Abnormalities of the cranial nerves are present 50-70% of cases. The most common abnormality is involvement of the facial nerve, which may lead to reduced power on one or both sides of the face (65% resp 35% of all cranial nerve cases), followed by reduction in visual perception due to optic nerve involvement. Rarer symptoms are double vision (oculomotor nerve, trochlear nerve or abducens nerve), decreased sensation of the face (trigeminal nerve), hearing loss or vertigo (vestibulocochlear nerve), swallowing problems (glossopharyngeal nerve) and weakness of the shoulder muscles (accessory nerve) or the tongue (hypoglossal nerve). Visual problems may also be the result of papilledema (swelling of the optic disc) due to obstruction by granulomas of the normal cerebrospinal fluid (CSF) circulation.

Seizures (mostly of the tonic-clonic/"grand mal" type) are present in about 15%, and may be the presenting phenomenon in 10%.

Meningitis (inflammation of the lining of the brain) occurs in 3-26% of cases. Symptoms may include headache and nuchal rigidity (being unable to bend the head forward). It may be acute or chronic.

Accumulation of granulomas in particular areas of the brain can lead to abnormalities in the function of that area. For instance, involvement of the internal capsule would lead to weakness in one or two limbs on one side of the body. If the granulomas are large, they can exert a mass effect and cause headache and increase the risk of seizures. Obstruction of the flow of cerebrospinal fluid, too, can cause headaches, visual symptoms (as mentioned above) and other features of raised intracranial pressure and hydrocephalus

Involvement of the spinal cord is rare, but can lead to abnormal sensation or weakness in one or more limbs, or cauda equina symptoms (incontinence to urine or stool, decreased sensation in the buttocks).

Granulomas in the pituitary gland, which produces numerous hormones, is rare but leads to any of the symptoms of hypopituitarism: amenorrhoea (cessation of the menstrual cycle), diabetes insipidus (dehydration due to inability to concentrate the urine), hypothyroidism (decreased activity of the thyroid) or hypocortisolism (deficiency of cortisol).

Affected individuals typically present with sudden painful proptosis, redness, and edema. Proptosis will vary according to the degree of inflammation, fibrosis, and mass effect. Occasionally, ptosis, chemosis, motility dysfunction (ophthalmoplegia), and optic neuropathy are seen. In the setting of extensive sclerosis there may be restriction, compression, and destruction of orbital tissue. Symptoms usually develop acutely (hours to days), but have also been seen to develop over several weeks or even months.Malaise, headaches, and nausea may accompany these symptoms. Other unusual presentations described include cystoid macular edema, temporal arteritis, and cluster headaches.

Pediatric IOI accounts for about 17% of cases idiopathic orbital inflammation. The most common sign is proptosis, but redness and pain are also experienced. Presentation varies slightly compared to adults with bilateral involvement, uveitis, disc edema and tissue eosinophilia being more common in this population. The presence of uveitis generally implies a poor outcome for pediatric IOI. Bilateral presentation may have a higher incidence of systemic disease.

The symptoms of cerebritis may range from mild to severe.

The severity of the symptoms varies based on the degree of swelling and on how elevated is the intracranial pressure. Mild symptoms include headaches, depression, anxiety and in some cases, memory loss. In some cases inflammation of brain can be seen if the brain or the nervous system is attacked as a result of problems with the immune system. The serious problems caused because of inflammation include headaches, seizures, vision problems, dizziness, behavior changes and even stroke.

Severe lupus cerebritis symptoms include psychosis, dementia, peripheral neuropathy, cerebellar ataxia (failure of muscular coordination, usually on one side of the body), and chorea (jerky, involuntary movements). Stroke incidence is 3-20% in systemic lupus patients, and is highest in the first five years of the disease. Peripheral neuropathy (carpal tunnel syndrome, for example) occurs in more than 20% of systemic lupus patients and cranial nerve palsies occur in 10-15%.

The involvement of the peripheral or central nervous system is relatively rare and only occurs in 3% of persons affected with RP, and is sometimes seen in a relation with concomitant vasculitis.

