Systemic sclerosis-associated pulmonary arterial hypertension in children

Abstract

Systemic sclerosis (SSc) is a rare disease in childhood and is characterized by a combination of vasculopathy, inflammation, autoimmunity, and fibrogenesis with individually varying expression pattern. Pulmonary arterial hypertension (PAH) is a serious complication of SSc and affects approximately 10% of SSc patients. SSc-PAH is complex and difficult to diagnose, as symptoms are non-specific and may be complicated by other SSc-associated diseases such as interstitial lung disease or left heart disease. SSc-PAH patients can deteriorate rapidly, and disease progression can occur even in patients with mild PAH symptoms at diagnosis. Therefore, interdisciplinary care of SSc patients is essential, and treating physicians must be aware of the association between SSc and PAH. In order to detect PAH early, children with SSc should be regularly screened for PAH by pediatric cardiologists. If PAH is detected, a systematic diagnostic approach by trained PH specialists including careful phenotyping of PAH is required. Relevant interstitial lung disease and left heart disease should be ruled out in the differential diagnosis of SSc-PAH before starting any targeted therapy. Due to the progressive character of SSc-PAH known from adult studies, it appears appropriate to initiate targeted PAH-therapy in juvenile SSc-PAH early. Adapted from adult treatment algorithms, combination therapy regimens (addressing at least two pathophysiological pathways) are increasingly used for pediatric PAH patients, and there is growing evidence to support this approach also in SSc-PAH patients.

Keywords: Pediatric pulmonary hypertension; cardiac catheterization; pediatric cardiology; pediatric rheumatology; pulmonary vascular disease; systemic sclerosis (SSc).

Figure 1

Typical clinical findings of systemic sclerosis in a teenaged girl who presented with evidence of PAH at echocardiographic examination and an elevated NT-pro BNP level of 1,286 ng/L (normal: <97 ng/L). She reported of general weakness, painful knee and wrist movement, paleness of fingers, loosing of hairs, and difficulties in swallowing resulting in weight loss of 5 kg in 6 weeks. (A) Symmetrical facial skin tightening; (B) painful limitations of motion in both wrists and flexion contractures in all metacarpophalangeal and proximal interphalangeal joints; (C) Raynaud’s phenomenon.

Figure 2

Fluorescence optical imaging of the same patient as in Figure 1 revealing active polyarthritis.

Figure 3

Magnetic resonance imaging of the upper torso and upper extremities in the same patient as in Figure 1 showing diffuse myositis.

Figure 4

Schematic presentation of the interdisciplinary team involved in the medical care for SSc patients. If PH is suspected, further specific diagnosis and treatment should be performed by trained PH experts.