Narasimhaiah Srinivasaiah, Mohammad K Zia and Vummiti Muralikrishnan

Bridgend, UK

Case Report

Peritonitis in myelofibrosis: a cautionary tale

Narasimhaiah Srinivasaiah, Mohammad K Zia and Vummiti Muralikrishnan

Bridgend, UK

BACKGROUND:Primary myelofibrosis (PMF) is a myeloproliferative disorder characterized by bone marrow fibrosis. Extra-medullary hematopoiesis sometimes occurs even in the peritoneal cavity, apart from organs such as the liver, spleen, and lymph nodes. This may sometimes be complicated by spontaneous infection and complications. We report a rather unusual case of PMF, who presented as an emergency with spontaneous peritonitis to general surgery department and had a fulminant clinical course.

METHOD:A clinical case note review was done and a literature search was undertaken.

RESULTS:A rather unusual case of PMF, who presented as an emergency with spontaneous peritonitis to general surgery department. The patient underwent a laparotomy and had a fulminant clinical course.

CONCLUSIONS:Peritonitis in myelofibrosis may have a number of causes. Clinicians need to be aware of them and provide conservative management prior to surgical treatment.

(Hepatobiliary Pancreat Dis Int 2010; 9: 651-653)

primary myelo fibrosis; hepato-splenomegaly; splenic rupture; extra-medullary hematopoiesis; sepsis; peritonitis

Introduction

Primary myelofibrosis (PMF) is a stem-cell-derived clonal myeloproliferative disorder[1]characterized by replacement of bone marrow with fibrous tissue, leading to malfunctioning of the hematopoietic system. Extra-medullary hematopoiesis (EMH) frequently occurs in the liver, spleen, and lymph nodes but rarely involves the skull, paranasal sinus, thyroid, pleura, vertebrae, kidneys, adrenal glands, mesentery, pelvic cavity, uterus, or skin.[2]Hepatosplenomegaly is a common sequela of PMF.[3]Ascites can develop as a consequence of EMH,[4]or pre-sinusoidal portal hypertension.[5]The presence of one or more of these can cause a diagnostic challenge and difficulty in decision-making. We present a rather unusual case of PMF who posed a diagnostic surgical problem. Both aseptic peritonitis and spontaneous bacterial peritonitis in patients with PMF should be considered as possibilities.

Case report

A 70-year-old male Caucasian was admitted from accident and emergency with significant abdominal pain, difficult to control with analgesics. His co-morbidity included myelofibrosis, type 2 diabetes mellitus, end-stage renal failure on hemodialysis, hypothyroidism, chronic diarrhoea, hypertension, focal segmental glomerulo-sclerosis and chronic abdominal pain (6 months).

He presented with lower abdominal pain which was characteristically sharp and continuous with no radiation, associated with nausea and vomiting. Examination revealed tachycardia with a temperature of 38.6 ℃. Systemic examination revealed a distended abdomen with peritonitis. Investigations revealed Hb 11 gm/dl, WBC 24.7, Neu 14.7, platelets 390, urea 22.5, creatinine 625, and CRP 85. Blood gases were pH 7.46, PO2-63 mmHg, and lactate 2.3 mmol/L. An erect chest X-ray showed no evidence of pneumoperitoneum. Ultrasound examination demonstrated splenomegaly with minimal free fluid. This led to a clinical diagnosis of a ruptured spleen or a hollow viscus perforation. Following initial resuscitation with fluids, oxygen, and antibiotics, the patient underwenta CT scan of the abdomen and pelvis, which raised the possibility of a splenic bleeding along with infarction (Fig.). Because of the possibility of a splenic bleeding the patient underwent laparotomy.

Fig. CT suggesting a splenic bleeding with possible infarction.

The findings included hepato-splenomegaly with areas of splenic infarction and 500 ml of sero-purulent fluid with fibrinous exudates. There was neither splenic rupture nor a hollow viscus perforation. A thorough lavage was done and the abdomen was closed with a drain.

The postoperative course included a stay in ICU with significant acidosis. Worsening sepsis with rising lactate and hypotension led to death due to multiple organ dysfunction syndrome. The peritoneal fluid cultures revealed coliforms and Gram-negative bacilli from the blood.

