Case Report

Acute right ventricular failure in lupus-associated protein-losing enteropathy

Abstract

Central pulmonary embolism with acute right ventricular failure usually represents an ominous sign and carries high risk of mortality. Across the broad spectrum of precipitating factors contributing to the prothrombotic milieu, protein- losing enteropathy has rarely been stressed to be associated with life-threatening thromboembolism. Of interest, protein- losing enteropathy can be the initial manifestation of systemic lupus erythematosus and harbinger of the autoim- mune inflammation process antedating the lupus phase by months to years. Herein, we reported a 44-year-old man with central pulmonary embolism as the presenting feature of lupus-associated protein-losing enteropathy preceding a full- blown lupus flare. This report details the clinical features, radiographic findings, pathogenesis, and treatment of this distinct manifestation.

A 44-year-old man with a 2-month history of severe pedal Pitting edema was referred because of rapid onset of chest pain along with progressively worsening dyspnea in the past 3 days. He reported no illicit drug use, and medical or family history. Upon examination, he was alert; and his blood pressure was 92/64 mm Hg, heart rate was 121 beats per minute, respiratory rate was 24 breaths per minute, and body temperature was 37.1?C. Hemogram showed hemoglobin of

10.1 g/dL, platelet count of 98 x 10⁹/L, and leukocyte count of 1.76 x 10⁹/L. Laboratory studies revealed the following: sodium, 138 mmol/L; potassium, 4.5 mmol/L; chloride, 101 mmol/L; blood urea nitrogen, 18 mg/dL; creatinine, 1.0 mg/dL; aspartate aminotransferase, 36 U/L; alanine amino- transferase, 20 U/L; and a normal panel of cardiac biomarkers. Arterial blood gas analysis with a fraction of inspired oxygen of 100% revealed pH of 7.31, PO₂ of 78.2 mm Hg, PCO₂ of 29.4 mm Hg, and HCO^- of 19.6 mmol/L. Electrocardiogram showed atrial fibrillation with a rapid ventricular rate without a Mcginn-White pattern. Transtho- racic echocardiography disclosed right ventricular dilatation and moderate hypokinesis with estimated pulmonary artery systolic pressure of 55 mm Hg. Although plain chest radiograph was unrevealing, contrast-enhanced computed tomographic scan of the chest confirmed the diagnosis of

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pulmonary embolism (Fig. 1). Percutaneous catheter-based rotational thrombus defragmentation was attempted, fol- lowed by institution of alteplase with a bolus of 5 mg and continuous infusion of 1 mg/h for 3 days coupled with Intravenous heparin administration. Gradual clinical and Hemodynamic improvement was observed, without major bleeding or any other complication. Further workups for prothrombotic state are shown in Table 1, indicating imbalanced regulators between coagulation and fibrinolytic cascades. Meanwhile, even through a stepwise nutrition support protocol, profound edema recurred rapidly. Hypo- proteinemia and dyslipidemia were evident (total protein, 4.2 g/dL; albumin, 2.5 g/dL; cholesterol, 310 mg/dL; triglycer- ide, 335 mg/dL).Results of urinalysis was normal, and the findings from gastrointestinal endoscopy were also incon- clusive. However, in the absence of compatible renal or hepatic disorders, the patient’s highly elevated stool ?-1 antitrypsin (4.8 mg/g dry weight sample) coupled with its raised fecal clearance (68 mL/d) was strongly diagnostic for protein-losing enteropathy (PLE). Of note, high serum titer of anti-nuclear antibody (1:1280) and anti-dsDNA (65 IU/mL) in the presence of leucopenia/thrombocytopenia, hypocom- plementemia (C3, 48.7 mg/dL; C4, 11 mg/dL), and negative anti-Ro/La/Ena/Sm autoantibody may suggest systemic lupus erythematosus as the responsible culprit. His symptoms resolved rapidly after one course of intravenous corticoste- roid pulse therapy but flared up associated with malar rash and nonerosive arthritis 6 months later.

