Chronic dyspnea with Raynaud's phenomenon and elevated ANA: A diagnosis of systemic sclerosis sine scleroderma

Abstract

Systemic sclerosis (SSc) should be considered in all patients initially diagnosed with idiopathic interstitial lung disease (ILD), even in the absence of classical scleroderma cutaneous features. Systemic sclerosis sine scleroderma (ssSSc) is a rare subtype of SSc, and the diagnosis requires the absence of characteristic skin thickening but the presence of the three following criteria: (A) Raynaud's phenomenon or the equivalent of abnormal nail fold capillaries, (B) positive antinuclear antibody (ANA), typically with nucleolar or speckled immunofluorescence pattern, and (C) at least one internal organ involvement of ILD, renal dysfunction, esophageal/bowel dysmotility or pulmonary arterial hypertension; in the absence of an alternative rheumatological diagnosis. The radiological and histopathological features of systemic sclerosis sine scleroderma-associated interstitial lung disease (ssSSc-ILD) are commonly those of non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP) that cannot help distinguish between idiopathic interstitial pneumonia, different types of connective tissue diseases, or even different subsets of SSc. Therefore, other than chest imaging, the use of nail fold capillaroscopy, positive serum ANA antibody, echocardiogram, and esophagram are essential, in conjunction with the clinical presentation for facilitating the diagnosis of ssSSc. We present a case of a 58-year-old woman presenting with chronic dyspnea, a positive review of systems for Raynaud's phenomenon, and found to have elevated nucleolar immunofluorescence pattern of ANA with chest imaging consistent with the diagnosis of ssSSc-ILD. The uniqueness of this case is that despite symptomatic alleviation with oral mycophenolate therapy, our patient's restrictive lung disease on pulmonary function tests continued to decline, requiring initiation of oral nintedanib therapy leading to stability and improvement. However, due to the rarity of ssSSc, the use of oral nintedanib for systemic sclerosis-associated ILD has only been formally assessed on patients with diffuse cutaneous systemic sclerosis and limited cutaneous systemic sclerosis.

Keywords: Systemic sclerosis; Systemic sclerosis sine scleroderma; Systemic sclerosis sine scleroderma-associated with interstitial lung disease; Systemic sclerosis-associated with interstitial lung disease.