The diagnosis is clinical, not based upon serology. At least seven sets of diagnostic criteria have been devised, however the Yamaguchi criteria have the highest sensitivity. Diagnosis requires at least five features, with at least two of these being major diagnostic criteria.

A complete blood count may reveal anemia, which commonly is caused by blood loss leading to iron deficiency (a microcytic anemia) or by vitamin B deficiency (a macrocytic anemia), usually caused by ileal disease impairing vitamin B absorption. Rarely autoimmune hemolysis may occur. Ferritin levels help assess if iron deficiency is contributing to the anemia. Erythrocyte sedimentation rate (ESR) and C-reactive protein help assess the degree of inflammation, which is important as ferritin can also be raised in inflammation. Serum iron, total iron binding capacity and transferrin saturation may be more easily interpreted in inflammation. Anemia of chronic disease results in a normocytic anemia. Other causes of anemia include medication used in treatment of inflammatory bowel disease, like azathioprine, which can lead to cytopenia, and sulfasalazine, which can also result in folate deficiency. Testing for "Saccharomyces cerevisiae" antibodies (ASCA) and antineutrophil cytoplasmic antibodies (ANCA) has been evaluated to identify inflammatory diseases of the intestine and to differentiate Crohn's disease from ulcerative colitis. Furthermore, increasing amounts and levels of serological antibodies such as ASCA, antilaminaribioside [Glc(β1,3)Glb(β); ALCA], antichitobioside [GlcNAc(β1,4)GlcNAc(β); ACCA], antimannobioside [Man(α1,3)Man(α)AMCA], antiLaminarin [(Glc(β1,3))3n(Glc(β1,6))n; anti-L] and antichitin [GlcNAc(β1,4)n; anti-C] associate with disease behavior and surgery, and may aid in the prognosis of Crohn's disease.

Low serum levels of vitamin D are associated with Crohn's disease. Further studies are required to determine the significance of this association.

A small bowel follow-through may suggest the diagnosis of Crohn's disease and is useful when the disease involves only the small intestine. Because colonoscopy and gastroscopy allow direct visualization of only the terminal ileum and beginning of the duodenum, they cannot be used to evaluate the remainder of the small intestine. As a result, a barium follow-through X-ray, wherein barium sulfate suspension is ingested and fluoroscopic images of the bowel are taken over time, is useful for looking for inflammation and narrowing of the small bowel. Barium enemas, in which barium is inserted into the rectum and fluoroscopy is used to image the bowel, are rarely used in the work-up of Crohn's disease due to the advent of colonoscopy. They remain useful for identifying anatomical abnormalities when strictures of the colon are too small for a colonoscope to pass through, or in the detection of colonic fistulae (in this case contrast should be performed with iodate substances).

CT and MRI scans are useful for evaluating the small bowel with enteroclysis protocols. They are also useful for looking for intra-abdominal complications of Crohn's disease, such as abscesses, small bowel obstructions, or fistulae. Magnetic resonance imaging (MRI) is another option for imaging the small bowel as well as looking for complications, though it is more expensive and less readily available. MRI techniques such as diffusion-weighted imaging and high-resolution imaging are more sensitive in detecting ulceration and inflammation compared to CT.

People with AOSD generally experience one of two patterns in the disease:

- a debilitating pattern of fevers, pain, and other systemic symptoms, or

- a somewhat less aggressive pattern, in which the main symptom is arthritis and chronic joint pain.

One set of 21 adult-onset Still's disease patients were divided into four types, according to clinical course patterns. These included monocyclic systemic disease, polycyclic systemic disease, chronic articular monocyclic systemic disease, and chronic articular polycyclic systemic disease. People with chronic articular disease and polyarticular disease were at higher risk to develop disabling arthritis.

Common clinical signs and symptoms of Whipple's disease include diarrhea, steatorrhea, abdominal pain, weight loss, migratory arthropathy, fever, and neurological symptoms. Weight loss and diarrhea are the most common symptoms that lead to identification of the process, but may be preceded by chronic, unexplained, relapsing episodes of non-destructive seronegative arthritis, often of large joints.

Diagnosis is made by biopsy, usually by duodenal endoscopy, which reveals PAS-positive macrophages in the lamina propria containing non-acid-fast gram-positive bacilli. Immunohistochemical staining for antibodies against "T. whipplei" has been used to detect the organism in a variety of tissues, and a PCR-based assay is also available. PCR can be confirmatory if performed on blood, vitreous fluid, synovial fluid, heart valves, or cerebrospinal fluid. PCR of saliva, gastric or intestinal fluid, and stool specimens is highly sensitive, but not specific enough, indicating that healthy individuals can also harbor the causative bacterium without the manifestation of Whipple's disease, but that a negative PCR is most likely indicative of a healthy individual.

