Sickle Cell Information Center Guidelines

Edited by James Eckman, M.D. and Allan Platt, PA-C

Pain in the bones, joints, and back is common in patients with sickle cell syndromes. Pain associated with a pain episode (crisis) is usually diffuse, however, it can be localized. Osteomyelitis, septic arthritis, gout, and bone infarctions also occur with increased incidence in sickling disorders. Aseptic necrosis of the hips and shoulders is common in hemoglobin SC disease and Sickle beta⁺thalassemia. Sickle dactylitis or hand - foot syndrome may the first presentation for children with sickle cell disease. Differentiating these is important because of very significant therapeutic and prognostic implications. Differentiating or excluding these complications provides a complex diagnostic challenge. The occurrence of local bone or joint pain with fever, swelling, effusions, erythemia, or warmth suggests one of these complications.

Clinical Findings

Subjective Data

Present Illness. Carefully document the onset of pain, severity, location (localized, diffuse, symmetric, migratory), radiation, preceding or following onset of crisis, erythemia, warmth, swelling, trauma, fever, skin rash, and past episodes. Note history of trauma.

Review of Symptoms. Define general health, weight change, fever, chills, night sweats, urethral or vaginal discharge, and general ROS.

Past Medical History. Document hemoglobin type, medications, recent pain crises, hospitalizations, allergies, past episodes of osteomyelitis, bone infarctions, gout, and dates of past x-rays of painful areas.

Objective Data

- Do a complete general physical examination. Document temperature.

- Extremities. Location of pain, tenderness, swelling or erythemia. Range of motion of all joints especially those affected by pain. Presence and distribution of synovial thickening or effusion. Subcutaneous nodules, rash, Heberden’s nodes, tophi, clubbing, muscular atrophy.

- Back. Deformities, range of motion, CVA tenderness, muscle spasm, leg raise, muscle strength, reflexes, sensation, fasciculations.

- Minimum Lab. CBC with differential, x-ray area if pain is localized or erythemia and swelling is present.

- Additional Evaluation. SMA 18, urinalysis, analysis of joint fluid, uric acid, rheumatoid factor, anti-nuclear antibodies, blood, joint, or bone cultures, plain x-rays, bone scan, gallium scan, indium labeled white cell scan, and MRI may be indicated.

Differential Diagnosis

- Pain Episode (Crisis). Pain of pain crisis is usually diffuse throughout extremities and back. In younger patients, pain may be localized and occur in different areas or same area with each crisis. Fever, swelling, warmth, erythemia, x-ray changes, and leukocytosis suggest another complication.

- Sickle Dactylitis. Symmetric swelling of both hands and feet occurring in infants and young children is characteristic. May be unilateral and associated with pain, irritability, fever, bone necrosis, and periosteal reaction. Can be difficult to differentiate from osteomyelitis, especially when unilateral. High fever, leukocytosis with left shift and failure to improve favor osteomyelitis.

- Bone Infarction. Severe localized pain with erythemia and swelling usually occurring in association with a severe pain episode often as the generalized pain is improving. The pain may persist for days, but it gradually improves. Leukocytosis and left shift are usually absent. Plain films may show periosteal reaction, bone scan often shows decreased uptake for about seven days then increased uptake after 10 to 14 days. Gallium scan may be negative or positive. Indium labelled white cell studies may be positive. The best diagnostic criteria is rapid improvement without antibiotic therapy.

- Sickle Arthropathy. Monoarticular swelling with effusion, warmth and tenderness usually occurring in association with a severe crisis. Joint fluid positive for sickle cells, may have high neutrophil count, is negative for crystals and bacteria, and has no growth on culture.

- Aseptic Necrosis. Pain in hip or shoulder often unrelated to occurrence of crisis, increases with weight bearing or motion, aching worse at night. Head of femur or humerus is usually involved. May occur more common in Hb SC and SThal. Lab unchanged over patient’s baseline values. X-rays are positive for degeneration in advanced cases. Bone scan shows decreased uptake early then increased uptake and MRI is useful in early diagnosis.

See an xray of AVN of the hips at http://rad.usuhs.mil/synapse/synapse.html?mode=image&imid=264&table=card

- Osteomyelitis. Pain, swelling, warmth, erythemia, abscess, or draining sinus may be present at site of infection. Systemic symptoms include fever, weight loss, and recurrent pain episodes. Leukocytosis with left shift is characteristic. Plain films may show bone destruction, new bone formation, soft tissue swelling or be negative. Bone scan and gallium scan are usually positive. Bone biopsy with cultures is usually diagnostic and the procedure of choice to diagnose or exclude osteomyelitis.

