|Year : 2022 | Volume
| Issue : 11 | Page : 1939-1944
A POEMS syndrome patient with idiopathic non-cirrhotic portal hypertension received the transjugular intrahepatic portosystemic shunt: a case report and literature review
Y Chen, J Lin, X Jiang, Q Zhou, H Zhang
Department of Gastroenterology, Wenzhou Central Hospital, Wenzhou, Zhejiang, China
|Date of Submission||21-May-2022|
|Date of Acceptance||25-Jul-2022|
|Date of Web Publication||18-Nov-2022|
Dr. H Zhang
Department of Gastroenterology, Wenzhou Central Hospital, Wenzhou - 325000, Zhejiang
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome is a rare plasma cell dyscrasia disease involving multiple organs combined with idiopathic non-cirrhotic portal hypertension. It has been reported only four times in the English literature. Here, we present the first case of a 62-year-old male POEMS syndrome patient with portal hypertension treated with the transjugular intrahepatic portosystemic shunt (TIPS), after he presented with a 10-day history of melena. The diagnosis of POEMS syndrome was given because the patient presented with polyneuropathy, monoclonal plasma cell proliferative disorder, sclerotic bone lesions, splenomegaly, lymphadenopathy, ascites, hypothyroidism, and hyperpigmentation. The presence of portal hypertension was confirmed by esophageal varices, congested and edematous stomach body, splenomegaly, and transudate ascites in which the serum-ascites albumin gradient of ascites fluid was over 11 g/L (a concentration considered to be associated with POEMS syndrome), as no other causes were found. The patient fasted and received conservative drug treatments on admission, but symptoms of melena soon recurred within 1 week after resuming his diet. After TIPS and venous embolization were performed, symptoms of bleeding were effectively controlled, while the patient subsequently developed hepatic encephalopathy, which ultimately led to death. The presence of gastrointestinal bleeding in POEMS syndrome with idiopathic non-cirrhotic portal hypertension indicates a poor prognosis. Given that this was the first patient to receive TIPS, and although the incidence of hepatic encephalopathy has increased, TIPS is still acceptable for refractory variceal bleeding.
Keywords: Idiopathic Non-cirrhotic Portal Hypertension, POEMS syndrome, transjugular intrahepatic portosystemic shunt
|How to cite this article:|
Chen Y, Lin J, Jiang X, Zhou Q, Zhang H. A POEMS syndrome patient with idiopathic non-cirrhotic portal hypertension received the transjugular intrahepatic portosystemic shunt: a case report and literature review. Niger J Clin Pract 2022;25:1939-44
|How to cite this URL:|
Chen Y, Lin J, Jiang X, Zhou Q, Zhang H. A POEMS syndrome patient with idiopathic non-cirrhotic portal hypertension received the transjugular intrahepatic portosystemic shunt: a case report and literature review. Niger J Clin Pract [serial online] 2022 [cited 2022 Nov 30];25:1939-44. Available from: https://www.njcponline.com/text.asp?2022/25/11/1939/361463
| Introduction|| |
Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome is a rare paraneoplastic disorder of plasma cell dyscrasia, which was first proposed by Bardwick in 1980. Due to its low incidence, slow progression, and easy misdiagnosis as other neurologic disorders, accurate diagnoses are often delayed by approximately 13–18 months. For the diagnosis of POEMS syndrome, a patient must experience polyneuropathy, monoclonal plasma cell proliferative disorder, and at least one minor criterion. Although signs of ascites are common in patients with POEMS syndrome, concurrent portal hypertension is extremely rare. Here, to the best of our knowledge, we present the first reported case of a POEMS syndrome patient with portal hypertension treated with the transjugular intrahepatic portosystemic shunt (TIPS) for recurrent bleeding caused by portal hypertensive gastropathy.
