Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used to treat musculoskeletal symptoms. For individuals with severe complications, corticosteroids or immunosuppressive drugs may be prescribed, and sometimes IVIG (intravenous immunoglobulin). Also, disease-modifying antirheumatic drugs (DMARDs) such as methotrexate may be helpful. Hydroxychloroquine (Plaquenil) is another option and is generally considered safer than methotrexate. However, these prescribed drugs have a range of side effects such as nausea, loss of appetite, dizziness, hair loss, stomach aches/cramps, headache, liver toxicity, and increased risk of infections. Also, people who take drugs to suppress the immune system are more likely to develop cancer later.

There is no current cure. The only way to treat this disease is by treating symptoms. Commonly patients are prescribed immunosuppressive drugs. Another route would be to take collagen regulation drugs.

For systemic symptoms, including fatigue, joint pain, myositis and neuropathy, biologic immunosuppressant drugs such as rituximab and belimumab that work via B-cell pathology are often used and have less toxic profiles than traditional immunosuppressive regimens.

Treatment largely depends upon individual disease progression and the nature of presenting symptoms. Antimalarials, corticosteroids, and other drugs may be prescribed, if deemed appropriate by the treating physician.

Topical treatment for the skin changes of scleroderma do not alter the disease course, but may improve pain and ulceration. A range of NSAIDs (nonsteroidal anti-inflammatory drugs) can be used to ease painful symptoms, such as naproxen. There is limited benefit from steroids such as prednisone. Episodes of Raynaud's phenomenon sometimes respond to nifedipine or other calcium channel blockers; severe digital ulceration may respond to prostacyclin analogue iloprost, and the dual endothelin-receptor antagonist bosentan may be beneficial for Raynaud's phenomenon. The skin tightness may be treated systemically with methotrexate and ciclosporin. and the skin thickness treated with penicillamine.

Scleroderma renal crisis, the occurrence of acute renal failure and malignant hypertension (very high blood pressure with evidence of organ damage) in people with scleroderma, is effectively treated with drugs from the class of the ACE inhibitors. The benefit of ACE inhibitors extends even to those who have to commence dialysis to treat their kidney disease, and may give sufficient benefit to allow the discontinuation of renal replacement therapy.

Treatment is targeted to the underlying cause. However, most vasculitis in general are treated with steroids (e.g. methylprednisolone) because the underlying cause of the vasculitis is due to hyperactive immunological damage. Immunosuppressants such as cyclophosphamide and azathioprine may also be given.

A systematic review of antineutrophil cytoplasmic antibody (ANCA) positive vasculitis identified best treatments depending on whether the goal is to induce remission or maintenance and depending on severity of the vasculitis.

There is no cure for dermatomyositis, but the symptoms can be treated. Options include medication, physical therapy, exercise, heat therapy (including microwave and ultrasound), orthotics and assistive devices, and rest. The standard treatment for dermatomyositis is a corticosteroid drug, given either in pill form or intravenously. Immunosuppressant drugs, such as azathioprine and methotrexate, may reduce inflammation in people who do not respond well to prednisone. Periodic treatment using intravenous immunoglobulin can also improve recovery. Other immunosuppressive agents used to treat the inflammation associated with dermatomyositis include cyclosporine A, cyclophosphamide, and tacrolimus. Physical therapy is usually recommended to prevent muscle atrophy and to regain muscle strength and range of motion. Many individuals with dermatomyositis may need a topical ointment, such as topical corticosteroids, for their skin disorder. They should wear a high-protection sunscreen and protective clothing. Surgery may be required to remove calcium deposits that cause nerve pain and recurrent infections.

Antimalarial medications, especially hydroxychloroquine and chloroquine, are used to treat the rashes, as they are in similar conditions.

Rituximab is used when people don't respond to other treatments.

As of 2016, treatments for amyopathic dermatomyositis in adults did not have a strong evidence base; published treatments included antimalarial medications, steroids, taken or orally or applied to the skin, calcineurin inhibitors applied to the skin, dapsone, Intravenous immunoglobulin (IVIG), methotrexate, azathioprine, and mycophenolate mofetil. None appear to be very effective but among them, IVIG has had the best outcomes.

There are no prospective randomized controlled trials studying therapies for relapsing polychondritis. Evidence for efficacy of treatments is based on case reports and series of small groups of patients.

