MRI: medial temporal lobe signal change bilateral hippocampal lesions, with signals that were hypointense in IR sequences and hyperintense in FLAIR.

Variable following immunotherapy with partial to excellent recovery.

Chronic sequelae due to hippocampal sclerosis and chronic epilepsy is also reported.

Clinical signs and symptoms of complement-mediated TMA can include abdominal pain, confusion, fatigue, edema (swelling), nausea/vomiting and diarrhea. aHUS often presents with malaise and fatigue, as well as microangiopathic anemia. However, severe abdominal pain and bloody diarrhea are unusual. Laboratory tests may also reveal low levels of platelets (cells in the blood that aid in clotting), elevated lactate dehydrogenase (LDH, a chemical released from damaged cells, and which is therefore a marker of cellular damage), decreased haptoglobin (indicative of the breakdown of red blood cells), anemia (low red blood cell count)/schistocytes (damaged red blood cells), elevated creatinine (indicative of kidney dysfunction), and proteinuria (indicative of kidney injury). Patients with aHUS often present with an abrupt onset of systemic signs and symptoms such as acute kidney failure, hypertension (high blood pressure), myocardial infarction (heart attack), stroke, lung complications, pancreatitis (inflammation of the pancreas), liver necrosis (death of liver cells or tissue), encephalopathy (brain dysfunction), seizure, or coma. Failure of neurologic, cardiac, kidney, and gastrointestinal (GI) organs, as well as death, can occur unpredictably at any time, either very quickly or following prolonged symptomatic or asymptomatic disease progression. For example, approximately 1 in 6 patients with aHUS initially will present with proteinuria or hematuria without acute kidney failure. Patients who survive the presenting signs and symptoms endure a chronic thrombotic and inflammatory state, which puts many of them at lifelong elevated risk of sudden blood clotting, kidney failure, other severe complications and premature death.

The main symptoms of Devic's disease are loss of vision and spinal cord function. Optic neuritis may manifest as visual impairment with decreased visual acuity, although visual field defects, or loss of color vision may occur in isolation or prior to formal loss of acuity. Spinal cord dysfunction can lead to muscle weakness, reduced sensation, or loss of bladder and bowel control. The typical patient has an acute and severe spastic weakness of the legs (paraparesis) or all four limbs (quadriparesis) with sensory signs, often accompanied by loss of bladder control.

Activated protein C resistance (APCR) is a hemostatic disorder characterized by a poor anticoagulant response to activated protein C (APC). This results in an increased risk of venous thrombosis, which can cause problems with circulation, such as pulmonary embolism.

The disorder can be acquired or inherited, the hereditary form having an autosomal dominant inheritance pattern.

An estimated 64 percent of patients with venous thromboembolism may have activated protein C resistance.

The signs and symptoms of DOCK8 deficiency are similar to the autosomal dominant form, STAT3 deficiency. However, in DOCK8 deficiency, there is no skeletal or connective tissue involvement, and affected individuals do not have the characteristic facial features of those with autosomal dominant hyper-IgE syndrome. DOCK8 deficient children often have eczema, respiratory and skin staphylococcus infections.

Beyond these, many other recurrent infections have been observed, including recurrent fungal infections and recurrent viral infections (including molluscum contagiosum, herpes simplex, and herpes zoster), recurrent upper respiratory infection (including "Streptococcus pneumoniae", "Haemophilus influenzae", respiratory syncytial virus, and adenovirus), recurrent sinusitis, recurrent otitis media, mastoiditis, pneumonia, bronchitis with bronchiectasis, osteomyelitis, candidiasis, meningitis (caused by cryptococcus or H. influenzae), pericarditis, salmonella enteritis, and giardiasis. Other dermatologic problems include squamous-cell carcinoma/dysplasia (vulvar, anal, and facial). Immune problems are also common, including autoimmune hemolytic anemia, severe allergies (both food and environmental), asthma, and reactive airway disease. The nervous system may also be affected; observed conditions in DOCK8 deficient people include hemiplegia, ischemic stroke, subarachnoid hemorrhage, and facial paralysis. Vascular complications are common, including aortic aneurysm, cerebral aneurysm, vessel occlusion and underperfusion, and leukocytoclastic vasculitis.

