A CASE OF PULMONARY HYPERTENSION ASSOCIATED WITH POEMS SYNDROME

INTRODUCTION: POEMS syndrome is a rare multisystem disorder characterized by polyneuropathy, organomegaly, endocrine abnormalities, a monoclonal protein and skin changes. Pulmonary hypertension (PH) has also been reported in 22 patients with POEMS with an estimated prevalence of 5%. We describe a patient who presented for management of PH and right heart failure subsequently diagnosed with POEMS syndrome. CASE PRESENTATION: A 37 year old female with profound lower extremity edema and ascites was evaluated in an outpatient pulmonary hypertension clinic. Past medical history included pulmonary embolism, atrial fibrillation, hypothyroidism and prior back surgery. PH had been diagnosed after the patient underwent a laminectomy and fusion from T10 through S1 for suspected chord compression. This was complicated by the development of ascites, lower extremity edema and a bilateral brachial plexopathy thought to be secondary to a thoracolumbarsacral orthosis. Evaluation was notable for hepatospelomegaly and an echocardiogram with moderate tricuspid regurgitation (TR), left ventricular septal flattening suggesting right ventricular pressure overload, and a starry sky appearance. Endomyocardial and liver biopsies were unremarkable. A right heart catetherization revealed a pulmonary artery pressure (PAP) of 58/13 (35) mmHg, pulmonary capillary wedge pressure (PCWP) of 10 mmHg and cardiac output (CO) of 12.1 L/min.Treatment with sildenafil and diuretics was initiated for mild PH, but edema and ascites persisted so bosentan was added. The patient was later hospitalized for diarrhea, ascites and edema resistant to diuresis with worsening renal function and subsequently transferred to our institution for consultation. Physical examination at that time was notable for a cachectic appearance, ascites, edema, diffuse adenopathy, bilateral claw hand deformities and white fingernails. Right heart catheterization was repeated and confirmed mild pulmonary hypertension (PAP 52/20 [31] mmHg, PCWP 14 mmHg, CO 13.4 L/min). Causes of high output heart failure such as liver dysfunction and B12 deficiency were ruled out. Testing revealed adrenal insufficiency, hypogonadotropic hypogonadism and an elevated prolactin level. A nerve conduction velocity study showed a severe sensory-motor polyneuropathy with axonal loss and demyelination. Serum protein electrophoresis was normal but immunofixation revealed an IGA lambda monoclonal band. A skeletal series was normal. A vascular endothelial growth factor (VEGF) level was 247 pg/ml (normal 31-86 pg/ml) confirming a diagnosis of POEMS syndrome. In retrospect, the history of thrombosis, hypothyroidism and neuropathy was likely secondary to early POEMS. DISCUSSIONS: The POEMS syndrome is a plasma cell dyscrasia defined by the five main features that give it its name and a variety of other features including sclerotic bone lesions, Castleman’s disease, papilledema, pleural effusion, edema, ascites and thrombocytosis. Features of POEMS associated PH are similar to those of idiopathic PH. Pathologic findings in lung tissue have shown medial hypertrophy, intimal proliferation and fibrosis, plexiform lesions and in situ microthrombosis identical to idiopathic PH. Elevated levels of Interleukin-1B (IL-1B), IL-6, (also demonstrated in idiopathic PH) tumor necrosis factor alpha, and more recently vascular endothelial growth factor (VEGF), have been implicated as the cause of the pulmonary and systemic vascular inflammatory process in POEMS. Resolution of POEMS associated PH has been demonstrated after treatment with steroids and immunosuppressive therapy in some patients. POEMS associated PH could be analogous to an early inflammatory “pre-disease” stage of other forms of PH that might be responsive to immunosuppressive therapy. CONCLUSION: POEMS syndrome is associated with PH and should be considered in patients with PH of uncertain etiology. Understanding of the pathophysiology and response to treatment of POEMS may improve our understanding of other forms of PH.