Endoscopy of the duodenum and jejunum can reveal pale yellow shaggy mucosa with erythematous eroded patches in patients with classic intestinal Whipple's disease, and small bowel X-rays may show some thickened folds. Other pathological findings may include enlarged mesenteric lymph nodes, hypercellularity of lamina propria with "foamy macrophages", and a concurrent decreased number of lymphocytes and plasma cells, per high power field view of the biopsy.

A D-Xylose test can be performed, which is where the patient will consume 4.5g of D-xylose, a sugar, by mouth. The urine excretion of D-Xylose is then measured after 5 hours. The majority of D-Xylose is absorbed normally, and should be found in the urine. If the D-Xylose is found to be low in the urine, this suggests an intestinal malabsorption problem such as bacterial overgrowth of the proximal small intestine, Whipple's Disease, or an autoimmune with diseases such as Celiac's Disease (allergy to gluten) or Crohn's Disease (autoimmune disease affecting the small intestine). With empiric antibiotic treatment after an initial positive D-Xylose test, and if a follow-up D-Xylose test is positive (decreased urine excretion) after antibiotic therapy, then this would signify it is not bacterial overgrowth of the proximal small intestine. Since Whipple's disease is so rare, a follow-up positive D-Xylose test more likely indicates a non-infectious etiology and more likely an autoimmune etiology. Clinical correlation is recommended to rule out Whipple's disease.

There is no specific pathological testing or technique available for the diagnosis of the disease, although the International Study Group criteria for the disease are highly sensitive and specific, involving clinical criteria and a pathergy test. Behçet's disease has a high degree of resemblance to diseases that cause mucocutaneous lesions such as "Herpes simplex" labialis, and therefore clinical suspicion should be maintained until all the common causes of oral lesions are ruled out from the differential diagnosis.

Visual acuity, or color vision loss with concurrent mucocutaneous lesions or systemic Behçet's disease symptoms should raise suspicion of optic nerve involvement in Behçet's disease and prompt a work-up for Behçet's disease if not previously diagnosed in addition to an ocular work-up. Diagnosis of Behçet's disease is based on clinical findings including oral and genital ulcers, skin lesions such as erythema nodosum, acne, or folliculitis, ocular inflammatory findings and a pathergy reaction. Inflammatory markers such ESR, and CRP may be elevated. A complete ophthalmic examination may include a slit lamp examination, optical coherence tomography to detect nerve loss, visual field examinations, fundoscopic examination to assess optic disc atrophy and retinal disease, fundoscopic angiography, and visual evoked potentials, which may demonstrate increased latency. Optic nerve enhancement may be identified on Magnetic Resonance Imaging (MRI) in some patients with acute optic neuropathy. However, a normal study does not rule out optic neuropathy. Cerebrospinal fluid (CSF) analysis may demonstrate elevated protein level with or without pleocytosis. Imaging including angiography may be indicated to identify dural venous sinus thrombosis as a cause of intracranial hypertension and optic atrophy.

Surgical treatment of arterial manifestations of BD bears many pitfalls, since the obliterative endarteritis of vasa vasorum causes thickening of the medial layer and splitting of elastin fibers. Therefore, anastomotic pseudoaneurysms are likely to form, as well as pseudoaneurysms at the site of puncture in case of angiography or endovascular treatment; furthermore, early graft occlusion may occur.

For these reasons, invasive treatment should not be performed in the acute and active phases of the disease when inflammation is at its peak. The evaluation of disease’s activity is usually based on relapsing symptoms, ESR (erythrocyte sedimentation rate), and serum levels of CRP (C‐reactive protein).

Endovascular treatment can be an effective and safe alternative to open surgery, with less postoperative complications, faster recovery time, and reduced need for intensive care, while offering patency rates and procedural success rates comparable with those of surgery. This notwithstanding, long‐term results of endovascular treatment in BD are still to be determined.

Bright's disease was historically 'treated' with warm baths, blood-letting, squill, digitalis, mercuric compounds, opium, diuretics, laxatives, and dietary therapy, including abstinence from alcoholic drinks, cheese and red meat. Arnold Ehret was diagnosed with Bright's disease and pronounced incurable by 24 of Europe's most respected doctors; he designed "The Mucusless Diet Healing System", which apparently cured his illness. William Howard Hay, MD had the illness and, it is claimed, cured himself using the Hay diet.

Adenocarcinoma of the bowel has been associated with coeliac disease.

Rheumatoid factor and ANA tests are generally negative in systemic JIA.

Lab findings: anemia of chronic disease, neutrophilia, thrombocytosis, elevated acute phase reactants (ESR, CRP, ferritin).