Neuromyelitis optica (NMO), also known as Devic's disease or Devic's syndrome, is a heterogeneous condition consisting of the simultaneous inflammation and demyelination of the optic nerve (optic neuritis) and the spinal cord (myelitis). It can be monophasic or recurrent.

Currently at least two different causes are proposed based on the presence of autoantibodies against AQP4. AQP4+ NMO is currently considered an autoimmune disease (autoimmune astrocytopathy, or autoimmune astrocytic channelopathy) in which a person's own immune system attacks the astrocytes of the optic nerves and spinal cord. The cause of the AQP4− variants is unknown.

Although inflammation may also affect the brain, the lesions are different from those observed in the related condition, multiple sclerosis. Spinal cord lesions lead to varying degrees of weakness or paralysis in the legs or arms, loss of sensation (including blindness), and/or bladder and bowel dysfunction.

Devic's disease is now studied along a collection of similar diseases called "Neuromyelitis optica spectrum diseases". Some cases of this spectrum resemble multiple sclerosis (MS) in several ways, but require a different course of treatment for optimal results.

In 2004, NMO-IgG (currently known as Anti-AQP IgG) was first described leading to the distinction between positive and negative cases.

In Anti-AQP positive variants, CNS astrocytes, which are the basis for the glymphatic system are the target of the autoimmune attack. NMO-IgG-negative cases are less understood. It seems currently that astrocytes are spared in these IgG negative cases.

EE is rarely symptomatic and is considered a subclinical condition. However, adults may have mild symptoms or malabsorption such as altered stool consistency, increased stool frequency and weight loss.

The characteristic symptom of Degos disease is the development of papules. Initially, individuals may have skin lesions or rashes, but they will proceed to develop distinct bumps, or papules. Papules are circular in shape, have a porcelain-white center and red border. As papules age, the white centers will skin in and only the border will remain raised. Typically, papules range from 0.5 to 1 cm in width. Papules appear on the trunk and upper extremities and are not found on the individual's palms, soles, scalp, or face.

Depending on whether an individual has the benign variant or malignant variant of the disease symptoms will vary. Both the benign and malignant forms have development of the characteristic papules. Individuals with the benign form will have the typical papules persisting anywhere from a few years to throughout their whole lives. In the benign form, no inner organs are affected. If an individual develops the malignant form, it means that not only are the papules present, but inner organs are involved. Most malignant cases involve problems of the gastrointestinal tract leading to small intestine lesions, abdominal pain, diarrhea, and bowel perforation. If the central nervous system is involved, symptoms can include headaches, dizziness, seizures, paralysis of cranial nerves, weakness, stroke, damage to small areas of the brain due to artery blockage (cerebral infarcts, and cerebral hemorrhage). Additional organs commonly impacted include the heart, lungs, and kidneys. Symptoms that may develop from damage to these organs include double vision (diploplia), clouding of lenses of eyes, swelling of the optic disc (papilledema), partial loss of vision, shortness of breath, chest pain, epilepsy,and thickening of pericardium.

Someone with the benign form may suddenly develop symptoms of the malignant form. Symptoms can last anywhere from a few weeks to several years. Onset of symptoms typically begins to manifest between the ages of 20-50. A few cases of this condition in newborns have also been described.

Prenatal stress (or prenatal maternal stress) is exposure of an expectant mother to stress, which can be caused by stressful life events or by environmental hardships. The resulting changes to the mother's hormonal and immune system may harm the fetus's (and after birth, the infant's) immune function and brain development.

Prenatal stress is shown to have several affects in fetal brain development. In the hippocampus of adult male rats, prenatal stress has shown to decrease the rate of proliferation and cell death in the hypothalamus-pituitary axis. Prenatal stressed animals have prolonged corticosterone response. Removing the adrenal glands of the mother eliminates the effect of the pup's corticosterone response. Supplementing the adrenalectamized mother with corticosterone, rescued the hypothalamic-pituitary-axis response to maternal stress for prenatally stressed offspring. Prenatal stress caused high glucocorticoids, which in turn affects the hypothalamic-pituitary-axis negative feedback.

