Connective Tissue Disease (Autoimmune)

This page focuses on autoimmune connective tissue diseases. For the broader group, including inherited conditions such as Ehlers-Danlos and Marfan syndromes, see connective tissue disorders.

What connective tissue is

Connective tissue holds the body together. It includes skin, tendons, ligaments, cartilage, blood vessel walls, and the linings around the lungs, heart and joints. It is made of proteins such as collagen and elastin. In autoimmune CTDs, the immune system makes antibodies and inflammatory cells that attack these tissues in many organs at once, which is why symptoms can be widespread and varied.

Main types

Rheumatoid arthritis, vasculitis and antiphospholipid syndrome are related autoimmune conditions that often appear alongside them.

Symptoms

Symptoms vary by type and can come and go in flares:

• joint pain and swelling, often in the hands
• fatigue, often severe
• Raynaud phenomenon: fingers turning white, then blue, then red in the cold or with stress
• skin changes: rashes, sun sensitivity, thickened or tight skin, calcium deposits
• dry eyes and dry mouth
• muscle weakness and aches
• mouth ulcers and hair loss
• low-grade fevers and weight loss
• chest pain on breathing from inflamed linings
• shortness of breath from lung involvement
• swallowing problems and reflux

Causes and risk factors

The exact cause is unknown. A combination of genetic susceptibility, female hormones and environmental triggers is thought to set off the immune response. Triggers can include ultraviolet light (lupus), some infections, silica dust and some medicines (drug-induced lupus). Most CTDs are more common in women. Lupus is more common and often more severe in Black, Hispanic and Asian people.

Diagnosis

A rheumatologist combines symptoms, examination and tests:

• ANA (antinuclear antibody): positive in nearly all people with lupus and most with other CTDs. A positive ANA alone is common in healthy people, especially at low levels, and does not mean disease.
• Specific antibodies: anti-dsDNA, anti-Sm, anti-Ro, anti-La, anti-RNP, anti-centromere, anti-Scl-70 and myositis panels.
• Complement levels, blood counts, kidney and liver function, CK (muscle enzyme), and inflammatory markers.
• Urine tests for protein and blood.
• Organ assessment: chest CT and lung function tests, echocardiogram, nailfold capillaroscopy, muscle MRI or biopsy, and skin or kidney biopsy as needed.

Treatment

Treatment is tailored to the disease and the organs involved:

• hydroxychloroquine: a cornerstone for lupus and helpful in other CTDs; requires regular eye screening
• corticosteroids: for flares, at the lowest effective dose
• immunosuppressants: methotrexate, azathioprine, mycophenolate, cyclophosphamide
• biologics and targeted drugs: belimumab and anifrolumab for lupus, rituximab, IVIG for myositis, nintedanib for scleroderma lung disease
• organ-specific treatments: calcium channel blockers for Raynaud, acid suppression for reflux, artificial tears and saliva substitutes, blood pressure control for kidney disease

Self-care

• sun protection, especially in lupus
• keeping warm, gloves and avoiding smoking for Raynaud
• regular exercise and paced activity for fatigue
• vaccinations, as advised, because of immune-suppressing treatment
• planning pregnancy with your rheumatologist

Outlook

With modern treatment, most people with autoimmune CTD lead full lives. Outcomes depend on the organs involved: kidney, lung and heart involvement need close monitoring. Undifferentiated CTD often stays mild, and only a minority evolve into a defined disease.

Frequently asked questions

What is connective tissue disease?

Connective tissue disease usually refers to a group of autoimmune conditions in which the immune system attacks connective tissues such as skin, joints, muscles and blood vessels. Examples include lupus, scleroderma, Sjogren's disease and myositis.

What are the symptoms of connective tissue disease?

Common symptoms are joint pain, fatigue, fingers changing color in the cold, rashes, sun sensitivity, dry eyes and mouth, muscle weakness, mouth ulcers and hair loss. Symptoms vary with the specific disease and often come in flares.

What is undifferentiated connective tissue disease?

It is a condition with some features of an autoimmune connective tissue disease and positive antibodies, but not enough to classify it as lupus, scleroderma or another specific disease. It is often mild, and many people never progress to a defined disease.

Does a positive ANA mean I have a connective tissue disease?

No. A positive ANA is found in many healthy people, especially at low levels and in older adults. It supports a diagnosis only when symptoms and other tests fit. A rheumatologist can interpret the result.