For mild cases limited to joint pain or arthritis, oral nonsteroidal anti-inflammatory drugs (NSAIDs) may be used. Other treatments typically involve medications to suppress the immune system. Corticosteroids are frequently used for more serious disease. Steroid-sparing medications such as azathioprine or methotrexate may be used to minimize steroid doses and limit the side effects of steroids. For severe disease cyclophosphamide is often given in addition to high dose intravenous steroids.

There is no cure for scleroderma, although relief of symptoms is often achieved. These include

- Raynaud's phenomenon with vasodilators such as calcium channel blockers, alpha blockers, serotonin receptor antagonists, angiotensin II receptor inhibitors, statins, local nitrates or iloprost

- Digital ulcers with phosphodiesterase 5 inhibitors (e.g., sildenafil) or iloprost

- Prevention of new digital ulcers with bosentan

- Malnutrition, secondary to intestinal flora overgrowth with tetracycline antibiotics like tetracycline

- Alveolitis with cyclophosphamide, azathioprine with or without corticosteroids

- Pulmonary arterial hypertension with endothelin receptor antagonists, phosphodiesterase 5 inhibitors and prostanoids

- Gastrooesophageal reflux disease with antacids or prokinetics

- Kidney crises with angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists

Systemic disease-modifying treatment with immunosuppressants is often used. Immunosuppressants used in its treatment include azathioprine, methotrexate, cyclophosphamide, mycophenolate, intravenous immunoglobulin, rituximab, sirolimus, alefacept and the tyrosine kinase inhibitors, imatinib, nilotinib and dasatinib.

Experimental therapies under investigation include endothelin receptor antagonsits, tyrosine kinase inhibitors, beta-glycan peptides, halofuginone, basiliximab, alemtuzumab, abatacept and haematopoietic stem cell transplantation.

Before the advent of modern treatments such as prednisone, intravenous immunoglobulin, plasmapheresis, chemotherapies, and other drugs, the prognosis was poor.

The cutaneous manifestations of dermatomyositis may or may not improve with therapy in parallel with the improvement of the myositis. In some people, the weakness and rash resolve together. In others, the two are not linked, with one or the other being more challenging to control. Often, cutaneous disease persists after adequate control of the muscle disease.

The risk of death from the condition is much higher if the heart or lungs are affected.

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.

Hypothyroidism caused by Hashimoto's thyroiditis is treated with thyroid hormone replacement agents such as levothyroxine, triiodothyronine or desiccated thyroid extract. A tablet taken once a day generally keeps the thyroid hormone levels normal. In most cases, the treatment needs to be taken for the rest of the person's life. In the event that hypothyroidism is caused by Hashimoto's thyroiditis, it may be recommended that the TSH levels be kept under 3.0 mIU/L.

Many individuals have mild symptoms, which recur infrequently, while others may have persistent problems that become debilitating or life-threatening.

An overlap syndrome is an autoimmune disease of connective tissue in which a person presents with symptoms of two or more diseases.

Examples of overlap syndromes include mixed connective tissue disease and scleromyositis. Diagnosis depends on which diseases the patient shows symptoms and has positive antibodies for in their lab serology.

In overlap syndrome, features of the following diseases are found (most common listed):

- Systemic lupus erythematosus (SLE),

- Systemic sclerosis,

- Polymyositis,

- Dermatomyositis,

- Rheumatoid arthritis (RA)

- Sjögren's syndrome

- Eosinophilic granulomatosis with polyangiitis (EGPA)

- Autoimmune thyroiditis

- Antiphospholipid antibody syndrome

The treatment of overlap syndrome is mainly based on the use of corticosteroids and immunosuppressants. Biologic drugs, i.e. anti-TNFα or anti-CD20 monoclonal antibodies, have been recently introduced as alternative treatments in refractory cases. There are some concerns with the use of anti-TNF agents in patients with systemic autoimmune diseases due to the risk of triggering disease exacerbations.

Disease progression may be slowed with immunosuppressives and other medications, and esophageal reflux, pulmonary hypertension and Raynaud phenomenon may benefit from symptomatic treatment. However, there is no cure for this disease as there is no cure for scleroderma in general.

Treatment of secondary cryofibrinoginemic disease may use the same methods used for treating the primary disease wherever necessary but focus on treating the associated infectious, malignant, premalignant, vasculitis, or autoimmune disorder with the methods prescribed for the associated disorder. Case report studies suggest that: corticosteroids and immunosuppressive drug regimens, antimicrobial therapy, and anti-neoplastic regimens can be effective treatments for controlling the cryfibrinoginemic disease in cases associated respectively with autoimmune, infectious, and premalignant/malignant disorders.

