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.

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.

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 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.

Medications can be helpful for moderate or severe RP.

- Vasodilators – calcium channel blockers, such as the dihydropyridines nifedipine or amlodipine, preferably slow release preparations – are often first line treatment. They have the common side effects of headache, flushing, and ankle edema; but these are not typically of sufficient severity to require cessation of treatment. The limited evidence available shows that calcium channel blockers are only slightly effective in reducing how often the attacks happen. Peoples whose RP is secondary to erythromelalgia often cannot use vasodilators for therapy as they trigger 'flares' causing the extremities to become burning red due to there being too much blood.

- People with severe RP prone to ulceration or large artery thrombotic events may be prescribed aspirin.

- Sympatholytic agents, such as the alpha-adrenergic blocker prazosin, may provide temporary relief.

- Losartan can, and topical nitrates may, reduce the severity and frequency of attacks, and the phosphodiesterase inhibitors sildenafil and tadalafil may reduce their severity.

- Angiotensin receptor blockers or ACE inhibitors may aid blood flow to the fingers, and there is some evidence that angiotensin receptor blockers (often losartan) reduce frequency and severity of attacks, and possibly better than nifedipine.

- The prostaglandin iloprost is used to manage critical ischemia and pulmonary hypertension in RP, and the endothelin receptor antagonist bosentan is used to manage severe pulmonary hypertension and prevent finger ulcers in scleroderma.

- Statins have a protective effect on blood vessels, and SSRIs such as fluoxetine may help RP symptoms but the data is weak.

Evidence does not support the use of alternative medicine, including acupuncture and laser therapy.

The management of lipodermatosclerosis may include treating venous insufficiency with leg elevation and elastic compression stockings; in some difficult cases, the condition may be improved with the additional use of the fibrinolytic agent, stanozol. Fibrinolytic agents use an enzymatic action to help dissolve blood clots.

Stanozol is injected directly into the affected area, Venous Ablation has also been known to help circulation in patients.

Many oral treatments have been studied, but results so far have been mixed. Some consider the use of nonsurgical approaches to be "controversial".

Collagenase clostridium histolyticum (marketed as Xiaflex by [Auxilium]), a drug originally approved by the FDA to treat Dupuytren's contracture, is now an FDA-approved injectable drug for treatment of Peyronie's disease. The drug is reported to work by breaking down the excess collagen in the penis that causes Peyronie's disease.

Vitamin E supplementation has been studied for decades, and some success has been reported in older trials, but those successes have not been reliably repeated in larger, newer studies. A combination of Vitamin E and colchicine has shown some promise in delaying progression of the condition.

Some newer agents targeting the basic mechanisms of inflammation have been studied in larger clinical trials. These include potassium para-aminobenzoate (Potaba), pentoxifylline (acting through TGFβ1 inhibition), and Coenzyme Q10.

The efficacy of Interferon-alpha-2b in the early stages of the disease has been reported in recent publications, but it was found to be less effective in cases where calcification of the plaque had occurred in common with many treatments.

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.

There is moderately strong evidence that Penile Traction Therapy is a well–tolerated, minimally invasive treatment for Peyronie's disease, but there is uncertainty about the optimal duration of stretching per day and per course of treatment, and the treatment course is difficult.

There is no cure or approved treatment for FOP. Attempts to surgically remove the bone result in explosive bone growth. While under anesthesia, people with FOP may encounter difficulties with intubation, restrictive pulmonary disease, and changes in the electrical conduction system of the heart. Activities that increase the risk of falling or soft tissue injury should be avoided, as even minor trauma may provoke heterotopic bone formation.

For those patients with periodontitis as a manifestation of hematologic disorders, coordination with the patient's physician is instrumental in planning periodontal treatment. Therapy should be avoided during periods of exacerbation of the malignancy or during active phases of chemotherapy, and antimicrobial therapy might be considered when urgent treatment must be performed when granulocyte counts are low.

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

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.

Treatment is by surgical excision (complete removal) of the fibrous tissue overgrowth and addressing the causative factor to prevent recurrence of the lesion. Other sources suggest that surgical excision may not be required in all cases. Common techniques for removal of the excess tissue include traditional removal with a surgical scalpel, electrical scalpel, or laser excision with a laser scalpel, e.g. a carbon dioxide laser, , Neodymium-YAG laser, or diode laser. The poorly fitting denture can be adapted to fit better (a "reline") or a new denture constructed. Alternatively, the section of flange that is sharp/over-extended can be smoothed and reduced with a drill.

There is no known cure for Winchester syndrome; however, there are many therapies that can aid in the treatment of symptoms. Such treatments can include medications: anti-inflammatories, muscle relaxants, and antibiotics. Many individuals will require physical therapy to promote movement and use of the limbs affected by the syndrome. Genetic counseling is typically prescribed for families to help aid in the understanding of the disease. There are a few clinical trials available to participate in. The prognosis for patients diagnosed with Winchester syndrome is positive. It has been reported that several affected individuals have lived to middle age; however,the disease is progressive and mobility will become limited towards the end of life. Eventually, the contractures will remain even with medical intervention, such as surgery.