The most common neurological manifestation are palsies of the cranial nerves V and VII. Also hemiplegia, ataxia, myelitis and polyneuropathy have been reported in scientific literature.

Very rare neurological manifestations include aseptic meningitis, meningoencephalitis, stroke, focal or generalized seizures and intracranial aneurysm.

Magnetic Resonance Imaging of the brain shows multifocal areas of enhancement consistent with cerebral vasculitis in some cases.

Involvement of the eye is rarely the initial symptom but develops in 60% of persons with RP. The most common forms of ocular involvement are usually mild and often consist of unilateral or bilateral episcleritis and/or scleritis, that is often anterior and could be lingering or relapsing. Scleritis that is necrotizing is found to be exceedingly rare. Less often, conjunctivitis occurs.

There are also other ocular manifestations that occur in persons with RP, these include keratoconjunctivitis sicca, peripheral keratitis (rarely with ulcerations), anterior uveitis, retinal vasculitis, proptosis, lid edema, keratoconus, retinopathy, iridocyclitis and ischemic optic neuritis that can lead to blindness.

Cataract also is reported in relation to either the disease or to glucocorticoid exposure.

Idiopathic orbital inflammatory (IOI) disease, or orbital pseudotumor, refers to a marginated mass-like enhancing soft tissue involving any area of the orbit. It is the most common painful orbital mass in the adult population, and is associated with proptosis, cranial nerve (Tolosa–Hunt syndrome), uveitis, and retinal detachment. Idiopathic orbital inflammatory syndrome, also known as orbital pseudotumor, was first described by Gleason in 1903 and by Busse and Hochhmein. It was then characterized as a distinct entity in 1905 by Birch-Hirschfeld. It is a benign, nongranulomatous orbital inflammatory process characterized by extraocular orbital and adnexal inflammation with no known local or systemic cause. Its diagnosis is of exclusion once neoplasm, primary infection and systemic disorders have been ruled-out. Once diagnosed, it is characterized by its chronicity, anatomic location or histologic subtype.

Idiopathic orbital inflammation has a varied clinical presentation depending on the involved tissue. It can range from a diffuse inflammatory process to a more localized inflammation of muscle, lacrimal gland or orbital fat. Its former name, orbital pseudotumor, is derived due to resemblance to a neoplasm. However, histologically it is characterized by inflammation. Although a benign condition, it may present with an aggressive clinical course with severe vision loss and oculomotor dysfunction.

Initial signs are extremely variable, and diagnosis can be severely delayed due to the nonspecific nature of the symptoms. In general, rhinitis is the first sign in most people.

- Kidney: rapidly progressive glomerulonephritis (75%), leading to chronic kidney failure

- Upper airway, eye and ear disease:

- Nose: pain, stuffiness, nosebleeds, rhinitis, crusting, "saddle-nose" deformity due to a perforated septum

- Ears: conductive hearing loss due to auditory tube dysfunction, sensorineural hearing loss (unclear mechanism)

- Oral cavity: strawberry gingivitis, underlying bone destruction with loosening of teeth, non-specific ulcerations throughout oral mucosa

- Eyes: pseudotumours, scleritis, conjunctivitis, uveitis, episcleritis

- Trachea: subglottal stenosis

- Lungs: pulmonary nodules (referred to as "coin lesions"), infiltrates (often interpreted as pneumonia), cavitary lesions, pulmonary haemorrhage causing haemoptysis, and rarely bronchial stenosis.

- Arthritis: Pain or swelling (60%), often initially diagnosed as rheumatoid arthritis

- Skin: nodules on the elbow, purpura, various others (see "cutaneous vasculitis")

- Nervous system: occasionally sensory neuropathy (10%) and rarely mononeuritis multiplex

- Heart, gastrointestinal tract, brain, other organs: rarely affected.

