Acromegaly is a rare disorder secondary to hypersecretion of the growth hormone from the pituitary gland, usually secondary to a pituitary adenoma. Presentation will differ between children with unfused growth plates and adults. In the former, there is excessive growth of bone leading to gigantism. In older children with fused growth plates and adults, there is also bone overgrowth but more so in width with related overgrowth of soft tissue and is termed acromegaly. Diagnosis is often delayed as symptoms and clinical features develop slowly.

There is coarsening of the facial features with an enlarged protruding jaw (prognathism) and forehead (frontal bossing), poor dental occlusion, enlargement of the tongue, and coarse skin. The hands are enlarged and often described as spade-like with soft tissue enlargement of the tufts, increased number of sesamoid bones, and exostoses at tufts with similar changes occurring in the feet. In addition, there is increased heel fat pad thickness, >25 mm. Common musculoskeletal presentations include arthralgia, osteoarthritis, CPPD arthropathy, carpal tunnel syndrome, and back pain.

There are characteristic features of the acromegaly. Radiographs of the hands demonstrate joint space widening due to cartilage overgrowth. The cartilage however is not as durable as normal cartilage and predisposes to early degenerative osteoarthritis. The short bones of the hand are widened particularly the bases of the distal phalanges. There are small bone outgrowths at the site of ligament and tendon attachments. In addition, there is widening of the tufts with small exostoses and overlying soft tissue thickening. The sesamoid at the first Metacarpophalangeal joint (MCPJ) is enlarged and has been used as a radiographic feature of acromegaly via the sesamoid index. Changes on foot radiographs are similar to those described for the hands.

A lateral skull radiograph may demonstrate prognathism, overgrowth of the paranasal sinuses that, via the frontal sinuses, contributes to frontal bossing. The pituitary fossa may be enlarged and there may be thickening of the skull vault. Spinal radiographs demonstrate enlargement of vertebrae in AP and lateral dimensions, prominent end plate osteophytosis, and posterior vertebral scalloping. The intervertebral disk is enlarged. There is increased thoracic kyphosis and lumbar lordosis.

Hemochromatosis, primary and secondary, is a disease of abnormal iron metabolism causing chronic iron overload and iron deposition in parenchymal organs. Primary hemochromatosis is a common autosomal recessive genetic disorder, which is caused by a defect in the HFE gene, the protein product of which regulates iron absorption from the gastrointestinal tract. Of two known important mutations in HFE, C282Y and H63D, C282Y is the most important and accounts for more than 95 % of symptomatic cases of hemochromatosis. Primary hemochromatosis affects 1:200 persons of Northern European decent with the highest prevalence being in people of Celtic origin. Although the genetic defect is distributed equally among men and women, the iron loss as a result of menstruation is protective, resulting in a clinical male predilection (M: F ~ 2–10:1). In men, the diagnosis usually becomes evident in middle age (30–40 years of age), whereas in women, clinical manifestation is delayed until the postmenopausal period.

Typical organs involved are the joints, liver, heart, pancreas, pituitary, nerves, and skin. The most common manifestation is hyperpigmented skin (“bronze” skin) and hepatomegaly. Arthralgia is present in up to 50 % of patients. Diabetes, heart failure, arrhythmia, hypothyroidism, hypogonadism, and hypopituitarism are other well-recognized clinical manifestations of hemochromatosis.

Secondary iron overload is rare but can be due to frequent blood transfusions, hemolytic anemia, myelodysplasia, juvenile hemochromatosis, and Friedreich’s ataxia.

Hemochromatosis can affect most joints in the body, but the primary articular manifestation of the disease is a characteristic symmetric, noninflammatory arthritis affecting the second and third MCPJs. Given this joint distribution, hemochromatosis may mimic rheumatoid arthritis. Absence of inflammatory features (increased warmth and erythema) helps to differentiate it from rheumatoid arthritis. Patients with hemochromatosis may also have recurrent attacks of pseudogout secondary to calcium pyrophosphate deposition (CPPD) (see chap.​ 8). Hemochromatosis arthropathy has an insidious onset and may occur at any stage during the course of the disease; in rare cases, it is the initial manifestation. Over time, large joints such as the hips, knees, and shoulders can be affected. The pathogenesis of hemochromatosis arthropathy has been associated with the presence of iron in joint tissue, a defect in cartilage metabolism, and immunological dysfunction. It is usually a slowly progressive non-deforming disease.

Hemophilia is a rare inherited bleeding disorder. Hemophilia A (factor VIII deficiency) affects less than 1 in 10,000 people. Hemophilia B (factor IX deficiency) is even less common, affecting approximately 1 in 50,000 people. The most severe forms of hemophilia almost always affect males due to X-linked inheritance pattern. Females can be seriously affected only if the father is a hemophiliac and the mother is a carrier or in the case of X-inactivation that occurs at an early stage of embryogenesis resulting in unusually low levels of factor VIII or IX. These cases are extremely rare. The degree of factor VIII deficiency correlates with the extent of bleeding, and hemophilia A can be classified as severe (<1 % activity), moderate (1–5 %), or mild (5–25 %). Common symptoms of hemophilia are surface bruising, hematuria, and peritoneal, retroperitoneal, and intracranial bleeding as well as MSK involvement.

Musculoskeletal involvement includes soft tissue muscle hemorrhage, hemarthrosis, and intraosseous hemorrhage. The most commonly affected joints are the large joints, i.e., knees, elbows, ankles, hips, and shoulders. In patients with severe form of hemophilia, spontaneous bleeding occurs with minimal or no trauma. Joint involvement in severe forms of hemophiliac patients occurs in up to 90 % of patients by the age of 10 years. Recurrent intra-articular bleeding resulting in arthropathy is a leading cause of morbidity in hemophilia.

Hemophilic arthropathy is a joint-destroying disorder that is more prevalent before adulthood. Hemorrhage begins in the synovium before extending into the joint space. Blood causes an inflammatory response in the synovium, resulting in synovial hypertrophy and joint hyperemia. These responses make further bleeding more likely. Intra-articular bleeding is associated with joint effusion that can persist for days without treatment. Recurrent intra-articular hemorrhages cause hemosiderin deposition. Periarticular osteoporosis and regional soft tissue swelling are commonly seen with repeated bleeding. Initially the joint space is preserved. As arthropathy progresses, symmetric cartilage destruction and joint space narrowing are observed. Later manifestations of hemophilic arthropathy include osseous irregularity and erosions with secondary severe degenerative joint disease, including osteophytes, large subchondral cysts, and sclerosis. Subchondral cystic changes are thought to be due to both synovial intrusions through fissures in the joint surface and primary intraosseous hemorrhage. Eventually joint ankylosis may occur.