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.

Clinical trials of isotretinoin, etidronate with oral corticosteroids, and perhexiline maleate have failed to demonstrate effectiveness, though the variable course of the disease and small prevalence induces uncertainty.

A handful of pharmaceutical companies focused on rare disease are currently in varying stages of investigation into different therapeutic approaches for FOP.

In August 2015, U.S. Food and Drug Administration (FDA) Office of Orphan Products Development granted La Jolla Pharmaceuticals orphan drug designation for two novel compounds for FOP. The compounds are small-molecule kinase inhibitors designed to selectively block ACVR1 (ALK2).

In August 2015, Clementia Pharmaceuticals also began the enrollment of children (ages 6 and above) into its Phase II clinical trial investigating palovarotene for the treatment of FOP. Preclinical studies demonstrated that palovarotene, a retinoic acid receptor gamma agonist, blocked abnormal bone formation in animal models via inhibition of secondary messenger systems in the BMP pathway. Clementia licensed palovarotene from Roche Pharmaceuticals, which previously evaluated the compound in more than 800 individuals including healthy volunteers and patients with chronic obstructive pulmonary disease. Palovarotene received Fast Track designation from the U.S. Food and Drug Administration (FDA) and orphan designations for the treatment of FOP from both the FDA and the European Medicines Agency (EMA).

In September 2015, Regeneron announced new insight into the mechanism of disease involving the activation of the ACVR1 receptor by activin A. In 2016, the company initiated a phase 1 study of its activin antibody, REGN 2477, in healthy volunteers; a phase 2 trial in FOP patients is planned for 2017.

Another potential therapeutic approach involves allele-specific RNA interference that targets mutated mRNA for degradation while preserving normal ACVR1 gene expression.

Further investigation into the mechanisms of heterotopic bone formation in FOP could aid in the development of treatments for other disorders involving extra-skeletal bone formation.

Massage therapy using trigger-point release techniques may be effective in short-term pain relief. Physical therapy involving gentle stretching and exercise is useful for recovering full range of motion and motor coordination. Once the trigger points are gone, muscle strengthening exercise can begin, supporting long-term health of the local muscle system.

Myofascial release, which involves gentle fascia manipulation and massage, may improve or remediate the condition.

A systematic review concluded that dry needling for the treatment of myofascial pain syndrome in the lower back appeared to be a useful adjunct to standard therapies, but that clear recommendations could not be made because the published studies were small and of low quality.

Posture evaluation and ergonomics may provide significant relief in the early stages of treatment. Movement therapies such as Alexander Technique and Feldenkrais Method may also be helpful.

Gentle, sustained stretching exercises within a comfortable range of motion have been shown to decrease pain thresholds. Regular, non-intense activity is also encouraged.

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).

Collagen disease is a term previously used to describe systemic autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue.

The term "collagen disease" was coined by Dr. Alvin F. Coburn in 1932, on his quest to discover streptococcal infection as the cause for rheumatic fever.

No curative treatment is available for prolidase deficiency at this time, although palliative treatment is possible to some extent.

The latter mainly focuses on treating the skin lesions through standard methods and stalling collagen degradation (or boosting prolidase performance, where possible), so as to keep the intracellular dipeptide levels low and give the cells time to resynthesise or absorb what proline they cannot recycle so as to be able to rebuild what collagen "does" degrade. Patients can be treated orally with ascorbate (a.k.a. vitamin C, a cofactor of prolyl hydroxylase, an enzyme that hydroxylates proline, increasing collagen stability), manganese (a cofactor of prolidase), suppression of collagenase (a collagen degrading enzyme), and local applications of ointments that contain L-glycine and L-proline. The response to the treatment is inconsistent between affected individuals.

A therapeutic approach based on enzyme replacement (administering functional prolidase) is under consideration.

Due to the weakened immune response in PD cases, it is also of paramount importance to keep any infections under control, often with heavy antibiotics.

Treatment is predominantly preventive. Avoidance of topical phenols and diets low in tyrosine may help. Replacement and repair of damaged tissue is also possible.

Mixed connective tissue disease (also known as Sharp's syndrome), commonly abbreviated as MCTD, is an autoimmune disease characterized by the presence of high blood levels of a specific autoantibody, now called anti-U1 ribonucleoprotein (RNP). The idea behind the "mixed" disease is that this specific autoantibody is also present in other autoimmune diseases such as systemic lupus erythematosus, polymyositis, scleroderma, etc. It was characterized in 1972, and the term was introduced by Leroy in 1980.

It is sometimes said to be the same as undifferentiated connective tissue disease, but other experts specifically reject this idea because undifferentiated connective tissue disease is not necessarily associated with serum antibodies directed against the U1-RNP, and MCTD is associated with a more clearly defined set of signs/symptoms.

Often, treatment is not necessary, because episcleritis is a self-limiting condition. Artificial tears may be used to help with irritation and discomfort. More severe cases can be treated with either topical corticosteroids or oral non-steroidal anti-inflammatory drugs.

Ketorolac, a topical NSAID, may be used, but it is not more effective than artificial tears and it causes more side effects.