Arthritis as a Manifestation of Systemic Disease Clinical Presentation

Diabetes

• Diabetic cheiroarthropathy is also known as diabetic hand syndrome with insidious development of flexion contractures in hands. Patients have limited joint mobility (Prayer sign) and it is seen in both insulin-dependent and noninsulin-dependent diabetes. It is associated with duration of diabetes and control of blood sugar.
• Charcot joint occurs in < 1% of all individuals with diabetes. Most patients are older than 40 years and have had long standing, poorly controlled diabetes. With progression of disease, patients can develop rocker bottom feet due to midtarsal collapse.
• Diabetic osteolysis is a condition specifically occurring in people with diabetes. The osteolysis is characterized by osteoporosis and variable degrees of resorption of distal metatarsal bones and proximal phalanges in the feet.
• Diabetic amyotrophy presents with severe pain and dysesthesia involving most commonly the proximal muscles of the pelvis and thighs. Patients are mostly men and may present with anorexia, weight loss, and unsteady gait. Etiology is unclear but inflammatory vasculopathy may play a role.
• Diabetic periarthritis, or frozen shoulder, occurs in 10-33% of those with diabetes. It is more commonly seen in females with long-term noninsulin-dependent diabetes. Up to 50% of the patients have bilateral involvement.
• Diffuse idiopathic skeletal hyperostosis (DISH), also known as Forestier disease occurs in up to 20% of those with noninsulin-dependent diabetes who are typically obese and older than 50 years. Patients present with neck and back stiffness and radiographs show at least 4 fused vertebrae as a result of ossification of the anterior longitudinal ligament.
• People with diabetes have more than 2 times the risk of carpal tunnel syndrome than those without diabetes; 6% of patients with carpal tunnel syndrome carry the diagnosis of diabetes.

Hypothyroidism

• Hypothyroidism can present with an arthritis that resembles early rheumatoid arthritis (RA). Patients complain of pain and stiffness, including morning stiffness, in a symmetrical distribution similar to that found in RA affecting small joints of the hands and wrists. Unlike most cases of RA, this is not a deforming arthritis.
• Myxedematous arthropathy usually affects large joints such as knees. Patients present with swelling and stiffness. Synovial thickening, ligamentous laxity and effusions are seen but radiographs are frequently normal.
• There is a well-known association between the occurrence of hypothyroidism and muscular disease. The spectrum of thyroid myopathy is broad, ranging from asymptomatic elevation in muscle enzymes, proximal weakness (especially in the hip flexors) and polymyositis-like syndrome to a constellation of muscle cramps, stiffness, and pseudohypertrophy, referred to as Hoffmann syndrome.
• Carpal tunnel syndrome is observed in up to 10% of patients with hypothyroidism.
• Raynaud phenomenon may be seen in hypothyroidism.
• Aching muscles with findings indistinguishable from fibromyalgia can be seen but are less common.

Hyperparathyroidism

• The classic musculoskeletal manifestation of primary hyperparathyroidism is osteitis fibrosa cystica, which consists of bone pain, osteopenia, and bony cysts.
• Painless proximal muscle weakness with normal CPK and a neuropathic or myopathic EMG is seen in hyperparathyroidism.
• Chondrocalcinosis has been described in up to 30% of patients with primary hyperparathyroidism. Acute pseudogout attacks occasionally may occur, especially after parathyroidectomy. While some patients discovered in this manner are asymptomatic, many of these patients have other symptoms. These include depression, fatigue, constipation, and joint pain. The joint pain is widespread and nonspecific.
• Diffuse osteopenia is commonly seen and erosions may be seen in the joints of hands and at the end of the clavicles.
• Spinal compression fractures are common.
• Discrete lytic lesions due to focal aggregates of osteoclastic giant cells known as Brown tumors may be seen.

Hyperthyroidism

• Thyroid acropachy is a rare (1%) complication of Grave disease consisting of soft tissue swelling of hands, digital clubbing, and periostitis. Radiographs are characteristic with periosteal reaction along the shafts of the metacarpals and phalanges. It is strongly associated with ophthalmopathy and pretibial myxedema.

Cushing disease

• The presenting musculoskeletal manifestation of Cushing disease may be osteoporosis with fracture.
• Proximal myopathy with muscle wasting is common in Cushing disease.
• It is not uncommon for patients with Cushing disease to present with a vertebral compression fracture. Occurrence of osteoporotic fractures in young adults may be the manifestation that triggers a workup for excess glucocorticoid production.
• Patients can also present with osteonecrosis. Iatrogenic Cushing disease is more likely to cause osteonecrosis than Cushing disease.

Acromegaly

• Arthropathy is common and is seen in 70% of the patients with acromegaly.
• Peripheral arthropathy is common in the large joints, such as the shoulders and knees. Severe osteoarthritis with crepitus and, eventually, pain, limited range of motion, and deformity can occur.
• An early manifestation may be involvement of the first carpometacarpal joint.
• Symptoms of carpal tunnel syndrome, OA, and proximal muscle weakness with normal CPK and normal EMG often occur.

Hyperlipidemia

• Familial hypercholesterolemia and mixed hypercholesterolemia are associated with tendon xanthomas, particularly of the Achilles tendon, as well as Achilles tendonitis.
• An association may exist between hyperlipidemia and oligoarthritis or a migratory polyarthritis.

