Many people with Crohn's disease have symptoms for years before the diagnosis. The usual onset is between 15 and 30 years of age, but can occur at any age. Because of the 'patchy' nature of the gastrointestinal disease and the depth of tissue involvement, initial symptoms can be more subtle than those of ulcerative colitis. People with Crohn's disease experience chronic recurring periods of flare-ups and remission.

Abdominal pain may be the initial symptom of Crohn's disease usually in the lower right area. It is often accompanied by diarrhea, especially in those who have had surgery. The diarrhea may or may not be bloody. The nature of the diarrhea in Crohn's disease depends on the part of the small intestine or colon involved. Ileitis typically results in large-volume, watery feces. Colitis may result in a smaller volume of feces of higher frequency. Fecal consistency may range from solid to watery. In severe cases, an individual may have more than 20 bowel movements per day and may need to awaken at night to defecate. Visible bleeding in the feces is less common in Crohn's disease than in ulcerative colitis, but may be seen in the setting of Crohn's colitis. Bloody bowel movements typically come and go, and may be bright or dark red in color. In the setting of severe Crohn's colitis, bleeding may be copious. Flatulence and bloating may also add to the intestinal discomfort.

Symptoms caused by intestinal stenosis are also common in Crohn's disease. Abdominal pain is often most severe in areas of the bowel with stenoses. Persistent vomiting and nausea may indicate stenosis from small bowel obstruction or disease involving the stomach, pylorus, or duodenum. Although the association is greater in the context of ulcerative colitis, Crohn's disease may also be associated with primary sclerosing cholangitis, a type of inflammation of the bile ducts.

Perianal discomfort may also be prominent in Crohn's disease. Itchiness or pain around the anus may be suggestive of inflammation, fistulization or abscess around the anal area or anal fissure. Perianal skin tags are also common in Crohn's disease and may appear with or without the presence of colorectal polyps. Fecal incontinence may accompany perianal Crohn's disease. At the opposite end of the gastrointestinal tract, the mouth may be affected by recurrent sores (aphthous ulcers). Rarely, the esophagus, and stomach may be involved in Crohn's disease. These can cause symptoms including difficulty swallowing (dysphagia), upper abdominal pain, and vomiting.

Crohn's disease, like many other chronic, inflammatory diseases, can cause a variety of systemic symptoms. Among children, growth failure is common. Many children are first diagnosed with Crohn's disease based on inability to maintain growth. As it may manifest at the time of the growth spurt in puberty, up to 30% of children with Crohn's disease may have retardation of growth. Fever may also be present, though fevers greater than 38.5 °C (101.3 °F) are uncommon unless there is a complication such as an abscess. Among older individuals, Crohn's disease may manifest as weight loss, usually related to decreased food intake, since individuals with intestinal symptoms from Crohn's disease often feel better when they do not eat and might lose their appetite. People with extensive small intestine disease may also have malabsorption of carbohydrates or lipids, which can further exacerbate weight loss.

Many people with gastritis experience no symptoms at all. However, upper central abdominal pain is the most common symptom; the pain may be dull, vague, burning, aching, gnawing, sore, or sharp. Pain is usually located in the upper central portion of the abdomen, but it may occur anywhere from the upper left portion of the abdomen around to the back.

Other signs and symptoms may include the following:

- Nausea

- Vomiting (if present, may be clear, green or yellow, blood-streaked, or completely bloody, depending on the severity of the stomach inflammation)

- Belching (if present, usually does not relieve the pain much)

- Bloating

- Early satiety

- Loss of appetite

- Unexplained weight loss

Common causes include "Helicobacter pylori" and NSAIDs. Less common causes include alcohol, cocaine, severe illness and Crohn disease, among others.

Signs and symptoms of a peptic ulcer can include one or more of the following:

- abdominal pain, classically epigastric strongly correlated to mealtimes. In case of duodenal ulcers the pain appears about three hours after taking a meal;

- bloating and abdominal fullness;

- waterbrash (rush of saliva after an episode of regurgitation to dilute the acid in esophagus - although this is more associated with gastroesophageal reflux disease);

- nausea and copious vomiting;

- loss of appetite and weight loss;

- hematemesis (vomiting of blood); this can occur due to bleeding directly from a gastric ulcer, or from damage to the esophagus from severe/continuing vomiting.