Treatment is with penicillin, ampicillin, tetracycline, or co-trimoxazole for one to two years. Any treatment lasting less than a year has an approximate relapse rate of 40%. Recent expert opinion is that Whipple's disease should be treated with doxycycline with hydroxychloroquine for 12 to 18 months. Sulfonamides (sulfadiazine or sulfamethoxazole) may be added for treatment of neurological symptoms.

Diagnosis of Dercum's disease is done through a physical examination. In order to properly diagnose the patient, the doctor must first exclude all other possible differential diagnosis. The basic criteria for Dercum's disease are patients with chronic pain in the adipose tissue (body fat) and patients who are also obese. Although rare, the diagnosis may not include obesity. Dercum's disease can also be inherited and a family medical history may aid in the diagnosis of this disease. There are no specific laboratory test for this disease. Ultrasound and magnetic resonance imaging can play a role in diagnosis.

GSE, particularly coeliac disease, increases the risk of cancers of specific types. There are two predominant cancers associated with coeliac disease, cancer of the esophagus and lymphoproliferative diseases such as gluten-sensitive enteropathy-associated T-cell lymphoma (EATL). For non-EATL cancers it is thought the mineralemias such as zinc and selenium may play a role in increasing risk. GSE associated cancers are invariably associated with advanced coeliac disease, however, in de-novo EATL, the cancer is frequently detected in advance of the coeliac diagnosis, also EATL is the most common neoplasm.

The symptoms and signs of Bright's disease were first described in 1827 by the English physician Richard Bright, after whom the disease was named. In his "Reports of Medical Cases", he described 25 cases of dropsy (edema) which he attributed to kidney disease. Symptoms and signs included: inflammation of serous membranes, hemorrhages, apoplexy, convulsions, blindness and coma. Many of these cases were found to have albumin in their urine (detected by the spoon and candle-heat coagulation), and showed striking morbid changes of the kidneys at autopsy. The triad of dropsy, albumin in the urine and kidney disease came to be regarded as characteristic of Bright's disease. Subsequent work by Bright and others indicated an association with cardiac hypertrophy, which was attributed by Bright to stimulation of the heart. Subsequent work by Mahomed showed that a rise in blood pressure could precede the appearance of albumin in the urine, and the rise in blood pressure and increased resistance to flow was believed to explain the cardiac hypertrophy.

It is now known that Bright's disease is due to a wide range of diverse kidney diseases; thus, the term "Bright's disease" is retained strictly for historical application. The disease was diagnosed frequently in patients with diabetes; at least some of these cases would probably correspond to a modern diagnosis of diabetic nephropathy.

25% of cases progress to severe destructive arthritis. In the United States and Canada, mortality is estimated at about 4% and in Europe, mortality is estimated at 21.7%.

Fabry disease is suspected based on the individual's clinical presentation, and can be diagnosed by an enzyme assay (usually done on leukocytes) to measure the level of alpha-galactosidase activity. An enzyme assay is not reliable for the diagnosis of disease in females due to the random nature of X-inactivation. Molecular genetic analysis of the "GLA" gene is the most accurate method of diagnosis in females, particularly if the mutations have already been identified in male family members. Many disease-causing mutations have been noted. Kidney biopsy may also be suggestive of Fabry disease if excessive lipid buildup is noted. Pediatricians, as well as internists, commonly misdiagnose Fabry disease.

The life span in patients with Schnitzler syndrome has not been shown to differ much from the general population. Careful follow-up is advised, however. A significant proportion of patients develops a lymphoproliferative disorder as a complication, most commonly Waldenström's macroglobulinemia. This may lead to symptoms of hyperviscosity syndrome. AA amyloidosis has also been reported in people with Schnitzler syndrome.

Poor prognostic factors include,

- Persistent synovitis

- Early erosive disease

- Extra-articular findings (including subcutaneous rheumatoid nodules)

- Positive serum RF findings

- Positive serum anti-CCP autoantibodies

- Carriership of HLA-DR4 "Shared Epitope" alleles

- Family history of RA

- Poor functional status

- Socioeconomic factors

- Elevated acute phase response (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP])

- Increased clinical severity.

The twins require the use of wheelchairs for mobility and are unable to speak without the assistance of electronic speaking aids. They experience persistent and painful muscle spasms which are worsened by emotional distress. They are currently living with their parents, with the assistance of hospice workers. Doctors continue to administer tests to the twins in search of a treatment.

Blood tests show a high concentration of specific gamma-globulins (monoclonal gammopathy) of the IgM type. It almost always has light chains of the κ-type. A variant in which IgG is raised has been described, which appears to be ten times as rare. The immunoglobulins may show up in the urine as Bence Jones proteins. Signs of inflammation are often present: these include an increased white blood cell count (leukocytosis) and a raised erythrocyte sedimentation rate and C-reactive protein. There can be anemia of chronic disease. Bone abnormalities can be seen on radiological imaging (often increased density or osteosclerosis) or biopsy.

