Arthritis as a Manifestation of Systemic Disease - How Does It Occur?

Introduction

Musculoskeletal symptoms may clinically manifest themselves in many systemic diseases. However, true arthritis is an early manifestation of the underlying pathology in some systemic disorders. This article will focus on systemic disorders in which an early clinical manifestation may be rheumatic (musculoskeletal) in nature. Early-onset arthritis can be seen during the course of the development of certain systemic diseases.

What Are the Systemic Diseases That Can Present Arthritis as a Manifestation?

Arthritis as a clinical manifestation occurs in various diseases. Some of these diseases include:

1. Endocrine Disorders:

• Diabetes mellitus.

• Thyroid disorders.

• Acromegaly.

2. Hematological Disorders:

• Hemochromatosis.

• Sickle cell disease.

• Hemophilia.

• Multiple myeloma.

3. Malignant Disorders:

• Metastatic disease.

• Leukemia or lymphoma.

• Paraneoplastic arthritis.

4. Metabolic Disorders:

• Amyloidosis

5. Hereditary Disorders:

• Wilson’s disease.

What Are the Factors That Determine the Differential Diagnosis of Arthritis Pain?

There are a plethora of factors available that provide clues to formulate the differential diagnosis for arthritic pain.

The factors responsible are:

• Gender.

• Race.

• Ethnicity.

• Age of onset.

• The pattern of arthritis.

• Patient’s response to the treatment therapy.

All these factors help in identifying the primary cause of the problem. It is crucial to diagnose the primary disease correctly for treatment and prognostic (to predict the likely course of the disease) purposes. Evaluation for underlying malignant pathology is considered in older patients or in patients whose symptoms are not in proportion to underlying arthritis. The initial symptom of arthritis may be observed in rare hereditary diseases like Wilson’s disease. Rheumatic manifestations are also quite common in sarcoidosis but are commonly misinterpreted. Osteoporosis and osteoarthritis in the early phase of the disease should raise suspicion for systemic disorders. Amyloid deposition can cause musculoskeletal symptoms mimicking classic primary rheumatic diseases.

How Is Arthritis Associated With Endocrine Disorders?

Arthritis is associated with endocrine disorders like acromegaly, thyroid disorders, and diabetes mellitus.

1. Acromegaly:

A myriad of musculoskeletal (muscles, joints, and bones) manifestations have been associated with endocrinological disorders. Acromegaly is caused due to excessive production of growth hormones. It is characterized by enlargement of the upper and lower extremities, thickening of the skin, and enlargement of the jaws, tongue, and various internal organs. Patients suffering from acromegaly might complain of pain in the lower back, muscle weakness, and osteoarthritis involving various joints. Due to bony overgrowth, there may be compression of the involved nerves leading to neuropathy. Carpal tunnel syndrome may also be a frequent clinical manifestation. Osteoarthritis most commonly affects the knees, shoulders, wrists, fingers, and hips.

2. Thyroid Disorders:

Autoimmune thyroid disease can cause painless swelling and edema of the soft tissues in fingers and toes, along with clubbing and periostitis. It is a rare condition. Hypothyroidism has been related to chronic swelling and inflammation of the tendons and carpal tunnel syndrome.

3. Diabetes Mellitus:

Diabetes mellitus is also frequently associated with various bone and joint abnormalities. These include osteoporosis, hyperostosis (bony hardening of ligaments at the place where they are attached to the spine), osteoarthritis, diabetic osteoarthropathy (lytic changes in the bone), cheiroarthropathy (syndrome of limited joint mobility occurring in diabetic patients), Dupuytren's contracture (hand deformity that occurs over the years), and periarthritis (inflammation of the structures like tendons, and muscles around the joint) of the shoulders. Neuropathic arthropathy (bone and joint changes that occur secondary to sensory loss) may also occur in diabetes. It usually involves the foot.

How Is Arthritis Associated With Hematological Disorders?

Arthritis is associated with hematological disorders like sickle cell disease, hemophilia, and hemochromatosis.

1. Sickle Cell Disease:

In sickle cell disease, small blood vessels are occluded by sickled red blood cells leading to necrosis of the bone marrow. This leads to numerous complications including painful crises (episodes of periodic pain), dactylitis (severe pain associated with the bones of the hands and feet and both), and osteonecrosis. Osteonecrosis commonly affects the shoulder and hip joints. There is a high frequency of osteomyelitis in sickle cell disease.

