Case Presentation: A 62-year-oldwoman with heart failure with preserved ejection fraction (HFpEF) presented with one week of worsening shortness of breath, bilateral lower extremity edema, and poor oral intake. Over the past year, the she had increasing early satiety resulting in a 93-pound weight loss and progressively decreasing exercise tolerance. She noted dry eyes, dry mouth, and increased sensitivity to cold, but no Raynaud’s phenomena. Diagnostic workup, including esophagogastroduodenoscopy and colonoscopy, was unrevealing. On admission, physical exam was notable for skin thickening of her hands, arms, and chest with hyperpigmentation of the dorsal surfaces. Chest X-ray revealed bilateral pleural effusions and echocardiogram showed left ventricular hypertrophy, left atrial enlargement, diastolic dysfunction, and a small pericardial effusion. CT was negative for interstitial lung disease, but pulmonary function tests showed a restrictive pattern. Esophagram showed aperistalsis. Labs showed hemoglobin 9.6g/dL, creatinine 1.19mg/dL, free light chains on serum protein electrophoresis, and positive SSA (anti-Sjogren’s syndrome A) with negative antinuclear antibodies (ANA) and SCL-70 (anti‐topoisomerase I). The combination of HFpEF, skin thickening, and esophageal dysmotility raised concern for amyloidosis, but fat pad biopsy was negative for amyloid. Skin biopsy revealed sclerosing dermatitis leading to a diagnosis of seronegative systemic sclerosis. Treatment with mycophenolate and methylprednisolone was initiated, and she was discharged on home oxygen. On follow-up, a feeding tube was placed for continued poor oral intake. She was readmitted for scleroderma renal crisis and treated with captopril, but required continued dialysis.
Discussion: Systemic sclerosis is a rare connective tissue disease involving the skin, gastrointestinal tract, lungs, kidneys, skeletal muscle and pericardium (1). Esophageal dysmotility, dry mouth, pericardial effusions, anemia, and decreased renal function as seen in the patient are all common. However, Raynaud phenomenon is seen in 95% of cases, and typically precedes visceral involvement, and ANA is positive in >90% of cases (1). Our patient’s presentation was atypical, and her negative serology and lack of Raynaud’s initially lead physicians to consider amyloidosis. However, given the presence of multiple systemic sclerosis symptoms, the diagnosis should be considered even with negative antibodies and absent Reynaud’s. This highlights a common phenomenon of delayed diagnosis of systemic sclerosis, which can result in preventable progression to end-organ damage (2). Early detection may also improve survival (2). Cases of seronegative systemic sclerosis in which patients are negative for Raynaud’s are associated with underlying malignancy as part of a paraneoplastic syndrome, but no malignancy was identified in our patient (3-5).
Conclusions: We present a rare, atypical presentation of systemic sclerosis, revealing the importance of a broad differential in the case of a complex, multifaceted presentation. While many conditions can result in skin thickening and comorbid conditions can present multiple potential explanations for multi-organ involvement, it is important to keep systemic sclerosis on the differential even in the absence of antibodies. Ultimately, a broad differential and comprehensive, multidisciplinary workup diagnosed the patient and ensured she was started on appropriate treatment with proper follow up.