Psoriatic Arthritis vs. Mixed Connective Tissue Disease: What Are the Differences?

Psoriatic arthritis (PsA) is a type of inflammatory arthritis that affects some people with the skin condition psoriasis. It frequently affects the joints and the entheses—the areas where tendons and ligaments meet bone.

PsA also causes joint pain, stiffness, and swelling, along with a skin rash that appears as skin plaques—raised red patches covered with a white buildup of dead skin cells called scales.

Mixed connective tissue disease (MCTD) is defined as having a specific immune disease marker, symptoms, and organ involvement, plus selected features commonly seen with other connective tissue diseases, including systemic lupus erythematosus (SLE lupus), scleroderma, and myositis.

People with MCTD might experience puffy and swollen fingers, numb fingertips, fatigue, malaise (a general unwell feeling), muscle and joint pain, and reddish patches on their knuckles.

In this article, we will discuss PsA versus MCTD, including symptoms, causes, treatment, and more.

Symptoms

Both PsA and MCTD are autoimmune diseases where the immune system, which is generally responsible for fighting off harmful substances, mistakenly attacks healthy tissues.

In PsA, these attacks cause inflammation of the joints and overproduction of skin cells. In MCTD, the immune system attacks the fibers that give framework and support to the body.

Psoriatic Arthritis

According to the National Psoriasis Foundation, PsA affects 30% of people with psoriasis. For many people, PsA starts around 10 years after they develop psoriasis, but it is possible to have PsA without ever developing or noticing psoriasis.

PsA can develop slowly with mild symptoms, or it can develop quickly and become severe. Symptoms of the condition can include:

• Chronic fatigue
• Pain, tenderness, and stiffness of multiple joints
• Affected joints on one or both sides of the body
• Reduced range of motion in affected joints
• Morning stiffness of joints
• Large joint involvement, especially in the knees and ankles, although any joint can be affected
• Nail symptoms, including pitting, crumbling, ridging, and nailbed separation
• Skin symptoms, including skin plaques
• Spine involvement called psoriatic spondylitis causes stiffness and pain in the back or neck and stiffness and pain with bending
• Enthesitis, which commonly affects the back of the heels and soles of the feet
• Dactylitis, which is inflammation of the fingers and toes (sometimes called “sausage digits” because it causes the digits to become so swollen, they look like small sausages)
• Uveitis, which is redness and pain in affected eyes

Mixed Connective Tissue Disease

MTCD is an uncommon systemic inflammatory rheumatic condition. It is defined by the presence of specific symptoms and organ involvement, plus symptoms that are also seen in SLE lupus, myositis, or scleroderma.

Common symptoms of MTCD include:

• A general unwell feeling, including fatigue and mild fever
• Swollen fingers or hands
• Raynaud’s phenomenon: Cold and numb fingers or toes in response to cold or stress
• Joint pain: Inflamed and swollen joints similar to what is seen in rheumatoid arthritis
• Myositis: Muscle inflammation and pain
• Rash: Reddish or red-brown skin patches over the knuckles

Some people with MTCD might experience:

• Chest pain or breathing problems related to increased blood pressure in the lungs or inflammation of lung tissue
• Stomach inflammation, acid reflux, and swallowing difficulties due to dysfunction of the esophagus
• Hardened or tight patches of skin like what is seen in scleroderma
• Lupus-like skin inflammation in sun-exposed areas and hair loss
• Pulmonary hypertension: Pressure in blood vessels leading from the heart to the lungs is too high
• Interstitial lung disease: A group of disorders that cause progressive lung tissue scarring

Causes

As with all autoimmune diseases, the causes of PsA and MTCD are unknown. One theory about autoimmune diseases is that some types of bacteria or viruses, or medications can trigger changes that confuse the immune system. This can occur in people who have genes that make them vulnerable to autoimmune diseases.

Psoriatic Arthritis

Researchers have identified genes that might influence the development of PsA. Of these, the most studied and well-known genes belong to a family of genes called the human leukocyte antigen (HLA) complex.

The HLA complex generally helps the immune system to distinguish the body’s healthy tissues from proteins made by foreign substances. Variations or mutations in HLA genes can increase the risk of developing PsA. They are also linked to PsA type, severity, and progression.

But having certain genes isn’t enough to cause the development of PsA. Both genes and environmental factors can play a role. Environmental triggers linked to PsA include infections, skin and other physical trauma, chronic stress, and obesity.

Certain risk factors can increase the risk for PsA, including:

• Psoriasis: People with psoriasis have the highest risk for PsA. About 30% of people with psoriasis will go on to develop PsA.
• Family history: A person’s risk for PsA is higher if PsA or psoriasis runs in their family. Up to 40% of people with PsA have a family member with psoriasis or PsA.
• Age: PsA seems to affect people of any sex equally. It most commonly affects people after age 30, but anyone can get PsA regardless of age.

