In the presence of suspicious symptoms a number of test are helpful in the diagnosis:

- Muscle enzymes are often elevated, i.e. creatine kinase

- Anti-Jo-1 antibody testing

- Electromyography

- Muscle biopsy

- Pulmonary function testing

- Lung biopsy

In certain situations, testing of other antibodies, specific imaging (MRI, thoracic high resolution computed tomography), and swallowing evaluation may be needed.

Unfortunately, treatment for the anti-synthetase syndrome is limited, and usually involves immunosuppressive drugs such as glucocorticoids. For patients with pulmonary involvement, the most serious complication of this syndrome is pulmonary fibrosis and subsequent pulmonary hypertension.

Additional treatment with azathioprine and/or methotrexate may be required in advanced cases.

Prognosis is largely determined by the extent of pulmonary damage.

CREST is not easily diagnosed as it closely mimics symptoms of other connective tissue and autoimmune diseases. Diagnoses are usually given when a patient presents three or more of the five major clinical symptoms. Additionally, blood exams can be given to test for a positive ANAs and ACAs or skin biopsies can be given to help confirm a diagnosis.

CREST syndrome can be noted in up to 10% of patients with primary biliary cirrhosis.

The diagnosis of GPS is often difficult, as numerous other diseases can cause the various manifestations of the condition and the condition itself is rare. The most accurate means of achieving the diagnosis is testing the affected tissues by means of a biopsy, especially the kidney, as it is the best-studied organ for obtaining a sample for the presence of anti-GBM antibodies. On top of the anti-GBM antibodies implicated in the disease, about one in three of those affected also has cytoplasmic antineutrophilic antibodies in their bloodstream, which often predates the anti-GBM antibodies by about a few months or even years. The later the disease is diagnosed, the worse the outcome is for the affected person.

Critics of the diagnosis complain that case evidence is spotty and lacking controlled clinical studies.

Diagnosis is achieved by examining the structure of the chromosomes through karyotyping; while once born, one can do the following to ascertain a diagnosis of the condition:

- MRI

- EEG

Those diagnosed are usually treated with taking a low dose (80–100 mg) Aspirin a day. Anticoagulants (e.g. Warfarin, Coumadin) or clopidogrel (Plavix) are often additionally prescribed following formation of a medically significant clot. Thrombelastography is more commonly being used to diagnose hypercoagulability and monitor anti-platelet therapy.

Patient should seek a physician for skin tests. Typically, after a consultation with rheumatologist, the disease will be diagnosed. A dermatologist is also another specialist that can diagnose.

Blood studies and numerous other specialized tests depending upon which organs are affected.

Ring chromosome 14 syndrome is extremely rare, the true rate of occurrence is unknown (as it is "less than" 1 per 1,000,000), but there are at least 50 documented cases in the literature.

Löfgren syndrome is associated with a good prognosis, with > 90% of patients experiencing disease resolution within 2 years. In contrast, patients with the disfiguring skin condition lupus pernio or cardiac or neurologic involvement rarely experience disease remission.

The major mainstay of treatment for GPS is plasmapheresis, a procedure in which the affected person's blood is sent through a centrifuge and the various components separated based on weight. The plasma, clear liquid part of the blood, contains the anti-GBM antibodies that attack the affected person's lungs and kidneys and is filtered out. The other parts of the blood, that is, the red blood cells, white blood cells, and platelets, are recycled and given intravenously as a replacement fluid. Most individuals affected by the disease also need to be treated with immunosuppressant drugs, especially cyclophosphamide, prednisone, and rituximab, to prevent the formation of new anti-GBM antibodies so as to prevent further damage to the kidneys and lungs. Other, less toxic immunosuppressants such as azathioprine may be used to maintain remission.

NSAIDs (non steroid anti-inflammatory drug) are the usual recommended treatment for Löfgren syndrome.

Diagnosis is mainly based on clinical features. However, biopsy has been useful in diagnosis as well as in differentiating between the different types of the disease.

There is no official diagnostic criteria for UCTD. Diagnostic testing generally aims to determine whether a patient has a "definite" or "undifferentiated" connective tissue disease.

Diagnosis of AIR can be difficult due to the overlap of symptoms with other disorders. Examination of the fundus (inner surface of eye) can show no results or it can show narrowing of the blood vessels, abnormal colouration of the optic disc, and retinal atrophy. Fundus examination results are not indicative of autoimmune retinopathy but they are used to initiate the diagnostic process. An electroretinogram (eye test used to see abnormalities in the retina) is used to detect AIR. An abnormal electroretinogram (ERG) with respect to light and dark adaptations indicates AIR. The ERG also allows differentiation between cancer-associated retinopathy and melanoma-associated retinopathy. If the ERG shows cone responses, CAR can be prematurely diagnosed. If the ERG shows a significant decrease in b-wave amplitude, MAR can be prematurely diagnosed. To confirm, analysis for anti-retinal antibodies through Western blotting of serum collected from the patient is done.

