In addition to the extent of involvement, people may also be characterized by the severity of their disease.

- "Mild disease" correlates with fewer than four stools daily, with or without blood, no systemic signs of toxicity, and a normal erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Mild abdominal pain or cramping may occur. Patients may believe they are constipated when in fact they are experiencing tenesmus, which is a constant feeling of the need to empty the bowel accompanied by involuntary straining efforts, pain, and cramping with little or no fecal output. Rectal pain is uncommon.

- "Moderate disease" correlates with more than four stools daily, but with minimal signs of toxicity. Patients may display anemia (not requiring transfusions), moderate abdominal pain, and low grade fever, .

- "Severe disease", correlates with more than six bloody stools a day or observable massive and significant bloody bowel movement, and evidence of toxicity as demonstrated by fever, tachycardia, anemia or an elevated ESR or CRP.

- "Fulminant disease" correlates with more than ten bowel movements daily, continuous bleeding, toxicity, abdominal tenderness and distension, blood transfusion requirement and colonic dilation (expansion). Patients in this category may have inflammation extending beyond just the mucosal layer, causing impaired colonic motility and leading to toxic megacolon. If the serous membrane is involved, a colonic perforation may ensue. Unless treated, the fulminant disease will soon lead to death.

As ulcerative colitis is believed to have a systemic (i.e., autoimmune) origin, patients may present with comorbidities leading to symptoms and complications outside the colon. The frequency of such extraintestinal manifestations has been reported as anywhere between 6 and 47 percent, and include the following:

- Aphthous ulcer of the mouth

- Ophthalmic

- Iritis or uveitis, which is inflammation of the eye's iris

- Episcleritis

- Musculoskeletal:

- Seronegative arthritis, which can be a large-joint oligoarthritis (affecting one or two joints), or may affect many small joints of the hands and feet

- Ankylosing spondylitis, arthritis of the spine

- Sacroiliitis, arthritis of the lower spine

- Cutaneous (related to the skin):

- Erythema nodosum, which is a panniculitis, or inflammation of subcutaneous tissue involving the lower extremities

- Pyoderma gangrenosum, which is a painful ulcerating lesion involving the skin

- Deep venous thrombosis and pulmonary embolism

- Autoimmune hemolytic anemia

- Clubbing, a deformity of the ends of the fingers.

- Primary sclerosing cholangitis, a distinct disease that causes inflammation of the bile ducts

According to recent studies, calcifications of channels seen in dementia can also occur in specific brain areas such as the visual complex in the occipital lobe. Such calcium channel blockages can cause visual problems or partial field hallucinations (Paroxysmal visual manifestations). Other papers show a link between migraine, visual aura and cerebral calcifications. Disturbances may be followed by

convulsions and associated with gastrointestinal phenomena.

Ten (of 75) young patients had neurologic findings such as febrile seizures, single generalized seizures, mild ataxia, and muscular hypotonia with retarded motor development, but magnetic resonance imaging detected unilateral and bilateral T2-hyperintensive white-matter lesions in 15 patients (20%)

LRBA deficiency presents as a syndrome of autoimmunity, lymphoproliferation, and humoral immune deficiency. Predominant clinical problems include idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), and an autoimmune enteropathy. Before the discovery of these gene mutations, patients were diagnosed with common variable immune deficiency (CVID), which is characterized by low antibody levels and recurrent infections. Infections mostly affect the respiratory tract, as many patients suffer from chronic lung disease, pneumonias, and bronchiectasis. Lymphocytic interstitial lung disease (ILD) is also observed, which complicates breathing and leads to impairment of lung function and mortality. Infections can also occur at other sites, such as the eyes, skin and gastrointestinal tract. Many patients suffer from chronic diarrhea and inflammatory bowel disease. Other clinical features can include hepatosplenomegaly, reoccurring warts, growth retardation, allergic dermatitis, and arthritis. Notably, LRBA deficiency has also been associated with type 1 diabetes mellitus. There is significant clinical phenotypic overlap with disease caused by CTLA4 haploinsufficiency. Since LRBA loss results in a loss of CTLA4 protein, the immune dysregulation syndrome of LRBA deficient patients can be attributed to the secondary loss of CTLA4. Because the predominant features of the disease include autoantibody-mediated disease (AIHA, ITP), Treg defects (resembling those found in CTLA4 haploinsufficient patients), autoimmune infiltration (of non-lymphoid organs, also resembling that found in CTLA4 haploinsufficient patients), and enteropathy, the disease has been termed LATAIE for LRBA deficiency with autoantibodies, Treg defects, autoimmune infiltration, and enteropathy.

