Arthritis Associated with Systemic Disease and Other Arthritides (Disorders of the Joints and Adjacent Tissues) (Rheumatology) Part 2

Treatment:

Neuropathic Joint Disease

The primary focus of treatment is to provide stabilization of the joint. Treatment of the underlying disorder, even if successful, does not usually alter the joint disease. Braces and splints are helpful. Their use requires close surveillance, since patients may be unable to appreciate pressure from a poorly adjusted brace. In the diabetic patient, early recognition and treatment of a Charcot’s foot by prohibiting weight bearing of the foot for at least 8 weeks may possibly prevent severe disease from developing. Fusion of a very unstable joint may improve function, but nonunion is frequent, especially when immobilization of the joint is inadequate.

Hypertrophic Osteoarthropathy and Clubbing

Hypertrophic osteoarthropathy (HOA) is characterized by clubbing of digits and, in more advanced stages, by periosteal new bone formation and synovial effusions. HOA occurs in primary or familial form and usually begins in childhood. The secondary form of HOA is associated with intrathoracic malignancies, suppurative lung disease, congenital heart disease, and a variety of other disorders and is more common in adults. Clubbing is almost always a feature of HOA but can occur as an isolated manifestation (Fig. 22-2).The presence of clubbing in isolation is generally considered to represent either an early stage or an element in the spectrum of HOA.The presence of only clubbing in a patient usually has the same clinical significance as HOA.


Clubbing of fingers.

FIGURE 22-2

Clubbing of fingers.

Pathology and Pathophysiology

In HOA, the bone changes in the distal extremities begin as periostitis followed by new bone formation. At this stage, a radiolucent area may be observed between the new periosteal bone and subjacent cortex. As the process progresses, multiple layers of new bone are deposited, which become contiguous with the cortex and result in cortical thickening. The outer portion of bone is laminated in appearance, with an irregular surface. Initially, the process of periosteal new bone formation involves the proximal and distal diaphyses of the tibia, fibula, radius, and ulna and, less frequently, the femur, humerus, metacarpals, metatarsals, and phalanges. Occasionally, scapulae, clavicles, ribs, and pelvic bones are also affected. In long-standing disease, these changes extend to involve metaphyses and musculotendinous insertions. The adjacent interosseous membranes may become ossified. The distribution of the bone manifestations is usually bilateral and symmetric. The soft tissue overlying the distal third of the arms and legs may be thickened. Mononuclear cell infiltration may be present in the adjacent soft tissue. Proliferation of connective tissue occurs in the nail bed and volar pad of digits, giving the distal phalanges a clubbed appearance. Small blood vessels in the clubbed digits are dilated and have thickened walls. In addition, the number of arteriovenous anastomoses is increased. The synovia of involved joints show edema, varying degrees of synovial cell proliferation, thickening of the subsynovium, vascular congestion, vascular obliteration with thrombi, and small numbers of lymphocyte infiltrates.

Several theories have been suggested for the pathogenesis of HOA. Most have been disproved or have not explained the development in all clinical disorders associated with HOA. Previously proposed neurogenic and humoral theories are no longer considered likely explanations for HOA. The neurogenic theory was based on the observation that vagotomy resulted in symptomatic improvement in a small number of patients with lung tumors and HOA. It was postulated that vagal stimuli from the tumor site led via a neural reflex to efferent nerve impulses to the distal extremities, resulting in HOA. This theory, however, did not explain HOA in conditions where vagal stimulation did not occur, as in cyanotic congenital heart disease or arterial aneurysms. The humoral theory postulated that soluble substances that are normally inactivated or removed during passage through the lung reached the systemic circulation in an active form and stimulated the changes of HOA. Substances proposed included prostaglandins, ferritin, bradykinin, estrogen, and growth hormone. These substances seemed unlikely candidates, since their blood levels in HOA patients overlapped those in individuals without HOA. Furthermore, these substances did not explain the development of localized HOA associated with arterial aneurysms or infected arterial grafts.