Mixed Connective Tissue Disease

MCTD occurs when the immune system attacks the connective tissues that provide the framework for the body. Some people with MCTD have a family history, but researchers have not established a clear genetic link.

Some studies have found a link between HLA genes and the development of MCTD. That research also confirmed that MTCD is a separate disease from other connective tissue conditions, including SLE lupus, scleroderma, and myositis.

Known risk factors for MCTD are:

• Sex: Females are more likely to get MCTD, and the female to male ratio for MCTD is 5 to 1.
• Age: The age of onset for MCTD can be anytime from early childhood to late adulthood. According to the National Organization for Rare Disorders, the average age of onset is 37.
  

Diagnosis

There is no specific test to diagnose PsA, and diagnosis is often based on symptom history and a physical examination. In addition, MCTD can be difficult to diagnose because it resembles other conditions and has dominant features of other connective tissue diseases.

Psoriatic Arthritis

A diagnosis of PsA starts with a physical examination of joints, entheses, skin, and nails:

• Joints: Your doctor will examine your joints by touch to look for swelling and tenderness. This includes the fingers and toes, hands, wrists, elbows, shoulders, hips, knees, ankles, sternum, and jaws.
• Entheses: Enthesitis classically affects the heels and soles of the feet, around the knees, the pelvis, spine, rib cage, shoulders, and elbows. Your doctor will examine the entheses to look for sore and tender areas.
• Skin and nails: Your doctor will examine your skin for signs of psoriasis, such as skin plaques. Nail involvement in PsA might show pitting, ridges, and nailbed separation.

Additional testing to help aid in a PsA diagnosis includes imaging and laboratory testing:

• Imaging: X-rays, magnetic resonance imaging (MRI), and ultrasound scans can look for specific joint changes seen in PsA that are not seen with other types of inflammatory arthritis, such as bone erosion.
• Laboratory testing: This includes rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) testing to rule out rheumatoid arthritis. Joint fluid testing might look for uric acid crystals seen in another type of inflammatory arthritis called gout. There is no specific blood test that can confirm a diagnosis of PsA.

Mixed Connective Tissue Disease

A diagnosis of MCTD is based on symptoms, a physical exam, lab testing, imaging studies, and sometimes, a muscle biopsy. Since symptoms of MCTD can resemble those of other connective tissue diseases, it can sometimes take months or even years to get a correct diagnosis.

A positive anti-RNP antibody test can help confirm a diagnosis of MCTD. Anti-RNP autoimmunity is also seen in people with SLE lupus. In people with MCTD, anti-RNP autoantibodies generally mean a favorable prognosis.

According to the Cleveland Clinic, four features point to MCTD rather than another connective tissue disorder. These are:

• High concentrations of anti-RNP antibody-protein
• Absence of severe kidney and central nervous system problems that are seen in SLE lupus
• Severe arthritis and pulmonary hypertension, which is rarely seen with SLE lupus and scleroderma
• Raynaud phenomenon, and swollen hands and fingers, which occur in only around 25% of people with SLE lupus

Additional testing for MTCD includes:

• Electromyogram imaging records the electronic activity of the muscles. It can help your doctor determine how well the nerves and muscles communicate with each other.
• A muscle biopsy involves taking a muscle tissue sample to examine under a microscope. In a person with MTCD, there will be signs of muscle fiber damage.

Treatment

Both PsA and MCTD are lifelong conditions that require long-term measures. Your doctor can recommend the best treatment options for each condition and their treatments can sometimes overlap.

Psoriatic Arthritis

There are many different treatment options available for treating PsA. Your doctor will prescribe treatments based on PsA type and disease severity.

Medicines used to treat PsA include:

