Enthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. It is also called enthesopathy, or any pathologic condition involving the entheses. The entheses are any point of attachment of skeletal muscles to the bone, where recurring stress or inflammatory autoimmune disease can cause inflammation or occasionally fibrosis and calcification. One of the primary entheses involved in inflammatory autoimmune disease is at the heel, particularly the Achilles tendon.

It is associated with HLA B27 arthropathies like ankylosing spondylitis, psoriatic arthritis, and reactive arthritis. Symptoms include multiple points of tenderness at the heel, tibial tuberosity, iliac crest, and other tendon insertion sites.

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.

Arthritis mutilans occurs mainly in people who have pre-existing psoriatic arthritis, but can occur, if less often, in advanced rheumatoid arthritis; it can also occur independently. Psoriasis and psoriatic arthritis are interrelated heritable diseases, occurring with greater heritable frequency than rheumatoid arthritis, primary Sjogren's syndrome and thyroid disease. Psoriasis affects 2–3% of the Caucasian population, and psoriatic arthritis affects up to 30% of those. Arthritis mutilans presents in about 5–16% of psoriatic arthritis cases, involves osteolysis of the DIP and PIP joints, and can include bone edema, bone erosions, and new bone growth. Most often psoratic arthitis is seronegative for rheumatoid factor (occurring in only about 13% of cases), and has genetic risk factor overlap with ankylosing spondylitis with HLA-B27, IL-23R77, and IL-1, however, as of 2016, immunopathogenesis is unclear.

Worldwide prevalence of spondyloarthropathy is approximately 1.9%.

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.

In medicine, an enthesopathy refers to a disorder involving the attachment of a tendon or ligament to a bone. This site of attachment is known as the entheses.

If the condition is known to be inflammatory, it can more precisely be called an enthesitis.

Enthesopathies may take the form of spondyloarthropathies (joint diseases of the spine) such as ankylosing spondylitis, plantar fasciitis, and Achilles tendinitis. Enthesopathy can occur at the elbow, wrist, carpus, hip, knee, ankle, tarsus, or heel bone, among other regions. Further examples include:

- Adhesive capsulitis of shoulder

- Rotator cuff syndrome of shoulder and allied disorders

- Periarthritis of shoulder

- Scapulohumeral fibrositis

- Synovitis of hand or wrist

- Periarthritis of wrist

- Gluteal tendinitis

- Iliac crest spur

- Psoas tendinitis

- Trochanteric tendinitis

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.

Spondyloarthropathy or spondyloarthrosis refers to any joint disease of the vertebral column. As such, it is a class or category of diseases rather than a single, specific entity. It differs from spondylopathy, which is a disease of the vertebra itself. However, many conditions involve both spondylopathy and spondyloarthropathy.

Spondyloarthropathy with inflammation is called axial spondyloarthritis. In the broadest sense, the term spondyloarthropathy includes joint involvement of vertebral column from any type of joint disease, including rheumatoid arthritis and osteoarthritis, but the term is often used for a specific group of disorders with certain common features, the group often being termed specifically seronegative spondylarthropathies. They have an increased incidence of HLA-B27, as well as negative rheumatoid factor and ANA. Enthesopathy is also sometimes present in association with seronegative.

Non-vertebral signs and symptoms of degenerative or other not-directly-infected inflammation, in the manner of spondyloarthropathies, include asymmetric peripheral arthritis (which is distinct from rheumatoid arthritis), arthritis of the toe interphalangeal joints, sausage digits, Achilles tendinitis, plantar fasciitis, costochondritis, iritis, and mucocutaneous lesions. However, lower back pain is the most common clinical presentation of the causes of spondyloarthropoathies; this back pain is unique because it decreases with activity.

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.

Because women may be underdiagnosed, the exact incidence of reactive arthritis is difficult to estimate. A few studies have been completed, though. In Norway between 1988 and 1990, the incidence was 563.3 cases per 100,000 for chlamydia-induced reactive arthritis and 5 cases per 100,000 for that induced by enteric bacteria. In 1978 in Finland, the annual incidence was found to be 5835.7 per 100,000.

Reactive arthritis may be self-limiting, frequently recurring, chronic or progressive. Most patients have severe symptoms lasting a few weeks to six months. 15 to 50 percent of cases involve recurrent bouts of arthritis. Chronic arthritis or sacroiliitis occurs in 15–30 percent of cases. Repeated attacks over many years are common, and patients sometimes end up with chronic and disabling arthritis, heart disease, amyloid deposits, ankylosing spondylitis, immunoglobulin A nephropathy, cardiac conduction abnormalities, or aortitis with aortic regurgitation. However, most people with reactive arthritis can expect to live normal life spans and maintain a near-normal lifestyle with modest adaptations to protect the involved organs.

Axial spondyloarthritis (also often referred to as axSpA) is a chronic, autoinflammatory disease predominantly affecting the axial skeleton (sacroiliac joints and spine). The most known member of the axial spondyloarthritis disease family is ankylosing spondylitis. Axial spondyloarthritis is an umbrella term that has been introduced in the year 2009 to characterize a diverse disease family that share clinical and genetic features, such as the involvement of the axial skeleton. The expression was introduced in order to unify (1) less severe forms of spondylitis, (2) the early phase of ankylosing spondylitis as well as (3) ankylosing spondylitis itself into one term.