- melena (tarry, foul-smelling feces due to presence of oxidized iron from hemoglobin);

- rarely, an ulcer can lead to a gastric or duodenal perforation, which leads to acute peritonitis, extreme, stabbing pain, and requires immediate surgery.

A history of heartburn, gastroesophageal reflux disease (GERD) and use of certain forms of medication can raise the suspicion for peptic ulcer. Medicines associated with peptic ulcer include NSAIDs (non-steroid anti-inflammatory drugs) that inhibit cyclooxygenase, and most glucocorticoids (e.g. dexamethasone and prednisolone).

In people over the age of 45 with more than two weeks of the above symptoms, the odds for peptic ulceration are high enough to warrant rapid investigation by esophagogastroduodenoscopy.

The timing of the symptoms in relation to the meal may differentiate between gastric and duodenal ulcers: A gastric ulcer would give epigastric pain during the meal, as gastric acid production is increased as food enters the stomach. Symptoms of duodenal ulcers would initially be relieved by a meal, as the pyloric sphincter closes to concentrate the stomach contents, therefore acid is not reaching the duodenum. Duodenal ulcer pain would manifest mostly 2–3 hours after the meal, when the stomach begins to release digested food and acid into the duodenum.

Also, the symptoms of peptic ulcers may vary with the location of the ulcer and the person's age. Furthermore, typical ulcers tend to heal and recur and as a result the pain may occur for few days and weeks and then wane or disappear. Usually, children and the elderly do not develop any symptoms unless complications have arisen.

Burning or gnawing feeling in the stomach area lasting between 30 minutes and 3 hours commonly accompanies ulcers. This pain can be misinterpreted as hunger, indigestion or heartburn. Pain is usually caused by the ulcer but it may be aggravated by the stomach acid when it comes into contact with the ulcerated area. The pain caused by peptic ulcers can be felt anywhere from the navel up to the sternum, it may last from few minutes to several hours and it may be worse when the stomach is empty. Also, sometimes the pain may flare at night and it can commonly be temporarily relieved by eating foods that buffer stomach acid or by taking anti-acid medication. However, peptic ulcer disease symptoms may be different for every sufferer.

Intestinal Connective tissue abnormality may cause Intestinal Desmosis The absence of the tendinous plexus layer was first described in 1998 by Meier-Ruge. Desmosis is implicated in disturbed gut motility.

Normal peristalsis depends upon the interaction between muscles, nerve cells and tendinous connective tissue. A malfunction of any of these leads to intestinal motility disorders.

Desmosis may be congenital (aplastic form) or acquired (atrophic form).

The "aplastic" form is rare. Typical clinical findings are hypoperistalsis, and pseudo-obstruction. These are found in premature infants, associated with low birth weight. The "atrophic" form is more frequent. Inflammation of the muscularis propria releases enzymes including collagenases which destroy the connective tissue of the bowel wall. Primarily newborns and small children are affected, although this manifestation can also be found in adults. The most common location is the colon with a necrotizing enterocolitis as well as Crohn Disease and diverticulitis. If the taenia are also affected, the disease is defined as complete atrophic desmosis, all other forms without involvement of the taenia are referred to as incomplete. Clinically, patients demonstrate chronic constipation.

As proposed by Giuseppe Martucciello, microscopic diagnosis requires laparoscopic intestinal full-thickness biopsies from colon. Histological findings are absence of the tendinous plexus layer and connective tissue fibers in longitudinal and circular muscle layer.

Peptic ulcer disease (PUD) is a break in the lining of the stomach, first part of the small intestine or occasionally the lower esophagus. An ulcer in the stomach is known as a gastric ulcer while that in the first part of the intestines is known as a duodenal ulcer. The most common symptoms of a duodenal ulcer are waking at night with upper abdominal pain or upper abdominal pain that improves with eating. With a gastric ulcer the pain may worsen with eating. The pain is often described as a burning or dull ache. Other symptoms include belching, vomiting, weight loss, or poor appetite. About a third of older people have no symptoms. Complications may include bleeding, perforation and blockage of the stomach. Bleeding occurs in as many as 15% of people.

