There are established epigenetic and environmental risk factors for RA. Smoking is an established risk factor for RA in Caucasian populations, increasing the risk three times compared to non-smokers, particularly in men, heavy smokers, and those who are rheumatoid factor positive. Modest alcohol consumption may be protective.

Silica exposure has been linked to RA.

RA reduces lifespan on average from three to twelve years. According to the UK's National Rheumatoid Arthritis Society, Young age at onset, long disease duration, the concurrent presence of other health problems (called co-morbidity), and characteristics of severe RA—such as poor functional ability or overall health status, a lot of joint damage on x-rays, the need for hospitalisation or involvement of organs other than the joints—have been shown to associate with higher mortality". Positive responses to treatment may indicate a better prognosis. A 2005 study by the Mayo Clinic noted that RA sufferers suffer a doubled risk of heart disease, independent of other risk factors such as diabetes, alcohol abuse, and elevated cholesterol, blood pressure and body mass index. The mechanism by which RA causes this increased risk remains unknown; the presence of chronic inflammation has been proposed as a contributing factor. It is possible that the use of new biologic drug therapies extend the lifespan of people with RA and reduce the risk and progression of atherosclerosis. This is based on cohort and registry studies, and still remains hypothetical. It is still uncertain whether biologics improve vascular function in RA or not. There was an increase in total cholesterol and HDLc levels and no improvement of the atherogenic index.

A rheumatoid nodule is a local swelling or tissue lump, usually rather firm to touch, like an unripe fruit, which occurs almost exclusively in association with rheumatoid arthritis. Very rarely rheumatoid nodules occur as rheumatoid nodulosis in the absence of arthritis. They are usually subcutaneous especially over bony prominences such as the olecranon (tip of the elbow) or the interphalangeal joints (finger knuckles). Less commonly they occur in the lining of the lung and other internal organs. The occurrence of nodules in the lung of miners exposed to silica dust was known as Caplan's syndrome. Nodules vary in size from that of a lentil or pea to that of a mandarin orange. Quite often they are associated with synovial pockets or bursae. About 5% of rheumatoid arthritis patients have such nodules within two years of disease onset, and the cumulative prevalence is about 25%. In the great majority of cases nodules are not painful or disabling in any way, being more of an unsightly nuisance, but in some cases they can be painful, especially if the overlying skin breaks down. Rarely, the nodules occur at diverse sites on body (e.g. upper eyelid, distal region of the soles of the feet, vulva and internally in the gallbladder, lung, heart valves, larynx, and spine).

The presence of rheumatoid arthritis alters how a person's immune system responds to foreign materials, such as dust from a coal mine. When a person with rheumatoid arthritis is exposed to such offensive materials, they are at an increased risk of developing pneumoconiosis.

Treatment of rheumatoid nodules is rarely a priority for people with rheumatoid arthritis. However, surgical removal is often successful, even if there is a tendency for nodules to regrow. Of the drug therapies commonly used in rheumatoid arthritis, methotrexate has the disadvantage of tending to make nodules worse. TNF inhibitors do not have a very reliable effect on nodules. B cell depletion with rituximab often leads to disappearance of nodules but this is not guaranteed.

25% of cases progress to severe destructive arthritis. In the United States and Canada, mortality is estimated at about 4% and in Europe, mortality is estimated at 21.7%.

Caplan syndrome occurs only in patients with both RA and pneumoconiosis related to mining dust (coal, asbestos, silica). The condition occurs in miners (especially those working in anthracite coal-mines), asbestosis, silicosis and other pneumoconioses. There is probably also a genetic predisposition, and smoking is thought to be an aggravating factor.

