Pulmonary Artery Hypertension in Ankylosing Spondylitis: A Review

Pulmonary arterial hypertension (PAH) is a severe condition characterized by an increase in mean pulmonary arterial pressure ≥ 20 mm Hg. According to the World Health Association, PAH is classified into several clinical subgroups, including hereditable causes, PAH due to left heart disease, due to chronic lung disease/ hypoxia, due to chronic thromboembolic pulmonary hypertension, idiopathic PAH, and, of course, primary PAH, which develops due to the pulmonary artery wall dysfunction with its increasing stiffness [1]. PAH associated with connective tissue diseases falls into the latter category. It is commonly described in systemic sclerosis patients, where it is observed with a high frequency that varies from 61% to 76% [2]. Pulmonary hypertension has also been reported in patients with systemic lupus erythematosus. The main factors contributing to its development include endothelial dysfunction caused by progressive systemic inflammation and vasculitis affecting small pulmonary vessels. Additionally, the thrombogenic effect of antiphospholipid autoantibodies may play a role. In patients with mixed connective tissue disease, fibrosis of the pulmonary artery may occur simultaneously with the progression of interstitial pneumonia and Raynaud’s phenomenon. Patients with rheumatoid arthritis are also at risk, as vasculitis and fibrosis in lung tissue may be exacerbated by the side effects of methotrexate [3]. PAH is rarely described in spondylarthritis, including ankylosing spondylitis.

Ankylosing spondylitis (AS) is known as a chronic systemic disease of the musculoskeletal system that progresses gradually, leading to the severe restriction of spinal mobility, inflammatory involvement of peripheral joints, and ligament calcification. Pathological inflammatory process is primarily observed in spinal joints, and also manifest as sacroiliitis, spondylitis, asymmetric arthritis, and tendinitis. The disease mainly manifests at the age of 20–30 years, but it usually takes at least 5–7 years to establish a diagnosis [4]. Fibrosis, primarily developing in joints and ligaments, may later affect both the respiratory and cardiovascular systems, which has a major impact on quality of life and prognosis in this condition. Heart valves and aorta are the most prone to alteration, that may lead to the progression of various arrhyth- mias. Myocarditis, pericarditis, and cardiomyopathy are less common [4]. Upper lobe fibrosis is the most often pulmonary complication. Pleural effusion and emphysematous processes with the possible bullae formation could also occur, and in rare cases pulmonary hypertension may also develop.

PATHOGENESIS OF PULMONARY DYSFUNCTION IN PATIENTSWITH ANKYLOSING SPONDYLITIS

Respiratory system dysfunction in AS is traditionally associated with a combination of limited chest mobility with a systemic inflammatory process progression and is described in 50–85% of cases [3, 5]. Patients note a gradual decrease in the respiratory excursion of the chest, shortness of breath during physical exertion, which may eventually occur at rest. Some patients don’t mention any symptoms and accidental radiological findings require differential diagnosis with the tuberculosis process. The predominance of the diaphragmatic type of breathing is a typical observation, since the intercostal muscles cannot fully participate in the respiratory act. Spirometry reveals a restrictive type of respiratory disorders with a decrease in vital lung capacity, forced vital lung capacity and total lung capacity. Thus, fibrosis of the lung parenchyma develops, the formation of emphysematous bullae, with the addition of a secondary infection process. Pleural lesions with the development of adhesion sites are rare [5].

LARGE VESSEL DYSFUNCTION IN PATIENTSWITH ANKYLOSING SPONDYLITIS

Large vessel dysfunction in AS is characterized by the involvement of mainly the ascending aorta with the development of an inflammatory infiltration in the intima, thickening of the intima–media complex, and the development of widespread fibrosis. These processes lead to increased left ventricular (LV) afterload and increased pressure, and, as a result, to diastolic dysfunction. In the clinical case described by Nikitin et al, a 36-year-old patient with a long history of AS was hospitalized with heart failure, arrhythmia, abdominal enlargement, and abdominal pain. The dramatic speed of cardiovascular complications leaded to a rapid deterioration of the patient’s condition [4].

