What are the other Names for this Condition? (Also known as/Synonyms)

• CTD-PAH (Connective Tissue Diseases and Pulmonary Arterial Hypertension)
• PAH Associated with Connective Tissue Diseases
• Pulmonary Arterial Hypertension in Connective Tissue Diseases

What is Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases? (Definition/Background Information)

• Pulmonary arterial hypertension (PAH) is a specific type of hypertension that is caused by increased blood pressure within the pulmonary (lung) arteries. When PAH is suspected to be the result of a specific associated condition, it is termed pulmonary arterial hypertension associated with other conditions
• In general, pulmonary hypertension (PH) is a disorder characterized by very high blood pressure (above normal) in the lungs due to a variety of causes. It should not be confused with systemic hypertension, otherwise known as ‘high blood pressure’
• The World Health Organization (WHO) has clinically classified pulmonary hypertension according to certain groups. Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases forms part of WHO group 1 (sub group 1.4.1.)
• Connective tissue diseases form a vast subset of diseases and disorders that involve the two proteins present in the connective tissues of the body, namely collagen and elastin. The condition results in the inflammation of tendons, ligaments, blood vessels, and skin, among other presentations. Some of the common connective tissue diseases include rheumatoid arthritis, systemic lupus erythematosus, and scleroderma
• The signs and symptoms of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases may include shortness of breath, chest pain, fatigue, and dizziness. The signs and symptoms also depend on the specific type of the underlying connective tissue disease
• Following a diagnosis of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases, the treatment measures may involve the use of medications, such as calcium channel blockers, and bringing about certain lifestyle modifications, among others. Connective tissue diseases are usually treated using appropriate prescription medications and physical therapy
• The prognosis of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases may be improved if the condition is diagnosed promptly and treated appropriately. However, the overall prognosis depends on several factors including on the severity of the underlying connective tissue disease; it may vary from one individual to another

Who gets Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases? (Age and Sex Distribution)

• The age, gender, and racial/ethnic distribution of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases depends on the specific underlying condition
• The presentation of symptoms most commonly occur between ages 15 to 21; however, this depends on the specific type of connective tissue disease
• Both males and females are affected. However, connective tissue diseases are generally more prevalent among women
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases? (Predisposing Factors)

The risk factors for Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases are dependent on the respective risk factors of the connective tissue disease. These may broadly include:

• Genetic factors, including a family history of the condition
• Environmental factors
• Lifestyle factors

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases? (Etiology)

Pulmonary arterial hypertension is caused by increased blood pressure within the lung arteries. Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases is associated with the underlying (specific) type of connective tissue disorder; it develops secondary to the disorder.

• The connective tissue diseases (CTDs) commonly causing pulmonary arterial hypertension is systemic sclerosis (scleroderma spectrum); in nearly 74% of the cases. Almost 8% of the cases are caused by systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) each
• Very infrequently, the condition may be caused by other CTDs such as rheumatoid arthritis (RA), Sjögren syndrome, and inflammatory idiopathic myopathies

In patients with connective tissue disease, several forms of pulmonary hypertension can exist. Broadly, connective tissue disease contributes to elevated pressures in the pulmonary vasculature via constriction of the small pulmonary arterioles, secondary to cardiac dysfunction, secondary to hypoxemia in advanced interstitial lung disease (ILD), or a combination thereof.

What are the Signs and Symptoms of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases?

The signs and symptoms of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases depends on a set of several factors that include age of the individual, overall health of the individual, and associated health conditions. The signs and symptoms can be directly related to pulmonary hypertension, and to the underlying connective tissue disease.

The common signs and symptoms of pulmonary arterial hypertension include:

• Progressive shortness of breath (especially while exercising), is the most common symptom
• Fatigue (frequent tiredness)
• Chest pain
• Dizziness and fainting
• Swelling of the ankles/legs
• Palpitations
• Bluish lips and skin, observed during the later stages
• Irregular heartbeat (arrhythmias)
• Fluid in the abdomen (ascites)

The signs and symptoms related to connective tissue disease depend on the particular form of the disease, its severity, and part(s) of the body affected such as the lungs, heart, and blood vessels.