These are also referred to as systemic autoimmune diseases. The autoimmune CTDs may have both genetic and environmental causes. Genetic factors may create a predisposition towards developing these autoimmune diseases. They are characterized as a group by the presence of spontaneous overactivity of the immune system that results in the production of extra antibodies into the circulation. The classic collagen vascular diseases have a "classic" presentation with typical findings that doctors can recognize during an examination. Each also has "classic" blood test abnormalities and abnormal antibody patterns. However, each of these diseases can evolve slowly or rapidly from very subtle abnormalities before demonstrating the classic features that help in the diagnosis. The classic collagen vascular diseases include:

- Systemic lupus erythematosus (SLE) – An inflammation of the connective tissues, SLE can afflict every organ system. It is up to nine times more common in women than men and strikes black women three times as often as white women. The condition is aggravated by sunlight.

- Rheumatoid arthritis – Rheumatoid arthritis is a systemic disorder in which immune cells attack and inflame the membrane around joints. It also can affect the heart, lungs, and eyes. Of the estimated 2.1 million Americans with rheumatoid arthritis, approximately 1.5 million (71 percent) are women.

- Scleroderma – an activation of immune cells that produces scar tissue in the skin, internal organs, and small blood vessels. It affects women three times more often than men overall, but increases to a rate 15 times greater for women during childbearing years, and appears to be more common among black women.

- Sjögren's syndrome – also called Sjögren's disease, is a chronic, slowly progressing inability to secrete saliva and tears. It can occur alone or with rheumatoid arthritis, scleroderma, or systemic lupus erythematosus. Nine out of 10 cases occur in women, most often at or around mid-life.

- Mixed connective tissue disease – Mixed connective-tissue disease (MCTD) is a disorder in which features of various connective-tissue diseases (CTDs) such as systemic lupus erythematosus (SLE); systemic sclerosis (SSc); dermatomyositis (DM); polymyositis (PM); anti-synthetase syndrome; and, occasionally, Sjögren syndrome can coexist and overlap. The course of the disease is chronic and usually milder than other CTDs. In most cases, MCTD is considered an intermediate stage of a disease that eventually becomes either SLE or Scleroderma.

- Undifferentiated connective tissue disease (UCTD) is a disease in which the body mistakenly attacks its own tissues. It is diagnosed when there is evidence of an existing autoimmune condition which does not meet the criteria for any specific autoimmune disease, such as systemic lupus erythematosus or scleroderma. Latent lupus and incomplete lupus are alternative terms that have been used to describe this condition.

- Psoriatic arthritis is also a collagen vascular disease.

A connective tissue disease is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds together, and protects organs. These tissues form a framework, or matrix, for the body, and are composed of two major structural protein molecules: collagen and elastin. There are many different types of collagen protein in each of the body's tissues. Elastin has the capability of stretching and returning to its original length—like a spring or rubber band. Elastin is the major component of ligaments (tissues that attach bone to bone) and skin. In patients with connective tissue disease, it is common for collagen and elastin to become injured by inflammation (ICT). Many connective tissue diseases feature abnormal immune system activity with inflammation in tissues as a result of an immune system that is directed against one's own body tissues (autoimmunity).

Diseases in which inflammation or weakness of collagen tends to occur are also referred to as collagen diseases. Collagen vascular diseases can be (but are not necessarily) associated with collagen and blood vessel abnormalities and that are autoimmune in nature. See also vasculitis.

Connective tissue diseases can have strong or weak inheritance risks, and can also be caused by environmental factors.

JIA occurs in both sexes, but like other rheumatological diseases, is more common in females. Symptoms onset is frequently dependent on the subtype of JIA and is from the preschool years to the early teenaged years.

Arthritis mutilans' parent condition psoriatic arthritis leaves people with a mortality risk 60% higher than the general population, with premature death causes mirroring those of the general population, cardiovascular issues being most common. Life expectancy for people with psoriatic arthritis is estimated to be reduced by approximately 3 years.

The worldwide prevalence of inflammatory arthritis is approximately 3%. Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and undifferentiated spondyloarthritis are the most common subtypes of inflammatory arthritis. The diseases occur most commonly in the 30-40 age group.

