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.

The prevalence of RA is around 0.3–1.2% (0.92% of Americans). Women are 2–3 times more susceptible than men. The prevalence of rheumatoid lung disease in patients with RA depends on the method used for diagnosis: chest X rays (5%), high resolution CT scans (10–40%).

A study showed 582 patients with RA and 603 subjects without RA were followed for a mean of 16.4 and 19.3 years, respectively. The lifetime risk of developing ILD was 7.7% for RA patients and 0.9% for subjects without RA. The risk of developing ILD was higher in patients with older age at RA onset, among male patients and for individuals with parameters that indicate more severe RA.

Survival of RA patients diagnosed with ILD was worse compared to RA patients without ILD. ILD contributed approximately 13% to the excess mortality of patients with RA patients when compared to the general population.

The cause of IPF is unknown but certain environmental factors and exposures have been shown to increase the risk of getting IPF. Cigarette smoking is the best recognized and most accepted risk factor for IPF, and increases the risk of IPF by about twofold. Other environmental and occupation exposures such as exposure to metal dust, wood dust, coal dust, silica, stone dust, biologic dusts coming from hay dust or mold spores or other agricultural products, and occupations related to farming/livestock have also been shown to increase the risk for IPF. There is some evidence that viral infections may be associated with idiopathic pulmonary fibrosis and other fibrotic lung diseases.

ILD may be classified according to the cause. One method of classification is as follows:

1. Inhaled substances

- Inorganic

- Silicosis

- Asbestosis

- Berylliosis

- printing workers (eg. carbon bblack, ink mist)

- Organic

- Hypersensitivity pneumonitis

2. Drug-induced

- Antibiotics

- Chemotherapeutic drugs

- Antiarrhythmic agents

3. Connective tissue and Autoimmune diseases

- Rheumatoid arthritis

- Systemic lupus erythematosus

- Systemic sclerosis

- Polymyositis

- Dermatomyositis

4. Infection

- Atypical pneumonia

- Pneumocystis pneumonia (PCP)

- Tuberculosis

- "Chlamydia" trachomatis

- Respiratory Syncytial Virus

5. Idiopathic

- Sarcoidosis

- Idiopathic pulmonary fibrosis

- Hamman-Rich syndrome

- Antisynthetase syndrome

6. Malignancy

- Lymphangitic carcinomatosis

7. Predominantly in children

- Diffuse developmental disorders

- Growth abnormalities deficient alveolarisation

- Infant conditions of undefined cause

- ILD related to alveolar surfactant region

The clinical course of IPF can be unpredictable. IPF progression is associated with an estimated median survival time of 2 to 5 years following diagnosis.

The 5-year survival for IPF ranges between 20–40%, a mortality rate higher than that of a number of malignancies, including colon cancer, multiple myeloma and bladder cancer.

Recently a multidimensional index and staging system has been proposed to predict mortality in IPF. The name of the index is GAP and is based on gender [G], age [A], and two lung physiology variables [P] (FVC and DL that are commonly measured in clinical practice to predict mortality in IPF. The highest stage of GAP (stage III) has been found to be associated with a 39% risk of mortality at 1 year. This model has also been evaluated in IPF and other ILDs and shown good performance in predicting mortality in all main ILD subtypes. A modified ILD-GAP Index has been developed for application across ILD subtypes to provide disease-specific survival estimates. In IPF patients, the overall mortality at 5 years rate is high but the annual rate of all-cause mortality in patients with mild to moderate lung impairment is relatively low. This is the reason why change in lung function (FVC) is usually measured in 1-year clinical trials of IPF treatments rather than survival.

In addition to clinical and physiological parameters to predict how rapidly patients with IPF might progress, genetic and molecular features are also associated with IPF mortality. For example, it has been shown that IPF patients who have a specific genotype in the mucin MUC5B gene polymorphism (see above) experience slower decline in FVC and significantly improved survival. Even if such data are interesting from a scientific point of view, the application in the clinical routine of a prognostic model based on specific genotypes is still not possible.

