Arthritis Can Be a Systemic Disease

Arthritis is a disease of the joints. But many types of arthritis go beyond the joints and affect other parts of the body.

When that happens, it's called "systemic disease," especially when it impacts multiple organ systems.

This article looks at systemic types of arthritis plus their symptoms, causes, and risk factors.

Arthritis Types

Systemic forms of arthritis include:

• Rheumatoid arthritis
• Systemic lupus erythematosus
• Juvenile idiopathic arthritis
• Psoriatic arthritis
• Sjögren's syndrome

While some systemic symptoms are shared by all of these conditions, some are only linked with one or a few of them.

Systemic Symptoms

When arthritis affects the whole body, it can cause a wide range of symptoms. These include:

• Fever
• Fatigue
• Weakness
• Nodules (small, firm lumps under the skin)
• Dry eyes and mouth
• Digestive problems
• Skin complications
• Kidney, lung, or heart disease
• Cancer
• Pregnancy complications

Arthritis doesn't need to be severe in order to have non-joint-related symptoms. Sometimes, systemic symptoms can appear in people with minimal joint pain.

Why Systemic Disease?

Researchers don't yet know why one person with arthritis develops systemic disease while another doesn't. They suspect a mix of genetic and environmental factors are behind the difference.

Early diagnosis and treatment may also help you avoid systemic complications.

Risk factors for systemic involvement vary by condition. People who have systemic symptoms tend to have a worse outlook than those with non-systemic disease.

Rheumatoid Arthritis

Rheumatoid arthritis is an autoimmune disease in which the immune system targets the lining of your joints. That causes inflammation, which eventually wears away your bones and joints. Over time, it can cause joint deformity and loss of function.

Non-systemic symptoms of RA include:

• Pain, swelling, and stiffness in more than one joint
• Symmetrical joint involvement (the same on both sides)
• Hot, red joints
• Morning stiffness lasting more than 30 minutes
• In advanced disease, joint deformity, misalignment, and dislocation

Symptoms typically hit the small joints (wrists, hands, feet) first.

Systemic Symptoms

About 40% of people with RA will have systemic involvement at some point. The symptoms depend on what organ or system RA targets. Common ones include:

• Pulmonary fibrosis (lung disease from damaged tissues)
• Pleural effusion (excessive fluid in the lungs)
• Atherosclerosis (fatty artery disease)
• Vasculitis (inflammation of blood vessels)
• Anemia
• Nodules
• Dry eyes
• Dry mouth
• Nerve problems
• Sexual dysfunction

Systemic RA symptoms may develop even if you don't have significant joint problems.

Who Gets Systemic Symptoms?

A few things make you more likely to develop systemic RA symptoms. They are:

• Severe inflammation
• Long-standing disease
• High levels of rheumatoid factor (an antibody involved in RA)
• High levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies
• Smoking
• Being biologically male
• Delayed (or lack of) treatment
  

While men are more likely to have systemic involvement, RA is significantly more common in women.

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is the most common form of lupus. It's an autoimmune disease that's highly inflammatory.

A healthy immune system creates a controlled amount of inflammation as part of the response to illness or injury. In SLE, certain parts of the immune system become overactive and inflammation isn't properly controlled.

Unlike many autoimmune diseases, the antibodies of SLE don't attack one particular type of cell or tissue. They can strike in many different places.

SLE is systemic by definition. Even so, it has a common set of symptoms that are localized as well as systemic symptoms and complications. Non-systemic SLE symptoms include:

• Joint pain and inflammation, especially in the hands and feet
• Puffiness around the eyes
• Sensitivity to sunlight or fluorescent light
• A butterfly-shaped rash across the cheeks and nose
• Hair loss
• Mouth sores

SLE usually involves flares (periods of intense symptoms) and remissions (periods of low or absent symptoms.)

Systemic Symptoms

Common systemic symptoms and complications of SLE include:

• Fever
• Fatigue
• Weakness
• Headaches
• Nerve problems
• Skin complications (rashes, sores, ulcers)
• Kidney disease (lupus nephritis)
• Memory problems and confusion
• Strokes
• Coronary artery disease
• Seizures
• Behavioral changes
• Pregnancy complications, including premature birth and miscarriage

The nature of the complications depends on where the inflammation is.

Who Gets Systemic Symptoms?

Risk factors for SLE complications vary. Not all complications have known risk factors. Some that are known include:

• Lupus nephritis: More likely in biological males, Black people, Hispanic people, and those of Asian descent
• Strokes: More likely with activity in many organs, high antiphospholipid antibodies, being in the first year of illness
• Heart problems: More likely in those who are biologically male, of a younger age, have a lower income, have traditional risk factors for heart disease
• Seizures: More likely at the onset of illness, in biological females, in those with high antiphospholipid or anti-ß2 glycoprotein antibodies, high disease activity
• Positive for ribosomal P antibody

If you're diagnosed with SLE and are at high risk for complications, let your healthcare provider know.

Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is an umbrella term for several forms of autoimmune or autoinflammatory arthritis that affect kids under 16. Two types are associated with systemic symptoms: systemic JIA and psoriatic JIA.

Common symptoms of JIA include joint pain and stiffness and joints that are warm, red, and swollen.

Systemic Symptoms

Systemic symptoms of JIA can include:

• Fatigue
• Blurry vision
• Dry, gritty eyes
• Rashes
• Loss of appetite
• High fever

Systemic JIA

In addition, systemic JIA may affect internal organs. Symptoms depend on which organ is under attack.

For example, scarring and inflammation in the lungs can lead to shortness of breath. Inflammation of the heart muscle may cause heart damage.

Psoriatic JIA

Psoriatic JIA affects the skin, causing a skin condition called psoriasis. Psoriasis causes raised, scaly patches on the skin called plaques. The plaques may be itchy or painful. They're most common on the elbows, knees, and scalp, but they can be anywhere.