Common causes include the bacteria "Helicobacter pylori" and non-steroidal anti-inflammatory drugs (NSAIDs). Other less common causes include tobacco smoking, stress due to serious illness, Behcet disease, Zollinger-Ellison syndrome, Crohn disease and liver cirrhosis, among others. Older people are more sensitive to the ulcer-causing effects of NSAIDs. The diagnosis is typically suspected due to the presenting symptoms with confirmation by either endoscopy or barium swallow. "H. pylori" can be diagnosed by testing the blood for antibodies, a urea breath test, testing the stool for signs of the bacteria, or a biopsy of the stomach. Other conditions that produce similar symptoms include stomach cancer, coronary heart disease, and inflammation of the stomach lining or gallbladder inflammation.

Diet does not play an important role in either causing or preventing ulcers. Treatment includes stopping smoking, stopping NSAIDs, stopping alcohol and giving medications to decrease stomach acid. The medication used to decrease acid is usually either a proton pump inhibitor (PPI) or an H2 blocker with four weeks of treatment initially recommended. Ulcers due to "H. pylori" are treated with a combination of medications such as amoxicillin, clarithromycin and a PPI. Antibiotic resistance is increasing and thus treatment may not always be effective. Bleeding ulcers may be treated by endoscopy, with open surgery typically only used in cases in which it is not successful.

Peptic ulcers are present in around 4% of the population. Newly ulcers were found in around 87.4 million people worldwide during 2015. About 10% of people develop a peptic ulcer at some point in their life. They resulted in 267,500 deaths in 2015 down from 327,000 deaths in 1990. The first description of a perforated peptic ulcer was in 1670 in Princess Henrietta of England. "H. pylori" was first identified as causing peptic ulcers by Barry Marshall and Robin Warren in the late 20th century, a discovery for which they received the Nobel Prize in 2005.

Substantial numbers of patients with intestinal malabsorption present initially with symptoms or laboratory abnormalities that point to other organ systems in the absence of or overshadowing symptoms referable to the gastrointestinal tract. For example, there is increasing epidemiologic evidence that more patients with coeliac disease present with anemia and osteopenia in the absence of significant classic gastrointestinal symptoms. Microcytic, macrocytic, or dimorphic anemia may reflect impaired iron, folate, or vitamin B12 absorption. Purpura, subconjunctival hemorrhage, or even frank bleeding may reflect hypoprothrombinemia secondary to vitamin K malabsorption. Osteopenia is common, especially in the presence of steatorrhea. Impaired calcium and vitamin D absorption and chelation of calcium by unabsorbed fatty acids resulting in fecal loss of calcium may all contribute. If calcium deficiency is prolonged, secondary hyperparathyroidism may develop. Prolonged malnutrition may induce amenorrhea, infertility, and impotence. Edema and even ascites may reflect hypoproteinemia associated with protein losing enteropathy caused by lymphatic obstruction or extensive mucosal inflammation. Dermatitis and peripheral neuropathy may be caused by malabsorption of specific vitamins or micronutrients and essential fatty acids.

Depending on the nature of the disease process causing malabsorption and its extent, gastrointestinal symptoms may range from severe to subtle or may even be totally absent. Diarrhea, weight loss, flatulence, abdominal bloating, abdominal cramps, and pain may be present. Although diarrhea is a common complaint, the character and frequency of stools may vary considerably ranging from over 10 watery stools per day to less than one voluminous putty-like stool, the latter causing some patients to complain of constipation. On the other hand, stool mass is invariably increased in patients with steatorrhea and generalized malabsorption above the normal with 150–200 g/day. Not only do unabsorbed nutrients contribute to stool mass but mucosal fluid and electrolyte secretion is also increased in diseases associated with mucosal inflammation such as coeliac disease. In addition, unabsorbed fatty acids, converted to hydroxy-fatty acids by colonic flora, as well as unabsorbed bile acids both impair absorption and induce secretion of water and electrolytes by the colon adding to stool mass. Weight loss is common among patients with significant intestinal malabsorption but must be evaluated in the context of caloric intake. Some patients compensate for fecal wastage of unabsorbed nutrients by significantly increasing their oral intake. Eliciting a careful dietary history from patients with suspected malabsorption is therefore crucial. Excessive flatus and abdominal bloating may reflect excessive gas production due to fermentation of unabsorbed carbohydrate, especially among patients with primary or secondary disaccharidase deficiency. Malabsorption of dietary nutrients and excessive fluid secretion by inflamed small intestine also contribute to abdominal distention and bloating. Prevalence, severity, and character of abdominal pain vary considerably among the various disease processes associated with intestinal malabsorption. For example, pain is common in patients with chronic pancreatitis or pancreatic cancer and Crohn disease, but it is absent in many patients with coeliac disease or postgastrectomy malabsorption.