Endothelial dysfunction is presumed as an important factor in the progression of large vascular lesions in AS. Its development involves chronic systemic inflammation with increased production of proinflammatory cytokines (TNF- α , IL-1b, IL-6, IL-17), which directly damage the endothelium of the pulmonary vessels. This leads to an imbalance between vasodilators (NO, prostacyclin) and vasoconstrictors (endothelin-1, thromboxane A2). Oxidative stress can also play a significant role. The production of reactive oxygen species affects both the endothelial cells of the pulmonary capillaries as well as acts directly on the alveolar epithelial cells, which additionally leads to the development of pulmonary emphysema with a bullous component. Arterial vasoconstriction leads to increased vascular resistance, which further promotes the remodeling of pulmonary vessels and the proliferation of smooth muscle cells with the development of fibrosis [3, 5].

PUBLICATION ANALYSIS

In this article, we aimed to review the published cases of PAH in AS (table 1a; 1b). An extensive literature search in PubMed and Elibrary databases was performed without any language restriction until July 2025. We excluded review articles and preclini-cal in vivo and in vitro studies. Only five articles were found on this topic, among them three case reports and two observational study with a total of 104 AS patients. Ages varied from 27 to 58 years, and disease duration from 15 to 32 years. A marked male predominance was observed, as expected. Clinical symptoms included exertional dyspnea, leg edema, and palpitations. Systolic pulmonary pressure ranged from 43 to 96 mm Hg on echocardiography. Right heart catheterization confirmed PAH, with a mean pulmonary artery pressure ranging from 78/44 to 85/23 mm Hg. Patients were treated with bosentan from 62.5 mg to 125 mg twice daily. Regarding outcomes, one case report showed improvement, and the other remained stable for 8 months of follow-up.

Egudina et al. [6] describe 79 patients with AS aged 15 to 66 years, where the cardiovascular and pulmonary complications were studied. Dysfunction of the electrical conduction of the heart and valvular disorders were detected in 68.4% of cases, interstitial pneumonitis, fibrosing alveolitis — in 13.9%. Pulmonary hypertension was described in 51.9%, peripheral vaso-neuropathy in 32.9%, changes in the left common carotid artery in 27.9%, dysfunction of the aorta and the right common carotid artery — 20,3%, arterial hypertension — in 15.2%, Raynaud’s syndrome — in 13.9%, dysfunction of the left internal carotid artery — in 11.4%, skin vasculitis — in 10.1%, and lesion of the right internal carotid artery — in 7.6%. According to the Brown — Forsythe test, the formation of vascular pathology was influenced by the degree of disease activity (BF = 4.13, p = 0.046), rheumatoid factor (RF) seronegativity (BF = 4.07, p = 0.047) and the presence of cardiac pathology (BF = 4.81, p = 0.03). Thus, angiopathy was observed in 85% of patients with AS, the development of which was directly related to the degree of activity of the pathological process and inversely to RF seropositivity [6].

The study by Poddubnyi et al. [7] included 102 patients aged 18 to 58 years with AS. Patients with pulmonary hypertension in their group were characterized by significantly higher age, body mass index, smoking duration, smoking index, AS duration, severity of functional disorders according to the BASFI index severity of spinal mobility limitations. There was also a significant role of endothelial dysfunction in the development of PH in AS [7].

Another study by the same research group evaluated the cardiovascular risk in patients with AS, focusing on the association between systemic inflammation and endothelial dysfunction. The 10-year coronary risk was 4.0%, which is significantly lower than the risk calculated for a similar population without ankylosing spondylitis. The 10-year risk of fatal cardiovascular events using the SCORE scale was 1%, which can be considered low. However, an analysis of additional risk factors in patients with ankylosing spondylitis revealed changes indicating an increased risk of thrombosis due to endothelial dysfunction [8].

CONCLUSION

Pulmonary arterial hypertension (PAH) in ankylosing spondylitis (AS) remains a rare but clinically significant complication with substantial implications for patient outcomes. Based on original studies and case reports, observed in this paper, PAH in AS was evaluated predominantly in middle-aged men with a long-

Table 1a

Study characteristics and clinical features in ankylosing spondylitis with pulmonary arterial hypertension

Table 1b

Cardiac findings, treatment, and outcomes in ankylosing spondylitis with pulmonary arterial hypertension

6MWD; 6 min walk distance; BID: twice a day; PAP: pulmonary arterial pressure; RV: right ventricle; SPAP: systolic pulmonary arterial pressure; TID: thrice a day; IV: intravenously.