The exact causes are not yet known, but a number of genetic associations have been identified in a genome-wide association study of psoriasis and psoriatic arthritis including HLA-B27.

In 1984, a joint effort led to the definition of specific classification criteria for ankylosing spondylitis, called the “Modified New York Criteria”. One of the central New York criteria was the existence of radiographically visible changes in the sacroiliac joints and/or spine, which have formed due to bone fusion, erosion and/or formation caused by the disease. Even though these criteria helped to improve uniformly define ankylosing spondylitis, such radiologic changes often only manifested several years after the first disease symptoms appeared. In order to be able to study also patients with early and less typical forms, new criteria were needed that could identify the disease already at an early stage. In 2009 the Modified New York criteria were extended by a broad set of new classification criteria that aimed to classify patients based on the presence of typical spondyloarthritis disease features. These included inflammatory back pain, family history for axial spondyloarthritis, response to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), past history of or current inflammation in the joints (arthritis), tendon-bone attachment of the heel (enthesitis), or eyes (uveitis), bowel (inflammatory bowel disease), skin (psoriasis) or signs of elevated inflammation (C-reactive protein and erythrocyte sedimentation rate. Important parts of the ASAS axSpA criteria is the biomarker HLA-B27 and magnetic resonance imaging (MRI). The criteria can only be applied in people that have chronic back pain (at least 3 months duration) started before the age of 45 years and only in those patients that already have a diagnosis of axial SpA. Since the disease ankylosing spondylitis was still defined by the Modified New York criteria of 1984, there was the need to find a new disease term that would also include the less severe forms or early onset of ankylosing spondylitis. This expression was found in the umbrella term axial spondyloarthritis. The 2009 classification criteria are called the ASAS (Assessment of SpondyloArthritis international Society) axial spondayloarthritis criteria.

The exact cause of sarcoidosis is not known. The current working hypothesis is, in genetically susceptible individuals, sarcoidosis is caused through alteration to the immune response after exposure to an environmental, occupational, or infectious agent. Some cases may be caused by treatment with TNF inhibitors like etanercept.

The heritability of sarcoidosis varies according to ethnicity. About 20% of African Americans with sarcoidosis have a family member with the condition, whereas the same figure for European Americans is about 5%. Additionally, in African Americans, who seem to experience more severe and chronic disease, siblings and parents of sarcoidosis cases have about a 2.5-fold increased risk for developing the disease. Investigations of genetic susceptibility yielded many candidate genes, but only few were confirmed by further investigations and no reliable genetic markers are known. Currently, the most interesting candidate gene is "BTNL2"; several "HLA-DR" risk alleles are also being investigated. In persistent sarcoidosis, the HLA haplotype "HLA-B7-DR15" are either cooperating in disease or another gene between these two loci is associated. In nonpersistent disease, there is a strong genetic association with HLA DR3-DQ2. Cardiac sarcoid has been connected to TNFA variants.

Uveitis may be an immune response to fight an infection inside the eye. While representing the minority of patients with uveitis, such possible infections include:

- brucellosis

- leptospirosis

- Lyme disease

- presumed ocular histoplasmosis syndrome

- syphilis

- toxocariasis

- toxoplasmic chorioretinitis

- tuberculosis

- Zika fever

Systemic disorders that can be associated with uveitis include:

- ankylosing spondylitis

- Behçet's disease

- chronic granulomatous disease

- enthesitis

- inflammatory bowel disease

- juvenile rheumatoid arthritis

- Kawasaki's disease

- multiple sclerosis

- polyarteritis nodosa

- psoriatic arthritis

- reactive arthritis

- sarcoidosis

- systemic lupus erythematosus

- Vogt–Koyanagi–Harada disease

- Whipple's disease

While the exact cause is unknown, Crohn's disease seems to be due to a combination of environmental factors and genetic predisposition. Crohn's is the first genetically complex disease in which the relationship between genetic risk factors and the immune system is understood in considerable detail. Each individual risk mutation makes a small contribution to the overall risk of Crohn's (approximately 1:200). The genetic data, and direct assessment of immunity, indicates a malfunction in the innate immune system. In this view, the chronic inflammation of Crohn's is caused when the adaptive immune system tries to compensate for a deficient innate immune system.

The increased incidence of Crohn's in the industrialized world indicates an environmental component. Crohn's is associated with an increased intake of animal protein, milk protein and an increased ratio of omega-6 to omega-3 polyunsaturated fatty acids.

Those who consume vegetable proteins appear to have a lower incidence of Crohn's disease. Consumption of fish protein has no association.

Smoking increases the risk of the return of active disease (flares). The introduction of hormonal contraception in the United States in the 1960s is associated with a dramatic increase in incidence, and one hypothesis is that these drugs work on the digestive system in ways similar to smoking. Isotretinoin is associated with Crohn's. Although stress is sometimes claimed to exacerbate Crohn's disease, there is no concrete evidence to support such claim. Dietary microparticles, such as those found in toothpaste, have been studied as they produce effects on immunity, but they were not consumed in greater amounts in patients with Crohn's.