MANAGEMENT AND THERAPY OF SICKLE CELL DISEASE

NIH Publication No. 95-2117, Revised December 1995 (Third Edition) National Institutes of Health, National Heart, Lung, and Blood Institute

Chapter 17--Bones and Joints

The bones and joints are frequently involved in sickle cell disease and are the major sites of pain in vaso-occlusive crises. Bone marrow hyperplasia occurs as a result of chronic hemolytic anemia, which can cause bone distortion in childhood, leading to such deformities as tower skull, bossing of the forehead, and gnathopathy (distortion of the maxilla resulting in protrusion of the upper incisors and overlapping of the upper jaw). Probably because the hyperplastic marrow is more vascular than fatty, bone marrow infarction is more common in SS disease than in other forms of sickle cell disease. In cancellous bones such as the vertebrae, infarction of bone trabeculae in the central part of the vertebral body, supplied by the nutrient artery, causes a collapse of the vertebral plates leading to compression and the classical radiographic appearance of "fish mouth" disc spaces and the "step" sign (a depression in the central part of the vertebral body). Back pain, a common symptom in sickle cell disease, probably indicates a continuation of this process.

Occasionally, other cancellous bones are involved such as the metaphysis and epiphysis of long bones involving the adjacent joint, the os calcis causing pain in the heel, and the bones of the face with resulting pain and swelling. In the long bones, because of the anatomic arrangement of the fine branches of the nutrient artery that penetrate the inner layers of bone to anastomose with vessels that form the periosteum, infarction frequently causes swelling and edema in the overlying soft tissues. This can mimic acute osteomyelitis. The earliest example of this is the hand-foot syndrome in infants that is discussed later in this chapter. Multiple long-bone infarcts occur frequently in sickle cell crises in older children and adults and can be demonstrated by bone scans. When long-bone infarcts heal, they can cause new layers of bone to be laid down in the central cavity, which in radiographs give the appearance of "a bone within a bone." Most patients with SS disease show these changes.

An approach to management of a patient with pain in a long bone is outlined (see Chapter 7, Painful Events). Perhaps the most difficult problem caused by acute pain and swelling of a long bone in sickle cell disease is the differential diagnosis from acute osteomyelitis. Although uncommon, infection must always be considered, but it can usually be ruled out by close clinical observation, blood cultures, and occasionally, aspiration of the affected area (see Chapter 6, Infection). Plain radiographs are not helpful in the early stages and should not be taken routinely. Bone scans are not usually helpful in differentiating a simple infarct from osteomyelitis.

OSTEONECROSIS OF THE FEMORAL AND HUMERAL HEADS (ASEPTIC NECROSIS)

This condition affects patients with all types of sickle cell disease. The hips and shoulder joints are about equally affected, although weight bearing makes femoral head necrosis more likely to cause severe disability. Although osteonecrosis can occur at any age (the earliest reported case was in a child age 3 years), a recent prospective study of a large number of patients by the Cooperative Study of Sickle Cell Disease showed a peak incidence in Hb SS patients between ages 25 and 35 years and at a slightly older age in patients with Hb SC disease and S beta + thal. The natural history of osteonecrosis in sickle cell disease has yet to be studied in a prospective fashion; it is clear that when the disease occurs before closure of the epiphyses, considerable healing can occur. However, patients in their late teens and early twenties presenting with the early development of a crescent sign (a fracture line within the necrotic femoral head beneath the cartilage) may have total collapse and destruction of the head, with persistent pain and difficulty in walking within a few months.

In older patients, sclerosis and even some considerable deformity of the femoral head apparent on the radiograph may persist with little change for many years without causing much discomfort or disability. The diagnosis of aseptic necrosis of the femoral head is usually made when the patient complains of intermittent or persistent pain in the groin or buttock. Occasionally, there may be an acute synovitis mimicking a septic arthritis. Any attempt to move the joint through its range of movement is resisted because of acute pain. Radiographs should be taken in the AP and "frog leg" positions and examined for evidence of changes in the bone density of the femoral head. In the early stages, however, the radiographs may appear normal. The earliest changes associated with pain can be detected by MRI and radionuclide imaging. If there is bilateral disease, however, the radionuclide scans may be difficult to interpret. MRI is very sensitive and can detect small areas of necrosis several months before symptoms occur; it frequently reveals bilateral disease when symptoms are still unilateral.

