culture and histologic assessment may be required. Unlike the clinical picture in persons not infected with HIV, osteomyelitis caused by atypical mycobacteria may proceed with rapid destruction of bone.
9. Lipodystrophy syndromes increasingly reported with the use of protease inhibitor therapy can give the appearance of muscle wasting.

Bibliography

Berman A, et al. Rheumatic manifestations in populations at risk for HIV infection: the added effect of HIV. J Rheumatol 1991;18:1564.

Cuellar ML. HIV infection-associated inflammatory musculoskeletal disorders. Rheum Dis Clin North Am 1998;24:403.

Espinoza LR, et al. Rheumatic manifestations associated with human immunodeficiency virus infection. Arthritis Rheum 1989;32:1615.

Itescu S, et al. A diffuse infiltrative CD8 lymphocytosis syndrome in human immunodeficiency virus (HIV) infection: a host immune response associated with HLA-DR5. Ann Intern Med 1990;112:3.

Rynes RI, et al. Acquired immunodeficiency syndrome-associated arthritis. Am J Med 1988;84:810.

Winchester R, et al. The co-occurrence of Reiter syndrome and acquired immunodeficiency. Ann Intern Med 1987;106:19.

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Copyright 2000 by Lippincott Williams & Wilkins
Stephen A. Paget, M.D., Allan Gibofsky, M.D., J.D. and John F. Beary, III, M.D.
Manual of Rheumatology and Outpatient Orthopedic Disorders

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