The hallmark of polymyositis is weakness and/or loss of muscle mass in the proximal musculature, as well as flexion of the neck and torso. These symptoms can be associated with marked pain in these areas as well. The hip extensors are often severely affected, leading to particular difficulty in ascending stairs and rising from a seated position. The skin involvement of dermatomyositis is absent in polymyositis. Dysphagia (difficulty swallowing) or other problems with esophageal motility occur in as many as 1/3 of patients. Low grade fever and peripheral adenopathy may be present. Foot drop in one or both feet can be a symptom of advanced polymyositis and inclusion body myositis. The systemic involvement of polymyositis includes interstitial lung disease (ILD) and cardiac disease, such as heart failure and conduction abnormalities.

Polymyositis tends to become evident in adulthood, presenting with bilateral proximal muscle weakness often noted in the upper legs due to early fatigue while walking. Sometimes the weakness presents itself as an inability to rise from a seated position without help or an inability to raise one's arms above one's head. The weakness is generally progressive, accompanied by lymphocytic inflammation (mainly cytotoxic T cells).

Cerebritis is an infection of the brain that normally leads to the formation of an abscess within the brain itself. It is the inflammation of the cerebrum, a structure within the brain, which performs a number of important functions, including most of the things which people associate with being human, such as memory and speech. It is also defined as a purulent nonencapsulated parenchymal infection of brain which is characterized by nonspecific features on CT (ill-defined low density area with peripheral enhancement) and cannot reliably be distinguished from neoplasms.

Cerebritis usually occurs as a result of an underlying condition, which causes the inflammation of the brain tissue. It is commonly found in patients with lupus. Lupus cerebritis may occur in adults and children. The duration of the central nervous system involvement may vary from a few minutes, as in classic migraine or a transient ischemic attack, to years, as in dementia. Resulting neurological deficits may be transient or permanent, occasionally resulting in death.

The symptoms of CVID vary between people affected. Its main features are hypogammaglobulinemia and recurrent infections. Hypogammaglobulinemia manifests as a significant decrease in the levels of IgG antibodies, usually alongside IgA antibodies; IgM antibody levels are also decreased in about half of people. Infections are a direct result of the low antibody levels in the circulation, which do not adequately protect them against pathogens. The microorganisms that most frequently cause infections in CVID are bacteria Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus. Pathogens less often isolated from people include Neisseria meningitidis, Pseudomonas aeruginosa and Giardia lamblia. Infections mostly affect the respiratory tract (nose, sinuses, bronchi, lungs) and the ears; they can also occur at other sites, such as the eyes, skin and gastrointestinal tract. These infections respond to antibiotics but can recur upon discontinuation of antibiotics. Bronchiectasis can develop when severe, recurrent pulmonary infections are left untreated.

In addition to infections, people with CVID can develop complications. These include:

- autoimmune manifestations, e.g. pernicious anemia, autoimmune haemolytic anemia (AHA), idiopathic thrombocytopenic purpura (ITP), psoriasis, vitiligo, rheumatoid arthritis, primary hypothyroidism, atrophic gastritis. Autoimmunity is the main type of complication in people with CVID, appearing in some form in up to 50% of individuals;

- malignancies, particularly Non-Hodgkin's lymphoma and gastric carcinoma;

- enteropathy, which manifests with a blunting of intestinal villi and inflammation, and is usually accompanied by symptoms such as abdominal cramps, diarrhea, constipation and, in some cases, malabsorption and weight loss. Symptoms of CVID enteropathy are similar to those of celiac disease, but don't respond to a gluten-free diet. Infectious causes must be excluded before a diagnosis of enteropathy can be made, as people with CVID are more susceptible to intestinal infections, e.g. by Giardia lamblia;

- lymphocytic infiltration of tissues, which can cause enlargement of lymph nodes (lymphadenopathy), of the spleen (splenomegaly) and of the liver (hepatomegaly), as well as the formation of granulomas. In the lung this is known as Granulomatous–lymphocytic interstitial lung disease.

Anxiety and depression can occur as a result of dealing with the other symptoms.

People generally complain of severe fatigue.

