Mixed Connective Tissue Disease (MCTD)

What is Mixed Connective Tissue Disease?

Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disease that has overlapping features of at least two connective tissue diseases, such as lupus, systemic sclerosis (scleroderma), polymyositis or dermatomyositis, and rheumatoid arthritis.^[1] It is defined by high levels of anti-U1-ribonucleoprotein (anti-U1 RNP) antibodies together with features such as Raynaud phenomenon.^{[1, 2]} It is the least common of the connective tissue diseases.^[2]

Common symptoms

Early disease is mainly Raynaud phenomenon, joint inflammation, puffy fingers and muscle pain or inflammation, and rarely facial nerve pain (trigeminal neuropathy).^[3] Other features include swollen joints, esophageal problems, muscle weakness and fingers that look sausage-like.^[4]

The disease can also affect the lungs, heart, kidneys, digestive tract and nervous system.^[4] Fatigue is a common symptom across rheumatic diseases.^[5]

Causes and risk factors

The cause is unknown. MCTD is strongly linked to certain HLA (immune-system) gene types, suggesting inherited susceptibility.^[2] It is more common in women. Environmental triggers are suspected but not established.

How it is diagnosed and treated conventionally

Diagnosis is made by a physician, usually a rheumatologist, from symptoms, blood tests showing a high anti-U1 RNP level, and testing of organs that may be involved. No internationally agreed criteria exist, and the diagnosis can be hard because the features overlap.^{[1, 3]}

Treatment depends on which organs are affected. Medicines typically include corticosteroids, hydroxychloroquine and immune-suppressing drugs, with specific treatment for lung or heart disease, and calcium channel blockers for Raynaud.^{[1, 6]} There is no full agreement on treatment, and low-dose steroids do not always work.^[4] Pulmonary hypertension and interstitial lung disease are the two main causes of death, so regular monitoring matters.^[3]

Why Mixed Connective Tissue Disease calls for a whole-person approach

MCTD affects many body systems, and symptoms such as pain, cold hands, fatigue and poor sleep add to the burden of disease even when the medicines are working. Supportive care aims at these day-to-day symptoms and does not treat the autoimmune process.

The factors below are relevant to many rheumatic diseases. Most have not been studied specifically in MCTD.

Blood vessel reactivity and Raynaud

Raynaud phenomenon is a defining feature, with fingers or toes that turn white or blue in the cold or with stress.^[1] In Raynaud linked to another disease, calcium channel blockers and iloprost have clear evidence of benefit, while other treatments have limited or conflicting evidence.^[6]

Joint and muscle pain

Joint inflammation and muscle pain are common and often the first features.^{[3, 4]} These are managed by your rheumatology team, and supportive care may help comfort and function.

Fatigue, sleep and mood

Fatigue is among the most common and disabling symptoms in rheumatic disease, and it is linked to depression, pain and sleep problems. In a review of systemic sclerosis, drug treatments were mostly ineffective for fatigue, while physical activity and complementary approaches gave more encouraging results.^[5]

Immune-suppressing medicines

Corticosteroids and other immunosuppressants affect infection risk, bone, liver and mood, and they can interact with herbs.^{[4, 7]} Complementary care has to be planned around them.

Acupuncture as supportive care in Mixed Connective Tissue Disease

What the research shows

No clinical trials of acupuncture in MCTD were found in PubMed. Acupuncture cannot be said to treat this disease. The research that exists is for conditions that overlap with it.

For Raynaud, a meta-analysis of six trials with 272 people found acupuncture was associated with more remissions and fewer daily attacks, but the authors rated the quality of evidence very low, with high risk of bias.^[8] A review of secondary Raynaud found only one acupuncture trial and no clear benefit, while calcium channel blockers had clear support.^[6] Another review of complementary treatments for Raynaud, covering two acupuncture trials, found most trials were negative or of poor quality.^[9]

For rheumatoid arthritis, results conflict. A network meta-analysis of 32 trials found acupuncture-related therapies added to disease-modifying drugs improved some disease scores and pain, though the review could not say which therapy was best because of limited studies.^[10] A separate review of 7 systematic reviews (20 trials) concluded acupuncture probably has little or no impact on rheumatoid arthritis.^[11] A meta-analysis of 24 trials found acupuncture improved sleep in insomnia, mainly after about three weeks.^[12]

How acupuncture may work

No mechanism has been shown in MCTD, and the Raynaud and arthritis reviews above did not establish one.

What treatment involves

Sessions use fine, sterile, single-use needles, usually left in for about 20 to 40 minutes, with a short course of visits followed by reassessment. Needles are not placed through skin with sores, ulcers or infection, which can occur with scleroderma-like skin changes.

