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Ovid: Oxford Handbook of Genitourinary Medicine, HIV, and Aids

Editors: Pattman, Richard; Snow, Michael; Handy, Pauline; Sankar, K. Nathan; Elawad, Babiker Title: Oxford Handbook of Genitourinary Medicine, HIV, and Aids, 1st Edition Copyright ©2005 Oxford University Press > Table of Contents > HIV/AIDS > Chapter 50 – HIV: musculo-skeletal disorders Chapter 50 HIV: musculo-skeletal disorders P.484
Introduction Prevalence of joint manifestations is uncertain. However, studies show that they are likely to be influenced by HIV risk factors:

  • injecting drug users (IDUs) and haemophiliacs are more susceptible to septic arthritis and osteomyelitis
  • homosexual ♂ are more likely to develop sexually acquired reactive arthritis (SARA).

Joint symptoms may also be a feature of other conditions found more commonly in those with HIV infection, e.g. haemophilia (with haemarthrosis), syphilis, gonorrhoea, hepatitis B and C virus, and chlamydial infections. They may also be due to the side-effects of drugs used to treat HIV and related conditions. Autoantibodies are commonly produced, except when CD4 counts are very low and may re-appear with immune reconstitution by HAART. When CD4 counts are >500cells/µL (early after seroconversion or immune restoration with treatment) autoimmune diseases may occur. Diseases reported include systemic lupus erythematosus, vasculitis, polymyositis, Raynaud’s phenomenon, Behçet’s disease, primary biliary cirrhosis, and Graves’ disease. Immune complex vasculitis is associated with counts 200–499cells/µL and spondyloarthropathy with counts <200cells/µL. Inflammatory arthropathies Arthralgia Most common joint manifestation occurring in up to 45%. Pathology is unclear but may involve cytokines or transient bone ischaemia. Can occur at any stage of HIV disease and may be the first manifestation, being reported in 50–70% of those presenting with 1° HIV infection. Usually mild to moderate in intensity. In up to 10% of those with advanced HIV infection a painful transient articular syndrome, characterized by an acute onset of severe pain in up to four joints, has been described. Knee most commonly affected, with shoulder and elbow also involved. Symptoms may mimic acute septic arthritis but no effusion, synovitis, or ↑ in joint fluid white cells. Radiology normal or may show periarticular osteopenia. Treated with standard analgesics/non-steroidal anti-inflammatory drugs (NSAIDs) though narcotics may be required. Diffuse idiopathic lymphocytic syndrome Similar to Sjögren’s syndrome and found at any stage of HIV infection. Presents with salivary gland enlargement (parotid swelling may be massive), xerostomia, xerophthalmia, and arthralgia. Treat with artificial saliva and tears. Zidovudine in HAART ↓ parotid enlargement. Acute symmetrical polyarthritis Resembles rheumatoid arthritis (RA). Characterized by involvement of small joints of the hand leading to ulnar deviation of the digits and P.485
swan-neck deformities. May be differentiated from RA by acute onset and negative rheumatoid factor. Radiological appearances similar to RA with periarticular osteopenia, joint-space narrowing, and marginal erosions. Gold treatment may be required. HIV-associated arthritis Asymmetrical, oligoarticular arthritis. Possibly caused by effects of local infection (HIV detected in joint fluid). More common in ♂. Typically presents with sudden onset of severe pain, mainly affecting knees and ankles. Self-limiting, usually lasting from a few weeks to 6 months. Synovial fluid commonly contains up to 2500 white blood cells/µL. Radiology may show osteopenia but no erosions. A chronic mononuclear cell infiltrate is found on synovial biopsy. Treat with NSAIDs or intra-articular corticosteroid injections for symptomatic relief. P.486
Hypertrophic osteoarthropathy May appear as a complication of Pneumocystis jiroveci (carinii) pneumonia (PCP). Affects bones, joints, and soft tissues. Presents with severe pain in the lower limbs, arthralgia, non-pitting oedema, and finger clubbing. Skin over affected areas (ankle, knees, and elbows) is shiny, warm, and oedematous. Extensive periosteal reaction and subperiosteal proliferative changes in the long bones of the legs are found on radiology with bone scans showing ↑ uptake along the cortical surfaces. Usually responds to treatment of underlying PCP. Reactive arthritis Probably no more frequent in those with HIV infection but tends to be more severe. Lower limb peripheral arthritis predominates. Synovial fluid is inflammatory (a few thousand polymorphonuclear leucocytes/mL), sterile with a glucose level at least 66% of the serum level. Treat initially with NSAIDs (as in HIV –ve). Other drugs may be required e.g. phenylbutazone, gold, methotrexate (with caution as immunosuppressive) and other disease modifying agents. HAART is likely to be beneficial. Psoriatic arthritis More common and severe than in HIV-negative individuals usually poly-articular and asymmetrical. Extra-articular manifestations occur in ~50%. Usually insidious with the appearance of bone erosions within weeks or months. Radiologic findings of the distal interphalangeal joints are pathognomonic. Joint and tendon involvement in HIV-associated psoriatic arthritis tends to be less responsive to NSAIDs (still 1st line therapy). Methotrexate and azathioprine are effective but require careful monitoring because of myelosuppression. Sulfasalazine may be helpful but skin rash occurs in 30%. Low-dose systemic corticosteroids ineffective and high doses may produce many side-effects. Gold, retinoids, phototherapy, cyclosporine, and zidovudine reported to improve the skin and joints in some. Osteonecrosis (avascular necrosis) Result of direct damage to the vascular supply, leading to death of subchondral bone. Additional risks are prior use of corticosteroid, testo-sterone, or anabolic steroids, hyperlipidaemia, hypercoagulability, sickle cell disease, alcohol abuse, and smoking. Most common site is femoral head followed by humeral head, with bilateral involvement in 40%. May be asymptomatic or cause severe disabling deep pain. As plain x-rays may be normal magnetic resonance imaging (MRI) recommended. In early stages rest may be adequate, but in advanced disease joint replacement or other surgery may be required. P.487
Infections Septic arthritis Usually mono-articular, with the hip being most frequently affected, although in IDUs there may be sternoclavicular joint involvement. Staphylococcus aureus followed by Streptococcus pneumoniae are the most common causative organisms. If CD4 count <100cells/µL multiple joint involvement and associated skin infection may occur with opportunistic infections (e.g. Mycobacterium avium complex, cryptococcosis, sporotrichosis). Diagnosed by Gram-stain and culture of synovial fluid. Blood cultures may be positive before synovial cultures. Treat with appropriate antibiotics, usually IV and monitor inflammatory markers. Osteomyelitis

