Musculoskeletal manifestations in sickle cell anemia
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0975-2870.218182
Keywords: Avascular necrosis, infarction, magnetic resonance imaging, osteomyelitis, sickle cell
Sickle cell anemia is an autosomal recessive genetic condition due to a mutation in the beta-globin gene resulting in the replacement of glutamic acid in position 6 of the beta globin chain by valine resulting in an abnormal sickle cell hemoglobin (HbS) molecule.[1] The term sickle cell disease applies to those patients who have at least one abnormal HbS chain and another abnormal beta chain. If the second abnormal chain is also an HbS chain, then; the patient is considered to be homozygous Hb SS-defined as sickle cell anemia. Alternatively, other abnormal hemoglobin chains such as Hb Cor thalassemia result in Hb SC and Hb S-thal, respectively. The combination of an abnormal HbS chain and a normal beta-globin chain is called sickle cell trait.[2] The abnormal HbS protein chain polymerizes reversibly in deoxygenated environment into a gelatinous network of fibrous polymers that stiffen the red blood cell (RBC) membrane, increases the viscosity, and causes dehydration resulting in a sickle shape. These abnormal cells lose their pliability and are abnormally sticky provoking unpredictable episodes of microvascular occlusions and premature hemolysis. The clinical and radiological manifestations of sickle cell anemia are numerous. Pathophysiologically, all of them, result from rigid adherent cells clogging small vessels, leading to tissue ischemia/infarction, and gradual end-organ damage.[3] Here, we present a case series on the various musculoskeletal manifestations of sickle cell disease.
Case 1 A 22-year-old young adult with a history of sickle cell anemia and chronic pain syndrome presented to the emergency department with complaints of the bilateral hip joint pain for 2 months not relieved with analgesics. Patient reports increased pain while walking and occasionally at rest. Multiple lytic lesions were noted involving the sacrum and bilateral iliac wings on computed tomography (CT) which suggested extramedullary erythropoiesis with bony ankylosis of bilateral sacroiliac joints [Figure 1].
Case 2 An 18-year-old young adult with a history of sickle cell anemia presented to orthopedics outpatient department with back pain not relieved with analgesics. CT of the lumbar spine revealed diffuse osteopenia with coarsened trabeculae, multiple cystic areas, and H-shaped vertebrae [Figure 2].
Case 3 A 32-year-old man with history of sickle cell anemia presented to the emergency department with complaints of low back ache and chronic left hip joint pain not relieved with analgesics. Magnetic resonance imaging (MRI) contrast study of the lumbar spine and pelvis showed multiple areas of T2 hyperintensity involving the lateral aspect of vertebral bodies and posterior elements of all lumbar vertebrae, bilateral iliac bones, left ischium, and few dorsal vertebrae – representing bone infarcts [Figure 3].
Case 4 A 45-year-old lady with sickle cell anemia presented with bilateral hip pain. CT study of the pelvis and bilateral hips revealed osteopenia of the bilateral femoral heads with subchondral cysts [Figure 4].
Case 5 A 58-year-old lady with sickle cell anemia presented with bilateral chronic hip pains. MRI contrast study of the pelvis revealed multiple geographic short tau inversion recovery (STIR) hyperintensities in the proximal femur, acetabulum, pelvic bones, and vertebrae with sclerosis – suggesting avascular necrosis (AVN) [Figure 5].
Patients with sickle cell anemia have reduced height. This is believed to be due to bone marrow hyperplasia and premature closure of growth plates.[4] Bones are generally shorter due to epiphyseal shortening subject to ischemia/infarction and vascular compromise to the growth plate. In the spine, AVN of the end plate produces a sharp central step in the vertebral body endplate, causing the H-shaped vertebra. In children, infarction within the small bones of the hand and feet result in painful dactylitis termed “hand-foot” syndrome.[5] In sickle cell anemia, there is persistence of red marrow in both axial and appendicular skeleton into adulthood with bone marrow hyperplasia. On T1-weighted MRI, normal fatty marrow shows high signal intensity, while hematopoietic red marrow is low in signal. Marrow hyperplasia results in widening of the medulla and cortical thinning, resulting in coarsening of the normal trabecular pattern with loss of corticomedullary differentiation in both long and flat bones.[6] This leads to osteopenia and makes the bones liable for fractures. Bone softening is noted in the vertebral bodies where the end plates assume a concavity described as fish mouth vertebrae. Widening of the diploic space in skull results in “hair on end” appearance.[7] AVN is a common entity involving the epiphyses of long bones.[8] Initial radiographs are normal. Late stages show sclerosis, subchondral collapse, and flattening of the epiphyses. T2-weighted (T2W) MRI sequence shows high signal intensity with a serpiginous low signal intensity line classically seen. As the necrosis progresses, sclerosis develops with collapse of the affected epiphysis. Medullary bone infarcts are more common in patients with sickle cell anemia. Initial radiographs of acute bone infarcts are normal. Later, stages show patchy lucency with periosteal reaction on plain radiographs progressing to sclerosis. On T2W, infarct is seen as an area of high signal intensity and may show peripheral enhancement postgadolinium.[9] Patients with sickle cell anemia have an increased incidence of septic arthritis and osteomyelitis as compared to the general population due to abnormal RBC's reducing the flow in small blood vessels resulting in relative ischemic zones. Osteomyelitis more commonly occurs in the diaphysis of the long bones. There is an increased incidence of Salmonella More Details osteomyelitis in sickle cell patients.