What is mixed connective tissue disease (MCTD)?

You’ve probably heard of conditions like systemic lupus or rheumatoid arthritis – autoimmune diseases affecting the musculoskeletal system. Each disease presents with a different set of symptoms, but Mixed Connective Tissue Disease (MCTD) is like a combination of several autoimmune diseases rolled into one. 

Let’s think of a simpler analogy. 

Imagine opening a moving box and finding a hairdryer, a frying pan, a pillow, and hiking boots. You’d wonder – is this for the kitchen, the bedroom, or the garage? MCTD is like that –  symptoms originate from different diseases, and it’s not clear what kind of condition a person is dealing with.

MCTD is a rare autoimmune disease where the body’s immune system mistakenly attacks its own tissues. Symptoms may vary from patient to patient, but often include joint and muscle pain, Raynaud’s syndrome, hair loss, elevated temperature, fatigue, and others.¹ The biggest challenge with MCTDs is detecting them at an early stage, when symptoms are usually not that prominent and could be easily mistaken for stress, exhaustion, an endocrine disorder, or even a vitamin deficiency. But MCTD could lead to serious complications affecting the heart, lungs, kidneys, or nervous system. That is why early detection matters. 

This article will break down the early-stage MCTD’s symptoms and offer the steps for what to do if you suspect the disease. 

Early symptoms of MCTD

In the early stages of the disease, symptoms may be general, such as fatigue, elevated temperature, and pain in joints (arthralgia), or they may also affect the skin. 

Skin involvement includes:²

• Raynaud’s Phenomenon (RP): The most common symptom. Fingers or toes turn white, blue, or red in response to cold
• Rash: Red flat or raised rash on different parts of the skin, including the face, upper limbs, and hips
• Puffy Hands: Swelling in the hands, making them feel tight or stiff
• Sclerodactyly: Thickening and tightening of the skin on the fingers
• Acrosclerosis: Hardening of the skin on the fingers or toes, limiting movement
• Calcinosis: Small, hard calcium deposits under the skin, often painful
• Ulcers: Open sores, typically on the fingers or toes, caused by poor circulation
• Digital Necrosis: Tissue death in the fingertips due to severe blood flow issues, a rare but serious sign
• Oral Ulcers: Painful sores inside the mouth, similar to those in lupus
• Discoid Lesions: Thick, scaly patches on the skin that may scar
• Panniculitis: Inflammation of the fat layer under the skin, causing tender lumps

These skin symptoms are common in systemic lupus erythematosus (SLE) and scleroderma (SD), other autoimmune diseases, which can add to the diagnostic confusion.

Other early symptoms of MCTD may include:¹

• Joint Involvement: Pain and swelling in the joints, usually appearing in the morning, like in rheumatoid arthritis
• Muscle Involvement: Muscle pain or weakness, particularly in the arms or shoulders

As MCTD progresses, systemic symptoms may appear, though they can sometimes show up early: 

• Gastrointestinal Issues:³ Common problems include heartburn from gastroesophageal reflux disease (GERD) or difficulty swallowing (dysphagia). Less common issues include slowed digestion, hepatitis, pancreatitis, malabsorption, or, in rare cases, small bowel perforation
• Lungs:⁴ Shortness of breath or a dry cough, which may signal early lung involvement like interstitial lung disease
• Cardiovascular System:⁴ Inflammation of the heart’s lining (pericarditis) or blood vessels, which can cause chest pain or irregular heartbeats

In later stages, MCTD can affect multiple systems, making early recognition crucial. 

Why doctors struggle to diagnose it

MCTD is a relatively new diagnosis, and it was assigned in the late 70s of the previous century. Many doctors, especially those outside rheumatology, may not be familiar with it.

Besides, MCTD mimics several other diseases, as mentioned above - SLE, scleroderma, rheumatoid arthritis, as well as non-autoimmune conditions like allergies, gastrointestinal diseases, or endocrine disorders. Early-stage symptoms may come and go, appear gradually, or start with general symptoms that are hard to distinguish. 

Blood tests, while helpful, aren’t definitive. General tests like complete blood counts or biochemistry panels may show abnormalities, but don’t confirm MCTD. Autoimmune markers, such as antinuclear antibodies (ANA), are often present in MCTD and other connective tissue diseases, but they’re not specific.¹ A positive anti-U1RNP antibody can point to MCTD, but it’s also found in lupus or scleroderma, so doctors should still rely on critical thinking and awareness.¹
By the way, did you know that some healthy people can have positive ANA tests, while early-stage MCTD patients may have normal antibody levels? This can add to confusion for diagnosis.

