Mononeuropathy is a type of neuropathy that only affects a single nerve. Diagnostically, it is important to distinguish it from polyneuropathy because when a single nerve is affected, it is more likely to be due to localized trauma or infection.

The most common cause of mononeuropathy is physical compression of the nerve, known as compression neuropathy. Carpal tunnel syndrome and axillary nerve palsy are examples. Direct injury to a nerve, interruption of its blood supply resulting in (ischemia), or inflammation also may cause mononeuropathy.

Peripheral neuropathy may be classified according to the number and distribution of nerves affected (mononeuropathy, mononeuritis multiplex, or polyneuropathy), the type of nerve fiber predominantly affected (motor, sensory, autonomic), or the process affecting the nerves; e.g., inflammation (neuritis), compression (compression neuropathy), chemotherapy (chemotherapy-induced peripheral neuropathy).

The mechanisms of diabetic neuropathy are poorly understood. At present, treatment alleviates pain and can control some associated symptoms, but the process is generally progressive.

As a complication, there is an increased risk of injury to the feet because of loss of sensation (see diabetic foot). Small infections can progress to ulceration and this may require amputation.

Globally diabetic neuropathy affects approximately 132 million people as of 2010 (1.9% of the population).

Diabetes is the leading known cause of neuropathy in developed countries, and neuropathy is the most common complication and greatest source of morbidity and mortality in diabetes. It is estimated that neuropathy affects 25% of people with diabetes. Diabetic neuropathy is implicated in 50–75% of nontraumatic amputations.

The main risk factor for diabetic neuropathy is hyperglycemia. In the DCCT (Diabetes Control and Complications Trial, 1995) study, the annual incidence of neuropathy was 2% per year but dropped to 0.56% with intensive treatment of Type 1 diabetics. The progression of neuropathy is dependent on the degree of glycemic control in both Type 1 and Type 2 diabetes. Duration of diabetes, age, cigarette smoking, hypertension, height, and hyperlipidemia are also risk factors for diabetic neuropathy.

A nerve may be compressed by prolonged or repeated external force, such as sitting with one's arm over the back of a chair (radial nerve), frequently resting one's elbows on a table (ulnar nerve), or an ill-fitting cast or brace on the leg (peroneal nerve). Part of the patient's body can cause the compression and the term "entrapment neuropathy" is used particularly in this situation. The offending structure may be a well-defined lesion such as a tumour (for example a lipoma, neurofibroma or metastasis), a ganglion cyst or a haematoma. Alternatively, there may be expansion of the tissues around a nerve in a space where there is little room for this to occur, as is often the case in carpal tunnel syndrome. This may be due to weight gain or peripheral oedema (especially in pregnancy), or to a specific condition such as acromegaly, hypothyroidism or scleroderma and psoriasis.

Some conditions cause nerves to be particularly susceptible to compression. These include diabetes, in which the blood supply to the nerves is already compromised, rendering the nerve more sensitive to minor degrees of compression. The genetic condition HNPP is a much rarer cause.

External pressure reduces flow in the vessels supplying the nerve with blood (the vasa nervorum). This causes local ischaemia, which has an immediate effect on the ability of the nerve axons to transmit action potentials. As the compression becomes more severe over time, focal demyelination occurs, followed by axonal damage and finally scarring.

Some viruses are thought to establish a persistent (or latent) infection without symptoms, e.g., the varicella-zoster virus and Epstein-Barr viruses, both of the herpes family. Reactivation of an existing (dormant) viral infection has been suggested as a cause of acute Bell's palsy. Studies suggest that this new activation could be preceded by trauma, environmental factors, and metabolic or emotional disorders, thus suggesting that a host of different conditions may trigger reactivation.

Familial inheritance has been found in 4–14% of cases. Bell's palsy is three times more likely to occur in pregnant women than non-pregnant women. It is also considered to be four times more likely to occur in diabetics than the general population.

One review found that antivirals (such as aciclovir) are ineffective in improving recovery from Bell's palsy beyond steroids alone in mild to moderate disease. Another review found a benefit but stated the evidence was not very good to support this conclusion.

In severe disease it is also unclear. One 2015 review found no effect regardless of severity. Another review found a small benefit when added to steroids in those with severe disease.

They are commonly prescribed due to a theoretical link between Bell's palsy and the herpes simplex and varicella zoster virus. There is still the possibility that they might result in a benefit less than 7% as this has not been ruled out.

The mechanism of axonal degeneration has not been clarified and is an area of continuing research on alcoholic polyneuropathy.

Further research is looking at the effect an alcoholics’ consumption and choice of alcoholic beverage on their development of alcoholic polyneuropathy. Some beverages may include more nutrients than others (such as thiamine), but the effects of this with regards to helping with a nutritional deficiency in alcoholics is yet unknown.

There is still controversy about the reasons for the development of alcoholic polyneuropathy. Some argue it is a direct result of alcohol's toxic effect on the nerves, but others say factors such as a nutritional deficiency or chronic liver disease may play a role in the development as well. This debate is ongoing and research is continuing in an effort to discover the real cause of alcoholic polyneuropathy.

