INTRODUCTION:The American College of Chest Physicians published guidelines in 2004 with recommendations for the evaluation and treatment of Pulmonary Arterial Hypertension (PAH). The current classification system does not include the diagnosis of Whipple’s Disease as a secondary cause. Four previously published case reports have suggested a possible causal relationship of Tropheryma whipplei infection and PAH. We are going to present a case of a 49 year old male who was diagnosed with PAH and Whipple’s Disease. After receiving appropriate treatment both processes resolved, further establishing this causal relationship.
CASE PRESENTATION:A previously healthy, 49 year old white male presented with complaints of an upper respiratory tract infection followed by six weeks of progressive dyspnea, increasing abdominal girth and lower extremity edema. His past medical history consisted of hypertension treated with benazepril and a remote history of tobacco dependence. He denied any significant occupational or environmental exposures. His family medical history was significant for rheumatoid arthritis, hypertension, hyperlipidemia, diabetes and coronary artery disease. He was afebrile with a pulse of 68, respiratory rate of 20, blood pressure of 100/65 and room air oximetry of 98%. Pertinent physical exam included: a loud P2 with an otherwise normal cardiopulmonary exam; ascites; guaiac positive stools; lower extremity edema; and normal neurologic exam. Pertinent laboratory studies revealed a low protein and albumin, an elevated brain natriuretic peptide, a leukocytosis with a left-shift, a microcytic-hypochromic anemia, iron studies consistent with iron deficiency, and an elevated thyroid stimulating hormone. A complete serologic workup for autoimmune diseases and an HIV test were negative. Transthoracic echocardiography was remarkable for normal systolic function, mild diastolic dysfunction, and a dilated right heart with a pulmonary artery pressure (PAP) of 120 mmHg. Computed tomography and ventilation-perfusion scans of the chest were negative for any significant cardiopulmonary process. Pulmonary function testing suggested a mixed obstructive-restrictive pattern. Overnight oximetry did not show any desaturations.A left heart catheterization was normal. A right heart catheterization revealed an elevated mean PAP and normal pulmonary capillary wedge pressure. Vasoreactivity testing with adenosine decreased the mean PAP from 50 to 39 mmHg and increased the cardiac output. Esophagogastroduodenoscopy revealed gastritis, duodenitis and jejunitis. Abundant macrophages with periodic acid schiff positive granular inclusions distending the cytoplasm were found on the biopsy specimens. Rapid polymerase chain reaction (PCR) testing was positive for the presence of Tropheryma whipplei.
DISCUSSIONS:After careful and complete evaluation of our patient, all of the secondary causes of PAH were ruled out and Whipple’s Disease was proven by biopsy/PCR. His PAH was treated with amlodipine 10 mg daily. He was also treated with a cephalosporin antibiotic for two weeks followed by trimethoprim/sulfamethoxazole twice daily thereafter. Two months after starting therapy repeat echocardiography revealed a PAP of 33 mmHg and complete resolution of his symptoms.A review of the literature found four case reports that propose an association between PAH and Whipple’s disease. In two of the cases, the PAH may have been related to valvulopathy secondary to Tropheryma whipplei endocarditis. In the other two cases there was not an absolute etiology found for the PAH, but after treatment the PAH improved or resolved.
CONCLUSION:It is our opinion, to date this is the best evidence to suggest that Whipple’s Disease should be ruled out as a secondary cause of PAH. As Tropheryma whipplei is a difficult bacterium to culture and its presentation is that of the “great imitator”, we hypothesize that undiagnosed Whipple’s Disease may be a cause of previously diagnosed Idiopathic PAH and treatment with appropriate antibiotics could result in better outcomes.
DISCLOSURE:Anthony Hericks, No Financial Disclosure Information; No Product/Research Disclosure Information