Interstitial lung disease in systemic sclerosis patients may benefit more from anti-reflux therapies than from immunosuppressants

We read with great interest the article by Iudici et al, who presented a narrative review about the management of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc). Data were presented by accurately distinguishing ILD from Idiopathic Pulmonary Fibrosis (IPF). In fact, these two entities, despite a certain degree of overlap in their clinical presentation and pathogenesis, present differences which in turn affect diagnosis, prognosis and management. We congratulate with the authors for having summarized with great clarity a complex topic such as the pathogenetic processes involved in scleroderma-related ILD, further providing concise suggestions to the readers about the medical approach to it. However, we believe that in this laudable attempt of synthesis, some aspects have been omitted while focusing all the attention on immunosuppressants. Immunologic dysregulation is indeed the keystone of pulmonary involvement in SSc, whose development and progression, however, is part of a multifactorial process where intrinsic factors are corroborated by others secondary to the disease, which can themselves perpetuating the inflammatory process. Among the latter ones, gastroesophageal reflux (GER), is the better studied and frankly related with both ILD and IPF. Indeed, the gastrointestinal tract is with no doubt the system more often involved after skin in SSc patients, mainly disguised as impairment of the upper, mid and lower digestive tract. First evidences of the relation between esophageal motility and pulmonary function in SSc were already provided by French authors in the early eighties. Thereafter, the same group reported in a series of 43 consecutive patients with SSc a direct correlation between esophageal manometric motor disturbances and evidence for ILD on pulmonary function test (PFT) and high resolution computerized tomography (HRCT) scan. Thus, they suggested a possible role for GER as a contributing factors in SSc-ILD and speculated that an early treatment of GERD may decrease the pulmonary function deterioration. Recently, our group observed that SSc patients with ILD have more severe GER with a greater number of reflux events and higher percentage of reflux episodes reaching the proximal esophagus, compared to SSc patients without pulmonary involvement. A subsequent study was conducted by our group in a court of 40 consecutive patients with IPF, whose prognosis is more aggressive than that of scleroderma-related ILD and therapeutic options are poorer. Likewise in scleroderma-related ILD, GER severity and proximal extension of reflux episodes were related to the degree of pulmonary involvement as assessed by means of HRCT. Moreover, we showed that higher concentration of bile acids and pepsin in bronchoalveolar lavage fluid were present in IPF patients compared to controls, thus underscoring the potential pathogenic role of weakly acid reflux and other components of the refluxate which must be taken into consideration for the treatment of both kinds of disease. These data are not surprising if we consider that SSc and IPF patients are likely to share some of the mechanisms by which GER is increased in them, such as the disruption of esophagogastric junction (i.e. anti-reflux barrier) due to the increased negative pressure in the thorax and the occurrence of a greater number of cough-related reflux episodes. Based on these preliminary studies, no conclusions can be drawn about the potential benefit of GERD treatment on ILD progression in SSc and IPF. However, recently, Lee et al. showed that the use of GER medications was associated with decreased radiologic fibrosis and was an independent predictor of longer survival time in IPF patients. Thus, it is reasonable to believe that the same approach has to be considered in patients with scleroderma-related ILD, although further data from prospective controlled studies are mandatory. In conclusion, given the limited effect of current therapies on GER development and the emerging evidences of its role in pulmonary involvement, we believe that strategies aimed at contrasting reflux events should be included in the management of SSc-ILD, as they may be helpful in decreasing and, potentially, preventing the progression of the lung involvement in these patients.