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.

Graft-versus-host disease (GvHD) is a medical complication following the receipt of transplanted tissue from a genetically different person. GvHD is commonly associated with stem cell transplant (bone marrow transplant), but the term also applies to other forms of tissue graft. Immune cells (white blood cells) in the donated tissue (the graft) recognize the recipient (the host) as foreign (nonself). The transplanted immune cells then attack the host's body cells. GvHD can also occur after a blood transfusion if the blood products used have not been irradiated or treated with an approved pathogen reduction system.

Whereas transplant rejection occurs when the host rejects the graft, GvHD occurs when the graft rejects the host. The underlying principle (alloimmunity) is the same, but the details and course may differ.

Patients with TAMA present with variable combinations of a morbilliform skin eruption, chronic diarrhea, and abnormal liver enzymes. The histopathology of the skin, liver, or bowel mucosa resembles GVHD.

The precise symptoms of a primary immunodeficiency depend on the type of defect. Generally, the symptoms and signs that lead to the diagnosis of an immunodeficiency include recurrent or persistent infections or developmental delay as a result of infection. Particular organ problems (e.g. diseases involving the skin, heart, facial development and skeletal system) may be present in certain conditions. Others predispose to autoimmune disease, where the immune system attacks the body's own tissues, or tumours (sometimes specific forms of cancer, such as lymphoma). The nature of the infections, as well as the additional features, may provide clues as to the exact nature of the immune defect.

Thymoma-associated multiorgan autoimmunity (TAMA) is a severe often fatal disease that presents in some patients with thymoma. It has also been referred to in the medical literature as "thymoma-associated graft-versus-host-like disease".

The symptoms are very similar to graft-versus-host disease (GVHD). This is because the patients have some T cells with limited levels of recombination with the mutant RAG genes. These T cells are abnormal and have a very specific affinity for self antigens found in the thymus and in the periphery. Therefore, these T cells are auto-reactive and cause the GVHD phenotype.

A characteristic symptom is chronic inflammation of the skin, which appears as a red rash (early onset erythroderma). Other symptoms include eosinophilia, failure to thrive, swollen lymph nodes, swollen spleen, diarrhea, enlarged liver, low immunoglobulin levels (except immunoglobulin E, which is elevated), low T cell levels, and no B cells.

Primary immunodeficiencies are disorders in which part of the body's immune system is missing or does not function normally. To be considered a "primary" immunodeficiency, the cause of the immune deficiency must not be secondary in nature (i.e., caused by other disease, drug treatment, or environmental exposure to toxins). Most primary immunodeficiencies are genetic disorders; the majority are diagnosed in children under the age of one, although milder forms may not be recognized until adulthood. While there are over 100 recognized PIDs, most are very rare. About 1 in 500 people in the United States are born with a primary immunodeficiency. Immune deficiencies can result in persistent or recurring infections, autoinflammatory disorders, tumors, and disorders of various organs. There are currently no cures for these conditions; treatment is palliative and consists of managing infections and boosting the immune system.

Persons afflicted with X-SCID often have infections very early in life, before three months of age. This occurs due to the decreased amount of immunoglobulin G (IgG) levels in the infant during the three-month stage. This is followed by viral infections such as pneumonitis, an inflammation of the lung which produces common symptoms such as cough, fever, chills, and shortness of breath. A telltale sign of X-SCID is candidiasis, a type of fungal infection caused by "Candida albicans". Candidiasis involves moist areas of the body such as skin, the mouth, respiratory tract, and vagina; symptoms of oral candidiasis include difficulty in swallowing, pain on swallowing and oral lesions. Recurrent eczema-like rashes are also a common symptom. Other common infections experienced by individuals with X-SCID include diarrhea, sepsis, and otitis media. Some other common symptoms that are experienced by X-SCID patients include failure to thrive, gut problems, skin problems, and muscle hypotonia.

In some patients symptoms may not appear for the first six months after birth. This is likely due to passive immunity received from the mother in order to protect the baby from infections until the newborn is able to make its own antibodies. As a result, there can be a silent period where the baby displays no symptoms of X-SCID followed by the development of frequent infections.

This syndrome shows a wide range of abnormalities and symptoms. The main characteristics of the syndrome are exocrine pancreatic dysfunction, hematologic abnormalities and growth retardation. Only the first two of these are included in the clinical diagnostic criteria.

- Hematologic abnormalities: Neutropenia may be intermittent or persistent and is the most common hematological finding. Low neutrophil counts leave patients at risk of developing severe recurrent infections that may be life-threatening. Anemia (low red blood cell counts) and thrombocytopenia (low platelet counts) may also occur. Bone marrow is typically hypocellular, with maturation arrest in the myeloid lineages that give rise to neutrophils, macrophages, platelets and red blood cells. Patients may also develop progressive marrow failure or transform to acute myelogenous leukemia.