Polymyositis and the associated inflammatory myopathies have an associated increased risk of malignancy. The features they found associated with an increased risk of cancer was older age, age greater than 45, male sex, dysphagia, cutaneous necrosis, cutaneous vasculitis, rapid onset of myositis (<4 weeks), elevated creatine kinase, higher erythrocyte sedimentation rate and higher C-reactive protein levels. Several factors were associated with lower-than-average risk, including the presence of ILD, arthritis/arthralgia, Raynaud's syndrome, or anti-Jo-1 antibody. The malignancies that are associated are nasopharyngeal cancer, lung cancer, non-Hodgkin's lymphoma and bladder cancer, amongst others.

Cardiac involvement manifests itself typically as heart failure, and is present in up to 77% of patients.

Interstitial lung disease is found in up to 65% of patients with polymyositis, as defined by HRCT or restrictive ventilatory defects compatible with ILD.

Initially red to pink, flat spots (formally, "macules") and raised bumps (formally, "papules") may be seen on the skin.

Once fully developed, the classic appearance is "non-blanching, palpable purpura". This appears as deep red to purple spots that feel raised to the touch. Purpura refers to the red-purple discolored spots, while palpable implies that these spots can be felt as raised from the surrounding skin. Additionally, when gently pressed, the color does not fade to a lighter color ("non-blanching"). The red-purple color of the lesions is due to the inflammation in the blood vessels causing red blood cells to escape into the dermis skin layer.

Small fluid-filled blisters (or "vesicles"), pus-filled bumps resembling a pimple (or "pustules"), or shallow ulcers may also develop but are less common.

The location of skin lesions varies but are most commonly found symmetrically below the waist, primarily on the buttocks and legs. Other distributions include localized areas on the upper body or over several areas of the body.

With treatment, the lesions typically resolve in weeks to months and leave behind flat spots that are darker than the surrounding skin. (see "Postinflammatory hyperpigmentation" on "Hyperpigmentation")

A portion of cases may be persistent or recurrent. This tends to occur when the vasculitis is associated with chronic conditions such as connective tissue diseases.

In most cases skin lesions do not cause symptoms, however itching, burning, or pain may occur.

Frequently reported symptoms include mild fever, muscle pain, joint pain, or an overall feeling of discomfort. Additional symptoms depend on the cause of the vasculitis and if other organ systems are involved. For example, if the vasculitis is a manifestation of Henoch-Schönlein purpura, individuals may also experience abdominal pain or blood in the urine.

Limited data from post mortems and nerve biopsy samples are consistent with a perivascular lymphocytic infiltration, i.e. an inflammatory aetiology.

Two or more of the following four criteria are required:

- Necrotizing ulcerating inflammation of nose, sinuses, mouth or pharynx

- Irregular lung infiltrates

- Nephritis

- Granulomatous vascular and perivascular inflammation

Starts with nonspecific symptoms such as:

- Localized joint pain

- Fever

- Fatigue

- Headaches

- Rashes

- Weight loss

- Diagnosis usually does not happen until the blockage causes deficient blood flow to the extremities or to a stroke.

Common variable immunodeficiency (CVID) is an immune disorder characterized by recurrent infections and low antibody levels, specifically in immunoglobulin (Ig) types IgG, IgM and IgA. Generally symptoms include high susceptibility to foreign invaders, chronic lung disease, and inflammation and infection of the gastrointestinal tract. However, symptoms vary greatly between people. CVID is a lifelong disease.

The cause of CVID is poorly understood. Deletions in genes that encode cell surface proteins and cytokine receptors, such as CD19, CD20, CD21, and CD80, is a likely cause. A deletion is a mutation in which part of the chromosome is lost during DNA replication which may include several genes, or as few as a single base pair. Additionally, the disease is defined by T cell defects, namely reduced proliferative capacity. The disease is hard to diagnose, taking on average 6–7 years after onset.

Treatment options are limited, and usually include lifelong immunoglobulin replacement therapy. This therapy is thought to help reduce bacterial infections. This treatment alone is not wholly effective, and many people still experience other symptoms like lung disease and noninfectious inflammatory symptoms.