Hemochromatosis

• Approximately 40-60% of patients with hemochromatosis have arthropathy. With some patients, the arthropathy is the first manifestation of the underlying disease.
• Any joint may be affected, but osteoarthritislike symptoms and changes in the second and third metacarpophalangeal (MCP) joints are involved most commonly.
• Chondrocalcinosis is present in as many as two thirds of patients with hemochromatosis.
• Hemochromatosis may be associated with an increased incidence of osteoporosis. One study reported 45% of patients with hemochromatosis also have osteoporosis, especially those patients with coexisting hypogonadism.

Sarcoidosis

• The clinical features of sarcoidosis may mimic those of many rheumatic diseases.
• Patients may present with an acute polyarthritis, especially involving ankles and knees. This arthritis may occur in isolation or as part of Lofgren syndrome, which is defined as a triad of hilar lymphadenopathy, acute polyarthritis, and erythema nodosum.
• Less commonly, a chronic arthritis may occur (typically involving the ankles, knees, and hands) that is rarely deforming.
• Occasionally, patients may have enthesitis, especially in the Achilles tendon, or granulomatous myopathy with pain, proximal muscle weakness, or both.
• Granulomatous bony lesions may occur, especially in the fingers, but are rare.

Malignancies

• Lung cancer can be associated with hypertrophic osteoarthropathy and Jaccoud type arthritis.
• Colon cancer and multiple myeloma may be associated with pyogenic arthritis.

Hypothyroidism

• The MCP and proximal interphalangeal (PIP) joints may be slightly tender. Soft tissues may be slightly swollen, though redness and increased warmth are unlikely.
• Signs of carpal tunnel syndrome may be present.
• Proximal muscle weakness may be present.

Hyperparathyroidism

• The joints are not swollen, red, or tender, except with acute pseudogout.

Diabetes

• Adhesive capsulitis of the shoulder is more common in patients with diabetes. The capsulitis is characterized by progressive, painful restriction of shoulder motion.
• Dupuytren contracture and flexor tenosynovitis may be present.
• Diabetic cheiroarthropathy presents with thick, tight skin over the dorsum of the hands and with flexion deformities of the MCP joints and interphalangeal joints. This condition can be shown clinically by the inability of the palms to come completely together with the wrists fully flexed, which is known as the prayer sign.
• Findings consistent with carpal tunnel syndrome may be present.
• Neuropathic arthropathy, also known as Charcot joint, is characterized by a painless, swollen, deformed joint. The most commonly affected joints are the metatarsophalangeal, tarsometatarsal, tarsus, ankle, and interphalangeal joints.

Cushing disease

• The patient may have the classic features of Cushing disease, such as striae, truncal obesity, plethora, and bruising.
• On the other hand, most or even all of these findings may be absent.
• Proximal weakness with muscle wasting may be present.

Acromegaly

• Hypertrophy of the joint, including thickening of bursae (eg, olecranon or prepatellar bursae), can be present.
• Patients may have a limited range of motion at the large joints, such as the shoulder.
• Physical findings of carpal tunnel syndrome may be present.

Hyperlipidemia

• The critical physical finding is the presence of tendon xanthomas. These appear in childhood in individuals with a complete defect in the low-density lipoprotein (LDL) particle receptor (ie, homozygous familial hypercholesterolemia).
• In heterozygous familial hypercholesterolemia, tendon xanthomas begin to develop in the second or third decade of life.

Hemochromatosis

• Bony swelling and mild tenderness of the second and third MCP joints may develop, though usually without redness or increased warmth.
• Shoulder, hip, and knee joints may be involved in a low-grade synovitis, especially in patients with CPPD.
• Full extension or full flexion may not be possible.

Sarcoidosis

• Acute sarcoid arthritis is often periarticular, with tenderness, erythema, and swelling. The ankles and knees are almost invariably involved, often with coexistent erythema nodosum. Other joints, such as the wrists, elbows, PIP joints, or MCP joints, are commonly involved. Joint motion is usually normal, and pain is absent or minimal. The axial skeleton is usually spared.
• The presence of erythema nodosum, acute arthritis, and bilateral hilar adenopathy is called Lofgren syndrome.
• Enthesitis may be observed upon physical examination.
• Chronic sarcoid arthritis can be evanescent, recurrent, or chronic. The knees, ankles, and PIP joints are most commonly involved. The chronic form often manifests as dactylitis, frequently with overlying cutaneous sarcoid.

• Hypothyroidism and hyperthyroidism are both autoimmune diseases.
• Hyperparathyroidism

  • The great majority of primary hyperparathyroidism cases are caused by a parathyroid adenoma.
  • Hyperplasia, a polyclonal process involving all 4 glands, is less common.
  • Parathyroid carcinoma rarely produces hyperparathyroidism.
• Diabetes

  • Type 1 diabetes is characterized by destruction of the pancreatic beta cells, leading to absolute insulin deficiency.
  • Type 2 diabetes is characterized by variable degrees of insulin deficiency and insulin resistance, with a strong genetic influence.
• Cushing disease

  • Approximately 85% of endogenous hypercortisolism is caused by pituitary overproduction of adrenocorticotropic hormone (ACTH).
  • In at least 90% of these cases, a basophilic microadenoma (< 1 cm by definition, but usually 1-2 mm) of the pituitary is present.
  • In the remainder, corticotroph hyperplasia is present without a discrete tumor.
• Acromegaly: A pituitary tumor secreting growth hormone is the only common cause of acromegaly.
• Hyperlipidemia: Familial hypercholesterolemia is caused by a genetic mutation in the LDL receptor gene.
• Hemochromatosis: This is a genetic disorder resulting in iron overload.
• Sarcoidosis: While much speculation exists, the etiology of sarcoidosis is unknown.