2. Hemophilia:

In hemophilia, due to repeated periodic intra-articular bleeding, chronic joint effusion along with inflammation of the synovial lining of the joint may occur. Bony changes may be observed that are permanent.

3. Hemochromatosis:

Hemochromatosis is an iron storage disorder. There is organ impairment due to iron deposition in parenchymal cells because of an excessive amount of iron absorption from the intestines. Arthritis usually occurs at the age of fifty and may be the earliest clinical symptom manifested in the disorder of hemochromatosis.

The small joints of the hands, and, later the larger joints of knees, ankles, hips, and shoulders are affected by arthropathy, which is an osteoarthritis-like disorder. The second and third metacarpophalangeal finger joints of both hands are usually the first and most commonly affected joints. This clinical presentation is an important diagnostic clue for hemochromatosis. Several other joints may be affected as well. Cystic lesions are commonly associated with narrowing of the joint space, sclerosis, and osteophytosis (bony lumps that grow on the bones of the spine or joints), as suggested by radiographic findings.

Diagnostic testing for hemochromatosis should be done immediately when the disease is suspected. Screening for all close relatives of the family has been suggested. A liver biopsy is mandatory for the diagnosis of hemochromatosis.

How Is Arthritis Associated With Malignant Disorders?

Malignant tumors often present with hypertrophic osteoarthropathy. It is characterized by the presence of clubbing of digits, the increased periosteal proliferation of the tubular bones, arthralgias (joint pain), and fluid effusion from the joints. It is caused due to abnormal fibrovascular proliferation of the skin, soft tissues, and bony tissues in the distal parts of the extremities.

Tumors of the primary bone, cartilage, or synovium may present with rheumatological (musculoskeletal) pain or appear as mass lesions. However, it is very crucial to diagnose malignant lesions in order to start the early treatment of the deadly disease. Diagnostic imaging tests like computed tomography or magnetic resonance imaging may be quite useful in the early recognition of the disease. But a biopsy is mandatory in such cases.

How Is Arthritis Associated With Amyloidosis?

Amyloidosis is characterized by the deposition of a fibrillar protein, which may affect many different organs. Immunoglobulin-related amyloid light chain amyloidosis usually presents with varied clinical manifestations including, arthritis. The joints that are most commonly affected are the shoulders, knees, wrists, hips, and metacarpophalangeal joints. The characteristic findings in such patients are the shoulder pad sign (an enlargement of the anterior shoulder due to deposition of amyloid) and carpal tunnel syndrome. The symptoms of carpal tunnel syndrome include numbness or tingling sensation, pain and tenderness, shock-like sensations, weakness in the hands, clumsiness, and dropping things. Confirmation of the deposition of amyloid may be obtained with a subcutaneous fat aspirate or by biopsy of the involved organs.

How Is Arthritis Associated With Wilson’s Disease?

Wilson's disease is a genetic disorder that is characterized by the deposition of copper in various tissues of the body. Osteopenia (a condition where there is below-normal bone mineral density) may be developed in the hands, feet, and spine of an individual. Subchondral cysts (fluid-filled sacs within the bones of the joint) have been found to be associated with Wilson's disease. Arthritis is commonly found in the disorder and usually affects the larger joints of the body.

What Should Be the Therapeutic Approach in Such Patients?

• An extensive and meticulous medical history and physical examination are essential.

• Diagnostic laboratory tests, including complete blood cell count, kidney function tests, liver function tests, C-reactive protein, and erythrocyte sedimentation rate, should be carried out.

• Computed tomography and magnetic resonance imaging are a few diagnostic imaging techniques that can be used to identify the underlying soft tissue pathologies.

• Biopsies should be mandatory where there is a doubt of underlying malignancy.

• Treatment should be delivered quickly according to the diagnosis established.

• Follow-up should be done for all patients for up to four to five months in such cases.

Conclusion

Many systemic disorders have musculoskeletal manifestations, including arthritis. The patient usually seeks medical advice due to these initial rheumatic symptoms. The differential diagnosis for systemic diseases is essential to broaden the therapeutic approach. Evaluation and diagnosis of the disease should be made at the earliest.