- Exocrine pancreatic dysfunction: Pancreatic exocrine insufficiency arises due to a lack of acinar cells that produce digestive enzymes. These are extensively depleted and replaced by fat. A lack of pancreatic digestive enzymes leaves patients unable to digest and absorb fat. However, pancreatic status may improve with age in some patients.

- Growth retardation: More than 50% of patients are below the third percentile for height, and short stature appears to be unrelated to nutritional status. Other skeletal abnormalities include metaphyseal dysostosis (45% of patients), thoracic dystrophy (rib cage abnormalities in 46% of patients), and costochondral thickening (shortened ribs with flared ends in 32% of patients). Skeletal problems are one of the most variable components of SDS, with 50% affected siblings from the same family discordant for clinical presentation or type of abnormality. Despite this, a careful review of radiographs from 15 patients indicated that all of them had at least one skeletal anomaly, though many were subclinical.

- Other features include metaphysial dysostosis, mild hepatic dysfunction, increased frequency of infections.

Omenn syndrome is an autosomal recessive severe combined immunodeficiency associated with hypomorphic missense mutations in immunologically relevant genes of T-cells (and B-cells) such as recombination activating genes (RAG1 and RAG2), IL-7 Receptor α gene (IL7Rα), DCLRE1C-Artemis, RMRP-CHH, DNA-Ligase IV, common gamma chain, WHN-FOXN1, ZAP-70 and complete DiGeorge anomaly (DiGeorge Syndrome; CHARGE).

Severe combined immunodeficiency, SCID, also known as alymphocytosis, Glanzmann–Riniker syndrome, severe mixed immunodeficiency syndrome, and thymic alymphoplasia, is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in heterogeneous clinical presentations. SCID involves defective antibody response due to either direct involvement with B lymphocytes or through improper B lymphocyte activation due to non-functional T-helper cells. Consequently, both "arms" (B cells and T cells) of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is the most severe form of primary immunodeficiencies, and there are now at least nine different known genes in which mutations lead to a form of SCID. It is also known as the bubble boy disease and bubble baby disease because its victims are extremely vulnerable to infectious diseases and some of them, such as David Vetter, have become famous for living in a sterile environment. SCID is the result of an immune system so highly compromised that it is considered almost absent.

SCID patients are usually affected by severe bacterial, viral, or fungal infections early in life and often present with interstitial lung disease, chronic diarrhoea, and failure to thrive. Ear infections, recurrent "Pneumocystis jirovecii" (previously carinii) pneumonia, and profuse oral candidiasis commonly occur. These babies, if untreated, usually die within one year due to severe, recurrent infections unless they have undergone successful hematopoietic stem cell transplantation.

Chronic conditions have often been used to describe the various health related states of the human body such as syndromes, physical impairments, disabilities as well as diseases. Epidemiologists have found interest in chronic conditions due to the fact they contribute to disease, disability, and diminished physical and/or mental capacity.

For example, high blood pressure or hypertension is considered to be not only a chronic condition itself but also correlated to diseases such as heart attack or stroke. Additionally, some socioeconomic factors may be considered as a chronic condition as they lead to disability in daily life. An important one that public health officials in the social science setting have begun highlighting is chronic poverty and racism.

The list below includes these chronic conditions and diseases:

In 2015 the World Health Organisation produced a report on non-communicable diseases, citing the four major types as:

- Cancers

- Cardiovascular diseases, including cerebrovascular disease, heart failure, and ischemic cardiopathy

- Chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD)

- Diabetes mellitus

Other examples of chronic diseases and health conditions include:

- Addiction

- Alzheimer's disease

- Atrial fibrillation

- Attention deficit hyperactivity disorder

- Autoimmune diseases, such as ulcerative colitis, lupus erythematosus, Crohn's disease, coeliac disease, Hashimoto's thyroiditis, and relapsing polychondritis

- Bipolar disorder

- Blindness

- Cerebral palsy (all types)

- Chronic graft-versus-host disease (GVHD)

- Chronic hepatitis

- Chronic kidney disease

- Chronic osteoarticular diseases, such as osteoarthritis and rheumatoid arthritis

- Chronic pain syndromes, such as post-vasectomy pain syndrome and complex regional pain syndrome

- Depression

- Deafness and hearing impairment

- Eating disorders

- Ehlers–Danlos syndrome (various types)

- Endometriosis

- Epilepsy

- Fibromyalgia

- HIV/AIDS

- Huntington's disease

- Hypertension

- Lyme disease

- Multiple sclerosis

- Myalgic encephalomyelitis ( chronic fatigue syndrome)

- Narcolepsy

- Obesity

- Osteoporosis

- Parkinson's disease

- Periodontal disease

- Postural orthostatic tachycardia syndrome

- Sickle cell anemia and other hemoglobin disorders

- Sleep apnea

- Thyroid disease

- Tobacco Use and Related Conditions

A cytokine storm, also known as cytokine cascade and hypercytokinemia, is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and white blood cells, with highly elevated levels of various cytokines. The term arose in the field of pathophysiology in discussions around immune disorders in 1993, was extended to discussions of infectious disease and sepsis, and has been used to describe severe manifestations of cytokine release syndrome, an adverse effect of some drugs.