Diverticulitis typically presents with left lower quadrant abdominal pain of sudden onset. There may also be fever, nausea, diarrhea or constipation, and blood in the stool.

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.

In complicated diverticulitis, an inflamed diverticulum can rupture, allowing bacteria to subsequently infect externally from the colon. If the infection spreads to the lining of the abdominal cavity (the peritoneum), peritonitis results. Sometimes, inflamed diverticula can cause narrowing of the bowel, leading to an obstruction. In some cases, the affected part of the colon adheres to the bladder or other organs in the pelvic cavity, causing a , or creating an abnormal connection between an organ and adjacent structure or other organ (in the case of diverticulitis, the colon and an adjacent organ).

Related pathologies may include:

- Bowel obstruction

- Peritonitis

- Abscess

- Bleeding

- Strictures

Depending on the level of obstruction, bowel obstruction can present with abdominal pain, swollen abdomen, abdominal distension, vomiting, fecal vomiting, and constipation.

Bowel obstruction may be complicated by dehydration and electrolyte abnormalities due to vomiting; respiratory compromise from pressure on the diaphragm by a distended abdomen, or aspiration of vomitus; bowel ischemia or perforation from prolonged distension or pressure from a foreign body.

In small bowel obstruction, the pain tends to be colicky (cramping and intermittent) in nature, with spasms lasting a few minutes. The pain tends to be central and mid-abdominal. Vomiting may occur before constipation.

In large bowel obstruction, the pain is felt lower in the abdomen and the spasms last longer. Constipation occurs earlier and vomiting may be less prominent. Proximal obstruction of the large bowel may present as small bowel obstruction.

LRBA deficiency is a rare genetic disorder of the immune system. This disorder is caused by a mutation in the gene "LRBA". LRBA stands for “Lipopolysaccharide (LPS)-responsive vesicle trafficking, beach- and anchor-containing” gene. This condition is characterized by autoimmunity, lymphoproliferation, and immune deficiency. It was first described by Gabriela Lopez-Herrera from University College London in 2012. Investigators in the laboratory of Dr. Michael Lenardo at National Institute of Allergy and Infectious Diseases, the National Institutes of Health and Dr. Michael Jordan at Cincinnati Children’s Hospital Medical Center later described this condition and therapy in 2015.

The risks associated with this syndrome include a strong tendency of developing cancer in a number of parts of the body. While the hamartomatous polyps themselves only have a small malignant potential (<3% - OHCM), patients with the syndrome have an increased risk of developing carcinomas of the pancreas, liver, lungs, breast, ovaries, uterus, testicles and other organs.

The average age of first diagnosis is 23, but the lesions can be identified at birth by an astute pediatrician or family physician. Prior to puberty, the mucocutaneous lesions can be found on the palms and soles. Often the first presentation is a bowel obstruction from an intussusception which is a common cause of mortality; an intussusception is a telescoping of one loop of bowel into another segment.

Causes of small bowel obstruction include:

- Adhesions from previous abdominal surgery (most common cause)

- Barbed sutures.

- Pseudoobstruction

- Hernias containing bowel

- Crohn's disease causing adhesions or inflammatory strictures

- Neoplasms, benign or malignant

- Intussusception

- Volvulus

- Superior mesenteric artery syndrome, a compression of the duodenum by the superior mesenteric artery and the abdominal aorta

- Ischemic strictures

- Foreign bodies (e.g. gallstones in gallstone ileus, swallowed objects)

- Intestinal atresia

After abdominal surgery, the incidence of small bowel obstruction from any cause is 9%. In those where the cause of the obstruction was clear, adhesions are the single most common cause (more than half).

Underlying causes include gastric ulcers, duodenal ulcers, appendicitis, gastrointestinal cancer, diverticulitis, inflammatory bowel disease, superior mesenteric artery syndrome, trauma and ascariasis. Typhoid fever, non-steroidal anti-inflammatory drugs, ingestion of corrosives may also be responsible.