- Septic Arthritis. Pain, effusion, warmth, erythemia over one joint. In gonococcal infection, there may be a history of urethral or vaginal discharge, migratory arthralgias, and skin rash. Fever and leukocytosis with a left shift is common. Joint aspirate is diagnostic showing increased neutrophils (to >100,000), bacteria, low glucose, and positive cultures.

- Gout. Severe pain of one joint, with swelling, erythemia, and exquisite tenderness. Tophi may be present. Mild fever and leukocytosis may occur. Uric acid is usually elevated. Joint fluid is diagnostic with high neutrophil count, low glucose, negative cultures and characteristic crystals.

- Degenerative Arthritis, Rheumatoid Arthritis, and SLE. May also occur in patients with hemoglobinopathies methods of evaluation are outlined in general pediatric and medical texts.

- Pain Crisis. Treatment and admission criteria the same as for pain crisis protocol.

- Sickle Dactylitis Treatment is with hydration, analgesics such as acetaminophen or aspirin, and observation. High fever, leukocytosis with left shift and failure to improve should prompt aspiration of inflamed area for gram stain and cultures. Blood cultures are indicated.

- Bone Infarction. Initial treatment is control of the crisis with bed rest, hydration and narcotics. Start non-steroidal anti-inflammatory drug such as aspirin or ibuprofen, 400 - 800 mg. P.O. q 6 h after infection has been ruled out.

- Sickle arthropathy. Treatment is the same as for bone infarction. Non-weight bearing is recommended while joint is swollen and painful. Arthrocentesis may be bold diagnostic and therapeutic.

- Aseptic Necrosis. No weight bearing, non-narcotic analgesia, ibuprofen, and orthopedic consultation. Vascularization procedures such as core decompression the femoral head reduce pain and may slow progression, however, no controlled trials are available to determine extent of benefit. When the process progresses and the patient is incapacitated, prosthetic replacement is indicated. The average prosthesis lasts about ten years in these active, young patients, making repeated replacement for loosening or infection the rule over the life of the patient.

- Osteomyelitis. Admission to the hospital for diagnosis and therapy. Antibiotics should not be started until biopsy for culture is obtained unless the patient appears septic. In this case, blood cultures should be obtained and the patient started on I.V. antibiotics to cover staphylococci, salmonella, and enteric gram negatives. Bone biopsy for culture should be obtained as soon as possible to identify the organism and plan antimicrobial therapy. Orthopedic input on surgical management is indicated.

- Septic Arthritis. Admission to the hospital is indicated for appropriate antibiotics based on smear and culture of the joint fluid. Gonorrhea and tuberculosis should be considered in culture negative purulent arthritis. Surgical drainage may be required based on the severity and organism.

- Gout. Administration of non-steroidal anti-inflammatory drug, colchicine, or steroids is indicated acutely. If chronic reduction of uric acid is indicated, urinary studies for daily output of uric acid will determine if probenecid or allopurinol should be used.

- DJD, Rheumatoid Arthritis, SLE. Non-steroidal anti-inflammatory drugs should be started and most patients should also be referred to rheumatology for evaluation and therapy.

NSAID Considerations for long term pain therapy:

Sodium salicylate. Enteric-coated preparations preferred; less potent analgesic than aspirin; does not inhibit platelet function; less gastric bleeding; effective anti-inflammatory agent; watch total sodium intake in patients with history of heart failure or hypertension.

(Choline salicylate. Very soluble; liquid form; negligible gastric bleeding; probably somewhat less effective than aspirin; no platelet dysfunction.

Choline magnesium trisalicylate (Trilisate). Dosage schedule tid; minimal gastric irritation; 500-mg tablets, 2 tablets PO tid.

Salsalate (Disalcid). Convenient bid dosage with minimal gastric irritation or platelet dysfunction; 500-mg and 750-mg tablets; usual dosage schedule, 2 tablets bid-tid.

COX-2 inhibitors are long acting NSAIDS that may have reduced gastric and renal toxicity.