The primary symptoms of a cytokine storm are high fever, swelling, redness, extreme fatigue, and nausea. In some cases the immune reaction will be fatal.

Initially, the clinical presentation of SDS may appear similar to cystic fibrosis. However, CF can be excluded with a normal chloride in sweat test but faecal elastase as a marker of pancreatic function will be reduced. The variation, intermittent nature, and potential for long-term improvement of some clinical features make this syndrome difficult to diagnose. SDS may present with either malabsorption, or hematological problems. Rarely, SDS may present with skeletal defects, including severe rib cage abnormalities that lead to difficulty in breathing. Diagnosis is generally based on evidence of exocrine pancreatic dysfunction and neutropenia. Skeletal abnormalities and short stature are characteristics that can be used to support the diagnosis. The gene responsible for the disease has been identified and genetic testing is now available. Though useful in diagnostics, a genetic test does not surmount the need for careful clinical assessment and monitoring of all patients.

X-linked severe combined immunodeficiency (X-SCID) is an immunodeficiency disorder in which the body produces very few T cells and NK cells. In the absence of T cell help, B cells become defective. It is an x-linked recessive trait, stemming from a mutated (abnormal) version of the IL2-RG gene located at xq13.1 on the X-chromosome, which is shared between receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21.

About half of US states are performing screening for SCID in newborns using real-time quantitative PCR to measure the concentration of T-cell receptor excision circles. Wisconsin and Massachusetts (as of February 1, 2009) screen newborns for SCID. Michigan began screening for SCID in October 2011. Some SCID can be detected by sequencing fetal DNA if a known history of the disease exists. Otherwise, SCID is not diagnosed until about six months of age, usually indicated by recurrent infections. The delay in detection is because newborns carry their mother's antibodies for the first few weeks of life and SCID babies look normal.

Congenital dyserythropoietic anemia (CDA) is a rare blood disorder, similar to the thalassemias. CDA is one of many types of anemia, characterized by ineffective erythropoiesis, and resulting from a decrease in the number of red blood cells (RBCs) in the body and a less than normal quantity of hemoglobin in the blood.

A chronic condition is a human health condition or disease that is persistent or otherwise long-lasting in its effects or a disease that comes with time. The term "chronic" is often applied when the course of the disease lasts for more than three months. Common chronic diseases include arthritis, asthma, cancer, COPD, diabetes and some viral diseases such as hepatitis C and HIV/AIDS.

In medicine, the opposite of chronic is acute. A chronic course is further distinguished from a recurrent course; recurrent diseases relapse repeatedly, with periods of remission in between.

The non-communicable diseases are also usually lasting medical conditions but are separated by their non-infectious causes. In contrast, some chronic diseases, such as HIV/AIDS, are caused by transmissible infections.

In the United States 25% of adults have at least two chronic conditions. Chronic diseases constitute a major cause of mortality, with the World Health Organization (WHO) attributing 38 million deaths a year to non-communicable diseases.

A maculopapular rash is a type of rash characterized by a flat, red area on the skin that is covered with small confluent bumps. It may only appear red in lighter-skinned people. The term "maculopapular" is a compound: "macules" are small, flat discolored spots on the surface of the skin; and "papules" are small, raised bumps. It is also described as erythematous, or red.

This type of rash is common in several diseases and medical conditions, including scarlet fever, measles, Ebola virus disease, rubella, secondary syphilis (Congenital syphilis, which is asymptomatic, the newborn may present this type of rash), erythrovirus (parvovirus B19), chikungunya (alphavirus), zika, and heat rash. It is also a common manifestation of a skin reaction to the antibiotic amoxicillin or chemotherapy drugs. Cutaneous infiltration of leukemic cells may also have this appearance. Maculopapular rash is seen in graft-versus-host disease (GVHD) developed after a hematopoietic stem cell transplant (bone marrow transplant), which can be seen within one week or several weeks after the transplant. In the case of GVHD, the maculopapular rash may progress to a condition similar to toxic epidermal necrolysis. In addition, this is the type of rash that some patients presenting with Ebola virus hemorrhagic (EBO-Z) fever will reveal but can be hard to see on dark skin people. It is also seen in patients with Marburg hemorrhagic fever, a filovirus not unlike Ebola.

This type of rash can be as a result of large doses of niacin or no-flush niacin (2000 – 2500 mg), used for the management of low HDL cholesterol.