| Case Report|| |
A 62-year-old man was admitted to our department with a 10-day history of melena in June 2020. Physical examination revealed cachexia, conjunctival pallor, hyperpigmentation, left supraclavicular lymphadenopathy, scleroderma-like skin thickening, and ascites with splenomegaly. A neurologic examination revealed a flexion deformity of the proximal interphalangeal joints and limited wrist movement with bilateral upper extremity numbness. The remaining systemic examination was normal. A detailed past history was taken on admission. He had experienced numbness of the upper extremities over 10 years, developed ascites 3 years ago, and was ultimately diagnosed with POEMS syndrome. The treatment history of POEMS syndrome included glucocorticoid substitution therapy and eight courses of chemotherapy with cyclophosphamide and dexamethasone. However, abdominal distension caused by ascites was not relieved after eight courses of treatment and long-term diuretic therapy. There was no history of drug, tobacco, or alcohol abuse.
The relevant examinations were completed immediately after admission. A complete blood count revealed a hemoglobin level of 67 g/L, indicating anemia, with decreased platelet and white blood cell counts. The liver test examination and electrolytes were normal, except for mild hypoalbuminemia (27.4 g/L). A renal function test showed an elevated creatinine level (142 μmol/L), and the 24-h urine total protein level was 0.81 g. Hyperglycemia was found after admission, and endocrine tests confirmed hypothyroidism. Serologic tests for human immunodeficiency virus, hepatitis B virus, hepatitis C virus, autoimmune hepatitis antibodies, anti-smooth muscle antibodies, and anti-nuclear antibodies were negative. No parasites or eggs were detected in the patient's stool. Ascitic fluid analysis showed a cell count of 390/mm3 with mononuclear predominance, and the serum-ascites albumin gradient (SAAG) was 14 g/L, compatible with transudate fluid. Monoclonal immunoglobulin A lambda protein was detected in the serum by protein electrophoresis and immunofixation. Electromyography indicated peripheral nerve injury in the extremities. Positron emission tomography (PET)/computed tomography (CT) revealed lytic lesions in the left iliac wing with a sclerotic rim. Abdominal contrast-enhanced computerized tomography confirmed varicosity in the esophageal, paraesophageal, gastric coronary, and perisplenic veins with enlarged spleen [Figure 1]a, [Figure 1]b, [Figure 1]c. Esophagogastroduodenoscopy revealed severe-grade esophageal varices in the lower esophagus with characteristic red color signs and congestion and edema in the mucosa of the gastric fundus and stomach body [Figure 2]a, [Figure 2]b. We then obtained a tissue biopsy of the liver, and pathological results indicated swelling in a portion of the hepatocytes with inclusion bodies seen in the nucleus and fibrous tissue proliferation seen in the portal area with lymphocytic infiltration and small bile duct proliferation [Figure 3]. There was no evidence of hepatitis or amyloid deposition. These findings are consistent with idiopathic non-cirrhotic portal hypertension.
|Figure 1: Abdominal contrast-enhanced computerized tomography. (a) CECT shows esophageal and paraesophageal varices. (b) CECT demonstrates thickened stomach wall and lobulated dilation of the gastric coronary veins. (c) CECT shows enlarged spleen and thickened and twisted perisplenic veins. CECT = contrast-enhanced computed tomography|
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|Figure 2: Esophagogastroduodenoscopy. (a) Esophagogastroduodenoscopy showed severe grade esophageal varices in the lower esophagus with characteristic red color signs. (b) Esophagogastroduodenoscopy confirmed that the mucosa of gastric fundus and stomach body were congested and edematous, suggesting portal hypertensive gastropathy|
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|Figure 3: Liver biopsy. Photomicrograph of hematoxylin and eosin-stained slide shows swelling in a portion of the hepatocytes with inclusion bodies seen in the nucleus and fibrous tissue proliferation seen in the portal area with lymphocytic infiltration and small bile duct proliferation|
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As mentioned above, the patient presented with polyneuropathy, monoclonal plasma cell proliferative disorder, sclerotic bone lesions, splenomegaly, lymphadenopathy, ascites, hypothyroidism, and hyperpigmentation, and the patient was diagnosed with POEMS syndrome. Furthermore, a diagnosis of idiopathic non-cirrhotic portal hypertension associated with POEMS syndrome was made because no other cause was found.