Total hip replacement has no place in the management of early osteonecrosis. Presently, initial treatment consists mainly of avoidance of weight bearing and judicious use of local heat and analgesics for pain relief up to 6 months. This is particularly important in children and teenagers for whom a considerable healing potential exists. In children, osteotomy with rotation to change the area of the head subjected to weight has been used in the past with variable results. For older patients with persistent hip pain and a positive MRI but without radiological evidence of collapse, core decompression of the femoral head performed by an orthopedic surgeon experienced in this technique can sometimes result in immediate pain relief. For an individual beyond adolescence who is severely incapacitated by hip pain and who cannot carry out activities of daily life and requires relief, surgical replacement of the entire joint must be considered, even when the patient is in his or her early twenties. The patient should be made aware that hip replacement is not always successful in eliminating symptoms and in restoring function in sickle cell disease patients; also, loosening and other complications may necessitate revision (removal and insertion of a new prostheses) at a later date. Infection is uncommon, but if removal of the prosthesis later becomes necessary because of infection, reinsertion is unlikely to be successful and is rarely considered. Aseptic necrosis of the shoulder may be quite disabling, especially in a person who needs to use both arms continuously at work. Although most painful shoulders settle down with NSAIDs, surgical intervention is occasionally warranted and can result in pain relief and improved range of movement.

HAND-FOOT SYNDROME

The hand-foot syndrome is a fairly common phenomenon that is seen almost exclusively in the infant and young child. It presents with pain, low-grade fever, and diffuse nonpitting edema of the dorsum of the hands and feet, which extends to the fingers and toes. One to four extremities may be affected at one time. Radiographic changes of elevation of the periosteum and necrosis are seen in the metacarpals and phalanges or metatarsals but may not appear for 1 week or more. The syndrome is best treated with analgesia, hydration, and parental reassurance. In spite of the often striking radiographic changes and swelling that may persist for several weeks, the syndrome is almost always self-limited, and bones usually heal without permanent deformity. Transfusions, antibiotics, and other measures are not necessary, but it should be noted that early osteomyelitis can have a similar presentation. Therefore, it is recommended that in the presence of fever and marked inflammation, or if there is no clinical improvement in 2 to 3 days, the patient should be evaluated for osteomyelitis with appropriate blood cultures and direct aspiration of the area involved.

OTHER BONE AND JOINT SYNDROMES

The differential diagnosis of joint effusions in patients with sickle cell disease is difficult because of a variety of possible etiologies. Effusions and periarticular swelling can occur secondary to synovial infarction or infarction in the end of the adjacent long bone. The knee is a common site. Gout, septic arthritis, osteoarthritis, or rheumatic or collagen vascular disease should be considered and ruled out by appropriate tests. Because treatments for these disorders differ, it is important to aspirate the joint for culture, protein, and microscopic analysis if the patient is febrile or there are signs of marked inflammation. Such a tap should be performed in the hospital by an experienced physician. If evidence for a coexistent disease is obtained, it should be treated as in other patients. In the absence of clear diagnostic findings (bacteria or uric acid crystals), simple supportive measures, including analgesia, local heat, hydration, and bedrest for 5 to 7 days, are indicated. NSAIDs are often very effective for 4 to 6 days and may be tried in teenagers or adults with normal renal function. Other anti-inflammatory agents may also be useful, but proper precautions should be taken to avoid gastric irritation. If signs of effusion persist, radiographic studies should be obtained, and joint fluid analysis may have to be repeated.

BIBLIOGRAPHY

Bohrer SP. Bone ischemia and infarction in sickle cell disease. St. Louis: Warren H. Green Inc., 1981.

Gaston MH. Sickle cell disease: an overview. Semin Roentgenol 1987;22:150-9.

Milner PF, Brown M. Bone marrow infarction in sickle cell anemia; correlation with hematologic profiles. Blood 1982;60:1411-8.

Milner PF, Joe C, Burke GJ. Bone and joint disease. In: Embury SH, Hebbel RP, Mohandes N, Steinberg M. Sickle cell disease. New York: Raven Press, 1994:645-61.

Milner PF, Kraus AP, Sebes JI, et al. Sickle cell disease as a cause of osteonecrosis of the femoral head. N Engl J Med 1991;325:1476-81.

Milner PF, Kraus AP, Sebes JI, Sleeper LA, et al. Osteonecrosis of the humeral head in sickle cell disease. Clin Orthop 1993;289:136-43.

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