A study by García-Cáceres et al. showed that prenatal stress decreases cell turnover and proliferation in the hypothalamus of adult rats, which reduces structural plasticity and reduces the response to stress in adulthood. This study also showed that when prenatally stressed rats were stressed in adulthood the females showed an increase in corticotropin-releasing hormone suggesting it to be an up-regulation in the hypothalamic-pituitary adrenal axis. Males showed no elevation of corticosterone levels. Increase in adrenocorticotropic hormone with no effect of adult stress and a decrease in the corticotropin-releasing hormone mRNA in the hypothalamus showed a down-regulation. The author concludes that this makes prenatally stressed females less reactive to later life stressors than males.

The current gold standard diagnostic test for EE is intestinal biopsy and histological analysis. Histological changes observed include:

- Villous blunting

- Crypt hypertrophy

- Villous fusion

- Mucosal inflammation

However, this procedure is considered too invasive, complex and expensive to be implemented as standard of care. As a result, there are various research efforts underway to identify biomarkers associated with EE, which could serve as less invasive, yet representative, tools to screen for and identify EE from stool samples.

In an effort to identify simple, accurate diagnostic tests for EE, the Bill and Melinda Gates Foundation (BMGF) has established an EE biomarkers consortium as part of their Global Grand Challenges initiative (specifically, the Discover Biomarkers of Gut Function challenge).

So far, various biomarkers have been selected and studied based on the current understanding of EE pathophysiology:

- Gut permeability/barrier function

- Dual sugar permeability (lactose-to-mannitol ratio)

- Intestinal inflammation

- Alpha-1 anti-trypsin

- Neopterin

- Myeloperoxidase

- Exocrine (hormonal) markers

- Bacterial translocation markers

- Endotoxin core antibody

- Markers of systemic inflammation

- Alpha-1 glycoprotein

- C-reactive protein (CRP)

It is postulated that the limited of understanding of EE is partially due to the paucity of reliable biomarkers, making it difficult for researchers to track the epidemiology of the condition and assess the efficacy of interventions.

The most distinctive clinical feature is the absence of overflow tears with emotional crying after age 7 months. This symptom can manifest less dramatically as persistent bilateral eye irritation. There is also a high prevalence of breech presentation. Other symptoms include weak or absent suck and poor tone, poor suck and misdirected swallowing, and red blotching of skin.

Symptoms in an older child with familial dysautonomia might include:

1. Delayed speech and walking

2. Unsteady gait

3. Spinal curvature

4. Corneal abrasion

5. Less perception in pain or temperature with nervous system.

6. Poor growth

7. Erratic or unstable blood pressure.

8. Red puffy hands

9. Dysautonomia crisis: a constellation of symptoms in response to physical and emotional stress; usually accompanied by vomiting, increased heart rate, increase in blood pressure, sweating, drooling, blotching of the skin and a negative change in personality.

Atypical hemolytic uremic syndrome (aHUS) is an extremely rare, life-threatening, progressive disease that frequently has a genetic component. In most cases it is caused by chronic, uncontrolled activation of the complement system, a branch of the body’s immune system that destroys and removes foreign particles. The disease affects both children and adults and is characterized by systemic thrombotic microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body, which can lead to stroke, heart attack, kidney failure, and death. The complement system activation may be due to mutations in the complement regulatory proteins (factor H, factor I, or membrane cofactor protein), or is occasionally due to acquired neutralizing autoantibody inhibitors of these complement system components, for example anti–factor H antibodies. Despite the use of supportive care, historically an estimated 33–40% of patients died or developed end-stage renal disease (ESRD) with the first clinical bout of aHUS. Including subsequent relapses, a total of approximately two-thirds (65%) of patients died, required dialysis, or had permanent renal damage within the first year after diagnosis despite plasma exchange or plasma infusion (PE/PI).