The rate of incidence of alcoholic polyneuropathy involving sensory and motor polyneuropathy varies from 10% to 50% of alcoholics depending on the subject selection and diagnostic criteria. If electrodiagnostic criteria is used, alcoholic polyneuropathy may be found in up to 90% of individuals being assessed. The distribution and severity the disease depends on regional dietary habits, individual drinking habits, as well as an individual’s genetics. Large studies have been conducted and show that alcoholic polyneuropathy severity and incidence correlates best with the total lifetime consumption of alcohol. Factors such as nutritional intake, age, or other medical conditions are correlate in lesser degrees. For unknown reasons, alcoholic polyneuropathy has a high incidence in women.

Certain alcoholic beverages can also contain congeners that may also be bioactive; therefore, the consumption of varying alcoholic beverages may result in different health consequences. An individual’s nutritional intake also plays a role in the development of this disease. Depending on the specific dietary habits, they may have a deficiency of one or more of the following: thiamine (vitamin B1), pyridoxine (vitamin B6), pantothenic acid and biotin, vitamin B12, folic acid, niacin (vitamin B3), and vitamin A.

In one study of 387 Behçet's disease (BD) patients that has been done for 20 years, 13% of men with BD developed to NBD and 5.6% of women developed to NBD.

Combining all statistical reports, approximately 9.4% (43 of 459) BD patients advanced to NBD. In addition, men were 2.8 times more likely to experience NBD than women. This fact indicates possible gender-based pathology.

In speaking about age of NBD patients, the general range was between 20 and 40. NBD patients with age less than 10 or more than 50 were very uncommon.

Because the cause of Behçet's disease is unknown, the cause responsible for neuro-Behçet's disease is unknown as well. Inflammation starts mainly due to immune system failure. However, no one knows what factors trigger the initiation of auto-immune disease like inflammation. Because the cause is unknown, it is impossible to eliminate or prevent the source that causes the disease. Therefore, treatments are focused on how to suppress the symptoms that hinders daily life activities.

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.

Research from 2007 suggested that in type 1 diabetics, the continuing autoimmune disease which initially destroyed the beta cells of the pancreas may also cause retinopathy, neuropathy, and nephropathy.

In 2008 it was even suggested to treat retinopathy with drugs to suppress the abnormal immune response rather than by blood sugar control.

A 1988 study over 41 months found that improved glucose control led to initial "worsening of complications" but was not followed by the expected improvement in complications. In 1993 it was discovered that the serum of diabetics with neuropathy is toxic to nerves, even if its blood sugar content is normal.

Research from 1995 also challenged the theory of hyperglycemia as the cause of diabetic complications. The fact that 40% of diabetics who carefully controlled their blood sugar nevertheless developed neuropathy made clear other factors were involved.

In a 2013 meta-analysis of 6 randomized controlled trials involving 27,654 patients, tight blood glucose control reduced the risk for some macrovascular and microvascular events but without effect on all-cause mortality and cardiovascular mortality.

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.

Fibromyalgia was found in 9% of adult patients relative to 0.03% in the general population with a link common to IBD. Concurrent IBS is found in 30% to 70%. Small intestinal bacterial overgrowth is associated is common with a transient response to antimicrobial therapy.

Adenocarcinoma of the bowel has been associated with coeliac disease.

SLE, like many autoimmune diseases, affects females more frequently than males, at a rate of about 9 to 1. The X chromosome carries immunological related genes, which can mutate and contribute to the onset of SLE. The Y chromosome has no identified mutations associated with autoimmune disease.

Hormonal mechanisms could explain the increased incidence of SLE in females. The onset of SLE could be attributed to the elevated hydroxylation of estrogen and the abnormally decreased levels of androgens in females. In addition, differences in GnRH signalling have also shown to contribute to the onset of SLE. While females are more likely to relapse than males, the intensity of these relapses is the same for both sexes.

In addition to hormonal mechanisms, specific genetic influences found on the X chromosome may also contribute to the development of SLE. Studies indicate that the X chromosome can determine the levels of sex hormones. A study has shown an association between Klinefelter syndrome and SLE. XXY males with SLE have an abnormal X–Y translocation resulting in the partial triplication of the PAR1 gene region.

There are assertions that race affects the rate of SLE. However, a 2010 review of studies which correlate race and SLE identified several sources of systematic and methodological error, indicating that the connection between race and SLE may be spurious. For example, studies show that social support is a modulating factor which buffers against SLE-related damage and maintains physiological functionality. Studies have not been conducted to determine whether people of different racial backgrounds receive differing levels of social support. If there is a difference, this could act as a confounding variable in studies correlating race and SLE. Another caveat to note when examining studies about SLE is that symptoms are often self-reported. This process introduces additional sources of methodological error. Studies have shown that self-reported data is affected by more than just the patients experience with the disease- social support, the level of helplessness, and abnormal illness-related behaviors also factor into a self-assessment. Additionally, other factors like the degree of social support that a person receives, socioeconomic status, health insurance, and access to care can contribute to an individual’s disease progression. Racial differences in lupus progression have not been found in studies that control for the socioeconomic status [SES] of participants. Studies that control for the SES of its participants have found that non-white people have more abrupt disease onset compared to white people and that their disease progresses more quickly. Non-white patients often report more hematological, serosal, neurological, and renal symptoms. However, the severity of symptoms and mortality are both similar in white and non-white patients. Studies that report different rates of disease progression in late-stage SLE are most likely reflecting differences in socioeconomic status and the corresponding access to care. The people who receive medical care have often accrued less disease-related damage and are less likely to be below the poverty line. Additional studies have found that education, marital status, occupation, and income create a social context which contributes to disease progression.

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.

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.

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