CVID was first diagnosed over 60 years ago, and since has emerged as the predominant class of primary antibody deficiencies. CVID is formally diagnosed by levels of IgG and IgA more than two standard deviations from the norm, and no other cause for hypogammaglobulinemia, an abnormally low level of immunoglobulins in the blood. It is thought to affect between 1 in 25,000 to 1 in 50,000 people worldwide.

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.

The age of onset is almost always before 3 months of age. Many infants are born preterm (1/3 cases) and dysmature. The babies are frequently small for dates. The placenta may be abnormal with non-specific inflammation on histology. Umbilical cord anomalies have occasionally been reported. In severe cases, signs in the brain may be detected on prenatal ultrasound.

The presentation is pleiomorphic, making the diagnosis difficult, but the most common features of this disease involve the skin, joints, and central nervous system.

All have a maculopapular urticarial skin rash that is often present at birth (75% cases). It is probably more correctly described as an urticarial-like rash. The presence of the rash varies with time, and biopsy of these skin lesions shows a perivascular inflammatory infiltrate including granulocytes.

In about 35-65% of cases, arthritis occurs. Joint signs are variably expressed and can lead to transient swelling without sequelae between crises, or to unpredictable anomalies of growth cartilage and long bones epiphyses suggestive of a pseudo-tumour. Biopsies reveal hypertrophic cartilage without inflammatory cells. This most commonly affects the large joints (knees, ankles, elbows, and wrists) but may also involve the small joints of the hands and feet. It is usually bilateral and painful. A common and characteristic feature is giant kneecaps. Severe cases may result in contractures (joint deformities).

Most patients eventually have neurological problems. These manifest themselves in three principal ways: chronic meningitis, involvement of both the optic tract and eye, and sensorineural hearing loss. The chronic meningitis presents with the features of chronically raised intracranial pressure: headaches, vomiting, ventriculomegaly, hydrocephalus, macromegaly, cerebral atrophy, and optic atrophy. Some of these features may be evidenced on prenatal ultrasound. In 50% of cases, intellectual deficit occurs. Seizures occur in 25% of cases, but other manifestations are rare. Histological examination shows infiltration of the meninges with polymorphs.

Ocular manifestations occur in 80% of cases and include uveitis (70%), papillary involvement, conjunctivitis, and optical neuritis. If untreated, these may result in blindness (25%). The sensorineural hearing loss occurs in 75%, and tends to be progressive leading to deafness in 20% of cases.

Almost all children are remarkably short and have growth delay. Fever is extremely common but inconstant and is most often mild. Anemia is frequent. Other findings that have been reported include macrocephaly (95%), large fontanelle, prominent forehead, flattening of the nasal bridge (saddleback nose), short and thick extremities, and finger clubbing. The liver and/or spleen may be enlarged. Lymph node enlargement may also be present.

Later in life, secondary amyloidosis may occur. Delayed puberty and secondary amenorrhoea are not uncommon. Hoarseness due to inflammation of the laryngeal cartilage has also been reported.

Histology of the affected area commonly shows dense perivascular lymphocytic infiltration with reticulated degeneration of the epidermis. A study by Iwatsuki et al. detected Epstein-Barr virus (EBV) positive T-cells in the perivascular infiltration on biopsy in 28/29 patients tested. Antibody titers to EBV were measured in 14 of these patients and only five had abnormal antibody patterns consistent with chronic active EBV infection.

Hydroa vacciniforme (HV) is a very rare, chronic photodermatitis-type skin condition with usual onset in childhood. It was first described in 1862 by Bazin. It is sometimes called "Bazin's hydroa vacciniforme". A study published in Scotland in 2000 reviewed the cases of 17 patients and estimated a prevalence of 0.34 cases per 100,000 population. In this study they reported an average age of onset of 7.9 years. Frequently the rash first appeared in the spring or summer months and involved sun-exposed skin. The rash starts as a vesicular eruption, later becoming umbilicated, and resulted in vacciniform scarring. It is most frequently found on the nose, cheeks, ears, dorsum of the hand, and arms (places that are most exposed to light).

