Systemic Sclerosis
In SSc, autoimmune inflammation drives fibrosis of body tissues.
Juvenile onset SSc (jSSc) is rare, comprising <10% of SSc
cases (incidence 0.27-1 per million children per year). Diagnosis of SSc
requires skin thickening [25], with other organ involvement
including ILD, pulmonary arterial hypertension (PAH), Raynaud’s
phenomenon, digital ulceration, myositis, arthritis, esophageal
dysmotility, and gastrointestinal reflux. All manifestations are not
typically present and needed to make the diagnosis. The average age of
onset is 8-11 years, with female predominance (4:1 ratio) [26].
Pulmonary disease, are major causes of morbidity and mortality in SSc,
with ILD present in 1/3 of jSSc patients and PAH present in
~2-5% [26]. There are three main subtypes of SSc:
limited cutaneous, diffuse cutaneous, and overlap. ILD can be a feature
in diffuse and overlap subtypes. In limited cutaneous SSc, vasculopathy,
including pulmonary hypertension, is more common [27-29].
With the development of ILD in SSc, imaging abnormalities may precede
clinical symptoms. Thus, baseline studies at diagnosis include
high-resolution chest CT, PFTs, echocardiogram (to assess for PAH), and
esophageal dysmotility studies (to assess for aspiration) [30, 31].
Children with esophageal involvement have been shown to have
significantly decreased forced expiratory volume in the first second
(FEV1), forced viral capacity (FVC), and vital capacity (VC) [32].
PFTs can also demonstrate restriction and low DLCO [33, 34], but
tight facial skin and reduced oral aperture may lead to technically
limited PFTs. PFTs have limited sensitivity and specificity in diagnosis
ILD in childhood SSc [35]. CT is more sensitive for diagnosis, with
findings including parenchymal/subpleural micronodules, ground glass,
linear and diffuse centrilobular opacities, honeycombing, and traction
bronchiectasis [36]. Lung biopsy is rarely indicated; however,
pathologic patterns described include bland interstitial fibrosis, usual
interstitial pneumonia (UIP), non-specific interstitial pneumonia
(NSIP), organizing pneumonia (OP), diffuse alveolar damage (DAD),
honeycomb remodeling, pulmonary hypertensive changes, findings
compatible with aspiration and rarely, alveolar hemorrhage with
capillaritis [37].
There have been several randomized controlled trials for ILD-related
outcomes in adults with SSc, with multiple sets of consensus guidelines
outlining organ-specific therapeutic approaches. Based on adult trials
[38-40] first line therapies to treat alveolar inflammation include
cyclophosphamide, mycophenolate mofetil, and tocilizumab. Rituximab has
some prospective cohort data to suggest its use as a second line
therapy. For patients with fibrosis, nintenadib, an oral tyrosine kinase
inhibitor, has shown benefit [41] in adults. As a
3rd/4th line option, autologous
hematopoietic stem cell transplantation (HSCT) has been shown to improve
cutaneous and pulmonary features based on RCT in Europe [42] and the
United States [43] comparing HSCT to cyclophosphamide. Depending on
the extent of lung fibrosis, some patients may require lung
transplantation. For PAH, endothelin receptor antagonists, PDE5
inhibitors, and intravenous prostacyclins may be used and have
additional benefit for severe Raynaud’s [29, 44]. In the pediatric
population there is one expert guideline for management [45]. In
this guideline for management of heart and lung involvement it is
recommended to first treat with mycophenolate mofetil and
cyclophosphamide and then if refractory move to biologic treatments. In
our practice given fertility considerations and the success of biologic
treatments we often add biologics before treating with cyclophosphamide.