All NSAIDs share the following potential toxicities: hepatitis, renal dysfunction, sodium and fluid retention, gastrointestinal irritation (dyspepsia, nausea or vomiting, peptic ulceration with or without hemorrhage or perforation), platelet dysfunction with increased bleeding risk when used with anticoagulants, skin rash, and central nervous system symptoms (headaches, dizziness, blurred vision). Patients who have true aspirin allergy (anaphylaxis or asthma, nasal polyposis) should not be given any of the other NSAIDs because of potential cross-reactivity. Misoprostol, a synthetic prostaglandin E1 analogue, can protect the gastric mucosa from the irritative effects of NSAIDs. Endoscopic studies have demonstrated that both 100 micro-g and 200 micro-g qid have a cytoprotective effect and thus prevent the development of gastric ulcers and gastritis in patients treated with varying types of NSAIDs.

Nursing Considerations:

 Patients should rate pain on a scale of 1 to 10, describe level and characteristic of pain, and have patients describe factors that intensify pain

Teach patients to differentiate treatment of chronic pain (Arthritis, bone infarcts, or other joint complications) from treatment of acute pain crisis.

 Assess the patient’s perception of pain, including its characteristics and usual methods to alleviate it

Administer analgesics as prescribed and needed

Pain in the older patients may be difficult to assess and is under reported because of dementia or cognitive impairments that prevent the use of pain tools, and the belief that pain is a normal part of the aging process

 The goal of therapy may be adequate long term management of chronic pain rather than immediate elimination of pain.

Prevention

Complete and careful evaluation of localized bone or joint pain to exclude an infectious or other treatable cause will prevent delay in diagnosis and long-term disability. If the work-up is negative, observation on analgesics without empiric use of antibiotics will usually separate crisis or bone infarct, which will improve, from infection which will not improve or get worse. Non-weight baring during periods of exacerbation of pain in aseptic necrosis will improve the acute problem and may slow progression.

Patient and Parent Education

It is very important to educate the patient that the pain of bone infarct, sickle arthritis, or other joint complications may persist from days to weeks and that persistent narcotic administration may be unwise. Patients need to differentiate the treatment of this chronic pain from treatment of acute pain episodes. They need reassurance that the pain will improve over time and that the use of NSAIDs may be therapeutic and analgesic.

References

Diggs LW. Bone and Joint lesions in sickle cell disease. Clin. Ortho. 52:119-142, 1967.

Chung SMK and Ralson EL. Necrosis of the femoral head associated with sickle-cell anemia and its genetic variants. J. Bone Joint Surg. 51:33-58, 1969.

Schumacher HR, Andrews R, McLaughlin G. Arthropathy in Sickle-cell disease. Ann. Intern. Med. 78:203-211, 1973.

Espinoza LR, Spilberg I, Osterland CK. Joint manifestations of sickle cell disease. Medicine 53:295-305.

Lee REJ, Golding JSR, Serjeant. The radiological features of avascular necrosis of the femoral head in homozygous sickle cell disease. Clin. Radiol. 32:205-214, 1981.

Stevens MCG, Padwick M, Serjeant GR. Observations on the natural history of dactylitis in homozygous sickle cell disease. Clin. Pediatr. 20:311-317, 1981.

Acute infarction of long bones in children with sickle cell anemia. J. Pediatr. 101:170-175, 1982.

Milner PF, Brown M. Bone infarction in sickle cell anemia; correlation with hematologic profiles. Blood 60:1411-1418, 1982.

Ebong WW. The treatment of chronic osteomyelitis in sickle cell anemia. Int. Surg. 67:361-365, 1982

Reynolds MD. Gout and hyperuricemia associated with sickle-cell anemia. Semin. Arth. Rheumat. 12:404-413, 1983.

Wethers DL and Grover R. Pitfalls in diagnosis of osteomyelitis in children with sickle cell disease. Clin. Pediatr. 22:614-618, 1983.

Koren (Kurlat) A, Garty I, Katzuni. Bone infarction in children with sickle cell disease: Early diagnosis and differentiation from osteomyelitis. Eur. J. Pediatr. 142:93-97, 1984.

de Ceulaer K, Forbes M, Roper D, Serjeant GR. Non-gouty arthritis in sickle cell disease: report of 37 consecutive cases. Ann. Rheum. Dis. 43:599-603, 1984.

Bishop AR, Robertson J, Eckman JR, Flemming LL. Total hip arthroplasty in patients who have sickle hemoglobinopathy. J. Bone Joint Surg. 70-A:853-855, 1988.

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Copyright © 1997 Sickle Cell Information Center
Last modified: November 03, 2000