• Nonsteroidal anti-inflammatory drugs to relieve pain and reduce inflammation. NSAIDs are recommended for managing symptoms of mild PsA. Advil (ibuprofen) and Aleve (naproxen sodium) are available without a prescription, but your doctor can prescribe a stronger NSAID. Severe side effects of NSAIDs include stomach irritation, liver and kidney damage, and heart problems.
• Conventional disease-modifying antirheumatic drugs (DMARDs) slow down disease progression to help save your joints and other tissues from permanent damage. The most commonly issued DMARD is methotrexate. Side effects of conventional DMARDs include infections, liver damage, lung inflammation, lung scarring, and bone marrow suppression.
• Biologic DMARDs target different parts of the immune system to stop inflammatory proteins. Biologic drugs used to treat PsA include Humira (adalimumab), Simponi (golimumab), Cimzia (certolizumab), Enbrel (etanercept), Orencia (abatacept), and Cosentyx (secukinumab). These drugs can increase your risk for serious infections. Biologics are given either as an injection under the skin or as an intravenous (IV) infusion.
• Janus kinase (JAK) inhibitors may be used in cases where conventional and biologic DMARDs have not been effective. Available as a pill, these drugs work by tapering down the immune system to prevent inflammation that leads to joint damage. These drugs can increase the risk for blood clots of the lungs, serious cardiac events, and cancer.
• Otezla (apremilast) is a newer drug that decreases the activity of an enzyme called phosphodiesterase type 4 (PDE4) to control inflammation within cells. It is often prescribed for people with mild to moderate PsA who cannot take conventional or biologic DMARDs. 
• Steroid injections are injected into an affected joint to reduce inflammation and pain.

Skin symptoms of PsA are treated with topical treatments, including corticosteroid creams and anti-inflammatory medications. Skin symptoms of PsA can also be treated by exposing skin to ultraviolet (UV) light, a process called phototherapy.  Phototherapy can reduce and manage itching and skin pain.

Additional therapies for managing PsA include:

• Physical therapy
• Occupational therapy
• Massage therapy
• A healthy diet
• Losing weight, if necessary, to reduce pressure off joints
• A light exercise program that includes activities like yoga, walking, and water therapy

Surgery can be recommended in cases where there is severe joint damage. Repairing joint damage can relieve pain and improve mobility.

Mixed Connective Tissue Disease

The goals of MCTD treatment are to control symptoms, maintain function, and reduce the risk for disease complications. Your doctor will tailor treatment to your specific needs and how severe your disease is. Some people with MTCD might only need treatment for managing flare-ups, while others need long-term measures.

Medications prescribed to treat MCTD include:

• Over-the-counter NSAIDs like ibuprofen and naproxen can treat joint pain and inflammation. Your doctor can also prescribe a stronger NSAID if you need more potent pain relief.
• Corticosteroids, like prednisone, can treat inflammation and stop the immune system from attacking healthy tissues. These medications can cause serious side effects, including high blood pressure and cataracts, so they are usually prescribed for short periods.
• Antimalarial drugs like Plaquenil (hydroxychloroquine) can help with mild MTCD and prevent disease flare-ups.
• Immunosuppressants like Imuran (azathioprine) treat severe MCTD that requires long-term treatment. These drugs suppress the immune system to slow disease progression and reduce inflammation.
• Lower-dose calcium channel blockers like Norvasc (amlodipine) manage symptoms of Raynaud’s phenomenon.
  
• High-dose calcium channel blockers such as Plendil (felodipine) and DynaCirc (isradipine) aim to prevent pulmonary hypertension from getting worse.

Prevention

Autoimmune diseases like PsA and MTCD are generally not preventable. If you have a family history of either condition or another autoimmune disease, ask your doctor about identifying risk factors for these conditions.

Doctors do not know of any ways to prevent PsA, and no treatment can guarantee that someone with psoriasis won’t go on to develop PsA. Doctors don’t fully understand how psoriasis progresses into PsA or who might be at risk for PsA. 

One day, research might bring about answers, but for now, doctors focus on managing psoriasis to help reduce the risk for PsA and reducing the severity of psoriasis and PsA. If you have concerns about your risk for PsA, talk to your doctor about all of your risk factors for the condition.

Little is known about what causes MCTD and the risk factors for the condition. This means that doctors don’t know if the condition can be prevented.

Summary

Psoriatic arthritis and mixed connective tissue disease are autoimmune diseases, conditions where the immune system mistakenly attacks healthy tissues. With PsA, the attacks lead to inflammation of joints and overproduction of skin cells, and with MTCD, the immune system attacks fibers that give framework and support to the body.

Because they are autoimmune diseases, the causes of PsA and MCTD are not always known. They are usually diagnosed by relying on family and symptom history, and with physical examination, blood work, imaging, and other tests.

Both PsA and MCTD are lifelong conditions, which means they will need long-term treatment. Your doctor can recommend a treatment plan for your condition, and treatments for these two conditions can sometimes overlap.

A Word From Verywell

If you are diagnosed with psoriatic arthritis or mixed connective tissue disease, make sure you regularly see your doctor. Both PsA and MCTD are progressive conditions and may get worse with time.

They also need strong medications to reduce the risk for serious complications. These conditions can affect your organs, so be sure to discuss any risk factors for other conditions, including symptoms and preventive measures.

You should work with a rheumatologist (a doctor specializing in rheumatic conditions) and other specialists to best manage these conditions. Keeping your condition well-managed improves your outlook and your quality of life.