Recent studies have suggested a role for platelets in the development of HOA. It has been observed that megakaryocytes and large platelet particles, present in venous circulation, were fragmented in their passage through normal lung. In patients with cyanotic congenital heart disease and in other disorders associated with right-to-left shunts, these large platelet particles bypass the lung and reach the distal extremities, where they can interact with endothelial cells. Platelet clumps have been demonstrated to form on an infected heart valve in bacterial endocarditis, in the wall of arterial aneurysms, and on infected arterial grafts. These platelet particles may also reach the distal extremities and interact with endothelial cells. Platelet-endothelial activation in the distal portion of extremities would then result in the release of platelet-derived growth factor (PDGF) and other factors leading to the proliferation of connective tissue and periosteum. Stimulation of fibroblasts by PDGF and transforming growth factor β results in cell growth and collagen synthesis. Elevated plasma levels of von Willebrand factor antigen have been found in patients with both primary and secondary forms of HOA, indicating endothelial activation or damage. Abnormalities of collagen synthesis have been demonstrated in the involved skin of patients with primary HOA. Fibroblasts from affected skin were shown to have increased collagen synthesis, increased a1(I) procollagen mRNA, and evidence for upregulation of collagen transcription. Other factors are undoubtedly involved in the pathogenesis of HOA, and further studies are needed to better understand this disorder.

Clinical Manifestations

Primary or familial HOA, also referred to as pachydermoperiostosis or Touraine-Solente-Golé syndrome, usually begins insidiously at puberty. In a smaller number of patients, the onset is in the first year of life. The disorder is inherited as an autosomal dominant trait with variable expression and is nine times more common in boys than in girls. Approximately one-third of patients have a family history of primary HOA.

Primary HOA is characterized by clubbing, periostitis, and unusual skin features. A small number of patients with this syndrome do not express clubbing. The skin changes and periostitis are prominent features of this syndrome. The skin becomes thickened and coarse. Deep nasolabial folds develop, and the forehead may become furrowed. Patients may have heavy-appearing eyelids and ptosis. The skin is often greasy, and there may be excessive sweating of the hands and feet. Patients may also experience acne vulgaris, seborrhea, and folliculitis. In a few patients, the skin over the scalp becomes very thick and corrugated, a feature that has been descriptively termed cutis verticis gyrata. The distal extremities, particularly the legs, become thickened owing to proliferation of new bone and soft tissue; when the process is extensive, the distal lower extremities resemble those of an elephant. The periostitis is usually not painful, as it may be in secondary HOA. Clubbing of the fingers may be extensive, producing large, bulbous deformities and clumsiness. Clubbing also affects the toes. Patients may experience articular and periarticular pain, especially in the ankles and knees, and joint motion may be mildly restricted owing to periarticular bone overgrowth. Noninflammatory effusions occur in the wrists, knees, and ankles. Synovial hypertrophy is not found. Associated abnormalities observed in patients with primary HOA include hypertrophic gastropathy, bone marrow failure, female escutcheon, gynecomastia, and cranial suture defects. In patients with primary HOA, the symptoms disappear when adulthood is reached.

HOA secondary to an underlying disease occurs more frequently than primary HOA. It accompanies a variety of disorders and may precede clinical features of the associated disorder by months. Clubbing is more frequent than the full syndrome of HOA in patients with associated illnesses. Because clubbing evolves over months and is usually asymptomatic, it is often recognized first by the physician and not the patient. Patients may experience a burning sensation in their fingertips. Clubbing is characterized by widening of the fingertips, enlargement of the distal volar pad, convexity of the nail contour, and the loss of the normal 15° angle between the proximal nail and cuticle. The thickness of the digit at the base of the nail is greater than the thickness at the distal interphalangeal joint. An objective measurement of finger clubbing can be made by determining the diameter at the base of the nail and at the distal interpha-langeal joint of all 10 digits. Clubbing is present when the sum of the individual digit ratios is >10.At the bedside, clubbing can be appreciated by having the patient place the dorsal surface of the distal phalanges of the fourth fingers together with the nails of the fourth fingers opposing each other. Normally, an open area is visible between the bases of the opposing fingernails; when clubbing is present, this open space is no longer visible. The base of the nail feels spongy when compressed, and the nail can be easily rocked on its bed. Marked periungual erythema is usually present. When clubbing is advanced, the finger may have a drumstick appearance, and the distal interphalangeal joint can be hyperextended. Periosteal involvement in the distal extremities may produce a burning or deep-seated aching pain. The pain can be quite incapacitating and is aggravated by dependency and relieved by elevation of the affected limbs. The overlying soft tissue may be swollen, and the skin slightly erythematous. Pressure applied over the distal forearms and legs may be quite painful.