Children with DOCK8 deficiency do not tend to live long; sepsis is a common cause of death at a young age. CNS and vascular complications are other common causes of death.

Blau Syndrome is an autosomal dominant genetic inflammatory disorder which affects the skin, eyes, and joints. It is caused by a mutation in the NOD2 (CARD15) gene. Symptoms usually begin before the age of 4, and the disease manifests as early onset cutaneous sarcoidosis, granulomatous arthritis, and uveitis.

Clinical evaluation and identification of characteristics papules may allow a dermatologist to diagnose Degos disease. The papules have a white center and are bordered with a red ring. After lesions begin to appear, the diagnosis for Degos disease can be supported by histological findings. Most cases will show a wedge-shaped connective tissue necoris in the deep corium. This shape is due to the blockage/occlusion of small arteries.

Individuals may be diagnosed with the benign form if only the papules are present. However, an individual may be diagnosed with the malignant form if involvement of other organs like the lungs, intestine and/or central nervous system occurs. The malignant, or systematic form of this condition may suddenly develop even after having papules present for several years. In order to quickly diagnose this shift to the malignant variant of the disease, it is important for individuals to have consistent follow-up evaluations.In these evaluations, depending on which organs are suspected to be involved, the following procedures and tests may be conducted: skin inspection, brain magnetic resonance tomography, colonoscopy, chest X-ray, and/or abdominal ultrasound.

Familial dysautonomia (FD), sometimes called Riley–Day syndrome and hereditary sensory and autonomic neuropathy type III (HSAN-III), is a disorder of the autonomic nervous system which affects the development and survival of sensory, sympathetic and some parasympathetic neurons in the autonomic and sensory nervous system resulting in variable symptoms, including insensitivity to pain, inability to produce tears, poor growth, and labile blood pressure (episodic hypertension and postural hypotension). People with FD have frequent vomiting crises, pneumonia, problems with speech and movement, difficulty swallowing, inappropriate perception of heat, pain, and taste, as well as unstable blood pressure and gastrointestinal dysmotility. FD does not affect intelligence. Originally reported by Drs. Conrad Milton Riley (1913–2005) and Richard Lawrence Day (1905–1989) in 1949, FD is one example of a group of disorders known as hereditary sensory and autonomic neuropathies (HSAN). All HSAN are characterized by widespread sensory dysfunction and variable autonomic dysfunction caused by incomplete development of sensory and autonomic neurons. The disorders are believed to be genetically distinct from each other.

Kyrle disease symptoms are chronic and have an onset during adulthood between the ages of 30 and 50 years of age. However, there were reported cases of early onset as early as 5 years of age and late onset as late as 75 years of age. The main symptom is the development of small papules into painless lesions that are surrounded by silvery scales. The lesions are painless, however, there is a chance that the patient may experience extreme urges to itch them. In time, these lesions grow up to a radius of 0.75 inch and develop into red-brown nodules with a central plug of keratin. As more lesions develop, they can come together and form larger keratotic plaques. These lesions are usually observed on the lower extremities, however, can also develop on the upper extremities, such as, the arms, the head and the neck. The only parts of the body that Kyrle disease do not form are the palms, soles, and mucous membranes. Lesions may heal spontaneously without treatment, however, new ones will develop in its place.

Other symptoms that may be observed:

- Hyperkeratotic cone-shaped papular plugs

- Hyperkeratotic verrucous plaques

- Diabetes mellitus

- Hepatic insufficiency

- Presence of albumin in the urine

- Excess sugar in the urine

The defining symptoms of fibromyalgia are chronic widespread pain, fatigue, sleep disturbance, and heightened pain in response to tactile pressure (allodynia). Other symptoms may include tingling of the skin (paresthesias), prolonged muscle spasms, weakness in the limbs, nerve pain, muscle twitching, palpitations, and functional bowel disturbances.