Interstitial lung disease (ILD), or diffuse parenchymal lung disease (DPLD), is a group of lung diseases affecting the interstitium (the tissue and space around the air sacs of the lungs). It concerns alveolar epithelium, pulmonary capillary endothelium, basement membrane, perivascular and perilymphatic tissues. It may occur when an injury to the lungs triggers an abnormal healing response. Ordinarily, the body generates just the right amount of tissue to repair damage. But in interstitial lung disease, the repair process goes awry and the tissue around the air sacs (alveoli) becomes scarred and thickened. This makes it more difficult for oxygen to pass into the bloodstream. The term ILD is used to distinguish these diseases from obstructive airways diseases.

In children, several unique forms of ILD exist which are specific for the young age groups. The acronym chILD is used for this group of diseases and is derived from the English name, Children’s Interstitial Lung Diseases – chILD.

Prolonged ILD may result in pulmonary fibrosis, but this is not always the case. Idiopathic pulmonary fibrosis is interstitial lung disease for which no obvious cause can be identified (idiopathic), and is associated with typical findings both radiographic (basal and pleural based fibrosis with honeycombing) and pathologic (temporally and spatially heterogeneous fibrosis, histopathologic honeycombing and fibroblastic foci).

In 2013 interstitial lung disease affected 595,000 people globally. This resulted in 471,000 deaths.

Before modern treatments, the 2-year mortality was over 90% and average survival five months. Death usually resulted from uremia or respiratory failure.

With corticosteroids and cyclophosphamide, 5-year survival is over 80%. Long-term complications are common (86%), mainly chronic kidney failure, hearing loss and deafness.

Today, drug toxicity is managed more carefully and long-term remissions are possible. Some patients are able to lead relatively normal lives and remain in remission for 20+ years after treatment.

Vasculitis secondary to connective tissue disorders. Usually secondary to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), relapsing polychondritis, Behçet's disease, and other connective tissue disorders.

Vasculitis secondary to viral infection. Usually due to hepatitis B and C, HIV, cytomegalovirus, Epstein-Barr virus, and Parvo B19 virus.

Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis (WG), is a systemic disorder that involves both granulomatosis and . It is a form of vasculitis (inflammation of blood vessels) that affects small- and medium-size vessels in many organs. Damage to the lungs and kidneys can be fatal. Treatment requires long-term immunosuppression.

Granulomatosis with polyangiitis is part of a larger group of vasculitic syndromes called systemic vasculitides or necrotizing vasculopathies, all of which feature an autoimmune attack by an abnormal type of circulating antibody termed ANCAs (antineutrophil cytoplasmic antibodies) against small and medium-size blood vessels. Apart from GPA, this category includes eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis. Although GPA affects small- and medium-size vessels, it is formally classified as one of the small vessel vasculitides in the Chapel Hill system.

Patients usually present with systemic symptoms with single or multiorgan dysfunction. Common (and nonspecific) complaints include fatigue, weakness, fever, arthralgias, abdominal pain, hypertension, renal insufficiency, and neurologic dysfunction. The following symptoms should raise a strong suspicion of a vasculitis:

- Mononeuritis multiplex. Also known as asymmetric polyneuropathy, in a non-diabetic this is suggestive of vasculitis.

- Palpable purpura. If patients have this in isolation, it is most likely due to cutaneous leukocytoclastic vasculitis. If the purpura is in combination with systemic organ involvement, it is most likely to be Henoch-Schonlein purpura or microscopic polyarteritis.

- Pulmonary-renal syndrome. Individuals who are coughing up blood and have kidney involvement are likely to have granulomatosis with polyangiitis, microscopic polyangiitis, or anti-GBM disease (Goodpasture's syndrome).

The condition affects adults more frequently than children and males more frequently than females. Most cases occur between the ages of 30 and 49. It damages the tissues supplied by the affected arteries because they do not receive enough oxygen and nourishment without a proper blood supply. Polyarteritis nodosa is more common in people with hepatitis B infection.