Often, the detection of the associated condition may help in determining the cause of pulmonary arterial hypertension.

How is Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases Diagnosed?

To diagnose Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases, a diagnosis of pulmonary hypertension (PH) must first be established. This involves certain preliminary diagnostic procedures. Depending on the results of these tests, confirmation will be made with a right-heart catheterization. After a diagnosis of PH is made, the healthcare provider may undertake further tests to diagnose the specific type of connective tissue disease causing the PH, as necessary.

The preliminary procedures may include:

• A complete physical examination of the patient 
• A thorough checking of the patient’s medical history and a detailed checking of the family history of the patient
• Blood tests:
  • Blood tests help rule out other diseases
  • They also help in checking the blood oxygen levels
  • The measurement of brain natriuretic peptide (BNP) can be used to assess the strain on one’s heart
• Chest X-ray: Chest X-rays can reveal structural signs of pulmonary hypertension by identifying changes in the pulmonary arteries or enlargement of the right side of the heart
• Electrocardiogram (ECG): An electrocardiogram checks the electrical impulses of the heart. There are certain identifiable patterns on an ECG that may indicate pulmonary hypertension. However, ECG is not specific enough to diagnose the condition by itself, so a combination of tests may be recommended by the healthcare provider
• Echocardiogram: In this procedure, a sonogram of the heart is taken and used to measure overall functioning as well as measure the pressure within the chambers of the right heart. An echocardiogram is also often times used to monitor a patient’s condition after diagnosis and during treatment
• Pulmonary function tests: These tests help measure the quality of breathing and check the functioning of the lungs (such as how much air is breathed in and out, as well as the quality of oxygen exchange)
• Exercise tolerance test (six-minute walk test): This helps to measure the patient’s ability to exercise
• Nuclear scan (ventilation/perfusion scan or V/Q scan): This tool helps identify any new or chronic blood clots in the vessels of the lungs that could be causing pulmonary hypertension

A diagnosis of connective tissue disease may additionally involve:

• Assessment of signs and symptoms
• Laboratory tests, including blood test to check for specific antibodies
• Imaging studies, as necessary, depending on the particular type of connective tissue disease

The gold standard for pulmonary hypertension diagnosis and management is right-heart catheterization and acute vasodilator challenge.

• Right-heart catheterization:
  • If pulmonary hypertension is suspected based off preliminary tests and procedures, a right-heart catheterization test is ordered to help confirm the diagnosis
  • This test can accurately quantify right-heart pressures (measure the pressure within the chambers of the right heart), especially the pressure inside the pulmonary arteries
  • During this procedure, a very small catheter is inserted into a large vein (either within the patient’s groin or neck) and passed into the patient’s heart and vasculature to measure the internal blood pressures 
• Vasodilator study (acute vasodilator challenge):
  • While this test is not used to necessarily “diagnose” pulmonary hypertension, it is used to evaluate the patient for possible therapeutic management
  • Like right-heart catheterization, a catheter is placed within the pulmonary artery to test for vasodilation (or relaxation) in response to a class of medications called calcium channel blockers (CCBs)
  • The response and dosing of CCBs can be evaluated with this procedure

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases?

The complications of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases depends on a set of several factors that include the age of the individual, overall health of the individual, underlying connective tissue disease, and promptness of diagnosis. 

Following are the possible complications that may arise due to the condition:

• Right-sided heart failure with hepatic congestion (due to deposition of stones in the liver)
• Pedal edema: Swelling of the leg or ankle
• Pleural effusions: Building-up of excess fluid around the lungs
• Worsening dyspnea (shortness of breath) upon exertion

The complications related to connective tissue disease depend on the specific type of the disease, and the parts of the body affected.