Patients may also experience joint pain, most often in the ankles, wrists, and knees. Joint effusions may be present; usually they are small and noninflammatory. The small joints of the hands are rarely affected. Severe joint or bone pain may be the presenting symptom of an underlying lung malignancy and may precede the appearance of clubbing. In addition, the progression of HOA tends to be more rapid when associated with malignancies, most notably bronchogenic carcinoma. Unlike primary HOA, excessive sweating and oiliness of the skin and thickening of the facial skin are uncommon in secondary HOA.

HOA occurs in 5-10% of patients with intrathoracic malignancies, the most common being bronchogenic carcinoma and pleural tumors (Table 22-3). Lung metastases infrequently cause HOA.

TABLE 22-3

DISORDERS ASSOCIATED WITH HYPERTROPHIC OSTEOARTHROPATHY

Pulmonary

Cardiovascular

Bronchogenic carcinoma and other neoplasms

Cyanotic congenital heart disease

Lung abscesses, empyema, bronchiectasis

Subacute bacterial endocarditis

Chronic interstitial pneumonitis

Infected arterial graftsa

Aortic aneurysmb

Cystic fibrosis

Aneurysm of major extremity arterya

Chronic obstructive lung disease

Patent ductus arteriosusb

Sarcoidosis

Gastrointestinal

Arteriovenous fistula of major extremity vessela

Inflammatory bowel disease

Sprue

Neoplasms: esophagus, liver, bowel

Thyroid (thyroid acropachy)

Hyperthyroidism

(Graves’ disease)

aUnilateral involvement.

bBilateral lower extremity involvement.

HOA is also seen in patients with intrathoracic infections, including lung abscesses, empyema, bronchiectasis, chronic obstructive lung disease, and, uncommonly, pulmonary tuberculosis. HOA may also accompany chronic interstitial pneumonitis, sarcoidosis, and cystic fibrosis. In the latter, clubbing is more common than the full syndrome of HOA. Other causes of clubbing include congenital heart disease with right-to-left shunts, bacterial endocarditis, Crohn’s disease, ulcerative colitis, sprue, and neoplasms of the esophagus, liver, and small and large bowel. In patients with congenital heart disease with right-to-left shunts, clubbing alone occurs more often than the full syndrome of HOA.

Unilateral clubbing has been found in association with aneurysms of major extremity arteries, with infected arterial grafts, and with arteriovenous fistulas of brachial vessels. Clubbing of the toes but not fingers has been associated with an infected abdominal aortic aneurysm and patent ductus arteriosus. Clubbing of a single digit may follow trauma and has been reported in tophaceous gout and sarcoidosis. While clubbing occurs more commonly than the full syndrome in most diseases, periostitis in the absence of clubbing has been observed in the affected limb of patients with infected arterial grafts.

Hyperthyroidism (Graves’ disease), treated or untreated, is occasionally associated with clubbing and periostitis of the bones of the hands and feet. This condition is referred to as thyroid acropachy. Periostitis is asymptomatic and occurs in the midshaft and diaphyseal portion of the metacarpal and phalangeal bones. The long bones of the extremities are seldom affected. Elevated levels of long-acting thyroid stimulator are found in the serum of these patients.

Laboratory Findings

The laboratory abnormalities reflect the underlying dis-order.The synovial fluid of involved joints has <500 white cells per microliter, and the cells are predominantly mononuclear. Radiographs show a faint radiolucent line beneath the new periosteal bone along the shaft of long bones at their distal end. These changes are observed most frequently at the ankles, wrists, and knees. The ends of the distal phalanges may show osseous resorption. Radionuclide studies show pericortical linear uptake along the cortical margins of long bones that may be present before any radiographic changes.

Treatment:

Hypertrophic Osteoarthropathy

The treatment of HOA is to identify the associated disorder and treat it appropriately.The symptoms and signs of HOA may disappear completely with removal or effective chemotherapy of a tumor or with antibiotic therapy and drainage of a chronic pulmonary infection.Vagotomy or percutaneous block of the vagus nerve leads to symptomatic relief in some patients. Aspirin, NSAIDs, or analgesics may help control symptoms of HOA.