According to a recent study, the main risk factors for RA-ILD are advancing age, male sex, greater RA disease activity, rheumatoid factor (RF) positivity, and elevated titers of anticitrullinated protein antibodies such as anticyclic citrullinated peptide. Cigarette smoking also appears to increase risk of RA-ILD, especially in patients with human leukocyte antigen DRB1.

A recently published retrospective study by a team from Beijing Chao-Yang Hospital in Beijing, China, supported three of the risk factors listed for RA-ILD and identified an additional risk factor. In that study of 550 RA patients, logistic regression analysis of data collected on the 237 (43%) with ILD revealed that age, smoking, RF positivity, and elevated lactate dehydrogenase closely correlated with ILD.

Recent studies have identified risk factors for disease progression and mortality. A retrospective study of 167 patients with RA-ILD determined that the usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) was a risk factor for progression, as were severe disease upon diagnosis and rate of change in pulmonary function test results in the first 6 months after diagnosis.

A study of 59 RA-ILD patients found no median survival difference between those with the UIP pattern and those without it. But the UIP group had more deaths, hospital admissions, need for supplemental oxygen, and decline in lung function.

Serositis is seen in numerous conditions:

- Lupus erythematosus (SLE), for which it is one of the criteria,

- Rheumatoid arthritis

- Familial Mediterranean fever (FMF)

- Chronic renal failure

- Juvenile idiopathic arthritis

- Inflammatory bowel disease (especially Crohn's disease)

- Acute appendicitis

- Diffuse cutaneous systemic sclerosis

The cause of JIA remains a mystery. However, the disorder is autoimmune — meaning that the body's own immune system starts to attack and destroy cells and tissues (particularly in the joints) for no apparent reason. The immune system is thought to be provoked by changes in the environment, in combination with mutations in many associated genes and/or other causes of differential expression of genes. Experimental studies have shown that certain mutated viruses may be able to trigger JIA. The disease appears to be more common in girls, and the disease is most common in Caucasians.

Associated factors that may worsen or have been linked to rheumatoid arthritis include:

- Genetic predisposition; When one family member has been diagnosed with rheumatoid arthritis or another autoimmune disorder, the chances are higher that other family members or siblings may also develop arthritis.

- Females are more likely to develop rheumatoid arthritis than males at all ages.

- A strong belief is held that psychological stress may worsen the symptoms of rheumatoid arthritis. However, when the emotional stress is under control, the arthritis symptoms do not always disappear, suggesting that the association is not straightforward.

- Though no distinct immune factor has been isolated as a cause of arthritis, some experts believe that the triggering factor may be something like a virus which then disappears from the body after permanent damage is done.

- Because rheumatoid arthritis is more common in women, perhaps sex hormones may play a role in causing or modulating arthritis. Unfortunately, neither sex hormone deficiency nor replacement has been shown to improve or worsen arthritis.

The cause of JIA, as the word "idiopathic" suggests, is unknown and an area of active research. Current understanding of JIA suggests that it arises in a genetically susceptible individual due to environmental factors.

The following are conditions commonly associated with pyoderma gangrenosum:

- Inflammatory bowel disease:

- Ulcerative colitis

- Crohn's disease

- Arthritides:

- Rheumatoid arthritis

- Seronegative arthritis

- Hematological disease:

- Myelocytic leukemia

- Hairy cell leukemia

- Myelofibrosis

- Myeloid metaplasia

- Monoclonal gammopathy

- Autoinflammatory disease:

- Pyogenic sterile arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome)

- Granulomatosis with polyangiitis

Serositis refers to inflammation of the serous tissues of the body, the tissues lining the lungs (pleura), heart (pericardium), and the inner lining of the abdomen (peritoneum) and organs within. It is commonly found with fat wrapping or creeping fat.

Though the cause is not well understood, the disease is thought to be due to immune system dysfunction, and particularly improper functioning of neutrophils. In support of an immune cause, a variety of immune mediators such as IL-8, IL-1β, IL-6, interferon (IFN)-γ, G-CSF, TNF, matrix metallopeptidase (MMP)-9, MMP-10, and Elafin have all been reported to be elevated in patients with pyoderma gangrenosum.