Pulmonary embolism is the most dreaded consequence of venous thromboembolism. The variability in timeframe and presenting symptoms, related to the extent and location, often makes this condition difficult to diagnose. Overall mortality for patients with massive pulmonary embolism is approximately 30%; but if the condition is not recognized associated with delayed treatment, up to 70% will experience cardiac arrest and death [1]. Variable causes of pulmonary embolism have been explored; but in protein-wasting diseases, it is less-recognized that the imbalance among prothrombotic factors (eg, increased Fibrinogen levels, increased Factor VIII levels, increased platelet adhesiveness), antithrombotic factors (eg, reduced antithrombin III levels, reduced protein C and S levels or activity), and impaired thrombolytic activity (decreased plasminogen levels, elevat- ed plasminogen activator inhibitor-1 levels or albumin deficiency-related impairment of the interaction of plasmin-

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845.e2 Case Report

Fig. 1 Contrast-enhanced computed tomographic scan of the chest showing central emboli over the bifurcation of both pulmonary arteries.

ogen-fibrin) can confer potent predisposition to thromboem- bolism [2].

Protein-losing enteropathy is not a specific disease but rather a group of system-based disorders with hypoprotei- nemia and edema in the absence of either proteinuria or defects in protein biosynthesis. The normal gastrointestinal tract does not contribute significantly to the catabolism of plasma proteins, accounting for only about 10% of the normal turnover of albumin and globulin. Once plasma proteins pass into the gastrointestinal tract, they are degraded

Table 1 Laboratory investigation for prothrombotic state

rapidly to amino acids and reabsorbed into the portal circulation. A wide variety of underlying causes has been described such as intestinal lymphangiectasia, right-side heart failure, hepatic Venous outflow obstruction, lymphoma/ leukemia, tuberculosis, bacterial overgrowth, parasitic infec- tion, sarcoidosis, amyloidosis, Whipple disease, tropical sprue, celiac disease, or inflammatory bowel diseases; however, lupus-associated PLE has rarely been identified [3]. ?-1 antitrypsin, a protein that accounts for approximately 4% of total serum proteins and is resistant to proteolysis, is a reliable diagnostic tool for quantitative measurement of intestinal protein loss. Its clearance greater than 24 mL/d in patients without diarrhea and greater than 56 mL/d in patients with diarrhea is strongly indicative of PLE [4].

Lupus-associated PLE antedating a full-blown lupus flare in man is very rare. It typically occurs in young women and was characterized by the onset of profound edema with hypoproteinemia. Although the mechanism remains unclear, autoantibody-mediated nonnecrotizing vasculitis involving the mesenteric or intestinal vessels has been supposed [5]. Previous studies suggested that intravascular activation and conversion of complements could cause increasing capillary permeability and enhanced exudation of protein-rich material across intestinal blood vessel walls, leading to expanded lymph vessels and edematous bowel wall. Some cytokines such as tumor necrosis factor-? and interleukin-6 secreted by inflammatory cells could increase the microvascular bed permeability, which in turn causes nonselective protein leakage from blood to the intestinal lumen.

Most patients have good outcome, as more than 60% respond well to oral corticosteroids alone. For those who were refractory to corticosteroids, additive immunosuppressive therapy such as cyclophosphamide, azathioprine, mycophe- nolate mofetil, or cyclosporine should be carried out [6]. Maintenance of Nutritional status with balanced protein intake and medium-chain triglycerides supplement is also important because reduction in intake of long-chain fatty acids reduces lymphatic flow and pressure within the lymphatic system and decreases the amount of lymph leakage.

The management of pulmonary embolism remains chal- lenging because it can rise from a wide variety of causes. Although acute central pulmonary embolism secondary to lupus-associated PLE is less addressed, it should always be considered in General practice, as systemic lupus erythematosus is a chronic, multifaceted inflammatory disease that can affect every organ system of the body with protean manifestations.

Yu-Tzu Tsao MD Division of Nephrology Department of Medicine

Tri-Service General Hospital National Defense Medical Center

Taipei, Taiwan Department of Critical Care Medicine Gangshan Armed Forced Hospital

Kaohsiung, Taiwan

Case Report 845.e3

Chia-Chao Wu MD, PhD

Yu-Juei Hsu MD Pauling Chu MD, PhD Division of Nephrology Department of Medicine

Tri-Service General Hospital National Defense Medical Center

Taipei, Taiwan E-mail address: [email protected]

doi:10.1016/j.ajem.2009.12.009

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