How is Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases Treated?

The treatment of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases depends on a set of several factors that include the severity of the signs and symptoms, age of the individual, and overall health of the individual.

• A treatment of the associated connective tissue disease is essential
• The treatment may include the use of over-the-counter medications, corticosteroids, and immune-suppressants, physical therapy, and bringing about certain lifestyle changes, as appropriate

PAH Associated with Connective Tissue Diseases is best treated at a medical center with appropriate expertise. Several medical treatments are highlighted below:

• Conventional medical therapies:
  • Calcium channel blockers (CCBs): These are a group of medications that help vasodilate (or relax) the arteries. However, CCBs are only appropriate for patients demonstrating a favorable response to the vasodilator study
  • Inotropic agents: These are medications that assist in the pumping of the heart 
  • Diuretics, salt limitation, and weight monitoring may be recommended, to limit excess strain on the heart
  • Supplemental oxygen may help an individual meet the ‘oxygen needs’ for normal daily activities
  • Blood thinners: These medications help prevent blood clots, especially in the lung blood vessels
  • Treating underlying diseases or conditions
• Oral, inhaled, subcutaneous, or intravenous treatment options:
  • Endothelin receptor antagonists (ERAs) help in preventing pulmonary blood vessels from narrowing which helps keep the pressures towards normal levels
  • Phosphodiesterase inhibitors (PDE 5 Inhibitors), prostacyclin analogues, and soluble guanylate cyclase (sGC) stimulators, all aid in allowing vessels of the lungs to vasodilate (or relax)
• Additional treatment options may include:
  • Lifestyle modifications, such as nutrition, exercise, avoiding tobacco, and limiting alcohol consumption, are beneficial
  • Judicious exercising may be effective in limiting deconditioning (by building stamina), improving the quality of life, and exercising capacities. Isometric exercises, such as heavy weightlifting, should be avoided
  • Other treatments, depending on the etiology (cause) of pulmonary hypertension, may include various cardiothoracic procedures
  • Lung transplantation may be required with advanced forms of the disorder

How can Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases be Prevented?

Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases may be prevented or controlled if appropriate treatment of the underlying connective tissue disease is considered.

• In many cases, it is not possible to prevent the development of connective tissue diseases. However, some of the preventative factors may depend on the specific forms of connective tissue disease
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Adhering to a healthy and nutritious diet and avoiding exposure to toxins may help prevent some forms of connective tissue diseases

The non-modifiable risk factors for pulmonary hypertension (PH), such as age, gender, and genetics (family history), cannot be controlled; and therefore, it may not be possible to prevent PH that develops from these factors. However, an early and effective treatment is critical and imperative.

• For those with a pre-existing condition that is a risk factor for pulmonary arterial hypertension, seeking medical attention at the onset of symptoms may help avoid worsening of the condition and complications 
• Avoidance of recreational drugs, various toxic agents, and inappropriate weight loss drugs is important

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases? (Outcomes/Resolutions)

The prognosis of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases differs from one individual to another, depending on its severity and on the underlying extent of connective tissue disease.

• The prognosis of individuals with connective tissue diseases depend on the specific disease type, its severity, early diagnosis and adequate treatment, and his/her response to treatment

• Pulmonary hypertension is a negative prognostic sign in many medical conditions, meaning that the presence of pulmonary hypertension makes the overall health outcomes worse
• Individuals with advanced heart disease, a suboptimal 6-minute walk test (exercise tolerance test to measure one’s ability to exercise without significant signs and symptoms), and with conditions, such as advanced liver disease and connective tissue disease, have poor prognosis

Additional and Relevant Useful Information for Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases:

The following DoveMed website links are useful resources for additional information:

https://www.dovemed.com/diseases-conditions/rheumatoid-arthritis-ra/

https://www.dovemed.com/diseases-conditions/systemic-lupus-erythematosus/