In the classical sense, acute graft-versus-host-disease is characterized by selective damage to the liver, skin (rash), mucosa, and the gastrointestinal tract. Newer research indicates that other graft-versus-host-disease target organs include the immune system (the hematopoietic system, e.g., the bone marrow and the thymus) itself, and the lungs in the form of immune-mediated pneumonitis. Biomarkers can be used to identify specific causes of GvHD, such as elafin in the skin. Chronic graft-versus-host-disease also attacks the above organs, but over its long-term course can also cause damage to the connective tissue and exocrine glands.

Acute GvHD of the GI tract can result in severe intestinal inflammation, sloughing of the mucosal membrane, severe diarrhea, abdominal pain, nausea, and vomiting. This is typically diagnosed via intestinal biopsy. Liver GvHD is measured by the bilirubin level in acute patients. Skin GvHD results in a diffuse red maculopapular rash, sometimes in a lacy pattern.

Mucosal damage to the vagina can result in severe pain and scarring, and appears in both acute and chronic GvHD. This can result in an inability to have sexual intercourse.

Acute GvHD is staged as follows: overall grade (skin-liver-gut) with each organ staged individually from a low of 1 to a high of 4. Patients with grade IV GvHD usually have a poor prognosis. If the GvHD is severe and requires intense immunosuppression involving steroids and additional agents to get under control, the patient may develop severe infections as a result of the immunosuppression and may die of infection.

In the oral cavity, chronic graft-versus-host-disease manifests as lichen planus with a higher risk of malignant transformation to oral squamous cell carcinoma in comparison to the classical oral lichen planus. Graft-versus-host-disease-associated oral cancer may have more aggressive behavior with poorer prognosis, when compared to oral cancer in non-hematopoietic stem cell transplantation patients.

Symptoms of BNS gradually progress over the span of a week or even a month, and there is typically a delay in diagnosis after the initial symptoms arise. Although BNS arises due to complications from WM, some individuals may experience symptoms of BNS without having a past history of WM.

Given that BNS is so rare, the symptoms are diverse and nonspecific. Symptoms range in severity from nausea to seizures and are characterized by how they interfere with the function of the CNS. Where certain symptoms are present depends on which branch of the CNS is being affected by plasma B-cells. People diagnosed with BNS experience some sensory symptoms as well. Some sensory symptoms include a pin and needles sensation experienced in the lower limbs, the hands, and in the arms, along with pain and extreme numbness.

Diagnosis of gluten-sensitive neuropathies without a clear cause is on the rise. These "idiopathic" neuropathies were first identified by screening for anti-gliadin IgG (AGA). The criteria have been critiqued because of the large misdiagnosis rate of coeliac disease (CD), and because AGA exists in the normal population at over 12%, far more abundant than cases of neuropathy. The problem in diagnosis arises because there are precursor states prior to coeliac disease. These are called coeliac disease and early gluten-sensitive enteropathy and are defined as Marsh grade 1 and 2 coeliac disease. Coeliac disease was diagnosed by duodenal biopsy, often misinterpreted as negative as high as grade 3 on the Marsh scale. Anti-gliadin antibodies may precede or lag the appearance of coeliac disease. Studies in Scandinavia found an increase of pathologies as much as 10 years before coeliac disease. These included gastrointestinal symptoms, anemia or other autoimmune disease. In addition IgG and IgA responses sometimes accompany allergic responses to proteins. Gliadin is exceptional in that it has several proteins which remain peptides of considerable length after digestion, and migrate into systemic circulation.

A subset of people with idiopathic neuropathies have only anti-gliadin antibodies but none of the other enteropathic criteria. About 1/3 have no DQ2 or DQ8 and an apparent abundance of HLA-DQ1. One percent of coeliacs in Europe have no DQ2 and DQ8 but have DQ1. The DQ1 serotype is very common in the normal population, over 65% of Americans have one copy, therefore the linkage is speculative.