[10] Plain film findings of osteomyelitis include osteopenia, periosteal reaction with or without cortical destruction, and sinus tract formation with soft tissue extension. Features of osteopenia and periosteal reaction are not specific to osteomyelitis and can also be seen in acute bone infarcts. MRI T2W images show areas of osteomyelitis as high signal intensity areas. On T1W, osteomyelitis is of low signal intensity. Focal fluid collections with soft tissue involvement may occur. Osteomyelitis will show areas of enhancement postgadolinium which tends to be more diffuse than in infarction. Rim enhancement may also be seen but is not specific as it is also seen in bone infarction.[9] Increased incidence of septic arthritis is noted in patients with sickle cell disease. Septic arthritis results from vaso-occlusion involving articular surfaces with subsequent infection. Early diagnosis and treatment are essential to prevent irreparable joint damage. Ultrasound may be used to confirm the presence of effusion and to guide joint aspiration. Diagnosis can be confirmed by culture of joint aspirate. MRI also demonstrates joint effusion. Synovial enhancement postgadolinium is noted.[11] Dactylitis also known as “hand-foot” syndrome is common between 6 months and 7 years of age.[12] These are symptomatic microinfarcts in the phalanges and metatarsal bones. Dactylitis presents with unilateral/bilateral painful swelling of the distal extremities associated with leukocytosis and fever.[13] The symptoms of dactylitis are self-limiting and usually, resolve within 1 month. Plain radiographs show a moth-eaten appearance of the digits. Treatment includes bed rest, elevation, immobilization, and analgesics. Patients with sickle cell disease present with diffuse osteopenia attributed to erythroid hyperplasia due increased hematopoietic activity in bone resorption. This leads to generalized osteopenia with central collapse. On radiographs, the vertebrae assume fishmouth configuration due to the effect of the intervening disc on the adjoining vertebral end plate.[14] The vertebral collapse also can occur due to thrombosis/infarction. This is a common sequelae of osteoporosis in sickle cell disease. Osteoporotic bones are prone for pathological fractures. Several forms of arthritis, both inflammatory and noninflammatory, have been described in association with sickle cell disease. Arthritis associated with sickle cell disease is usually polyarticular with a predilection for large joints and lower extremities. Periarticular osteopenia, bone erosions, synovitis, and joint space narrowing are plain radiograph features.[15] In Case 1, extramedullary hematopoiesis was demonstrated on CT showing multiple lytic lesions involving the sacrum and bilateral iliac wings on CT with bony ankylosis of bilateral sacroiliac joints vertebral endplate depression due to central infarction also is depicted. Extramedullary hematopoiesis occasionally is seen in sickle cell anemia. The most common site is the liver, but the spleen also may be affected, and soft-tissue hematopoietic masses may develop in the thorax, adrenal glands, and skin. In Case 2, diffuse osteopenia with coarsened trabeculae of the lumbar spine with multiple cystic areas and H-shaped vertebrae was demonstrated on CT. The H-shaped vertebral deformity is thought to be a result of central growth plate infarction. It can be distinguished from marrow hyperplasia by the characteristic sharp step-like appearance of the vertebral endplate. In Case 3, bone infarcts in the lateral aspect of vertebral bodies and posterior elements of all lumbar vertebrae, bilateral iliac bones, left ischium, and few dorsal vertebrae were demonstrated. Acute infarcts cause osteolysis. Later, intramedullary lucency and sclerosis become evident with a patchy distribution. If the cortical bone is also infarcted, subperiosteal new bone may form either thickening of the cortex or through layered deposits along the inner surface of the cortex (causing a laminated, “bone-within-bone” appearance). In Case 4, osteopenia of the bilateral femoral heads with subchondral cysts was demonstrated on CT. Epiphyseal ischemic necrosis in sickle cell anemia is common, frequently seen in the femoral and humeral heads, and more often bilateral than AVN in other diseases. In Case 5, STIR hyperintensities in the proximal femur, acetabulum, pelvic bones, and vertebrae were demonstrated on MRI. Initial radiographs appear normal, and the earliest signs of AVN are seen on MR images (in particular, T2W inversion recovery images), which show regions of high signal intensity indicative of bone marrow edema. The differential diagnoses that were considered for our patients in Case 3 and Case 5 were - rheumatoid arthritis, ankylosing spondylitis, and SLE. However, due to the classic crescent sign on CT which is a linear area of subchondral lucency seen most frequently in the anterolateral aspect of the proximal femoral head and the reactive interface line on MRI which is a focal serpentine low signal line with fatty center, we considered a diagnosis of AVN and bone infarcts.
Sickle cell disease is a genetic disorder with multisystem involvement. Sickle cell disease is an inherited disorder of abnormal hemoglobin with varied osteoarticular and nonosseous complications that mimic surgical conditions. Radiological changes of the bone are seen secondary to hyperplasia of the marrow and ischemic osteonecrosis. MRI is critical for the detection of spine and pelvic pathology in sickle cell disease. MR helps in differentiating discitis and osteomyelitis from bone infarcts and also in the characterization of muscle and soft tissue changes. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
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