Because it is such a rare condition (as of September 2014, only 281 cases have been reported), it is important to rule out other conditions which can cause periodic fevers, paraproteins or chronic hives. These include (and are not limited to) autoimmune or autoinflammatory disorders such as adult-onset Still's disease, angioedema, hematological disorders such as lymphoma or monoclonal gammopathy of undetermined significance, other causes of hives, cryoglobulinemia, mastocytosis, chronic neonatal onset multisystem inflammatory disease or Muckle–Wells syndrome.

It is however possible to have more than one rare condition as seen by a patient with Schnitzler's syndrome and cold induced urticaria.

A meeting of experts, including Dr Liliane Schnitzler (then retired) took place in Strasbourg in May 2012 and drew up diagnostic criteria known as the "Strasbourg Criteria". These included two obligate criteria (chronic urticarial rash and monoclonal IgM or IgG) and several minor criteria; a definite diagnosis requires the two obligate criteria and two minor criteria if IgM, three if IgG; a probable diagnosis requires the two obligate criteria and one (IgM) or two (IgG) minor criteria.

The disease may be diagnosed by its characteristic grouping of certain cells (multinucleated globoid cells), nerve demyelination and degeneration, and destruction of brain cells. Special stains for myelin (e.g.; luxol fast blue) may be used to aid diagnosis.

RA reduces lifespan on average from three to twelve years. According to the UK's National Rheumatoid Arthritis Society, Young age at onset, long disease duration, the concurrent presence of other health problems (called co-morbidity), and characteristics of severe RA—such as poor functional ability or overall health status, a lot of joint damage on x-rays, the need for hospitalisation or involvement of organs other than the joints—have been shown to associate with higher mortality". Positive responses to treatment may indicate a better prognosis. A 2005 study by the Mayo Clinic noted that RA sufferers suffer a doubled risk of heart disease, independent of other risk factors such as diabetes, alcohol abuse, and elevated cholesterol, blood pressure and body mass index. The mechanism by which RA causes this increased risk remains unknown; the presence of chronic inflammation has been proposed as a contributing factor. It is possible that the use of new biologic drug therapies extend the lifespan of people with RA and reduce the risk and progression of atherosclerosis. This is based on cohort and registry studies, and still remains hypothetical. It is still uncertain whether biologics improve vascular function in RA or not. There was an increase in total cholesterol and HDLc levels and no improvement of the atherogenic index.

Pogosta disease is a viral disease, established to be identical with other diseases, Karelian fever and Ockelbo disease. The names are derived from the words Pogosta, Karelia and Ockelbo, respectively.

The symptoms of the disease include usually rash, as well as mild fever and other flu-like symptoms; in most cases the symptoms last less than 5 days. However, in some cases, the patients develop a painful arthritis. There are no known chemical agents available to treat the disease.

It has long been suspected that the disease is caused by a Sindbis-like virus, a positive-stranded RNA virus belonging to the Alphavirus genus and family Togaviridae. In 2002 a strain of Sindbis was isolated from patients during an outbreak of the Pogosta disease in Finland, confirming the hypothesis.

This disease is mainly found in the Eastern parts of Finland; a typical Pogosta disease patient is a middle-aged person who has been infected through a mosquito bite while picking berries in the autumn. The prevalence of the disease is about 100 diagnosed cases every year, with larger outbreaks occurring in 7-year intervals.

Individuals found to have circulating cryoglobulins but no signs or symptoms of cryoglobulinemic diseases should be evaluated for the possibility that their cryoglobulinemia is a transient response to a recent or resolving infection. Those with a history of recent infection that also have a spontaneous and full resolution of their cryoglobulinemia need no further treatment. Individuals without a history of infection and not showing resolution of their cryoglobulinemia need to be further evaluated. Their cryoglobulins should be analyzed for their composition of immunoglobulin type(s) and complement component(s) and examined for the presence of the premalignant and malignant diseases associated with Type I disease as well as the infectious and autoimmune diseases associated with type II and type III disease. A study conducted in Italy on >140 asymptomatic individuals found five cases of hepatitis C-related and one case of hepatitis b-related cryoglobulinemia indicating that a complete clinical examination of asymptomatic individuals with cryoglobulinemia offers a means for finding people with serious but potentially treatable and even curable diseases. Individuals who show no evidence of a disease underlying their cryoglobulinemia and who remain asymptomatic should be followed closely for any changes that may indicate development of cryoglobulinemic disease.

All patients with symptomatic cryoglobulinemia are advised to avoid, or protect their extremities, from exposure to cold temperatures. Refrigerators, freezers, and air-conditioning represent dangers of such exposure.