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 Table of Contents  
Year : 2014  |  Volume : 5  |  Issue : 2  |  Page : 65-68

Appendicitis and intestinal infarction due to aspergillosis in a patient with acute myeloid leukemia

1 Department of Oncology, Division of Adult Hematology and HSCT; King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
2 Department of Medicine, Division of Internal Medicine, Riyadh, Saudi Arabia
3 Department of Oncology, Division of Adult Hematology and HSCT, Riyadh, Saudi Arabia
4 Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia

Date of Web Publication19-Jul-2014

Correspondence Address:
Ahmed Alaskar
Division of Adult Hematology and SCT, King Abdullah International Medical Research Center, Ministry of National Guard-Health Affairs, Riyadh - 11426
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1658-5127.137157

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Small bowel infarction is a rare and fatal complication of invasive aspergillosis following chemotherapy in acute myeloid leukemia (AML) patients. We describe a case of an adult patient with an AML who developed appendicitis and intestinal infarction secondary to aspergillosis following anti-leukemic chemotherapy. The diagnosis was made histologically at laparotomy. The patient died later despite antifungal therapy.

Keywords: Acute myeloid leukemia, appendicitis and intestinal infarction, aspergillosis

How to cite this article:
Alaskar A, Salih SB, Alshammari K, Bakkar M, Alkushi A. Appendicitis and intestinal infarction due to aspergillosis in a patient with acute myeloid leukemia. J Appl Hematol 2014;5:65-8

How to cite this URL:
Alaskar A, Salih SB, Alshammari K, Bakkar M, Alkushi A. Appendicitis and intestinal infarction due to aspergillosis in a patient with acute myeloid leukemia. J Appl Hematol [serial online] 2014 [cited 2020 Jul 11];5:65-8. Available from: http://www.jahjournal.org/text.asp?2014/5/2/65/137157

  Introduction Top

Aspergillosis is a rapidly progressive fungal infection that may affect immunocompromised patients. [1],[2],[3] The disease carries a high degree of mortality and morbidity. Gastrointestinal involvement of the disease is uncommon, and carries a serious complication risk, one of which could be bowel ischemia and resultant bowel infarction. [4],[5],[6] Diagnosis of such disease could be challenging early on due to the nonspecific clinical manifestations. [7] However, having a high degree of suspicion and perhaps anti-Aspergillus prophylaxis treatment may be of benefit.

  Case report Top

This is a case of a 62-year-old woman, with a few weeks history of fatigue, body ache, and exertional dyspnea. She denied fever or bleeding tendencies. Prior to presenting to our institution, the patient had initial investigations, which revealed a hemoglobin (Hb) level of 55 g/L, white blood cell count (WBC) - 2.6 × 10 9 /L, platelet (Plt) count - 101 × 10 9 /L, and a bone marrow biopsy showing 90% blast cells consistent with acute myeloid leukemia (AML) M6.

Upon consult, the patient's vital signs were as follows; temperature of 37.9°C, heart rate (HR) of 98 beats/min, blood pressure (BP) 158/77 mmHg, and respiratory rate (RR) of 20/min. Her initial laboratory values are: WBC - 1.4 × 10 9 /L, Hb - 96 g/L, Plt - 72 × 10 9 /L, absolute neutrophil count (ANC) - 0.2 × 10 9 /L. Her lactate dehydrogenase level was 315 U/L, and she had a uric acid level of 214 μmol/L. Albumin was 38 g/L, total bilirubin 11.1 μmol/L, aspartate transaminase - 13 U/L, alanine transaminase - 10 U/L, alkaline phosphatase - 61 U/L, calcium level - 2.2 mmol/L, phosphorus - 1.47 mmol/L, magnesium - 0.85 mmol/L, ferritin. - 718 μg/L, Vitamin B12-112 pmol/L and serum folate - 13.9 nmol/L. Bone marrow aspirate analysis had shown a reduced megakaryocyte count and erythroid precursor cells that constituted 5% of all nucleated cells and some of them had shown dysplastic changes like vacuolations and binuclear cells. The myeloblasts had made up 46% of the sample cells. Other examinations are within normal limits.

Upon admission, a diagnosis of AML M6 was made and started on induction chemotherapy protocol, which consisted of cytarabine for 7 days and idarubicin for 3 days. The patient developed loose bowel motions with no blood or mucus on day 8 of chemotherapy, and empirically started oral metronidazole and prophylactic fluconazole. She complained of abdominal pain on day 16, and physical exam revealed rebound tenderness at the right iliac fossa. Her WBC was 0.6 × 10 9 /L, ANC - 0 × 10 9 /L, Hb - 99 g/L, Plt - 3 × 10 9 and renal function was normal. The differential diagnosis included appendicitis and typhilits. Cefepime was added at a dose of 2 g every 8 h. A computed tomography (CT) of the abdomen was done the next day that showed inflammatory changes and fat stranding surrounding the appendix. It had a diameter of 1 cm, which was suggestive of acute appendicitis. There was a small amount of free fluid at the pelvis and a small hiatus hernia. Low cut of the chest revealed a focal pneumonia at the base of right lung.