Reflex Sympathetic Dystrophy Syndrome

The reflex sympathetic dystrophy syndrome is now referred to as complex regionalpain syndrome, type 1,by the new Classification of the International Association for the Study of Pain. It is characterized by pain and swelling, usually of a distal extremity, accompanied by vasomotor instability, trophic skin changes, and the rapid development of bony demineralization. Further detail about reflex sympathetic dystrophy and its treatment can be found in Harrison’s Principles of Internal Medicine, 17th edition, Chap. 371.

Tietze Syndrome and Costochondritis

Tietze syndrome is manifested by painful swelling of one or more costochondral articulations.The age of onset is usually before 40, and both sexes are affected equally. In most patients only one joint is involved, usually the second or third costochondraljoint.The onset of anterior chest pain may be sudden or gradual.The pain may radiate to the arms or shoulders and is aggravated by sneezing, coughing, deep inspirations, or twisting motions of the chest.The term costochondritis is often used interchangeably with Tietze syndrome, but some workers restrict the former term to pain of the costochondral articulations without swelling. Costochondritis is observed in patients over age 40; tends to affect the third, fourth, and fifth costochondral joints; and occurs more often in women. Both syndromes may mimic cardiac or upper abdominal causes of pain. Rheumatoid arthritis, ankylosing spondylitis, and Reiter’s syndrome may involve costochondral joints but are distinguished easily by their other clinical features. Other skeletal causes of anterior chest wall pain are xiphoidalgia and the slipping rib syndrome, which usually involves the tenth rib. Malignancies such as breast cancer, prostate cancer, plasma cell cytoma, and sarcoma can invade the ribs, thoracic spine, or chest wall and produce symptoms suggesting Tietze syndrome. They should be easily distinguishable by radiographs and biopsy. Analgesics, anti-inflammatory drugs, and local glucocorticoid injections usually relieve symptoms.

Myofascial Pain Syndrome

Myofascial pain syndrome is characterized by localized musculoskeletal pain and tenderness in association with trigger points. The pain is deep and aching and may be accompanied by a burning sensation. Myofascial pain may follow trauma, overuse, or prolonged static contraction of a muscle or muscle group, which may occur when reading or writing at a desk or working at a computer. In addition, this syndrome may be associated with underlying osteoarthritis of the neck or low back. Trigger points are a diagnostic feature of this syndrome. Pain is referred from trigger points to defined areas distant from the original tender points. Palpation of the trigger point reproduces or accentuates the pain. The trigger points are usually located in the center of a muscle belly, but they can occur at other sites, such as costosternal junctions, the xiphoid process, ligamentous and tendinous insertions, fascia, and fatty areas. Trigger point sites in muscle have been described as feeling indurated and taut, and palpation may cause the muscle to twitch. These findings, however, have been shown not to be unique for myofascial pain syndrome, since in a controlled study they were also present in fibromyalgia patients and normal subjects. Myofascial pain most often involves the posterior neck, low back, shoulders, and chest. Chronic pain in the muscles of the posterior neck may involve referral of pain from the trigger point in the erector neck muscle or upper trapezius to the head, leading to persistent headaches, which may last for days. Trigger points in the paraspinal muscles of the low back may refer pain to the buttock. Pain may be referred down the leg from a trigger point in the gluteus medius and can mimic sciatica. A trigger point in the infraspinatus muscle may produce local and referred pain over the lateral deltoid and down the outside of the arm into the hand. Injection of a local anesthetic such as 1% lidocaine into the trigger point site often results in pain relief. Another useful technique is first to spray from the trigger point toward the area of referred pain with an agent such as ethyl chloride and then to stretch the muscle. This maneuver may need to be repeated several times. Massage and application of ultrasound to the affected area also may be beneficial. Patients should be instructed in methods to prevent muscle stresses related to work and recreation. Posture and resting positions are important in preventing muscle tension. The prognosis in most patients is good. In some patients, myofascial pain syndrome may evolve into fibromyalgia (Chap. 21). Patients at risk for developing fibromyalgia are thought to be those with anxiety, depression, nonrestorative sleep, and fatigue.

