Autoimmune Manifestations of AIDS

AIDS and Autoimmunity

Although AIDS causes immune suppression, there is also some immune activation (this is necessary for viral replication)

AIDS is associated with proinflammatory cytokines (TNF, IL-6, IL-2 receptors), cellular activation, and high gammaglobulin
AIDS is associated with autoantibodies – ANA, rheumatoid factor, anticardiolipid antibody – some cause CT diseases

Why does HIV produce antibodies? – virus increases CD5-bearing B-cells, which then produce antibody

many viruses can cause immune-complex mediated tissue destruction through molecular mimicry, hypersensitivity, etc.

Note: While AIDS-induced immune dysfunction compromises immunity to infections and neoplasms, it also causes high-grade remission of inflammatory diseases (SLE and RA); they reappear with HIV treatment.

"immune reconstitution disease" – appearance of inflammation (autoimmune or to infections) upon treatment of HIV

Non-articular Connective Tissue Diseases Associated with HIV

Diffuse Infiltrative Lymphocytosis Syndrome (DILS) – looks like Sjorgan’s, but there are no anti-SSA/SSB antibodies

Symptoms – lymphadenopathy, sicca (dryness) of eyes and mouth, interstitial nephritis, vasculitis causing rash

unlike Sjorgan’s, there is parotid gland enlargement

slowly progressive, but can develop into lymphocytic leukemia

Etiology – activated CD8⁺ cells driven by antigen

Myositis – polymyositis, more rarely dermatomyositis

Symptoms – same as primary myositis (proximal weakness, usually of lower extremity; facial heliotrope; etc.)

unlike primary myositis, there is nerve conduction delay (due to nervous diasthesis caused by HIV)

Etiology – inflammatory infiltrate of CD8⁺ lymphocytes

Vasculitis – both small vessel and granulomatous

Symptoms – indistinguishable from vasculitis caused by other diseases (purpura, etc.)

circulating immune complexes can destroy platelets, producing immune mediated thrombocytopenic purpura

Etiology – may not be caused by HIV at all (but anti-retroviral drugs often make it go away)

maybe due to treatment, HIV-containing immune complexes, or direct infection of endothelium by HIV

Articular Diseases Associated with HIV – 8% of AIDS patients get arthritis

Arthralgia (joint pain) – usually intermittent, mild, polyarticular, and in late stage of infection

Reiter’s Syndrome (undifferentiated spondyloarthropathy) – often occurs with asymptomatic HIV

Symptoms – arthritis of lower extremities (with axial sparing), urethritis, ocular inflammation, skin lesions
unlike classical Reiter’s, there is sparing of the spine and skin lesions

enthesopathy of ankle tendons cause patients to walk on outside margins of feet – "AIDS foot"

Etiology – possibly due to infection – predisposition associated with HLA-B27
HIV may be stimulus that causes appearance of Reiter’s syndrome in genetically predisposed individuals

Psoriatic arthritis – 500x as common in HIV as general population – psoriasis progresses to arthritis more often with HIV

Symptoms – skin lesions (seborrheic dermatitis to pyroderma gangrenosum), asymmetric arthritis, enthesopathy

retroviral therapy alleviates skin but not joint problems

Etiology – associated with HLA-B27 (no correlation in psoriatic arthritis patients without HIV)

Other HIV-associated Arthritis – idiopathic seronegative arthritis with low synovial fluid cell counts

Painful Articular Syndrome (PAS) – acute oligoarticular arthritis affecting knees/ankles, lasting hours to days
Acute Symmetric Polyarthritis – wide clinical presentation

Therapies for AIDS-related Autoimmune Diseases

a clinical paradox: autoimmune diseases require immunosuppressive agents, but AIDS patients are already immunosuppressed!

not all HIV patients have significant leukopenia; if CD4⁺ > 500 mm^-1, can use immunosuppressive therapy safely

must weigh the risks of the two diseases – treat underlying infections first, provide antimicrobial prophylaxis if necessary