Studies on the treatment of cryofibrinoginemic disease have involved relatively few patients, are limited primarily to case reports, and differ based on whether the disease is primary or secondary. In all cases of cryofibrinogenemic disease, however, patients should avoid the exposure of afflicted body parts to cold weather or other environmental triggers of symptoms and avoid using cigarettes or other tobacco products. In severe cases, these individuals also risk developing serious thrombotic events which lead to tissue necrosis that may result in secondary bacterial infections and require intensive antimicrobial therapy and/or amputations. Careful treatment of these developments is required.

Treatment for children suspected of PANDAS is generally the same as the standard treatments for TS and OCD. These include cognitive behavioral therapy and medications to treat OCD such as selective serotonin reuptake inhibitors (SSRIs); and "conventional therapy for tics".

A controlled study (Garvey, Perlmutter, "et al", 1999) of prophylactic antibiotic treatment of 37 children found that penicillin V did not prevent GABHS infections or exacerbation of other symptoms; however, compliance was an issue in this study. A later study (Snider, Lougee, "et al", 2005) found that penicillin and azithromycin decreased infections and symptom exacerbation. The sample size, controls, and methodology of that study were criticized. Murphy, Kurlan and Leckman (2010) say, "The use of prophylactic antibiotics to treat PANDAS has become widespread in the community, although the evidence supporting their use is equivocal. The safety and efficacy of antibiotic therapy for patients meeting the PANDAS criteria needs to be determined in carefully designed trials"; de Oliveira and Pelajo (2009) say that because most studies to date have "methodologic issues, including small sample size, retrospective reports of the baseline year, and lack of an adequate placebo arm ... it is recommended to treat these patients only with conventional therapy".

Evidence is insufficient to determine if tonsillectomy is effective.

The prognosis of mixed connective tissue disease is in one third of cases worse than that of systemic lupus erythematosus (SLE). In spite of prednisone treatment, this disease is progressive and may in many cases evolve into a progressive systemic sclerosis (PSS), also referred to as diffuse cutaneous systemic scleroderma (dcSSc) which has a poor outcome. In some cases though the disease is mild and may only need aspirin as a treatment and may go into remission where no Anti-U1-RNP antibodies are detected, but that is rare or within 30% of cases. Most deaths from MCTD are due to heart failure caused by pulmonary arterial hypertension (PAH).

For more severe disease, oral corticosteroids may be necessary to reduce the inflammatory response. When large amounts of steroids are required or if the disease is severe and is not responding to steroid therapy, other immunosuppressive medications often are recommended. These immunosuppressive drugs include methotrexate, cyclophosphamide, cyclosporine or azathioprine. In some cases, combinations of these medicines are prescribed. Occasionally, if the disease has damaged blood vessels, cochlear implantation may

need to be done to correct the problem.

Cinnarizine is mainly used to treat nausea and vomiting associated with motion sickness, vertigo, Ménière's disease, or Cogan's syndrome. Studies have shown it to produce significant improvement in hearing loss in some patients.

A connective tissue disease is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds together, and protects organs. These tissues form a framework, or matrix, for the body, and are composed of two major structural protein molecules: collagen and elastin. There are many different types of collagen protein in each of the body's tissues. Elastin has the capability of stretching and returning to its original length—like a spring or rubber band. Elastin is the major component of ligaments (tissues that attach bone to bone) and skin. In patients with connective tissue disease, it is common for collagen and elastin to become injured by inflammation (ICT). Many connective tissue diseases feature abnormal immune system activity with inflammation in tissues as a result of an immune system that is directed against one's own body tissues (autoimmunity).

Diseases in which inflammation or weakness of collagen tends to occur are also referred to as collagen diseases. Collagen vascular diseases can be (but are not necessarily) associated with collagen and blood vessel abnormalities and that are autoimmune in nature. See also vasculitis.

Connective tissue diseases can have strong or weak inheritance risks, and can also be caused by environmental factors.

Prophylactic antibiotic treatments for tics and OCD are experimental and controversial; overdiagnosis of PANDAS may have led to overuse of antibiotics to treat tics or OCD in the absence of active infection.