In prospective studies, about 9 in 100 patients had a minor reaction such as soreness or bleeding at a needle site, and serious events occurred in about 1 in 10,000 patients.^[13] Tell the practitioner first if you take immunosuppressants or corticosteroids, have skin ulcers, a bleeding disorder, take blood thinners, are pregnant, or have a pacemaker (relevant to electroacupuncture). People with MCTD who have pulmonary hypertension or lung disease should tell us so that treatment is planned with their physician.

Ayurvedic medicine as supportive care in Mixed Connective Tissue Disease

The Ayurvedic view

Ayurveda has no classical name for MCTD. Autoimmune and joint conditions are traditionally discussed in terms of Vata and Pitta imbalance, impaired digestion (agni) and accumulated toxins (ama), and cold fingers and joint pain fit Vata descriptions. These are traditional explanatory frameworks, not medical diagnoses.

Therapies that may be used

Care is individual and may include diet and daily-routine advice, stress-reducing practices, gentle warm oil massage, and herbs chosen by the practitioner. Warm-oil approaches are used with care where skin is thickened or fragile.

Panchakarma procedures are not appropriate during pregnancy, acute illness or frailty, and generally not for people with organ involvement or taking strong immunosuppressants unless the treating physician agrees.

What the research shows

No studies of Ayurvedic treatment for MCTD were found, so evidence is none. Ayurvedic herbs have not been tested for Raynaud or other MCTD features in trials we could rely on.

One study of Ayurvedic medicines sold online found detectable lead, mercury or arsenic in about one fifth of them, and more often in those combining herbs with metals or minerals.^[14] Ayurvedic herbs can also interact with prescribed drugs, as other herbs do.^[7] Contamination is a particular concern for people taking immunosuppressants and for those with kidney problems.

Herbal medicine as supportive care in Mixed Connective Tissue Disease

Herbs and formulas that have been studied

No herbs or formulas have been studied in MCTD. Research exists for primary Raynaud, for which Chinese formulas such as Danggui Sini Tang have been tested, and for related rheumatic diseases, including curcumin from turmeric and Tripterygium wilfordii (thunder god vine).^{[15, 16, 17]}

What the research shows

A review of eight trials (674 people) of Chinese herbal medicine in primary Raynaud found possible benefit over nifedipine in global symptoms, but the trial quality was generally poor and the authors called the benefit inconclusive. Primary Raynaud is not the same as Raynaud in a connective tissue disease.^[15]

A review of curcumin in 10 autoimmune diseases, including 2 trials in lupus, found improvements in some trials but too few small trials to draw firm conclusions.^[16] A Cochrane review of herbal therapy in rheumatoid arthritis found some benefit from Tripterygium wilfordii products, but oral use was linked with serious side effects in one study, and many trials had design flaws.^[17]

Safety and herb-drug interactions

Herbs can interact with the medicines used in MCTD. Reviews describe interactions with immune-suppressing drugs such as ciclosporin and tacrolimus, and with warfarin.^{[7, 18]} Herbs with blood-thinning effects matter for anyone on anticoagulants, which are used in some patients with lung disease.^[19]

Herbal supplements are a recognized cause of liver injury.^[20] Some immune-suppressing medicines also affect the liver, so your physician should know about any herb. Tell us about pregnancy, breastfeeding, and liver or kidney disease. Herbs should come from tested sources and be prescribed individually. Do not start any herb without your rheumatologist knowing.

Translating traditional medicine into modern biological language

This section is interpretation, not equivalence. Chinese medicine often describes cold fingers and painful joints as cold or damp obstructing qi and blood, or blood stasis. Researchers studying related problems look at blood vessel tone, circulation and inflammatory signaling.^{[8, 15]}

Ayurveda's Vata, ama and impaired agni can be read loosely as ideas about circulation, chronic inflammation and digestion. No study has shown that these traditional concepts correspond to the biology of MCTD.

How this care fits with your medical care

MCTD needs ongoing specialist care. For a condition like this, we ask that you are under a physician's care for it and that your treating team knows you are receiving complementary care. We do not diagnose or manage MCTD, order or interpret its tests, or prescribe or change prescription drugs.

Do not stop or change prescribed medicines. Please bring your diagnosis, antibody and other test results, any lung, heart or kidney reports, a full list of medicines and supplements, and your rheumatologist's name.

When to seek urgent medical care

MCTD can affect the lungs, heart and kidneys, and these problems can worsen quickly.^{[3, 4]}

• New or worsening shortness of breath, or chest pain
• Fainting, or a racing or irregular heartbeat
• A cold, pale or blue finger or toe with a new sore, severe pain or black skin
• Fever with a new illness while taking immunosuppressants
• Severe headache with stiff neck, new weakness, or difficulty swallowing or breathing
• Sharp drop in urine output, or swelling of the legs and face

If you have any of these, call 911 or go to the nearest emergency department.