Diagnosis of tenosynovitis is typically made clinically after a thorough patient history and physical exam. Aspirated fluid can also be cultured to identify the infectious organism. X-rays are typically unremarkable but can help rule out a broken bone or a foreign body

The differential diagnosis of Kikuchi disease includes systemic lupus erythematosus (SLE), disseminated tuberculosis, lymphoma, sarcoidosis, and viral lymphadenitis. Clinical findings sometimes may include positive results for IgM/IgG/IgA antibodies.

For other causes of lymph node enlargement, see lymphadenopathy.

The heterophile antibody test works by agglutination of red blood cells from guinea pig, sheep and horse. This test is specific but not particularly sensitive (with a false-negative rate of as high as 25% in the first week, 5–10% in the second, and 5% in the third). About 90% of patients have heterophile antibodies by week 3, disappearing in under a year. The antibodies involved in the test do not interact with the Epstein–Barr virus or any of its antigens.

The monospot test is not recommended for general use by the CDC due to its poor accuracy.

The presence of an enlarged spleen, and swollen posterior cervical, axillary, and inguinal lymph nodes are the most useful to suspect a diagnosis of infectious mononucleosis. On the other hand, the absence of swollen cervical lymph nodes and fatigue are the most useful to dismiss the idea of infectious mononucleosis as the correct diagnosis. The insensitivity of the physical examination in detecting an enlarged spleen means it should not be used as evidence against infectious mononucleosis. A physical examination may also show petechiae in the palate.

It is diagnosed by lymph node excision biopsy.

Kikuchi disease is a self-limiting illness which has symptoms which may overlap with Hodgkin's lymphoma leading to misdiagnosis in some patients.

Antinuclear antibodies, antiphospholipid antibodies, anti-dsDNA, and rheumatoid factor are usually negative, and may help in differentiation from systemic lupus erythematosus.

Treatment for infectious tenosynovitis is more effective the earlier the condition is identified and treated. Factors that worsen patient outcomes include being older than 43, having diabetes mellitus, and a polymicrobial infection.

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.

Synovitis symptoms can be treated with anti-inflammatory drugs such as NSAIDs. An injection of steroids may be done, directly into the affected joint. Specific treatment depends on the underlying cause of the synovitis.

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.

There is no specific test for this condition. Diagnosis is based on signs and symptoms, and exclusion of other conditions.

There are no set standards for the diagnosis of suspected transient synovitis, so the amount of investigations will depend on the need to exclude other, more serious diseases.

Inflammatory parameters in the blood may be slightly raised (these include erythrocyte sedimentation rate, C-reactive protein and white blood cell count), but raised inflammatory markers are strong predictors of other more serious conditions such as septic arthritis.

X-ray imaging of the hip is most often unremarkable. Subtle radiographic signs include an accentuated pericapsular shadow, widening of the medial joint space, lateral displacement of the femoral epiphyses with surface flattening (Waldenström sign), prominent obturator shadow, diminution of soft tissue planes around the hip joint or slight demineralisation of the proximal femur. The main reason for radiographic examination is to exclude bony lesions such as occult fractures, slipped upper femoral epiphysis or bone tumours (such as osteoid osteoma). An anteroposterior and frog lateral (Lauenstein) view of the pelvis and both hips is advisable.

An ultrasound scan of the hip can easily demonstrate fluid inside the joint capsule (Fabella sign), although this is not always present in transient synovitis. However, it cannot reliably distinguish between septic arthritis and transient synovitis. If septic arthritis needs to be ruled out, needle aspiration of the fluid can be performed under ultrasound guidance. In transient synovitis, the joint fluid will be clear. In septic arthritis, there will be pus in the joint, which can be sent for bacterial culture and antibiotic sensitivity testing.

More advanced imaging techniques can be used if the clinical picture is unclear; the exact role of different imaging modalities remains uncertain. Some studies have demonstrated findings on magnetic resonance imaging (MRI scan) that can differentiate between septic arthritis and transient synovitis (for example, signal intensity of adjacent bone marrow). Skeletal scintigraphy can be entirely normal in transient synovitis, and scintigraphic findings do not distinguish transient synovitis from other joint conditions in children. CT scanning does not appear helpful.

Biochemical tests used in the identification of infectious agents include the detection of metabolic or enzymatic products characteristic of a particular infectious agent. Since bacteria ferment carbohydrates in patterns characteristic of their genus and species, the detection of fermentation products is commonly used in bacterial identification. Acids, alcohols and gases are usually detected in these tests when bacteria are grown in selective liquid or solid media.

The isolation of enzymes from infected tissue can also provide the basis of a biochemical diagnosis of an infectious disease. For example, humans can make neither RNA replicases nor reverse transcriptase, and the presence of these enzymes are characteristic of specific types of viral infections. The ability of the viral protein hemagglutinin to bind red blood cells together into a detectable matrix may also be characterized as a biochemical test for viral infection, although strictly speaking hemagglutinin is not an "enzyme" and has no metabolic function.