Beyond psoriasis, research suggests this disease may be linked to:

• Depression
• Eye inflammation (uveitis)
• High blood pressure (hypertension)
• Diabetes
• Inflammatory bowel disease

Who Gets Systemic Symptoms?

Little is known about why some kids develop systemic and psoriatic JIA. Researchers are just beginning to understand why some of them develop systemic complications.

Systemic JIA

Research suggests children with systemic JIA are more likely to develop lung disease if they:

• Developed the condition at a younger age
• Have bad reactions to biologic drugs
• Have high levels of certain inflammation-causing cells, including an overlapping condition called macrophage activation syndrome (MAS)

Psoriatic JIA

The conditions that may be related to psoriatic JIA all involve inflammation, Some of them may share common genetic differences, as well.

This is an area that still needs considerable research into the relationships and risk factors.

Psoriatic Arthritis

Psoriatic arthritis (PsA) typically causes joint inflammation and plaques on the skin (psoriasis).

Common localized symptoms of PsA include:

• Swollen fingers and toes
• Pain, stiffness, inflammation, and throbbing in one or more joints
• Reduced range of motion
• Morning stiffness
• Nail pitting or separation from the nail bed
• In rare but severe cases, enthesitis (pain and inflammation where connective tissues attach to bones)

The severity of psoriasis and arthritis symptoms have little relationship to each other. You may have severe skin symptoms but low joint pain or vice versa.

Systemic Symptoms

Systemic symptoms of PsA may include:

• Fatigue
• Lack of energy
• Anemia
• Uveitis
• Inflammatory bowel disease
• Heart disease
• Stroke
• Serious infection
• Nonmelanoma skin cancer
• Metabolic syndrome (hypertension, high cholesterol, obesity, diabetes/insulin resistance)
  

Who Gets Systemic Symptoms?

Little is known about why some people with PsA develop systemic symptoms. Research suggests:

• Cardiac events such as heart disease may be more common in people who've had PsA for a long time. PsA treatment may lower the risk.
• Skin cancer may be more likely in people with especially severe psoriasis. The use of high-dose immunosuppressant medications to treat PsA may also contribute to the risk.
• Serious infections, including pneumonia and hepatitis, are likely due to the immune system irregularities of PsA and possibly the use of immunosuppressants.
  

This is an area that needs considerably more research.

Sjögren's Syndrome

Sjögren's syndrome (SS) isn't a true form of arthritis but it is an autoimmune disease that often causes joint pain and inflammation.

In SS, the immune system attacks moisture-producing glands, especially those that make tears and saliva. It may also attack other organs or systems.

Common localized SS symptoms are:

• Dry eyes, mouth, skin, nasal passages, throat, and vagina
• Acid reflux
• Swollen glands in the face and neck
  

The dryness of SS goes beyond just an annoyance. Untreated, it may lead to vision impairment or blindness, destruction of teeth, and serious mouth infections. SS is common alongside other autoimmune diseases.

Systemic Symptoms

When the immune-system attacks go beyond the glands, systemic symptoms may include:

• Joint pain
• Muscle aches and weakness
• Skin rashes
• Fatigue
• Sleep problems
• Concentration and memory deficits
• Numbness, tingling, and weakness in the hands and feet
• Dysautonomia (autonomic nervous system dysfunction)
• Fetal heart block (a rare pregnancy complication)
• Lung disease
• Lymphoma (cancer of infection-fighting cells called lymphocytes), often in the salivary glands

Lymphoma is uncommon, only affecting between 5% and 10% of people with SS.

Who Gets Systemic Symptoms?

Researchers don't yet know why some people develop systemic SS symptoms. Some studies have started to shed light on this subject, though.

Research suggests risk factors for lymphoma include:

• Raynaud's phenomenon (extremely cold hands and feet that turn purple)
• Purpura (small blood vessel hemorrhages that cause discolored skin or mucous membranes)
• Enlarged spleen (splenomegaly)
• Peripheral nervous system involvement
• Low white blood cells (lymphopenia)
• Anemia
• Positive rheumatoid factor tests
• Positive tests for SS antibodies (anti-Ro/SSA, anti-La/SSB)
• Salivary gland enlargement
• Lymphadenopathy
• Monoclonal gammopathy
• Hypocomplementemia

Some genetic profiles are being developed for lung disease in SS, but this work is in its early stages.

Fetal heart block is a rare pregnancy complication of SS. It's potentially fatal to the baby, either in the womb or after birth. It's believed to be associated with high levels of anti-Ro/SSA antibodies. If you're pregnant and have SS, you should be monitored for this complication Hydroxychloroquinw is considered the first-line treatment for this complication.

Summary

Several types of arthritis can have symptoms outside of the joints. Sometimes they're in multiple bodily systems. This is called systemic disease.

Rheumatoid arthritis, lupus, juvenile idiopathic arthritis, and Sjögren's syndrome can have systemic involvement, as well as spondylarthritis (which includes psoriatic arthritis), ankylosing spondylitis, IBD-associated arthritis, and reactive arthritis.

Symptoms of systemic disease may involve fatigue, fevers, nerve problems, disease of the heart, lungs, and kidneys, cancer, and much more.

The causes of systemic involvement are unknown but researchers have identified some risk factors.

A Word From Verywell

The thought of living with a chronic, systemic disease can be frightening. The most important thing for you to do is talk to your healthcare provider.

Make an appointment right away if:

• You're not diagnosed with arthritis but have symptoms
• You have arthritis and think you're developing systemic symptoms
• You have arthritis/autoimmune disease and you're pregnant

Early diagnosis and treatment are the best ways to manage the disease and prevent systemic problems.