The most common symptoms of pancreatitis are severe upper abdominal or left upper quadrant burning pain radiating to the back, nausea, and vomiting that is worse with eating. The physical examination will vary depending on severity and presence of internal bleeding. Blood pressure may be elevated by pain or decreased by dehydration or bleeding. Heart and respiratory rates are often elevated. The abdomen is usually tender but to a lesser degree than the pain itself. As is common in abdominal disease, bowel sounds may be reduced from reflex bowel paralysis. Fever or jaundice may be present. Chronic pancreatitis can lead to diabetes or pancreatic cancer. Unexplained weight loss may occur from a lack of pancreatic enzymes hindering digestion.

Signs and symptoms may include a sudden pain in the epigastrium to the right of the midline indicating the perforation of a duodenal ulcer. In a gastric ulcer perforation creates a history of burning pain in epigastrium, with flatulence and dyspepsia.

In intestinal perforation, pain starts from the site of perforation and spreads across the abdomen.

Gastrointestinal perforation results in severe abdominal pain intensified by movement, nausea, vomiting and hematemesis. Later symptoms include fever and or chills. In any case, the abdomen becomes rigid with tenderness and rebound tenderness. After some time the abdomen becomes silent and heart sounds can be heard all over. Patient stops passing flatus and motion, abdomen is distended.

The symptoms of esophageal rupture may include sudden onset of chest pain.

TRIANGLE disease is a rare genetic disorder of the immune system. TRIANGLE stands for “TPPII-related immunodeficiency, autoimmunity, and neurodevelopmental delay with impaired glycolysis and lysosomal expansion” where "TPP2" is the causative gene. This disease manifests as recurrent infection, autoimmunity, and neurodevelopmental delay. TRIANGLE disease was first described in a collaborative study by Dr. Helen C. Su from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Dr. Sophie Hambleton from the University of Newcastle and their collaborators in 2014. The disease was also described by the group of Ehl et al.

Peutz–Jeghers syndrome (often abbreviated PJS) is an autosomal dominant genetic disorder characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa (melanosis). This syndrome can be classed as one of various hereditary intestinal polyposis syndromes and one of various hamartomatous polyposis syndromes. It has an incidence of approximately 1 in 25,000 to 300,000 births.

An enterocutaneous fistula (ECF) is an abnormal communication between the small or large bowel and the skin that allows the contents of the stomach or intestines to leak through an opening in the skin.

The initial affected individual described in 1986 had a complex phenotype, and was later found to have both beta-mannosidosis and Sanfilippo syndrome. People have been described with a wide spectrum of clinical presentations from infants and children with intellectual disability to adults who present with isolated skin findings (angiokeratomas). Most cases are identified in the first year of life with respiratory infections, hearing loss and intellectual disability. Because of its rarity, and non-specific clinical findings, beta-mannosidosis can go undiagnosed until adulthood, where it can present with intellectual disability and behavioral problems, including aggression.

Berdon syndrome, also called Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIH syndrome), is an autosomal recessive fatal genetic disorder affecting newborns. In a 2011 study of 227 children with the syndrome, "the oldest survivor [was] 24 years old." The Ann Arbor News reported a five year old survivor at the end of 2015.

It is more prevalent in females, 7 females to 3 males, and is characterized by constipation and urinary retention, microcolon, giant bladder (megacystis), intestinal hypoperistalis, hydronephrosis, and dilated small bowel. The pathological findings consist of an abundance of ganglion cells in both dilated and narrow areas of the intestine. It is a familial disturbance of unknown cause.

Walter Berdon "et al." in 1976 first described the condition in five female infants, two of whom were sisters. All had marked dilatation of the bladder and some had hydronephrosis and the external appearance of prune belly. The infants also had microcolon and dilated small intestines.

Early complications include shock, infection, systemic inflammatory response syndrome, low blood calcium, high blood glucose, and dehydration. Blood loss, dehydration, and fluid leaking into the abdominal cavity (ascites) can lead to kidney failure. Respiratory complications are often severe. Pleural effusion is usually present. Shallow breathing from pain can lead to lung collapse. Pancreatic enzymes may attack the lungs, causing inflammation. Severe inflammation can lead to intra-abdominal hypertension and abdominal compartment syndrome, further impairing renal and respiratory function and potentially requiring management with an open abdomen to relieve the pressure.