This type of rash can also be a symptom of Sea bather's eruption. This stinging, pruritic, maculopapular rash affects swimmers in some Atlantic locales (e.g., Florida, Caribbean, Long Island). It is caused by hypersensitivity to stings from the larvae of the sea anemone (e.g., "Edwardsiella lineate") or the thimble jellyfish ("Linuche unguiculata"). The rash appears where the bathing suit contacts the skin.

This type of rash can also be a symptom of acute arsenic intoxication, appearing 2 weeks later.

The symptoms and signs of congenital dyserythropoietic anemia are consistent with:

- Tiredness (fatigue)

- Weakness

- Pale skin

Ductopenia refers to a reduction in the number of ducts in an organ. It is the histological hallmark of vanishing bile duct syndrome (typically <0.5 bile ducts per portal triad). The most common cause of ductopenia is primary biliary cholangitis.

Other causes of ductopenia include failing liver transplant, Hodgkin's lymphoma, graft-versus-host disease (GVHD), sarcoid, Cytomegalovirus infection, HIV and medication toxicity.

Gilbert's syndrome produces an elevated level of unconjugated bilirubin in the bloodstream, but normally has no serious consequences. Mild jaundice may appear under conditions of exertion, stress, fasting, and infections, but the condition is otherwise usually asymptomatic. Severe cases are seen by yellowing of the skin tone and yellowing of the sclera in the eye.

GS has been reported to possibly contribute to an accelerated onset of neonatal jaundice, especially in the presence of increased red blood cell destruction due to diseases such as G6PD deficiency. This situation can be especially dangerous if not quickly treated, as the high bilirubin causes irreversible neurological disability in the form of kernicterus.

Gilbert's syndrome (GS) is a mild liver disorder in which the liver does not properly process bilirubin. Many people never have symptoms. Occasionally a slight yellowish color of the skin or whites of the eyes may occur. Other possible symptoms include feeling tired, weakness, and abdominal pain.

Gilbert's syndrome is due to a mutation in the UGT1A1 gene which results in decreased activity of the bilirubin uridine diphosphate glucuronosyltransferase enzyme. It is typically inherited in an autosomal recessive pattern and occasionally in an autosomal dominant pattern depending on the type of mutation. Episodes of jaundice may be triggered by stress such as exercise, menstruation, or not eating. Diagnosis is based on higher levels of unconjugated bilirubin in the blood without either signs of other liver problems or red blood cell breakdown.

Typically no treatment is needed. If jaundice is significant phenobarbital may be used. Gilbert's syndrome affects about 5% of people in the United States. Males are more often diagnosed than females. It is often not noticed until late childhood to early adulthood. The condition was first described in 1901 by Augustin Nicolas Gilbert.

The following symptoms are typical ones which lead to testing for JMML, though children with JMML may exhibit any combination of them: pallor, fever, infection, bleeding, cough, poor weight gain, a maculopapular rash (discolored but not raised, or small and raised but not containing pus), lymphadenopathy (enlarged lymph nodes), moderate hepatomegaly (enlarged liver), marked splenomegaly (enlarged spleen), leukocytosis (high white blood cell count in blood), absolute monocytosis (high monocyte count in blood), anemia (low red blood cell count in blood), and thrombocytopenia (low platelet count in blood). Most of these conditions are common, nonspecific signs and symptoms.

Children with JMML and neurofibromatosis 1 (NF1) (about 14% of children with JMML are also clinically diagnosed with NF1, though up to 30% carry the NF1 gene mutation) may also exhibit any of the following symptoms associated with NF1 (in general, only young children with NF1 are at an increased risk of developing JMML):

- 6 or more café-au-lait (flat, coffee-colored) spots on the skin

- 2 or more neurofibromas (pea-size bumps that are noncancerous tumors) on or under the skin

- Plexiform neurofibromas (larger areas on skin that appear swollen)

- Optic glioma (a tumor on the optic nerve that affects vision)

- Freckles under the arms or in the groin

- 2 or more Lisch nodules (tiny tan or brown-colored spots on the iris of the eye)

- Various bone deformations including bowing of the legs below the knee, scoliosis, or thinning of the shin bone

Noonan syndrome (NS) may predispose to the development of JMML or a myeloproliferative disorder (MPD) associated with NS (MPD/NS) which resembles JMML in the first weeks of life. However, MPD/NS may resolve without treatment. Children with JMML and Noonan's syndrome may also exhibit any of the following most-common symptoms associated with Noonan's syndrome:

- Congenital heart defects, in particular, pulmonic stenosis (a narrowing of the valve from the heart to the lungs)

- Undescended testicles in males

- Excess skin and low hair line on back of neck

- Widely set eyes

- Diamond-shaped eyebrows

- Ears that are low-set, backward-rotated, thick outer rim

- Deeply grooved philtrum (upper lip line)

- Learning delays