Osteoarthropathy has been well described in thalassemia major, but rarely in thalassemia minor. There is a 50% incidence of osteoarthropathy in thalassemia major, which occurs in the second and third decade and primarily affects the ankle joint, but also has been noted in the knee and hip. The pathomechanics of arthropathy in thalassemia major are unknown, but are attributed to the underlying bony changes.1 Other skeletal changes - such as cortical thinning of long and flat bones, coarse trabeculation, osteopenia, and evidence of microfractures - reflect marrow hyperplasia as a result of the hemolytic process.
Osteoarthropathy is rarely associated with thalassemia minor, although bilateral avascular necrosis of the femoral heads has been reported. This case report describes a patient with thalassemia minor presenting with severe degenerative joint disease of the hip.
A 36-year-old white woman presented with a three-year history of increasing left hip pain. There was no prior history of trauma, infection, or joint disease. The patient's pain occurred at rest, at night, and resulted in a significant functional handicap. On examination, she walked without aid but had a pronounced antalgic gait. Her range of motion of the hip was within normal limits with the exception of internal rotation, which was limited to 0° and was extremely painful.
Routine roentgenograms of the left hip revealed a poorly circumscribed, radiodense, periarticular lesion in the ilium, symmetrical joint space narrowing, and subchondral cysts within the femoral head and acetabulum (Fig. 1). A skeletal survey revealed no other evidence of arthropathy, osteopenia, or trabecular or cortical thinning. Laboratory values were normal (ESR 30; WBC 5.0; RA nonreactive; ANA nonreactive;Ca9.5; PO 3.4; Alkaline phosphatase 35). A hip arthrogram suggested no abnormality of the synovial lining. Aerobic, anaerobic, fungal, and tuberculosis cultures of the synovial fluid were negative.
Fig. 1: Roentgenogram of left hip reveals poorly circumscribed lesion in the ilium, symmetrical joint space marrowing, and subchondral cysts within the femoral head and acetabulum.
Fig. 2: Roentgenogram of left hip after total hip arthroplasty.
Fig. 3: Biopsy specimen of cancellous bone demonstrates increased thickness of the trabecular with no evidence of marrow hyperplasia (20X).
She was medically evaluated for her history of chronic anemia. Although she had no relatives of Mediterranean decent, she had a brother who had thalassemia minor. She had never received transfusions but did take iron supplements during her pregnancy. A laboratory evaluation revealed a hypochromic microcytic anemia (Hemoglobin 9.8; Hematocrit 28.7; MCV 60; MCH 20.6; Reticulocyte 4.3; Platelets 375; Iron 74 (49-179); TIBC 279 (275-445); Sickle prep, negative). A hemoglobin electrophoresis confirmed the diagnosis of thalassemia minor in this patient (HBF 4.0%, A2 scan 7.9, A2 Col 8.4).
Because of her pain and functional limitations (Harris hip score 57), the patient elected to undergo a total hip arthroplasty (Fig. 2). Pathologic examination of the synovium and cartilage was consistent with degenerative arthritis. The subchondral and cancellous bone had marked increased thickness of the trabeculae with no evidence of marrow hyperplasia (Fig. 3). Microfracture and secondary ossified callus within the cancellous bone was noted within the ilium. At 12 months followup she had complete relief of pain, excellent function, and no other symptoms of anemia or osteoarthropathy.
Hemoglobinopathies are known for their differential distribution among the human races, with thalassemia found in a broad belt extending from the Mediterranean basin into India and the Orient.1,2 Beta thalassemia is a disorder of the production of the beta chain of hemoglobin; hemoglobin being composed of four intertwined polypeptide chains, a pair of alpha chains and a pair of beta chains. In the homozygous state, thalassemia major, the hemoglobin is nonfunctional, producing a severe anemia requiring multiple transfusions and a decreased life expectancy as a result of iron overload. In the heterozygous state, thalassemia minor, only one of the beta chains is affected. Thalassemia minor is a benign hemoglobinopathy traditionally described as an asymptomatic disease often diagnosed by chance.1,3 Thalassemia intermedia is a syndrome of intermediate severity between thalassemia major and minor. It can be of either heterozygous or homozygous geneotype. but is usually homozygous. Clinically, signs and symptoms are similar to thalassemia major but of lesser magnitude. These patients have chronic anemia, but do not require transfusions except in association with an intercurrent illness or pregnancy.2
There are two major mechanisms for arthritis in hemoglobinopathies. The first is bone infarction resulting in avascular necrosis, subchondral fracture, and then cartilage destruction; this mechanism is demonstrated in sickle cell anemia. The second mechanism, as seen in thalassemia, is chronic anemia in which the marrow compensates by increasing its rate of erythropoiests by marrow hypertrophy. This results in decreased trabeculations, thinning of the cortices, and microfractures, which then causes increased joint stresses and cartilage degeneration.1,3
Fig. 4: Biopsy specimen of cancellous bone from ilium demonstrates callus formation (2Ox).
This patient presented with a chronic asymptomatic anemia with no radiographic or pathologic evidence of medullary hyperplasia, decreased trabeculations, or thin cortices. She did, however, have evidence of microfracture and callus formation in die periarticular bone. One can speculate that during a hematologically stressful period in the past, such as a pregnancy, she may have had a transient episode of medullary hyperplasia in the area of the left hip, causing the subsequent arthropathy with secondary bone changes. With the resolution of the hematological stress, her marrow then returned to its former state.
This case report calls attention to the radiographic changes in the hip that are rarely associated with thalassemia minor. Furthermore, one may speculate as to the pathophysiologic changes that preceded the onset of arthritis, which were probably marrow hyperplasia with secondary weakening of the trabecular bone, fracture, repair, and arthritis.
1. Gratwick G, Bullough P, Bohne W. Markenson A. Feteison G: Thalassemia osteoarthropathy. Ann Intern Med 1978; 88:495-501.
2. Wintrobe M: The thalassemia related disasters, in Wintrobe MM. et al (eds): Clinical Hematology, ed 8. Philadelphia. Ua & Febiger, 1981, pp 869-898,
3. Middlemis JH, Rapcr AB: Skeletal changes in the hemoglobinopathies. J Bone Joint Surg I960; 48B(4):693.
4. Comming DE: Thalassemia, in Williams WJ (ed): Hematology. New York. McGraw Hill. 1972. pp 328-349.
5. Rizk N. Nasr F, Frayha R: Avascular necrosis in thalassemia minor. Arthritis Rheum 1977; 20:1147.