Serological methods are highly sensitive, specific and often extremely rapid tests used to identify microorganisms. These tests are based upon the ability of an antibody to bind specifically to an antigen. The antigen, usually a protein or carbohydrate made by an infectious agent, is bound by the antibody. This binding then sets off a chain of events that can be visibly obvious in various ways, dependent upon the test. For example, "Strep throat" is often diagnosed within minutes, and is based on the appearance of antigens made by the causative agent, "S. pyogenes", that is retrieved from a patients throat with a cotton swab. Serological tests, if available, are usually the preferred route of identification, however the tests are costly to develop and the reagents used in the test often require refrigeration. Some serological methods are extremely costly, although when commonly used, such as with the "strep test", they can be inexpensive.

Complex serological techniques have been developed into what are known as Immunoassays. Immunoassays can use the basic antibody – antigen binding as the basis to produce an electro-magnetic or particle radiation signal, which can be detected by some form of instrumentation. Signal of unknowns can be compared to that of standards allowing quantitation of the target antigen. To aid in the diagnosis of infectious diseases, immunoassays can detect or measure antigens from either infectious agents or proteins generated by an infected organism in response to a foreign agent. For example, immunoassay A may detect the presence of a surface protein from a virus particle. Immunoassay B on the other hand may detect or measure antibodies produced by an organism's immune system that are made to neutralize and allow the destruction of the virus.

Instrumentation can be used to read extremely small signals created by secondary reactions linked to the antibody – antigen binding. Instrumentation can control sampling, reagent use, reaction times, signal detection, calculation of results, and data management to yield a cost effective automated process for diagnosis of infectious disease.

A list of the more common and well-known diseases associated with infectious pathogens is provided and is not intended to be a complete listing.

Once PVNS is confirmed by biopsy of the synovium of an affected joint, a synovectomy of the affected area is the most common treatment. Bone lesions caused by the disorder are removed and bone grafting is performed as needed. Because diffuse PVNS has a relatively high rate of recurrence, radiation therapy may be considered as a treatment option. In some cases, a total joint replacement is needed to relieve symptoms when PVNS causes significant joint destruction.

Pain in or around the hip and/or limp in children can be due to a large number of conditions. Septic arthritis (a bacterial infection of the joint) is the most important differential diagnosis, because it can quickly cause irreversible damage to the hip joint. Fever, raised inflammatory markers on blood tests and severe symptoms (inability to bear weight, pronounced muscle guarding) all point to septic arthritis, but a high index of suspicion remains necessary even if these are not present. Osteomyelitis (infection of the bone tissue) can also cause pain and limp.

Bone fractures, such as a toddler's fracture (spiral fracture of the shin bone), can also cause pain and limp, but are uncommon around the hip joint. Soft tissue injuries can be evident when bruises are present. Muscle or ligament injuries can be contracted during heavy physical activity —however, it is important not to miss a slipped upper femoral epiphysis. Avascular necrosis of the femoral head (Legg-Calvé-Perthes disease) typically occurs in children aged 4–8, and is also more common in boys. There may be an effusion on ultrasound, similar to transient synovitis.

Neurological conditions can also present with a limp. If developmental dysplasia of the hip is missed early in life, it can come to attention later in this way. Pain in the groin can also be caused by diseases of the organs in the abdomen (such as a psoas abscess) or by testicular disease. Rarely, there is an underlying rheumatic condition (juvenile idiopathic arthritis, Lyme arthritis, gonococcal arthritis, ...) or bone tumour.

Given the wide range of bacteria, viruses, and other pathogens that cause debilitating and life-threatening illness, the ability to quickly identify the cause of infection is important yet often challenging. For example, more than half of cases of encephalitis, a severe illness affecting the brain, remain undiagnosed, despite extensive testing using state-of-the-art clinical laboratory methods. Metagenomics is currently being researched for clinical use, and shows promise as a sensitive and rapid way to diagnose infection using a single all-encompassing test. This test is similar to current PCR tests; however, amplification of genetic material is unbiased rather than using primers for a specific infectious agent. This amplification step is followed by next-generation sequencing and alignment comparisons using large databases of thousands of organismic and viral genomes.

Metagenomic sequencing could prove especially useful for diagnosis when the patient is immunocompromised. An ever-wider array of infectious agents can cause serious harm to individuals with immunosuppression, so clinical screening must often be broader. Additionally, the expression of symptoms is often atypical, making clinical diagnosis based on presentation more difficult. Thirdly, diagnostic methods that rely on the detection of antibodies are more likely to fail. A broad, sensitive test for pathogens that detects the presence of infectious material rather than antibodies is therefore highly desirable.