  • Septic: may follow direct extension or haematogenous spread from an infected joint. Suspect if septic arthritis fails to respond despite adequate treatment.
  • Tuberculous: develops from the haematogenous spread of an acute or reactivated infection. The spine, especially the thoracic and lumbar, is most commonly affected, starting in the vertebral body and spreading to the adjacent disk spaces. Vertebral wedging leads to gibbus formation. In addition to antibiotics surgical intervention with irrigation and debridement may be required.
  • Bacillary angiomatosis due to Bartonella henselae may cause osteomyelitis. Occurs in the immunosuppressed and characterized by vascular proliferation involving the nervous system (aseptic meningitis, intracerebral mass lesions), liver (peliosis hepatitis), lymph nodes (adenitis) and bone.

Osteopenia/osteoporosis HIV infection is associated ↓ bone mineral density (BMD) determined by measurement of x-ray absorption e.g. dual energy x-ray absorptiometry (DEXA) scan. A DEXA scan T-score (number of standard deviations from the mean value in young, healthy individuals) is diagnostic. Scores between –1 and –2.5 indicate osteopenia (pre-symptomatic) and –2.5 or less osteoporosis. Osteopenia found in up to 65% and osteoporosis up to 25% of those with HIV infection. Duration of infection significantly associated. Other factors are HIV wasting, low body mass index, malnutrition, immobilization, hypogonadism, menopause, steroids, alcohol excess, and smoking. HAART, especially with protease inhibitors, suggested as a contributor but conflicting evidence. Occur mainly in the vertebrae, lower arms, and hips. Osteoporosis often asymptomatic but may cause pain (low back, neck, hip), loss of height, kyphosis, and fractures. Bone metabolism should be assessed (serum calcium, phosphate, and alkaline phosphatase). Management should include advice on diet, exercise, and avoidance of alcohol/nicotine. Osteopenia can be managed with vitamin D (400–800IU daily) and calcium supplements (calcium-rich diet or calcium tablets 1.2g/day). Osteoporosis should be treated with bisphosphonates (with additional vitamin D and calcium supplementation). P.489
Neoplasia Non-Hodgkin lymphoma 1° or 2° bone involvement occurs in 20–30%. May present as a pathological fracture, especially of the lower limbs. Radiology shows an area of osteolysis with cortical destruction. A periosteal reaction and soft tissue mass may also be present. Findings similar to bacterial osteomyelitis, therefore biopsy recommended. Treated with chemotherapy, radiation, and possibly surgical debridement. Kaposi’s sarcoma Rarely reported and usually associated with widespread dissemination. Frequently asymptomatic, otherwise bone pain, with radiology either normal or demonstrating lesions usually lytic, occasionally sclerotic. Diagnosis by biopsy. Radiotherapy may alleviate bone pain. Muscle disease 1° myopathy is uncommon and a polymyositis syndrome occurs very rarely. The most important cause of 2° myopathy is prolonged zidovudine therapy, associated with ↑ creatinine kinase level in 16% and symptomatic weakness in 6%. Probably caused by mitochondrial dysfunction because of the inhibition of mitochondrial DNA γ-polymerase by zidovudine. Muscle weakness and wasting is proximal with preserved reflexes and sensory function. Electromyographical evidence of myopathy found in >90%. Ragged, red fibres (due to the accumulation of abnormal mitochondria) may be seen on muscle biopsy. Treatment involves discontinuation of the drug but for some patients prednisolone (starting with 60–80mg daily, reducing over several months) may be required to restore muscle strength.

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