Also in support of an immune cause is the finding that at least half of all pyoderma gangrenosum patients suffer from immune-mediated diseases. For instance, ulcerative colitis, rheumatoid arthritis, and multiple myeloma (MM) have all been associated with pyoderma gangrenosum. It can also be part of a syndromes such as PAPA syndrome.

One hallmark of pyoderma gangrenosum is pathergy, which is the appearance of new lesions at sites of trauma.

Seventy percent of people who develop psoriatic arthritis first show signs of psoriasis on the skin, 15 percent develop skin psoriasis and arthritis at the same time, and 15 percent develop skin psoriasis following the onset of psoriatic arthritis.

Psoriatic arthritis can develop in people who have any level severity of psoriatic skin disease, ranging from mild to very severe.

Psoriatic arthritis tends to appear about 10 years after the first signs of psoriasis. For the majority of people, this is between the ages of 30 and 55, but the disease can also affect children. The onset of psoriatic arthritis symptoms before symptoms of skin psoriasis is more common in children than adults.

More than 80% of patients with psoriatic arthritis will have psoriatic nail lesions characterized by nail pitting, separation of the nail from the underlying nail bed, ridging and cracking, or more extremely, loss of the nail itself (onycholysis).

Enthesitis is observed in 30 to 50% of patients and most commonly involves the plantar fascia and Achilles’ tendon, but it may cause pain around the patella, iliac crest, epicondyles,

and supraspinatus insertions

Men and women are equally affected by this condition. Like psoriasis, psoriatic arthritis is more common among Caucasians than African or Asian people.

Inflammatory arthritis can be disabling to the point where people with the diseases can lose their jobs, which can cause psychological distress. Because it is typically progressive, those who lose their jobs are unlikely to re-enter the workforce after leaving due to their diagnosis. Programs now aim to retain those with inflammatory arthritis by preventing work-related injuries and by making necessary accommodations in the workplace. A 2014 Cochrane review found low-quality evidence that work focused interventions, including counseling, education, advocacy, and occupational medicine consultations, were effective in retaining workers with inflammatory arthritis.

Psoriatic arthritis is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage-like appearance. This often happens in association with changes to the nails such as small depressions in the nail (pitting), thickening of the nails, and detachment of the nail from the nailbed. Skin changes consistent with psoriasis (e.g., red, scaly, and itchy plaques) frequently occur before the onset of psoriatic arthritis but psoriatic arthritis can precede the rash in 15% of affected individuals. It is classified as a type of seronegative spondyloarthropathy.

Genetics are thought to be strongly involved in the development of psoriatic arthritis. Obesity and certain forms of psoriasis are thought to increase the risk.

Psoriatic arthritis affects up to 30% of people with psoriasis and occurs in both children and adults. Approximately 40-50% of individuals with psoriatic arthritis have the HLA-B27 genotype. The condition is less common in people of Asian or African descent and affects men and women equally.

Collagen disease is a term previously used to describe systemic autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue.

The term "collagen disease" was coined by Dr. Alvin F. Coburn in 1932, on his quest to discover streptococcal infection as the cause for rheumatic fever.

The disease mechanism (pathophysiology) of RS3PE remains unknown. One study suggested a possible role for vascular endothelial growth factor. A study using magnetic resonance imaging found that tenosynovitis of the extensors of the hands and feet is the major contributor to edema.

Rheumatoid pleuritis, a form of pleural effusion, is an uncommon complication of rheumatoid arthritis, occurring in 2-3% of patients (Walker and Wright, 1967; Naylor, 1990)

Rheumatoid vasculitis is skin condition that is a typical feature of rheumatoid arthritis, presenting as peripheral vascular lesions that are localized purpura, cutaneous ulceration, and gangrene of the distal parts of the extremities.