A single study of PANDAS patients showed efficacy of immunomodulatory therapy (intravenous immunoglobulin (IVIG) or plasma exchange) to symptoms, but these results are unreplicated by independent studies as of 2010. Kalra and Swedo wrote in 2009, "Because IVIG and plasma exchange both carry a substantial risk of adverse effects, use of these modalities should be reserved for children with particularly severe symptoms and a clear-cut PANDAS presentation. The US National Institutes of Health and American Academy of Neurology 2011 guidelines say there is "inadequate data to determine the efficacy of plasmapheresis in the treatment of acute OCD and tic symptoms in the setting of PANDAS" and "insufficient evidence to support or refute the use of plasmapheresis in the treatment of acute OCD and tic symptoms in the setting of PANDAS", adding that the investigators in the only study of plasmapherisis were not blind to the results. The Medical Advisory Board of the Tourette Syndrome Association said in 2006 that experimental treatments based on the autoimmune theory such as IVIG or plasma exchange should not be undertaken outside of formal clinical trials. The American Heart Association's 2009 guidelines state that, as PANDAS is an unproven hypothesis and well-controlled studies are not yet available, they do "not recommend routine laboratory testing for GAS to diagnose, long-term antistreptococcal prophylaxis to prevent, or immunoregulatory therapy (e.g., intravenous immunoglobulin, plasma exchange) to treat exacerbations of this disorder".

These are also referred to as systemic autoimmune diseases. The autoimmune CTDs may have both genetic and environmental causes. Genetic factors may create a predisposition towards developing these autoimmune diseases. They are characterized as a group by the presence of spontaneous overactivity of the immune system that results in the production of extra antibodies into the circulation. The classic collagen vascular diseases have a "classic" presentation with typical findings that doctors can recognize during an examination. Each also has "classic" blood test abnormalities and abnormal antibody patterns. However, each of these diseases can evolve slowly or rapidly from very subtle abnormalities before demonstrating the classic features that help in the diagnosis. The classic collagen vascular diseases include:

- Systemic lupus erythematosus (SLE) – An inflammation of the connective tissues, SLE can afflict every organ system. It is up to nine times more common in women than men and strikes black women three times as often as white women. The condition is aggravated by sunlight.

- Rheumatoid arthritis – Rheumatoid arthritis is a systemic disorder in which immune cells attack and inflame the membrane around joints. It also can affect the heart, lungs, and eyes. Of the estimated 2.1 million Americans with rheumatoid arthritis, approximately 1.5 million (71 percent) are women.

- Scleroderma – an activation of immune cells that produces scar tissue in the skin, internal organs, and small blood vessels. It affects women three times more often than men overall, but increases to a rate 15 times greater for women during childbearing years, and appears to be more common among black women.

- Sjögren's syndrome – also called Sjögren's disease, is a chronic, slowly progressing inability to secrete saliva and tears. It can occur alone or with rheumatoid arthritis, scleroderma, or systemic lupus erythematosus. Nine out of 10 cases occur in women, most often at or around mid-life.

- Mixed connective tissue disease – Mixed connective-tissue disease (MCTD) is a disorder in which features of various connective-tissue diseases (CTDs) such as systemic lupus erythematosus (SLE); systemic sclerosis (SSc); dermatomyositis (DM); polymyositis (PM); anti-synthetase syndrome; and, occasionally, Sjögren syndrome can coexist and overlap. The course of the disease is chronic and usually milder than other CTDs. In most cases, MCTD is considered an intermediate stage of a disease that eventually becomes either SLE or Scleroderma.

- Undifferentiated connective tissue disease (UCTD) is a disease in which the body mistakenly attacks its own tissues. It is diagnosed when there is evidence of an existing autoimmune condition which does not meet the criteria for any specific autoimmune disease, such as systemic lupus erythematosus or scleroderma. Latent lupus and incomplete lupus are alternative terms that have been used to describe this condition.

- Psoriatic arthritis is also a collagen vascular disease.

Topical and intralesional (injected into the affected areas) corticosteroid drugs may be used, such as fluocinonide, clobetasol propionate or triamcinolone acetonide. Oral candidiasis may develop with long term topical steroid use, and sometimes antimycotics such as miconazole gel or chlorhexidine mouthwash are used to prevent this. Topical ciclosporin is sometimes used.

Dapsone is sometimes used as a steroid sparing agent. The dose is often increased very slowly in order to minimize side effects. Systemic steroids, such as prednisone or prednisolone may be needed in severe cases. Many other drugs have been used to treat mucous membrane pemphoid, including azathioprine, cyclophosphamide, methotrexate, thalidomide, mycophenolate mofetil, leflunomide, sulphasalazine, sulphapuridine, sulphamethoxypiridazine, tetracyclines (e.g. minocycline, doxycycline) and nicotinamide.