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.

A broad range of autoimmune diseases have been reported to be associated with cryofibrinogenemia. These diseases include systemic lupus erythematosis, Sjorgren's syndrome, rheumatoid arthritis, mixed connective tissue disease, polymyositis, dermatomyositis, systemic sclerosis, antiphospholipid antibody syndrome, Hashimoto disease, Graves disease, sarcoidosis, pyoderma gangrenosum, spondyloarthropathy, Crohn disease, and ulcerative colitis.

Cryofibrinogenmic disease commonly begins in adults aged 40–50 years old with symptoms of the diseases occurring in the almost always affected organ, skin. Cutaneous symptoms include on or more of the following: cold contact-induced urticarial (which may be the first sign of the disease); painful episodes of finger and/or toe arterial spasms termed Ranaud phenomena; cyanosis, s palpable purpura termed Cryofibrinogenemic purpura), and a lace-like purplish discoloration termed livedo reticularis all of which occur primarily in the lower extremities but some of which may occur in the nose, ears, and buttocks; non-healing painful ulcerations and gangrene of the areas impacted by the cited symptoms. Patients also have a history of cold sensitivity (~25% of cases), arthralgia (14-58%), neuritis (7-19%), myalgia (0-14%); and overt thrombosis of arteries and veins (25-40%) which may on rare occasions involve major arteries such of those of the brain and kidney. Signs of renal involvement (proteinuria, hematuria, decreased glomerular filtration rate, and/or, rarely, renal failure) occur in 4-25% of cases. Compared to secondary cryofibrinogemia, primary crygofibrinogenemia has a higher incidence of cutaneous lesions, arthralgia, and cold sensitivity while having a far lower incidence of renal involvement. Patients with secondary cryofibrinogenemia also exhibit signs and symptoms specific to the infectious, malignant, premalignant vasculitis, and autoimmune disorders associated with their disease. While rare, individuals with cryofibrinogemic disease may experience pathological bleeding due to the consumption of blood clotting factors consequential to the formation of cryofibrinogen precipitates.

Most mammals normally cease to produce lactase and become lactose intolerant, after weaning.

Lactose intolerance primarily refers to a syndrome having one or more symptoms upon the consumption of food substances containing lactose. Individuals may be lactose intolerant to varying degrees, depending on the severity of these symptoms. "Lactose malabsorption" refers to the physiological concomitant of lactase deficiency (i.e., the body does not have sufficient lactase capacity to digest the amount of lactose ingested). Hypolactasia (lactase deficiency) is distinguished from alactasia (total lack of lactase), a rare congenital defect.

Lactose intolerance is not an allergy, because it is not an immune response, but rather a sensitivity to dairy caused by lactase deficiency. Milk allergy, occurring in only 4% of the population, is a separate condition, with distinct symptoms that occur when the presence of milk proteins trigger an immune reaction.

In 1985 Edward Blau, a pediatrician in Marshfield, Wisconsin, reported a family that over four generations had granulomatous inflammation of the skin, eyes and joints. The condition was transmitted as an autosomal dominant trait. In the same year Jabs et al. reported a family that over two generations had granulomatous synovitis, uveitis and cranial neuropathies. The condition was transmitted in an autosomal dominant fashion. In 1981 Malleson et al. reported a family that had autosomal dominant synovitis, camptodactyly, and iridocyclitis. One member died of granulomatous arteritis of the heart and aorta. In 1982 Rotenstein reported a family with granulomatous arteritis, rash, iritis, and arthritis transmitted as an autosomal dominant trait over three generations. Then in 1990 Pastores et al. reported a kindred with a phenotype very similar to what Blau described and suggested that the condition be called Blau Syndrome (BS). They also pointed out the similarities in the families noted above to BS but also pointed out the significant differences in the phenotypes.