Distinguishing laboratory characteristics are a positive, speckled anti-nuclear antibody and an anti-U1-RNP antibody.

Clinically, IPH manifests as a triad of haemoptysis, diffuse parenchymal infiltrates on chest radiographs, and iron deficiency anaemia. It is diagnosed at an average age of 4.5 plus or minus 3.5 years, and it is twice as common in females. The clinical course of IPH is exceedingly variable, and most of the patients continue to have episodes of pulmonary haemorrhage despite therapy. Death may occur suddenly from acute pulmonary haemorrhage or after progressive pulmonary insufficiency resulting in chronic respiratory failure.

Most patients will maintain a diagnosis of undifferentiated connective tissue disease. However, about one third of UCTD patients will differentiate to a specific autoimmune disease, like rheumatoid arthritis or systemic sclerosis. About 12 percent of patients will go into remission.

Severe vitamin D deficiency has been associated with the progression of UCTD into defined connective tissue diseases. The presence of the autoantibodies anti-dsDNA, anti-Sm, and anti-cardiolipin has been shown to correlate with the development of systemic lupus erythematosus, specifically.

Serum analysis often aids in the diagnosis of a specific underlying disease. The presence of anti-Glomerular basement membrane (GBM) antibodies suggests type I RPGN; antinuclear antibodies (ANA) may support a diagnosis of systemic lupus erythematosus and type II RPGN; and type III and idiopathic RPGN are frequently associated with anti-neutrophil cytoplasmic antibodies (ANCA)-positive serum.

Impaired renal functions in an individual with 3 months or less of the condition is an indication of RPGN. An ultrasonographic examination of the abdomen should also be done. Upon urine examination, urinary sediment (proteinuria) can indicate proliferative glomerulonephritis, many cases of rapidly progressive glomerulonephritis need a renal biopsy to make a diagnosis.

Immunoglobulin samples are obtained from a large pool of healthy, matched donors (10000 - 20000). The immunoglobulin mixture is then administered through IV at a rate of 0.4g/kg/day for 5 days. Antibodies in the IVIG mixture interact with binding sites of the disease-associated antibodies (such as anti-recoverin antibodies). This prevents binding to proteins targeted as antigenic and reduces disease activity. Responses to this treatment can vary and are impacted if the patient is diagnosed with any type of cancer. Patients who respond positively show improvement in the clarity of their vision and their visual field.

Arterial blood gases may reveal hypoxemia when tested in a lab. Respiratory alkalosis may also be present. Peripheral lymphocytosis can be observed. A lung biopsy may also be indicated.

RPGN can be classified into three types, based upon the immunofluorescence patterns:

Breathing difficulties can occur, resulting from neuromyotonic activity of the laryngeal muscles. Laryngeal spasm possibly resulting from neuromyotonia has been described previously, and this highlights that, in patients with unexplained laryngospasm, neuromytonia should be added to the list of differential diagnoses.

Studies have shown subtly decreased metabolism on positron emission tomography (PET) and single photon emission computed tomography (SPECT) in the left inferior frontal and left temporal lobes. and or basal ganglia hypermetabolism. Ancillary laboratory tests including MRI and brain biopsy have confirmed temporal lobe involvement. Cranial MRI shows increased signal in the hippocampus.

Cerebral spinal fluid (CSF) shows normal protein, glucose, white blood cell, and IgG index but there are weak oligoclonal bands, absent in the blood. Marked changes in circadian serum levels of neurohormones and increased levels of peripheral neurotransmitters were also observed. The absence of morphological alterations of the brain pathology, the suggestion of diffusion of IgG into the thalamus and striatum, more marked than in the cortex (consistent with effects on the thalamolimbic system) the oligoclonal bands in the CSF and the amelioration after PE all strongly support an antibody-mediated basis for the condition. Raised CSF IgG concentrations and oligoclonal bands have been reported in patients with psychosis. Anti-acetylcholine receptors (anti-AChR) antibodies have also been detected in patients with thymoma, but without clinical manifestations of myasthenia gravis. There have also been reports of non-paraneoplastic limbic encephalitis associated with raised serum VGKC suggesting that these antibodies may give rise to a spectrum of neurological disease presenting with symptoms arising peripherally, centrally, or both. Yet, in two cases, oligoclonal bands were absent in the CSF and serum, and CSF immunoglobulin profiles were unremarkable.

Most patients reported in the literature have been given treatments suitable for autoimmune neurological diseases, such as corticosteroids, plasmapheresis and/or intravenous immunoglobulin, and most have made a good recovery. The condition is too rare for controlled trials to have been undertaken.