Many people experience cognitive dysfunction (known as "fibrofog"), which may be characterized by impaired concentration, problems with short and long-term memory, short-term memory consolidation, impaired speed of performance, inability to multi-task, cognitive overload, and diminished attention span. Fibromyalgia is often associated with anxiety and depressive symptoms.

Other symptoms often attributed to fibromyalgia that may be due to a comorbid disorder include myofascial pain syndrome, also referred to as chronic myofascial pain, diffuse non-dermatomal paresthesias, functional bowel disturbances and irritable bowel syndrome, genitourinary symptoms and interstitial cystitis, dermatological disorders, headaches, myoclonic twitches, and symptomatic hypoglycemia. Although fibromyalgia is classified based on the presence of chronic widespread pain, pain may also be localized in areas such as the shoulders, neck, low back, hips, or other areas. Many sufferers also experience varying degrees of myofascial pain and have high rates of comorbid temporomandibular joint dysfunction. 20–30% of people with rheumatoid arthritis and systemic lupus erythematosus may also have fibromyalgia.

Fibromyalgia is classed as a disorder of pain processing due to abnormalities in how pain signals are processed in the central nervous system. The American College of Rheumatology classifies fibromyalgia as being a functional somatic syndrome. The expert committee of the European League Against Rheumatism classifies fibromyalgia as a neurobiological disorder and as a result exclusively give pharmacotherapy their highest level of support. The International Classification of Diseases (ICD-10) lists fibromyalgia as a diagnosable disease under "Diseases of the musculoskeletal system and connective tissue," under the code M79-7, and states that fibromyalgia syndrome should be classified as a functional somatic syndrome rather than a mental disorder. Although mental disorders and some physical disorders commonly are co-morbid with fibromyalgia – especially anxiety, depression, irritable bowel syndrome, and chronic fatigue syndrome – the ICD states that these should be diagnosed separately.

Differences in psychological and autonomic nervous system profiles among affected individuals may indicate the existence of fibromyalgia subtypes. A 2007 review divides individuals with fibromyalgia into four groups as well as "mixed types":

1. "extreme sensitivity to pain but no associated psychiatric conditions" (may respond to medications that block the 5-HT3 receptor)

2. "fibromyalgia and comorbid, pain-related depression" (may respond to antidepressants)

3. "depression with concomitant fibromyalgia syndrome" (may respond to antidepressants)

4. "fibromyalgia due to somatization" (may respond to psychotherapy)

Human exposure to bioaerosols has been documented to give rise to a variety of adverse health effects. Building occupants complain of symptoms such as sensory irritation of the eyes, nose, or throat; neurotoxic or general health problems; skin irritation; nonspecific hypersensitivity reactions; infectious diseases; and odor and taste sensations. Exposure to poor lighting conditions has led to general malaise.

Extrinsic allergic alveolitis has been associated with the presence of fungi and bacteria in the moist air of residential houses and commercial offices. A very large 2017 Swedish study correlated several inflammatory diseases of the respiration tract with objective evidence of damp-caused damage in homes.

The WHO has classified the reported symptoms into broad categories, including: mucous membrane irritation (eye, nose, and throat irritation), neurotoxic effects (headaches, fatigue, and irritability), asthma and asthma-like symptoms (chest tightness and wheezing), skin dryness and irritation, gastrointestinal complaints and more.

Several sick occupants may report individual symptoms which do not appear to be connected. The key to discovery is the increased incidence of illnesses in general with onset or exacerbation within a fairly close time frame—usually within a period of weeks. In most cases, SBS symptoms will be relieved soon after the occupants leave the particular room or zone. However, there can be lingering effects of various neurotoxins, which may not clear up when the occupant leaves the building. In some cases—particularly in sensitive individuals—there can be long-term health effects.

