Severe pulmonary hypertension (PAH) generally has a poor prognosis. This case report illustrates an apparent reversible cause of PAH due to vitamin C deficiency.
A seventy-three year old female never having smoked complained of worsening exertional dyspnea over three months. She could walk no more than 20 feet (6 meters) and her exercise tolerance was categorized as NYHA class III.On presentation, her vital signs were within normal limits. Physical examination, however, demonstrated a severely emaciated appearance, weighing 43.1kg (BMI 16.4). Cardiac auscultation showed grade 3/6 systolic murmur. The lungs were clear to auscultation. She had multiple dark, pigmented, hyperkeratotic skin lesions with excoriations covering all her extremities and trunk. Oral examination showed gingivitis, dental decay, and severe halitosis. The remaining examination was insignificant. The initial concern was acute coronary syndrome and pulmonary embolism. Her coronary angiogram showed normal coronary arteries. Pulmonary embolism was ruled out with V/Q scan. An echocardiogram showed normal left ventricular ejection fraction, normal wall motion abnormality, moderate tricuspid regurgitation, and severe PAH. Right-side heart catheterization revealed pulmonary artery pressure (PAP) 73/32 mmHg (mean 48), cardiac index (CI) 1.2 L/min, normal pulmonary capillary wedge pressure, without evidence of right heart failure. PAP was improved to 51/18 mmHg (mean 30), and CI to 1.2 L/min after adenosine infusion. Pulmonary function test (PFT) showed a mildly restrictive ventilation defect: FVC of 2.81 L (65%), FEV1 of 2.12 L (63%), FEV1/FVC ratio of 96%, with DLCO at 46% of the predicted level. A chest CT scan showed biapical parenchymal scarring with mild emphysematous changes.On further questioning, the patient believed she was sensitive to multiple foods and could not tolerate any citrus. Her vitamin C level was undetectably low. Given the appearance of her skin lesion, the clinical team considered the possibility of a vasculitis versus scurvy. Her anti-nuclear-antigen was mildly elevated, but all other vasculitis associated rheumatologic markers or SCL-70 antibodies were negative. A skin punch biopsy showed no features of vasculitis; instead showing perivascular mononuclear cell infiltrate with extravasated red blood cells, which supported a diagnosis of scurvy.The patient was discharged with Nifedipine 10mg three times a day and vitamin C supplementation. At a three month follow-up, she no longer had dyspnea or exercise limitation. Her weight had increased to 49.0 kg (BMI 18.6). The vitamin C level rose above the normal reference range and the skin lesions had resolved. Her echocardiogram showed a markedly improved estimated PAP of 35 mmHg above the right atrium pressure. A repeat chest CT showed resolution of the parenchymal changes. Complete PFT demonstrated a normalization of lung volumes, though DLCO remained reduced at 45% of the predicted level.
Vitamin C deficiency is rarely seen in developed countries. Vitamin C is essential to cross-link propeptides in collagen synthesis. Purpura due to vessel wall fragility is a well known manifestation of scurvy. It would be reasonable to assume vitamin C deficiency affected the vascular elasticity of the pulmonary arterial wall, however, its effect on pulmonary artery endothelial cells or smooth muscle is not clearly understood. Similar to our patient, rare cases of pseudovasculitis, secondary to vitamin C deficiency in anorexia nervosa, have been reported (1). Our case is unique in that, first, given we had ruled out other potential etiologies, her severe PAH was likely due to vitamin C deficiency. Second, her PAH responded dramatically to low dose vasodilators; and thirdly, her PAH was symptomatically improved and objectively reversed after vitamin C replacement.
We report the case of PAH secondary to vitamin C deficiency, which was successfully reversed after vitamin replacement.
Soichiro Nagamatsu, No Financial Disclosure Information; No Product/Research Disclosure Information