Pulmonary hypertension in connective tissue disease: epidemiology, pathogenesis, and treatment

Systemic autoimmune diseases are inflammatory diseases characterized by multiorgan involvement, including the heart and lungs
.
In rheumatic disease, all cardiac structures (valves, transmission system, myocardium, endocardium, pericardium, and coronary arteries) and pulmonary arteries may be affected
.
Pulmonary hypertension (PH) is characterized by elevated pulmonary artery pressure, which, like other cardiovascular diseases, not only impairs quality of life but also leads to significant morbidity and mortality
.
CTD-PH is the second most common cause of PAH, after the idiopathic form, classified in group
I.
In addition to PAH, different types of PH
can be detected in CTD.
PH due to the high prevalence of interstitial lung disease (ILD) is very common, especially in
SSc.
In some cases, the cause of PH may also be multifactorial
.
However, the most common type of PH in patients with CTD is PAH (Group 1).

Epidemiology of pulmonary hypertension in connective tissue disease

REVEAL is a multicenter (55-center) observational PH registry study designed to characterize
the patient population with PH in the US.
The study evaluated 2525 eligible patients
based on criteria for a diagnosis of RHC as PH.
The mean age of patients ranged from 53.
0 ± 14.
0 years, of whom 80.
3% were female
.
According to the etiological classification, pulmonary hypertension with other conditions (APAH) was in 50.
6% of cases, and IPAH
was in 46.
2% of cases.
Patients with APAH were further divided into a subset of collagen vascular disease/connective tissue disease (CVD/CTD), accounting for 49.
9%.

The UK PH Registry evaluated 484 patients
with CTD-PH.
In their records, the most common cause was SSc-PH, which accounted for 74%, followed by SLE, MCTD, and dermatomyositis/polymyositis (DM/PM).

On the other hand, data from China and South Korea show that SLE-PH is more common
than SSc-PH.

Pathogenesis of connective tissue disease pulmonary hypertension

The pathophysiology of PH is not fully understood
.
As with IPAH, endothelial dysfunction plays a key role
in the pathogenesis of CTD-PH.
Impaired production of vasoactive mediators, increased production of vasoconstrictors, and proliferative mediators affect vascular tone, and PH develops
due to progressive remodeling of the small to moderate pulmonary vascular system.
While the exact mechanism of this remodeling remains unclear, a number of factors are thought to play a role
.
The main pathways responsible for the pathogenesis of CTD-PH are endothelin 1, nitric oxide, and prostacyclin pathways
.
In addition, it has been proposed that, unlike idiopathic forms, inflammation and autoimmunity may contribute to the initiation and progression
of CTD-PH.
Infiltrative macrophages and lymphocytes, antinuclear antibodies, rheumatoid factor, and complement have been detected in pulmonary vessels in patients with CTD-PH
.
Many factors, such as vasculitis, thrombosis, and interstitial pulmonary fibrosis, are also responsible for the pathogenesis of PH, particularly in patients
with SLE.

Conclusions:

CTD-associated PH remains an obvious cause
of dysfunction, morbidity, and mortality.
CTD-PH accounts for a large proportion
of all causes of PH.
While the possibility of developing PH in certain rheumatic diseases, particularly SSc, SLE, and MCTD, is well established, it should be borne in mind that PH can also occur in other rheumatic diseases, including pSS, IIM, Behcet disease, and adult-onset Still disease
.
In Europe and the US, the most common cause of CTD-related PH is SSc, while in Asia, SLE-related PH is more common
.
PH experience gained by rheumatologists in the SSc setting should be applied to other rheumatisms
.
The better you know about CTD/rheumatological PH, the more information
you will learn about PH during these diseases.

References:

Cansu DÜ, Korkmaz C.
Pulmonary hypertension in connective tissue diseases: epidemiology, pathogenesis, and treatment.
Clin Rheumatol.
2022 Nov 17.
doi: 10.
1007/s10067-022-06446-y.
Epub ahead of print.
PMID: 36396789.