Arthropathy of Acromegaly
Acromegaly is the result of excessive production of growth hormone by an adenoma in the anterior pituitary gland (Chap. 339). The excessive secretion of growth hormone along with insulin-like growth factor I stimulates proliferation of cartilage, periarticular connective tissue, and bone, resulting in several musculoskeletal problems, including osteoarthritis, back pain, muscle weakness, and carpal tunnel syndrome.
Osteoarthritis is a common feature, most often affecting the knees, shoulders, hips, and hands. Single or multiple joints may be affected. Hypertrophy of cartilage initially produces radiographic widening of the joint space. The newly synthesized cartilage is abnormally susceptible to fissuring, ulceration, and destruction. Ligamental laxity of joints further contributes to the development of osteoarthritis. Cartilage degrades, the joint space narrows, and subchondral sclerosis and osteophytes develop. Joint examination reveals crepitus and laxity. Joint fluid is noninflammatory. Calcium pyrophosphate dihydrate crystals are found in the cartilage in some cases of acromegalyarthropathy and, when shed into the joint, these can elicit attacks of pseudogout. Chondrocalcinosis may be observed on radiographs. Back pain is extremely common, perhaps as a result of spine hypermobility. Spine radiographs show normal or widened intervertebral disk spaces, hypertrophic anterior osteophytes, and ligamental calcification. These changes are similar to those observed in patients with diffuse idiopathic skeletal hyperostosis. Dorsal kyphosis in conjunction with elongation of the ribs contributes to the development of the barrel chest seen in acromegalic patients. The hands and feet become enlarged, owing to soft tissue proliferation. The fingers are thickened and have spadelike distal tufts. One-third of patients have a thickened heel pad. Approximately 25% of patients have Raynaud's phenomenon. Carpal tunnel syndrome occurs in about half of patients. The median nerve is compressed by excess connective tissue in the carpal tunnel. Patients with acromegaly could develop proximal muscle weakness, which is thought to be caused by the effect of growth hormone on muscle. Serum muscle enzyme levels and electromyography are normal. Muscle biopsy specimens show muscle fibers of varying size but with no inflammation.
Arthropathy of Hemochromatosis
Hemochromatosis is a disorder of iron storage. Excessive amounts of iron are absorbed from the intestine, leading to iron deposition in parenchymal cells, which results in impairment of organ function (Chap. 357). Symptoms of hemochromatosis usually begin between the ages of 40 and 60 but can occur earlier. Arthropathy, which occurs in 20–40% of patients, usually begins after the age of 50 and may be the first clinical feature of hemochromatosis. The arthropathy is an osteoarthritis-like disorder affecting the small joints of the hands, followed later by larger joints such as knees, ankles, shoulders, and hips. The second and third metacarpophalangeal joints of both hands are often the first and prominent joints affected; this may provide an important clue to the possibility of hemochromatosis because these joints are not predominantly affected by “routine” osteoarthritis. Patients experience some morning stiffness and pain with use of involved joints. The affected joints are enlarged and mildly tender. Radiographs show narrowing of the joint space, subchondral sclerosis, subchondral cysts, and juxtaarticular proliferation of bone with frequent hooklike osteophytes. The synovial fluid is noninflammatory. The synovium shows mild to moderate proliferation of iron containing lining cells, fibrosis, and some mononuclear cell infiltration. In approximately half of patients, there is evidence of calcium pyrophosphate deposition disease (CPPD), and some patients experience episodes of acute pseudogout.
Iron may damage the articular cartilage in several ways. Iron catalyzes superoxide-dependent lipid peroxidation, which may play a role in joint damage. In animal models, ferric iron has been shown to interfere with collagen formation and increase the release of lysosomal enzymes from cells in the synovial membrane. Iron inhibits synovial tissue pyrophosphatase in vitro and, therefore, may inhibit pyrophosphatase in vivo, resulting in chondrocalcinosis.
Treatment: Arthropathy of Hemochromatosis
The treatment of hemochromatosis is repeated phlebotomy. Unfortunately, this treatment has little effect on established arthritis, which, along with chondrocalcinosis, may progress. Symptomatic treatment of the arthritis consists of administration of acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), as tolerated. Acute pseudogout attacks are treated with high doses of an NSAID or a short course of glucocorticoids. Hip or knee total joint replacement has been successful in advanced disease.
Hemophilia is a sex-linked recessive genetic disorder characterized by the absence or deficiency of factor VIII (hemophilia A, or classic hemophilia) or factor IX (hemophilia B, or Christmas disease) (Chap. 116). Hemophilia A constitutes 85% of cases. Spontaneous hemarthrosis is a common problem with both types of hemophilia and can lead to a deforming arthritis. The frequency and severity of hemarthrosis are related to the degree of clotting factor deficiency. Hemarthrosis is not common in other disorders of coagulation such as von Willebrand disease, factor V deficiency, warfarin therapy, or thrombocytopenia.
Hemarthrosis occurs after one year of age, when the child begins to walk and run. In order of frequency, the joints most commonly affected are the knees, ankles, elbows, shoulders, and hips. Small joints of the hands and feet are occasionally involved.
In the initial stage of arthropathy, hemarthrosis produces a warm, tensely swollen, and painful joint. The patient holds the affected joint in flexion and guards against any movement. Blood in the joint remains liquid because of the absence of intrinsic clotting factors and the absence of tissue thromboplastin in the synovium. The synovial blood is resorbed over a period of a week or longer, depending on the size of the hemarthrosis. Joint function usually returns to normal or baseline in about two weeks. Low-grade temperature elevation may accompany hemarthrosis, but a fever >101 warrants concern for infection.
Recurrent hemarthrosis may result in chronic arthritis. The involved joints remain swollen, and flexion deformities develop. Joint motion may be restricted and function severely limited. Restricted joint ...