Tumors of Joints

Primary tumors and tumor-like disorders of synovium are uncommon but should be considered in the differential diagnosis of monarticular joint disease. In addition, metas-tases to bone and primary bone tumors adjacent to a joint may produce joint symptoms.

Pigmented villonodular synovitis is characterized by the slowly progressive, exuberant, benign proliferation of synovial tissue, usually involving a single joint. The most common age of onset is in the third decade, and women are affected slightly more often than men. The cause of this disorder is unknown.

The synovium has a brownish color and numerous large, finger-like villi that fuse to form pedunculated nodules. There is marked hyperplasia of synovial cells in the stroma of the villi. Hemosiderin granules and lipids are found in the cytoplasm of macrophages and in the interstitial tissue. Multinucleated giant cells may be present. The proliferative synovium grows into the subsynovial tissue and invades adjacent cartilage and bone.

The clinical picture of pigmented villonodular synovitis is characterized by the insidious onset of swelling and pain in one joint, most commonly the knee. Other joints affected include the hips, ankles, calcaneocuboid joints, elbows, and small joints of the fingers or toes.The disease may also involve the common flexor sheath of the hands or fingers. Less commonly, tendon sheaths in the wrist, ankle, or foot may be involved. Symptoms may be mild and intermittent and may be present for years before the patient seeks medical attention. Radiographs may show joint space narrowing, erosions, and subchondral cysts. The joint fluid contains blood and is dark red or almost black in color. Lipid-containing macrophages may be present in the fluid. The joint fluid may be clear if hemorrhages have not occurred.

The treatment of pigmented villonodular synovitis is complete synovectomy. With incomplete synovectomy, the villonodular synovitis recurs, and the rate of tissue growth may be faster than it was originally. Irradiation of the involved joint has been successful in some patients.

Synovial chondromatosis is a disorder characterized by multiple focal metaplastic growths of normal-appearing cartilage in the synovium or tendon sheath. Segments of cartilage break loose and continue to grow as loose bodies. When calcification and ossification of loose bodies occur, the disorder is referred to as synovial osteochondromatosis. The disorder is usually monarticular and affects young to middle-aged individuals. The knee is most often involved, followed by hip, elbow, and shoulder. Symptoms are pain, swelling, and decreased motion of the joint. Radiographs may show several rounded calcifications within the joint cavity. Treatment is synovectomy; however, the tumor may recur.

Hemangiomas occur in synovium and in tendon sheaths. The knee is affected most commonly. Recurrent episodes of joint swelling and pain usually begin in childhood. The joint fluid is bloody. Treatment is excision of the lesion. Lipomas occur most often in the knee, originating in the subsynovial fat on either side of the patellar tendon. Lipomas also appear in tendon sheaths of the hands, wrists, feet, and ankles. In some instances, surgical removal is necessary.

Synovial sarcoma is a malignant neoplasm often found near a large joint of both upper and lower extremities,being more common in the lower extremity. It seldom arises within the joint itself. Synovial sarcomas constitute 10% of soft-tissue sarcomas. The tumor is believed to arise from primitive mesenchymal tissue that differentiates into epithelial cells and/or spindle cells. Small foci of calcification may be present in the tumor mass. It occurs most often in young adults and is more common in men. The tumor presents as a slowly growing deep-seated mass near a joint, without much pain.The area of the knee is the most common site, followed by the foot, ankle, elbow, and shoulder. Other primary sites include the buttocks, abdominal wall, retroperitoneum, and mediastinum. The tumor spreads along tissue planes. The most common site of visceral metastasis is lung. The diagnosis is made by biopsy. Treatment is wide resection of the tumor including adjacent muscle and regional lymph nodes, followed by chemotherapy and radiation therapy. Currently used chemotherapeutic agents are doxorubicin, ifosfamide, and cisplatin. Amputation of the involved distal extremity may be required. Chemotherapy may be beneficial in some patients with metastatic disease. Isolated pulmonary metastasis can be surgically removed. The 5-year survival with treatment is variable depending on the staging of the tumor, ranging from approximately 25-60% or higher. Synovial sarcomas tend to recur locally and eventually metastasize to regional lymph nodes, lungs, and skeleton.

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