STEC-HUS occurs after ingestion of a strain of bacteria expressing Shiga toxin(s), usually types of "E. coli", that expresses verotoxin (also called Shiga-like toxin). "E. coli" can produce stx1 and/or stx2 Shiga toxins, the latter being more dangerous and a combination of both toxins in certain ratios is usually associated with HUS. These Shiga toxins bind GB3 receptors, globotriaosylceramide, which are present in renal tissue more than any other tissue and are also found in central nervous system neurons and other tissue. Children have more GB3 receptors than adults which may be why children are more susceptible to HUS. Cattle, swine, deer, and other mammals do not have GB3 receptors, but can be asymptomatic carriers of Shiga toxin-producing bacteria. Some humans can also be asymptomatic carriers. Once the bacteria colonizes, diarrhea followed by bloody diarrhea, hemorrhagic colitis, typically follows. HUS develops about 5–10 days after onset of diarrhea, with decreased urine output (oliguria), blood in the urine (hematuria), kidney failure, thrombocytopenia (low levels of platelets) and destruction of red blood cells (microangiopathic hemolytic anemia). Hypertension is common. In some cases, there are prominent neurologic changes.

Patients with HUS commonly exhibit the signs and symptoms of thrombotic microangiopathy (TMA), which can include abdominal pain, low platelet count, elevated lactate dehydrogenase LDH, a chemical released from damaged cells, and which is therefore a marker of cellular damage) decreased haptoglobin (indicative of the breakdown of red blood cells) anemia (low red blood cell count)/schistocytes (damaged red blood cells), elevated creatinine (a protein waste product generated by muscle metabolism and eliminated renally, proteinuria (indicative of kidney injury), confusion, fatigue, edema (swelling), nausea/vomiting, and diarrhea. Additionally, patients with aHUS typically present with an abrupt onset of systemic signs and symptoms such as acute kidney failure, hypertension (high blood pressure), myocardial infarction (heart attack), stroke, lung complications, pancreatitis (inflammation of the pancreas), liver necrosis (death of liver cells or tissue), encephalopathy (brain dysfunction), seizure, and coma. Failure of neurologic, cardiac, renal, and gastrointestinal (GI) organs, as well as death, can occur unpredictably at any time, either very quickly or following prolonged symptomatic or asymptomatic disease progression.

Sick building syndrome (SBS) is a medical condition where people in a building suffer from symptoms of illness or feel unwell for no apparent reason. The symptoms tend to increase in severity with the time people spend in the building, and improve over time or even disappear when people are away from the building. The main identifying observation is an increased incidence of complaints of symptoms such as headache, eye, nose, and throat irritation, fatigue, and dizziness and nausea. These symptoms appear to be linked to time spent in a building, though no specific illness or cause can be identified. SBS is also used interchangeably with "building-related symptoms", which orients the name of the condition around patients rather than a "sick" building. A 1984 World Health Organization (WHO) report suggested up to 30% of new and remodeled buildings worldwide may be subject of complaints related to poor indoor air quality.

Sick building causes are frequently pinned down to flaws in the heating, ventilation, and air conditioning (HVAC) systems. However, there have been inconsistent findings on whether air conditioning systems result in SBS or not. Other causes have been attributed to contaminants produced by outgassing of some types of building materials, volatile organic compounds (VOC), molds (see mold health issues), improper exhaust ventilation of ozone (byproduct of some office machinery), light industrial chemicals used within, or lack of adequate fresh-air intake/air filtration (see Minimum efficiency reporting value).

Kyrle disease or hyperkeratosis follicularis et parafollicularis in cutem penetrans is identified as a form of an acquired perforating disease. Other major perforating diseases are elastosis perforans serpiginosa and reactive perforating collagenosis. Recently, however, there is a controversy on categorizing Kyrle disease with perforating dermatosis or a subtype of acquired perforating collagenosis.

Kyrle disease was first described by Josef Kyrle in 1916 when a diabetic woman presented generalized hyperkeratotic nodules. The disease is distinguished by large papules with central keratin plus on the skin, usually on the legs of the patient and is often in conjunction with hepatic, renal or diabetic disorders. It can affect both females and males with a 6:1 ratio. The papules usually show up on the patient with an average age of 30 years. Kyrle disease is a rare disease unless there is a high count of patients with chronic renal failure. The disease seems to be more prevalent in African Americans, which can be correlated to the high incidence of diabetes mellitus and renal failure in the population.