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Arthritis as a Manifestation of Systemic Disease Clinical Presentation

  • Author: Ritu Khurana, MD; Chief Editor: Herbert S Diamond, MD  more...
 
Updated: Nov 10, 2014
 

History

Diabetes

See the list below:

  • 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.
  • Diabetes is a common cause for trigger finger.
  • Unlike DISH, the predisposition of diabetic patients to the development of osteopenia is not clearly defined. To the extent that it does exist, osteopenia is more common in type 1 diabetic patients compared with type 2 diabetic patients. It is reported to involve those patients more frequently who have poorer control of their disease.[4]

Hypothyroidism

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  • 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.
  • There can be mild elevations of creatine phosphokinase (CPK), but few patients actually show muscle weakness.
  • 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.
  • Hypothyroidism is also a common cause of trigger finger.

Hyperparathyroidism

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  • 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 although these are rare.
  • Advanced renal disease and associated secondary hyperparathyroidism can lead to metastatic calcification of muscles and soft tissues.

Hyperthyroidism

See the list below:

  • 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.
  • Patients can present with myopathy, with dramatic increases in CPK and severe proximal muscle weakness, similar to disease seen in polymyositis.

Cushing disease

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  • 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

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  • 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 overgrowth of cartilage and joint space widening.
  • Most commonly, osteoarthritis of the first metacarpal joint is seen early in the disease.
  • Symptoms of carpal tunnel syndrome, OA, and proximal muscle weakness with normal CPK and normal EMG often occur.

Hyperlipidemia

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  • 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

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  • 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

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  • 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.
  • Advanced disease can show lytic lesions in the bones of peripheral joints.

Malignancies

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  • Adenocarcinoma of the lung, mesotheliomas, and lymphomas can be associated with hypertrophic pulmonary osteoarthropathy.
  • Lung cancer can present with Jaccoud–like arthropathy.
  • Colon cancer and multiple myeloma may be associated with pyogenic arthritis.
  • Paraneoplastic syndromes can manifest as remitting seronegative symmetric synovitis with pitting edema.[5]
  • Patients with pancreatic cancer can present with a combination of arthritis and panniculitis.
  • Thymoma can present as lupuslike syndrome.

HIV disease

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  • Patients with HIV disease may report osteomyelitis, osteonecrosis, reactive arthritis, and/or psoriatic arthritis.
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Physical

Hypothyroidism

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  • Patients complain of generalized muscle pains similar to fibromyalgia.
  • Frank myxedematous arthropathy can also exist, classically involving the large peripheral joints like knees.
  • 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.
  • Patients can present with joint swelling and have chondrocalcinosis.
  • Charcot-like destructive process in joints has been reported.

Hyperparathyroidism

See the list below:

  • The joints are not swollen, red, or tender, except with acute chondrocalcinosis, which is frequently seen in these patients.
  • Bony erosions, especially in metacarpal and carpal bones, can be seen.
  • In advanced stages, osteitis fibrosa cystica can be seen.
  • Proximal muscle weakness and calciphylaxis can be seen with hyperparathyroidism.

Diabetes

See the list below:

  • 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, and this condition can be confused with osteomyelitis on radiographs.
  • Thyroid acropachy with periosteitis and diffuse soft tissue swelling is seen and can look like scleredema.
  • Findings like DISH and osteopenia are rare but can be seen in diabetic patients.

Cushing disease

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  • 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

See the list below:

  • 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

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  • 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

See the list below:

  • 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

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  • 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.
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Causes

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  • 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.
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Contributor Information and Disclosures
Author

Ritu Khurana, MD Chief of Rheumatology, Crozer Chester Medical Center, Upland, PA

Ritu Khurana, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Lawrence H Brent, MD Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, American College of Rheumatology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Janssen<br/>Serve(d) as a speaker or a member of a speakers bureau for: Abbvie; Genentech; Pfizer; Questcor.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Kristine M Lohr, MD, MS Professor, Department of Internal Medicine, Interim Chief, Division of Rheumatology, Director, Rheumatology Training Program, University of Kentucky College of Medicine

Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors R Hal Scofield, MD and Linda A Zacharias, MD to the development and writing of this article.

References
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This picture shows a 42-year-old white man who was admitted with acute back pain. In this frontal view, note the lower-face fullness that obscures his ears and the plethora of his cheeks.
Focal osteolytic changes seen in the phalanges in a patient with chronic sarcoid arthritis.
Osteolysis has left a lacy trabecular pattern in this phalanx (arrow).
 
 
 
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