The patient fasted and received conservative drug treatments on admission, but symptoms of melena soon recurred within 1 week after resuming his diet. His ascites had deteriorated while he was on diuretic therapy and after undergoing repeated therapeutic paracentesis. Considering the patient's condition, imaging findings, and esophagogastroduodenoscopy results, we speculated that the upper gastrointestinal bleeding was caused by portal hypertensive gastropathy. Coupled with the patient's past history of refractory ascites, TIPS and venous embolization were subsequently performed after obtaining consent from the patient and his family. According to the radiography findings [Figure 4], the gastric coronary vein was embolized with a releasable spring coil (Interlock; Boston Scientific Corporation, Marlborough USA) and a shunt was established with a cover stent (8 mm × 7 cm, VIATORR; W.L. Gore & Associa tes, New york USA). The portosystemic gradient (PSG) decreased from 18 to 11 mmHg. The patient's ascites and bleeding were effectively controlled after TIPS treatment, but severe grade 3 and 4 hepatic encephalopathy developed in the following 2 months. He then developed acute respiratory failure due to severe hepatic encephalopathy with hyperammonemia (290.2 μmol/L) despite continued use of the maximum prescribed medical therapy. The patient received endotracheal intubation soon after acute respiratory failure due to hepatic encephalopathy. Then, intermittent fevers occurred during hospitalization in the intensive care unit, accompanied by a large amount of pleural effusion. Serologic tests showed an elevated C-reactive protein level (109.3 mg/L), and his procalcitonin concentration reached 11.53 μg/L. Unfortunately, the patient subsequently developed septic shock within 2 weeks, and his blood pressure fluctuated between 76/43and 119/67 mmHg on using norepineph rine to maintain blood pressure. Because of financial difficulties, the patient's family refused further treatment, and the patient ultimately died at home. As no autopsy was conducted, the exact cause of death is unknown. However, we speculate the development of sepsis was due to aspiration pneumonia during his hepatic coma and finally led to his death.
|Figure 4: The angiography images demonstrate that the gastric coronary varices were embolized with a releasable spring coil and that the blood flow was smooth in TIPS without the varicose vein. TIPS = transjugular intrahepatic portosystemic shunt|
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| Discussion|| |
POEMS syndrome, a rare multisystemic disease, remains poorly understood and is easily misdiagnosed due to its rarity and complicated clinical manifestations. The national incidence of POEMS syndrome is estimated to be 0.3/100,000 in Japan, while its incidence in other countries or regions is still unknown. The mean age at onset is 46 years (range, 10–81 years), and the ratio of males to females is approximately 2.23 in the Chinese population. Presenting symptoms for POEMS syndrome include peripheral neuropathy, edema and exudate, endocrinopathy, skin changes, and organ enlargement, accounting for 60.44%, 15.72%, 9.87%, 8.05%, and 2.13% of patients, respectively. Although hepatomegaly is the most common liver manifestation of POEMS syndrome and 39.6-54% of patients have ascites, POEMS syndrome with definite portal hypertension is extremely rare.,
In our patient, portal hypertension was indirectly confirmed by esophageal varices, a congested and edematous stomach body, splenomegaly, and transudate ascites in which SAAG of the ascites fluid was over 11 g/L, as finally directly confirmed by a portal venous pressure of 37 mmHg. As no other evidence could suggest the presence of cirrhosis or other common causes of portal hypertension, we considered portal hypertension to be associated with POEMS syndrome.