Diagnostic tools and their challenges

Diagnosing MCTD depends on a patient’s specific symptoms and requires a combination of clinical evaluation and testing. 

Laboratory tests include:

• Complete Blood Count (CBC): Checks for anaemia or other blood abnormalities
• Biochemistry Panel: Assesses organ function, like liver or kidney functions
• Antibody Assessment: Tests for ANA and anti-U1RNP antibodies, which can suggest MCTD

These tests provide clues but don’t give a clear answer, so the clinical evaluation remains important. 

A quick note to remember: the number of antibodies doesn’t predict disease severity, and results can vary over time. 

What about an instrumental evaluation? 

Since the most common early stage symptom is Raynaud’s Phenomenon, usually doctors prescribe a Nailfold Videocapillaroscopy (NVC)¹. This diagnostic tool is cheap and easy to perform, and it detects changes in the arteries of the nailfold region. NVC could detect early changes in the arteries in almost half patients with MCTDs. 

Other instrumental methods, such as Pulmonary function tests (PFTs) or Echocardiograms, could detect changes in patients’ hearts and lungs, but may not show issues early on. 

The lack of a single, definitive test means doctors must piece together symptoms, test results, and patient history and make a hard decision in diagnosing or excluding the disease. 

Why an early diagnosis matters

Generally, if diagnosed at an early stage, MCTD has a good prognosis. But if undiagnosed or untreated, it can progress to life-threatening complications. The main reasons for mortality among MCTD patients are pulmonary hypertension, interstitial pneumonitis, and its complications.⁵ The mortality rate varies between 3.1% and 10%.⁵ 

Other complications, such as infections, cardiovascular complications, and malignancies, can shorten life expectancy. Involvement of the kidneys, gastrointestinal tract, or nervous system can significantly lower the quality of life.

That is why early detection is important. The progression could be prevented at an early stage and potentially improve the quality of life. 

What are the treatment options? 

Treatment usually depends on the system involvement. It could include symptomatic, anti-inflammatory, and immunosuppressive medications.

For Raynaud’s phenomenon, lifestyle changes can make a big difference, like quitting smoking, avoiding caffeine and alcohol, and keeping hands and feet warm, reducing the triggers. Eating healthy food could also be helpful, as MCTD increases the risk of atherosclerosis and heart disease.⁶

Is exercise good for MCTD?

Yes! Gentle exercise, like walking or yoga, can improve blood flow, reduce joint stiffness, and increase circulation, especially for those with Raynaud’s phenomenon. But before doing any exercises, it’s better to check with your doctor.

Are there any ways to prevent it? 

Unfortunately, autoimmune diseases remain a big mystery, so there’s no known way to prevent them. Research is ongoing, but for now, early detection and management are the best strategies.

What you can do if you suspect MCTD

If you notice the symptoms, here’s a list of steps you could take:

• Keep track of symptoms. Try to connect them with possible triggers
• See a doctor: it could be a general practitioner, dermatologist, endocrinologist, rheumatologist, or other specialists if needed. Sometimes it could require a multidisciplinary team to suspect an autoimmune disease. Don’t worry about that. It’s better to exclude the disease than to skip and leave it to progression
• Don’t hesitate to get a second opinion
• Ask about autoimmune testing 
• Follow Up Regularly: If MCTD is diagnosed or suspected, don’t forget to visit the doctor's office for a check-up. Usually, the frequency depends on the activity, severity, and involvement of the symptoms disease. The doctor will tell a patient when to come for your visit

Summary

MCTD is a tough autoimmune condition in terms of early diagnosis, even for good doctors. MCTD resembles several other autoimmune diseases and is easy to misdiagnose. But recognising the signs like Raynaud’s phenomenon, joint pain, or unexplained fatigue and finding answers can lead to earlier diagnosis and better outcomes. Early action can make all the difference in managing this complex disease. Share this article with anyone you know with these symptoms. And if you have been diagnosed with MCTD, don’t forget your regular doctor’s visits and join autoimmune support groups for community support.

Frequently asked questions

Is MCTD hereditary?

There’s no clear evidence that MCTD is directly inherited, but autoimmune diseases can run in families due to genetic predispositions.¹

Is there a cure for MCTD?

There’s no cure yet, but there are treatments that can help manage symptoms and prevent complications. 

Can children get MCTD?

Yes, but it’s rare. MCTD is more common in adults, particularly women in their 20s to 40s, but it can affect children and teens.⁷