Human Immunodeficiency Virus

Edward Parrish

INTRODUCTION

A number of musculoskeletal complaints and inflammatory phenomena develop in individuals infected with the human immunodeficiency virus (HIV). These patients are exposed 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 suggest an increased occurrence of the manifestations listed in Table 45-1. Highly active antiretroviral therapy (HAART) has decreased the frequency in populations with access to these life-extending agents.
Highly active antiretroviral therapy (HAART) has changed the natural history of HIV infection and also modified the frequency and expression of some HIV-related musculoskeletal syndromes. In a study of 75 HIV positive patients who presented at one center with musculoskeletal symptoms, septic complications were the most common (41%) and the frequency of spondyloarthropathy was lower compared to the studies pre-HAART.
The immune reconstitution inflammatory syndrome (IRIS) that occurs in 25% of patients treated with HAART may result in the aggravation of pre-existing conditions (i.e., sarcoidosis, SLE) or the development of new ones (i.e., Grave’s disease, Sjögren’s syndrome, reactive arthritis, or SLE).
The general approach to the individual infected with HIV and rheumatic complaints includes the same principles of sound medical practice as those for uninfected individuals.

Suspicion of infection or neoplasia should be paramount. Many clinical 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. Complicating factors include the following:

High incidence of neuropathy, which may coexist with or mimic a number of rheumatic diseases.

Table 45-1 Rheumatologic Manifestations in Human Immunodeficiency Virus (HIV)-infected Individuals

Arthralgias
   Painful articular syndromes
   Osteonecrosis
   Enthesopathy/periosteal syndromes
   Hypertrophic osteoarthropathy
Arthritis
   Reactive
   Psoriatic
   HIV-associated arthropathy
   Septic
Myopathy
Vasculitis
   Necrotizing
   Eosinophilic
   Leukocytoclastic
   Angiitis of the central nervous system
Sicca syndrome
   Diffuse infiltrative lymphocytosis syndrome
Bone disorders
   Osteoporosis
   Osteonecrosis
   Osteomyelitis

HIV, Human immunodeficiency virus.

Table 45-2 Contributing Factors to Myopathy in Human Immunodeficiency Virus (HIV) Infection

Infection	Metabolic	Drug/toxic
HIV	Thyroid disorders	Alcohol
HTLV-I	Adrenal insufficiency	Cocaine
Hepatitis C		AZT
Pyomyositis		Sulfonamides
Mycobacteria		Penicillin
Microsporidia		Rifampin
Toxoplasma		Phenytoin
AZT, azidothymidine; HTLV-1, human T lymphotropic virus type 1; HIV, human immunodeficiency virus.

Drug regimens that are used to treat individuals infected with HIV may cause both rheumatic and neurologic complaints.
Use of illicit drugs that can lead to confounding signs and symptoms.
The extensive use of “alternative” pharmaceuticals, megavitamins, herbs, and “health foods” by individuals with HIV can complicate the clinical picture.
The frequency of autoantibodies is increased in this population, reflecting the presence of chronic infections, immune dysregulation, and the use of medication.
- Antinuclear antibodies, rheumatoid factor, antiplatelet antibodies, and direct antiglobulin (Coombs’) antibodies can be seen in patients who are HIV positive; however, a few have clinical significance, including those associated with the development of anemia and thrombocytopenia. While antiphospholipid antibodies occur in 85% of individuals infected with HIV, they do not appear to be associated with as high a frequency of thrombotic events as in uninfected patients with the antiphospholipid syndrome.
- 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.

MYOPATHY

I. ETIOPATHOGENESIS

(Table 45-2)

HIV infects CD4+ T cells, macrophages, and dendritic cells, which are often found in the affected muscle. HIV also infects cardiac muscle and there is some evidence of direct skeletal myocyte infection.
The range of histologic findings in muscle from individuals infected with HIV is broad. Variable fiber fallout consistent with neuropathy is present in many. Others have features indistinguishable from those of idiopathic autoimmune polymyositis—that is, variation in fiber size, often with an inflammatory mononuclear cell infiltrate. Frank necrosis may be present and may be associated with polymorphonuclear cell infiltration. Nemaline rods may be present, usually without inflammation.
Red, ragged fibers, also seen in thyroid-associated myopathy, were found in patients treated with azidothymidine (AZT). The defect appears at the mitochondrial level. Other toxins may cause myocyte death or fiber contractility (see Table 45-2).
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 the muscle locally or diffusely.
Neoplastic infiltration, especially with lymphoma, is not uncommon.

II. PREVALENCE

Myopathy is likely the most common rheumatologic problem encountered, yet it is often overlooked because of its highly variable clinical expression.
Approximately 92% of patients with untreated HIV have histologic evidence of muscle disease. Of these, half show features of an inflammatory infiltrate similar to polymyositis and half are consistent with neuropathic myopathy.
Myalgia has been reported in 10% to 35% of patients. One study reported the incidence of muscle atrophy at 6%.

III. CLINICAL MANIFESTATIONS

Most cases are silent and uncovered incidentally as transient increases in muscle enzymes. Typically, symptoms and findings will wax and wane with little persistent clinical consequence. Pain is often absent, although sometimes patients are “achy.”
Although usually proximal, as in idiopathic polymyositis, it can be distal, and in this distal form, is frequently confused with neuropathy. Indeed, superimposed neurogenic complaints and findings are common.
For clinically significant disease to develop, additional insults such as intercurrent infection, drugs, or metabolic abnormalities contribute, as listed in Table 45-2.
Atrophy may gradually develop in the muscle groups involved, with consequent motor weakness, leading to falls.
HIV wasting illness, more prevalent in the pre-HAART era, may present as diffuse muscle atrophy and weakness. The cause is likely to be multifactorial.

IV. PHYSICAL EXAMINATION

INSPECTION MAY REVEAL DIFFUSE OR LOCALIZED ATROPHY.
It must be determined if the patient is truly weak or if the apparent weakness is related to pain.
Tenderness elicited by palpation or movement is more indicative of an inflammatory process, although hyperesthesia from a neuropathy can occur.
Distal wasting or weakness is more likely in neuropathic and paraneoplastic disease.
In HIV-wasting disease, there is diffuse atrophy of both muscle and adipose tissues.
Fever likely indicates intercurrent infection or malignancy.