To explore the treatment and prognosis of patients with POEMS syndrome complicated with portal hypertension, we performed a comprehensive review of published cases of POEMS syndrome with idiopathic non-cirrhotic portal hypertension in the English literature dating back to 2010 [Table 1].,,, As shown in [Table 1], since 2010, even with our report, only five cases of POEMS syndrome with portal hypertension have been reported. It is worth noting that this is the first case treated with TIPS, and our patient was significantly older than others; additionally, his disease course was as long as 10 years. We reviewed the duration of POEMS syndrome in all patients: ascites mainly presented as the initial manifestation of POEMS syndrome with idiopathic non-cirrhotic portal hypertension and could be improved greatly after the systemic treatment. However, although the 10-year overall survival rate of POEMS syndrome patients can reach more than 80%, the prognosis of these patients may not be optimistic (including our patient, two patients with a 10-year disease course died). With increasing pressure on the portal vein, gastrointestinal bleeding often occurs in the late stage of the disease. Endoscopic hemostasis is acceptable for esophageal variceal bleeding confirmed by gastroscopy, while TIPS became a relatively good choice for recurrent gastrointestinal bleeding caused by portal hypertensive gastropathy in our case. Although TIPS could effectively reduce the pressure of portal vein that ascites and bleeding symptoms of our patient were effectively controlled in the following 2 months, the incidence of hepatic encephalopathy did increase.
|Table 1: POEMS syndrome with idiopathic non-cirrhotic portal hypertension as reported in the literature|
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In addition to the effect of TIPS on hemodynamics, the other reasons contributing to hyperammonemia in our case are as follows. First, a decreased urea synthesis rate due to hypothyroidism can lead to increased blood ammonia; however, the underlying mechanisms have not been identified. In addition, hypothyroidism can also cause constipation, increasing the intestinal absorption of ammonia. Second, as a common complication of POEMS syndrome, renal impairment can decrease the excretion of blood ammonia from the urine. Finally, the plasma cells in POEMS syndrome may be capable of producing ammonium directly or by causing the overexpression of some enzymes of the urea cycle, indirectly increasing the levels of blood ammonia.
The association between portal hypertension and POEMS syndrome has yet to be confirmed since the mechanism remains unknown. The hypothesis that a congenital vascular anomaly is the origin of changes in the portal tract was proposed, while vascular malformations were not found in most cases reported. Increased levels of inflammatory cytokines, such as vascular endothelial growth factor (VEGF), interleukin-1β, interleukin-6, interleukin-12, tumor necrosis factor-α, and tumor growth factor-β, were reported in POEMS syndrome.,,, The majority of reports support an acquired vascular defect hypothesis to explain the association. Infections, progressive fibrosis of the portal veins, exposure to several toxins or medications, aberrations in the thrombin–antithrombin complex, an immunological basis, and elevations in the levels of inflammatory cytokines were comprehensively considered in this hypothesis, and it is believed that portal hypertension is caused by the combined action of these factors in POEMS syndrome.
POEMS syndrome with idiopathic non-cirrhotic portal hypertension is extremely rare, and only four cases have been reported in the published English literature worldwide. Symptoms of ascites such as abdominal distension, anorexia, and abdominal pain are the common clinical features and can be greatly improved after systemic treatment. However, with a prolonged disease course, symptoms of gastrointestinal bleeding, such as melena and hematemesis, will inevitably occur due to gradually increased pressure on the portal vein. Measurement of the hepatic vein pressure gradient (HVPG) is recommended for each patient to assess the progression of portal hypertension and for early intervention. The best treatment remains controversial due to the lack of sufficient patients to compare the efficacy of different treatments. Endoscopic hemostasis is a good choice for esophageal variceal bleeding. Given the great decreasing effect of TIPS on portal pressure, it is still considered as the first-line treatment for refractory variceal bleeding, but clinicians should be highly alert on the occurrence of hepatic encephalopathy.
| Conclusion|| |
In conclusion, this report presents an extremely rare case of POEMS syndrome with idiopathic non-cirrhotic portal hypertension treated with TIPS. Patients with this disease eventually develop gastrointestinal bleeding due to portal hypertension, suggesting a poor prognosis. Although the incidence of hepatic encephalopathy does increase, TIPS is still acceptable for refractory variceal bleeding.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
The authors declare that they have no competing interests.
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