Late complications include recurrent pancreatitis and the development of pancreatic pseudocysts—collections of pancreatic secretions that have been walled off by scar tissue. These may cause pain, become infected, rupture and bleed, block the bile duct and cause jaundice, or migrate around the abdomen. Acute necrotizing pancreatitis can lead to a pancreatic abscess, a collection of pus caused by necrosis, liquefaction, and infection. This happens in approximately 3% of cases, or almost 60% of cases involving more than two pseudocysts and gas in the pancreas.

The initial description of AGS suggested that the disease was always severe, and was associated with unremitting neurological decline, resulting in death in childhood. As more cases have been identified, it has become apparent that this is not necessarily the case, with many patients now considered to demonstrate an apparently stable clinical picture, alive in their 4th decade. Moreover, rare individuals with pathogenic mutations in the AGS-related genes can be minimally affected (perhaps only with chilblains) and are in mainstream education, and even affected siblings within a family can show marked differences in severity.

In about ten percent of cases, AGS presents at or soon after birth (i.e. in the neonatal period). This presentation of the disease is characterized by microcephaly, neonatal seizures, poor feeding, jitteriness, cerebral calcifications (accumulation of calcium deposits in the brain), white matter abnormalities, and cerebral atrophy; thus indicating that the disease process became active before birth i.e. "in utero". These infants can have hepatosplenomegaly and thrombocytopaenia, very much like cases of transplacental viral infection. About one third of such early presenting cases, most frequently in association with mutations in "TREX1", die in early childhood.

Otherwise the majority of AGS cases present in early infancy, sometimes after an apparently normal period of development. During the first few months after birth, these children develop features of an encephalopathy with irritability, persistent crying, feeding difficulties, an intermittent fever (without obvious infection), and abnormal neurology with disturbed tone, dystonia, an exaggerated startle response, and sometimes seizures.

Glaucoma can be present at birth, or develop later. Many children retain apparently normal vision, although a significant number are cortically blind. Hearing is almost invariably normal. Over time, up to 40% of patients develop so-called chilblain lesions, most typically on the toes and fingers and occasionally also involving the ears. They are usually worse in the winter.

Clinically, TRIANGLE disease is characterized combined immunodeficiency, severe autoimmunity, and developmental delay. Patients typically present in early childhood with recurrent bacterial and viral infections of the middle ear and respiratory tract. Additionally, patients develop severe, difficult to treat autoimmunity. This autoimmunity includes auto-antibody mediated destruction of red blood cells, neutrophils, and platelets; central nervous system lupus erythematous with stroke; and hepatitis. Patients also have mild to moderate developmental delay.

Beta-mannosidosis, also called lysosomal beta-mannosidase deficiency, is a disorder of oligosaccharide metabolism caused by decreased activity of the enzyme beta-mannosidase. This enzyme is coded for by the gene "MANBA", located at 4q22-25. Beta-mannosidosis is inherited in an autosomal recessive manner. Affected individuals appear normal at birth, and can have a variable clinical presentation. Infantile onset forms show severe neurodegeneration, while some children have intellectual disability. Hearing loss and angiokeratomas are common features of the disease.

Aicardi–Goutières syndrome (AGS), which is completely distinct from the similarly named Aicardi syndrome, is a rare, usually early onset childhood, inflammatory disorder most typically affecting the brain and the skin (neurodevelopmental disorder). The majority of affected individuals experience significant intellectual and physical problems, although this is not always the case. The clinical features of AGS can mimic those of "in utero" acquired infection, and some characteristics of the condition also overlap with the autoimmune disease systemic lupus erythematosus (SLE). Following an original description of eight cases in 1984, the condition was first referred to as 'Aicardi–Goutières syndrome' (AGS) in 1992, and the first international meeting on AGS was held in Pavia, Italy, in 2001.

AGS can occur due to mutations in any one of a number of different genes, of which seven have been identified to date, namely: TREX1, RNASEH2A, RNASEH2B, RNASEH2C (which together encode the Ribonuclease H2 enzyme complex), SAMHD1, ADAR1, and IFIH1 (coding for MDA5). This neurological disease occurs in all populations worldwide, although it is almost certainly under-diagnosed. To date (2014) at least 400 cases of AGS are known.