The third and final stage, and hallmark of EGPA, is inflammation of the blood vessels, and the consequent reduction of blood flow to various organs and tissues. Local and systemic symptoms become more widespread and are compounded by new symptoms from the vasculitis.

Severe complications may arise. Blood clots may develop within the damaged arteries in severe cases, particularly in arteries of the abdominal region, which is followed by infarction and cell death, or slow atrophy. Many patients experience severe abdominal complaints; these are most often due to peritonitis and/or ulcerations and perforations of the gastrointestinal tract, but occasionally due to acalculous cholecystitis or granulomatous appendicitis.

The most serious complication of the vasculitic stage is heart disease, which is the cause of nearly one-half of all deaths in patients with EGPA. Among heart disease-related deaths, the most usual cause is inflammation of the heart muscle caused by the high level of eosinophils, although some are deaths due to inflammation of the arteries that supply blood to the heart or pericardial tamponade. Kidney complications have been reported as being less common.

Eosinophilic granulomatosis with polyangiitis consists of three stages, but not all patients develop all three stages or progress from one stage to the next in the same order; whereas some patients may develop severe or life-threatening complications such as gastrointestinal involvement and heart disease, some patients are only mildly affected, "e.g." with skin lesions and nasal polyps. EGPA is consequently considered a highly variable condition in terms of its presentation and its course.

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.

HSP occurs more often in children than in adults, and usually follows an upper respiratory tract infection. Half of affected patients are below the age of six, and 90% are under ten. It occurs about twice as often in boys as in girls. The incidence of HSP in children is about 20 per 100,000 children per year, making it the most common vasculitis in children.

Cases of HSP may occur anytime throughout the year, but some studies have found that fewer cases occur during the summer months.

With Behçet's disease as an intercurrent disease in pregnancy, the pregnancy does not have an adverse effect on the course of Behçet's disease and may possibly ameliorate its course. Still, there is a substantial variability in clinical course between patients and even for different pregnancies in the same patient. Also, the other way around, Behçet's disease confers an increased risk of pregnancy complications, miscarriage and Cesarean section.

Behçet's can cause male infertility, either as a result of the condition itself or of a side effect of concomitant medication such as Colchicine, which is known to lower sperm count.

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.

Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis. Vasculitis is primarily caused by leukocyte migration and resultant damage.

Although both occur in vasculitis, inflammation of veins (phlebitis) or arteries (arteritis) are their own are separate entities.

Overall prognosis is good in most patients, with one study showing recovery occurring in 94% and 89% of children and adults, respectively (some having needed treatment). In children under ten, the condition recurs in about a third of all cases and usually within the first four months after the initial attack. Recurrence is more common in older children and adults.

Treatment involves medications to suppress the immune system, including prednisone and cyclophosphamide. In some cases, methotrexate or leflunomide may be helpful. Some patients have also noticed a remission phase when a four-dose infusion of rituximab is used before the leflunomide treatment is begun. Therapy results in remissions or cures in 90% of cases. Untreated, the disease is fatal in most cases. The most serious associated conditions generally involve the kidneys and gastrointestinal tract. A fatal course usually involves gastrointestinal bleeding, infection, myocardial infarction, and/or kidney failure.

In case of remission, about 60% experience relapse within five years. In cases caused by hepatitis B virus, however, recurrence rate is only around 6%.

Vasculitis can be classified by the cause, the location, the type of vessel or the size of vessel.

- "Underlying cause". For example, the cause of syphilitic aortitis is infectious (aortitis simply refers to inflammation of the aorta, which is an artery.) However, the causes of many forms of vasculitis are poorly understood. There is usually an immune component, but the trigger is often not identified. In these cases, the antibody found is sometimes used in classification, as in ANCA-associated vasculitides.

- "Location of the affected vessels". For example, ICD-10 classifies "vasculitis limited to skin" with skin conditions (under "L"), and "necrotizing vasculopathies" (corresponding to systemic vasculitis) with musculoskeletal system and connective tissue conditions (under "M"). Arteritis/phlebitis on their own are classified with circulatory conditions (under "I").