In 1996 Tromp et al. conducted a genome wide search using affected and non affected members of the original family. A marker D16S298gave a maximum LOD score of 3.75 and put the BS susceptibility locus within the 16p12-q21 interval. Hugot et al. found a susceptibility locus for Crohn disease a granulomatous inflammation of the bowel on chromosome 16 close to the locus for BS. Based on the above information Blau suggested in 1998 that the genetic defect in BS and Crohn Disease might be the same or similar.

Finally in 2001 Miceli-Richard et al. found the defect in BS to be in the nucleotide-binding domain of CARD15/NOD2. They commented in their article that mutations in CARD15 had also been found in Crohn's Disease. Confirmation of the defect in BS being in the CARD15 gene was made by Wang et al. in 2002 using the BS family and others. With that information the diagnosis of BS was not only determined by phenotype but now by genotype.

Early onset sarcoidosis is BS without a family history, BS has been diagnosed in patients who have not only the classic triad but granuloma in multiple organs. Treatment has included the usual anti inflammatory drugs such as adrenal glucocorticoids, anti-metabolites and also biological agents such as anti-TNF and infliximab all with varying degrees of success.

The elucidation that the gene defect in BS involves the CARD15/NOD2 gene has stimulated many investigators, to define how this gene operates as part of the innate immune system, that responds to bacterial polysaccharides, such as muramyl dipeptide, to induce signaling pathways that induce cytokine responses, and protect the organism. In BS the genetic defect seems to lead to over expression, and poor control of the inflammatory response leading to widespread granulomatous, inflammation and tissue damage This reference provides an excellent review of the clinical aspects of BS, and the presumed pathogenetic mechanisms brought about by the gene defect.

What stimulus activates the aberrant immune response, and what would then lead to the discovery of more precise therapy, and the relationship to the specific gene defect and phenotype, require further research.

- List of cutaneous conditions

In 1994, Stephen Crohn became the first person discovered to be completely resistant to HIV in all tests performed. In early 2000, researchers discovered a small group of sex workers in Nairobi, Kenya who were estimated to have sexual contact with 60 to 70 HIV positive clients a year without signs of infection. Researchers from Public Health Agency of Canada have identified 15 proteins unique to those virus-free sex workers. Later, however some sex workers were discovered to have contracted the virus, leading Oxford University researcher Sarah Rowland-Jones to believe continual exposure is a requirement for maintaining immunity.

A small proportion of humans show partial or apparently complete inborn resistance to HIV, the virus that causes AIDS. The main mechanism is a mutation of the gene encoding CCR5, which acts as a co-receptor for HIV. It is estimated that the proportion of people with some form of resistance to HIV is under 1%.

Circulating tumor cells (CTCs) are cells that have shed into the vasculature or lymphatics from a primary tumor and are carried around the body in the circulation. CTCs thus constitute "seeds" for the subsequent growth of additional tumors (metastases) in vital distant organs, triggering a mechanism that is responsible for the vast majority of cancer-related deaths. CTCs also have the potential to provide a mechanism for early patient prognoses and to determine appropriate tailored treatments.

CTCs were observed for the first time in 1869 in the blood of a man with metastatic cancer by Thomas Ashworth, who postulated that “cells identical with those of the cancer itself being seen in the blood may tend to throw some light upon the mode of origin of multiple tumours existing in the same person”. A thorough comparison of the morphology of the circulating cells to tumor cells from different lesions led Ashworth to conclude that “One thing is certain, that if they [CTC] came from an existing cancer structure, they must have passed through the greater part of the circulatory system to have arrived at the internal saphena vein of the sound leg”.

The importance of CTCs in modern cancer research began in the mid 1990s with the demonstration that CTC's exist early on in the course of the disease.

Those results were made possible by exquisitely sensitive magnetic separation technology employing Ferrofluids (colloidal magnetic nanoparticles) and high gradient magnetic separators invented by Paul Liberti and motivated by theoretical calculations by Liberti and Leon Terstappen that indicated very small tumors shedding cells at less than 1.0% per day should result in detectable cells in blood. A variety of other technologies have been applied to CTC enumeration and identification since that time.