Infectious pathogen-associated diseases include many of the most common and costly chronic illnesses. The treatment of chronic diseases accounts for 75% of all US healthcare costs (amounting to $1.7 trillion in 2009).

Two elements are considered: radiology and joint fluid analysis.

Radiology has a large role to play in finding chondrocalcinosis, with radiographs, CT scans, MRIs, US, and nuclear medicine all having a part. CT scans and MRIs show calcific masses (usually within the ligamentum flavum or joint capsule), however radiography is more successful. At ultrasound, chondrocalcinosis may be depicted as echogenic foci with no acoustic shadow within the hyaline cartilage. As with most conditions, CPPD can present with similarity to other diseases such as ankylosing spondylitis and gout.

Arthrocentesis, or removing synovial fluid from the affected joint, is performed to test the synovial fluid for the calcium pyrophosphate crystals that are present in CPPD. When stained with H&E stain, calcium pyrophosphate crystals appears deeply blue ("basophilic"). However, CPP crystals are much better known for their rhomboid shape and weak positive birefringence on polarized light microscopy, and this method remains the most reliable method of identifying the crystals under the microscope. However, even this method suffers from poor sensitivity, specificity, and inter-operator agreement.

These two modalities currently define CPPD disease but lack diagnostic accuracy, and are potentially epiphenomenological.

PVNS is radiologically diagnosed by magnetic resonance imaging (MRI). The disorder is difficult to identify and is often not diagnosed for four years or more after presentation due to nonspecific symptoms or a general paucity of symptoms.

Once established, periods of remissions and relapse can persist indefinitely.

While IH may remit spontaneously for most people the condition is long-lasting. Treatments as described above can be effective in reducing the frequency and degree of effusions. Deformative changes to joints are not a common feature of this mostly non-inflammatory condition.

Ultrasonography and magnetic resonance imaging of the hands and/or feet have been proposed as useful diagnostic investigations in RS3PE.

Some studies linked RS3PE to HLA-B27 whereas others have not.

Bisphosphonate therapy has been suggested as a first-line therapeutic option in many case reports and series.

Treatment with tumor necrosis factor alpha antagonists (TNF inhibitors) have been tried in few patients with limited success. Other drugs that are used in psoriatic arthritis, to which SAPHO syndrome is closely related, have also been used in this condition. They include NSAIDs, corticosteroids, sulfasalazine, methotrexate, ciclosporin and leflunomide.

Some patients have responded to antibiotics. The rationale for their use is that Propionibacterium acnes, a bacterium known for its role in acne, has been isolated from bone biopsies of SAPHO patients.

There is no specific treatment for infectious mononucleosis, other than treating the symptoms. In severe cases, steroids such as corticosteroids may be used to control the swelling of the throat and tonsils. Currently, there are no antiviral drugs or vaccines available.

It is important to note that symptoms related to infectious mononucleosis caused by EBV infection seldom last for more than 4 months. When such an illness lasts more than 6 months, it is frequently called chronic EBV infection. However, valid laboratory evidence for continued active EBV infection is seldom found in these patients. The illness should be investigated further to determine if it meets the criteria for chronic fatigue syndrome, or CFS. This process includes ruling out other causes of chronic illness or fatigue.

lymphadenopathy is a common biopsy finding, and may often be confused with malignant lymphoma. It may be separated into major morphologic patterns, each with its own differential diagnosis with certain types of lymphoma. Most cases of reactive follicular hyperplasia are easy to diagnose, but some cases may be confused with follicular lymphoma. There are seven distinct patterns of benign lymphadenopathy:

- Follicular hyperplasia: This is the most common type of reactive lymphadenopathy.

- Paracortical hyperplasia/Interfollicular hyperplasia: It is seen in viral infections, skin diseases, and nonspecific reactions.

- Sinus histiocytosis: It is seen in lymph nodes draining limbs, inflammatory lesions, and malignancies.

- Nodal extensive necrosis

- Nodal granulomatous inflammation

- Nodal extensive fibrosis (Connective tissue framework)

- Nodal deposition of interstitial substance

These morphological patterns are never pure. Thus, reactive follicular hyperplasia can have a component of paracortical hyperplasia. However, this distinction is important for the differential diagnosis of the cause.

Synovitis is the medical term for inflammation of the synovial membrane. This membrane lines joints that possess cavities, known as synovial joints. The condition is usually painful, particularly when the joint is moved. The joint usually swells due to synovial fluid collection.

Synovitis may occur in association with arthritis as well as lupus, gout, and other conditions. Synovitis is more commonly found in rheumatoid arthritis than in other forms of arthritis, and can thus serve as a distinguishing factor, although it is also present in many joints affected with osteoarthritis. Long term occurrence of synovitis can result in degeneration of the joint.