- "Type or size of the blood vessels" that they predominantly affect. Apart from the arteritis/phlebitis distinction mentioned above, vasculitis is often classified by the caliber of the vessel affected. However, there can be some variation in the size of the vessels affected.

According to the size of the vessel affected, vasculitis can be classified into:

- Large vessel: Polymyalgia rheumatica, Takayasu's arteritis, Temporal arteritis

- Medium vessel: Buerger's disease, Kawasaki disease, Polyarteritis nodosa

- Small vessel: Behçet's syndrome, Eosinophilic granulomatosis with polyangiitis, Cutaneous vasculitis, Henoch–Schönlein purpura, Microscopic polyannulomatosis ConditionofSome disorders have vasculitis as their main feature. The major types are given in the table below:

Takayasu's arteritis, polyarteritis nodosa and giant cell arteritis mainly involve arteries and are thus sometimes classed specifically under arteritis.

Furthermore, there are many conditions that have vasculitis as an accompanying or atypical feature, including:

- Rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and dermatomyositis

- Cancer, such as lymphomas

- Infections, such as hepatitis C

- Exposure to chemicals and drugs, such as amphetamines, cocaine, and anthrax vaccines which contain the Anthrax Protective Antigen as the primary ingredient.

In pediatric patients varicella inflammation may be followed by vasculitis of intracranial vessels. This condition is called post varicella angiopathy and this may be responsible for arterial ischaemic strokes in children.

Several of these vasculitides are associated with antineutrophil cytoplasmic antibodies. These are:

- Granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis)

- Eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss syndrome)

- Microscopic polyangiitis

The syndrome is rare in the United States, Africa and South America, but is common in the Middle East and Asia, suggesting a possible cause endemic to those tropical areas. A theory suggested that past exposure to lethal infectious agents might have fixed the genetic susceptibility factors to Behçet's disease in those area. It is not associated with cancer, and links with tissue-types (which are under investigation) are not certain. It also does not follow the usual pattern for autoimmune diseases. However, one study has revealed a possible connection to food allergies, particularly to dairy products. An estimated 15,000 to 20,000 Americans have been diagnosed with this disease. In the UK, it is estimated to have about 1 case for every 100,000 people. Globally, males are affected more frequently than females. In the United States, more females are affected than males.

In an epidemiologic study, 56 percent of patients with Behçet's disease developed ocular involvement at a mean age of 30. Ocular involvement was the first manifestation of Behçet's disease in 8.6 percent of patients. Ocular Behçet's disease with involvement of the optic nerve is rarely reported. Among patients with ocular Behçet's disease funduscopic findings of optic atrophy, and optic disc paleness have been identified with a frequency of 17.9 percent and 7.4 percent, respectively. Other fundoscopic findings include vascular sheathing (23.7%), retinal hemorrhage (9%), macular edema (11.3%), branch retinal vein occlusion (5.8%), and retinal edema (6.6%). However, optic atrophy was the most significant cause of visual impairment identified in 54 percent of patients with ocular Behçet's disease and permanent visual impairment.

The prevalence of this disease increases from North to South. It follows a more severe course in patients with an early age of onset particularly in patients with eye and gastrointestinal involvement.

Urticarial vasculitis (also known as "chronic urticaria as a manifestation of venulitis", "hypocomplementemic urticarial vasculitis syndrome", "hypocomplementemic vasculitis" and "unusual lupus-like syndrome") is a skin condition characterized by fixed urticarial lesions that appear histologically as a vasculitis.

Alpha-1 antitrypsin deficiency panniculitis is a panniculitis associated with a deficiency of the α-antitrypsin enzyme.

Antibodies are usually raised against foreign proteins, such as those made by a replicating virus or invading bacterium. Virus or bacteria with antibodies opsonized or "stuck" to them highlight them to other cells of the immune system for clearance.

Antibodies against self proteins are known as autoantibodies, and are not found in healthy individuals. These autoantibodies can be used to detect certain diseases.