Modern cancer research has demonstrated that CTCs derive from clones in the primary tumor, validating Ashworth's remarks.

The significant efforts put into understanding the CTCs biological properties have demonstrated the critical role circulating tumor cells play in the metastatic spread of carcinoma. Furthermore, highly sensitive, single-cell analysis demonstrated a high level of heterogeneity seen at the single cell level for both protein expression and protein localization and the CTCs reflected both the primary biopsy and the changes seen in the metastatic sites.

Tissue biopsies are poor diagnostic procedures: they are invasive, cannot be used repeatedly, and are ineffective in understanding metastatic risk, disease progression, and treatment effectiveness. CTCs thus could be considered a “liquid biopsy” which reveals metastasis in action, providing live information about the patient’s disease status.

Analysis of blood samples found a propensity for increased CTC detection as the disease progressed in individual patients. Blood tests are easy and safe to perform and multiple samples can be taken over time. By contrast, analysis of solid tumors necessitates invasive procedures that might limit patient compliance. The ability to monitor the disease progression over time could facilitate appropriate modification to a patient's therapy, potentially improving their prognosis and quality of life. The important aspect of the ability to prognose the future progression of the disease is elimination (at least temporarily) of the need for a surgery when the repeated CTC counts are low and not increasing; the obvious benefits of avoiding the surgery include avoiding the risk related to the innate tumor-genicity of cancer surgeries. To this end, technologies with the requisite sensitivity and reproducibility to detect CTCs in patients with metastatic disease have recently been developed.

The hallmark of a stone that obstructs the ureter or renal pelvis is excruciating, intermittent pain that radiates from the flank to the groin or to the inner thigh. This pain, known as renal colic, is often described as one of the strongest pain sensations known. Renal colic caused by kidney stones is commonly accompanied by urinary urgency, restlessness, hematuria, sweating, nausea, and vomiting. It typically comes in waves lasting 20 to 60 minutes caused by peristaltic contractions of the ureter as it attempts to expel the stone.

The embryological link between the urinary tract, the genital system, and the gastrointestinal tract is the basis of the radiation of pain to the gonads, as well as the nausea and vomiting that are also common in urolithiasis. Postrenal azotemia and hydronephrosis can be observed following the obstruction of urine flow through one or both ureters.

Pain in the lower left quadrant can sometimes be confused with diverticulitis because the sigmoid colon overlaps the ureter and the exact location of the pain may be difficult to isolate due to the close proximity of these two structures.

About 5–10% of all stones are formed from uric acid. People with certain metabolic abnormalities, including obesity, may produce uric acid stones. They also may form in association with conditions that cause hyperuricosuria (an excessive amount of uric acid in the urine) with or without hyperuricemia (an excessive amount of uric acid in the serum). They may also form in association with disorders of acid/base metabolism where the urine is excessively acidic (low pH), resulting in precipitation of uric acid crystals. A diagnosis of uric acid urolithiasis is supported by the presence of a radiolucent stone in the face of persistent urine acidity, in conjunction with the finding of uric acid crystals in fresh urine samples.

As noted above (section on calcium oxalate stones), people with inflammatory bowel disease (Crohn's disease, ulcerative colitis) tend to have hyperoxaluria and form oxalate stones. They also have a tendency to form urate stones. Urate stones are especially common after colon resection.

Uric acid stones appear as pleomorphic crystals, usually diamond-shaped. They may also look like squares or rods which are polarizable.

Patients with hyperuricosuria can be treated with allopurinol which will reduce urate formation. Urine alkalinization may also be helpful in this setting.

Some drugs are particularly effective against cancers which fit certain requirements. For example, Herceptin is very effective in patients who are Her2 positive, but much less effective in patients who are Her2 negative. Once the primary tumor is removed, biopsy of the current state of the cancer through traditional tissue typing is not possible anymore. Often tissue sections of the primary tumor, removed years prior, are used to do the typing. Further characterisation of CTC may help determining the current tumor phenotype. FISH assays has been performed on CTC to as well as determination of IGF-1R, Her2, Bcl-2, [ERG (gene)|ERG], PTEN, AR status using immunofluorescence. Single cell level qPCR can also be performed with the CTCs isolated from blood.