Discussion

PMF is a stem-cell-derived clonal myeloproliferative disorder,[1]which is characterized by bone marrow fibrosis, extramedullary hematopoiesis, and the presence of JAK2 mutations.[1]It is a disease process characterized by deficiency of the marrow stem cells, leading to replacement of bone marrow by fibrous tissue. Myelofibrosis can be categorized into primary or secondary. PMF is idiopathic; however the secondary can be due to any processes affecting the bone marrow. These include metastatic cancer, Hodgkin's disease, polycythemia vera, lymphoma, HIV infection, chronic myelogenous leukemia, multiple myeloma, acute leukemia, radiation, and toxins (benzene). The process leads to malfunctioning of the bone marrow. EMH frequently occurs in the liver, spleen, and lymph nodes in patients with PMF, and rarely involves the skull, paranasal sinus, thyroid, pleura, vertebrae, kidneys, adrenal glands, mesentery, pelvic cavity, uterus, or skin.[2]EMH results in a number of manifestations. Hepatosplenomegaly is a common sequela of PMF.[3]Ascites can develop as a consequence of EMH,[4]or pre-sinusoidal portal hypertension.[5]The ascites may result from peritoneal implants of extramedullary hematopoietic tissue, especially seeded from the spleen.[6-9]

The most common initial symptoms are fatigue, weakness, and anorexia. Other features include hepatosplenomegaly-related symptoms and complications. Rare unusual features include EMH in mesentery, ascites secondary to mesenteric EMH,[10]spontaneous infection of ascitic fluid with tubercular bacilli,[11]splenic sub-capsular bleeding,[12]and infarction along with lymphomas.[13]Patients can experience excruciating pain due to aseptic peritonitis or splenic infarcts. Myelofibrosis patients have a range of debilitating disease manifestations, eg, massive splenomegaly, cytopenias, constitutional symptoms, and transformation to a treatment-refractory blast phase.[14]

Treatment aims at relieving symptoms. Symptomatic treatment is provided with blood transfusions, recombinant human erythropoietin, and supplemental folic acid. The anti-gout drug allopurinol is prescribed when uric acid levels are elevated, to avoid kidney stones. Surgical removal of the spleen may be indicated in cases where spleen enlargement causes severe problems in the patient, such as pain or difficulty in eating. Hydroxyurea has been tried in the treatment of ascites.[10]Allogeneic stem-cell transplantation is an option.[14]However, this therapy is either inappropriate or not feasible for the majority of patients. Splenectomy or radiotherapy offers benefit for symptomatic splenomegaly, in addition to JAK2 inhibitors.[14]There are cases reported in the literature on the use of radiotherapy for splenomegaly with subcapsular hematomas due to spontaneous rupture.[12]

Our patient presented with symptoms and signs suggestive of peritonitis. Laparotomy showed features of primary peritonitis with no apparent cause. There was peritoneal EMH and spontaneous bacterial peritonitis evidenced by the growth of Gram-negative organisms from the peritoneal fluid. Hepato-splenomegaly and EMH may lead to bacterial translocation into the peritoneum.

In conclusion, peritonitis in myelofibrosis can be due to a number of causes. Clinicians need to be aware of them and conservative management strategies may be considered before embarking on a surgical option, which is usually futile. The possibility of both aseptic peritonitis and spontaneous bacterial peritonitis in patients with PMF should be considered. Different management options for splenomegaly such as surgery or radiotherapy should be explored in association with the hematologists early in the management of these patients.

Funding:None.

Ethical approval:Not needed.

Contributors:SN and ZMK proposed the article, collected and summarized the data. SN wrote the first draft, corrected by both ZMK and MV. All authors contributed to the intellectual context and approved the final version. SN is the guarantor.

Competing interest:No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

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March 3, 2010

Accepted after revision June 28, 2010

Author Affiliations: Department of General Surgery, Princess of Wales Hospital, City Road, Bridgend CF31 1RQ, UK (Srinivasaiah N, Zia MK and Muralikrishnan V)

Mr. Narasimhaiah Srinivasaiah, No. 11, Felsted Close, Pontprennau, Cardiff CF23 8LR, UK (Tel: 0044-2920735978; Email: simha_anu@yahoo.com)

? 2010, Hepatobiliary Pancreat Dis Int. All rights reserved.