General surgery team have seen the patient and decided the need for an urgent appendectomy after correcting her Plt count. She was given intravenous immunoglobulin (IVIG) and steroids with Plt transfusions. However, she had refractory thrombocytopenia, and her repeated Plt count was 3 × 10 9 . Due to her high risk of perioperative bleeding secondary to thrombocytopenia, it was decided that she is for conservative management. Her antibiotics were upgraded to meropenem 1 g every 8 h, and amikacin 1.2 g daily, and filgrastim (granulocyte-colony stimulating factor) was added.

On day 20, the patient became febrile with 38.2°C. Chest X-ray is normal. Vancomycin 1 g every 12 h was added. The next day she was found to be tachypneic and tachycardic with an RR of 38, and HR of 118. Intensive care unit (ICU) team was consulted and voriconazole was added to her antibiotic regime. Myelosuppresion continued WBC - 0.3 × 10 9 , Hb - 7.1 g/L, Plt - 1 × 10 9 , and ANC - 0. Repeat abdominal CT showed an interval increase of free fluid around liver, spleen, and paracolic gutter. Small bowel loop thickening and mucosal development were noted. Fat stranding was also seen of the whole mesenteric fat and around the appendix, with evidence of dilation. She was evaluated by the general surgery team and the impression of a subphrenic abscess 5 cm × 8 cm with the possibility of intra-abdominal bleeding secondary to thrombocytopenia was concluded. It was decided to proceed with an urgent exploratory laparotomy. She was transferred to the ICU during that time. IVIG and 18 units of Plt were transfused in preparation for the operation. Factor VIIA was prepared to be on standby in case of intra-operative bleeding. Laboratory investigations prior to the operation showed a creatinine level of 136 μmol/L, and a blood urea nitrogen of 14 mmol/L. Bowel ischemia was found during the operation, and the surgeons did a small bowel resection, and a right hemicolectomy plus creation of a small bowel ileostomy.

Postoperatively, she was continued on amikacin, metronidazole, vancomycin, meropenem, and voriconazole. She was intubated and mechanically ventilated in ICU, and was on 3 ionotropes. She was still myelosuppressed with a WBC - 0.3 × 10 9 /L, ANC - 0 × 10 9 /L and Plt of 7 × 10 9 /L. On day 24, she had an episode of atrial flutter and amiodarone was started. Her creatinine rose to 229 μmol/L (from 93 the previous day) and nephrology team was consulted to consider starting continuous renal replacement therapy. However, her BP continued to drop despite being on maximal doses of 3 ionotropic agents. She had a pulseless electrical activity arrest on day 26 and died after the failure of resuscitation attempts.


The specimen was received fresh for fixation at pathology laboratory. It consisted of a 2.5 m segment of small bowel, and 60 cm segment of cecum and ascending colon. The attached appendix measured 12 cm × 1.5 cm and the attached greater omentum was 50 cm × 30 cm × 5 cm. The outer surface of bowel was dark dusky-red with foci of exudates. The appendix and ileocecal area were black in color and looked gangrenous. There was no gross bowel perforation. The mucosa was hemorrhagic and partially sloughed. The gross evaluation did not show evidence of tumorous growth.

Microscopic evaluation of multiple sections from the bowel and appendix showed transmural intestinal infarction with hemorrhagic plugs within the intestine blood vessels [Figure 1]. Fungal hyphae with septation and branching angles were noted within the hemorrhagic plugs of blood vessels [Figure 2]. Special stain for fungi on histological section (GMS) disclosed the morphological features of these fungi [Figure 3]. The morphological features are compatible with Aspergillus species. Unfortunately, culture was not possible from the histological specimen, as this has not been suspected prior to specimen fixation in 10% buffered formalin.
Figure 1: Low-power microscopic view (×4) showing hemorrhagic trans-mural intestinal infarction

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Figure 2: High power microscopic view (×40) showing two blood vessels with hemorrhagic plugs loaded with fungal hyphae

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Figure 3: High power microscopic view (×40) of GMS stain to illustrate the fungal morphology

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  Discussion Top

Invasive fungal infections in patients with hematological malignancies are mainly caused by Aspergillus and Candida. [8] Aspergillus can cause limited allergic reactions of the lower respiratory tract and fungus ball formation in persons with normal immunity, and severe invasive infection in immunosupressed patients. Aspergillus, which is an inhaled fungus, has the capacity to overcome natural tissue barriers such as cartilage, and muscle including the tunica media of blood vessels. This could result in septic thromboembolism and infarction such as what happened to our case.

Approximately, one-quarter of all patients with invasive pulmonary aspergillosis develop disseminated infection through hematogenous spread. [9] Gastrointestinal involvement has an incidence of 41-47% among those patients with disseminated infection. [3] Diagnosis of bowel involvement can be challenging due to the fact that symptoms of abdominal pain, and bowel obstruction may be masked by the systemic effects of sepsis. Therefore making ante-mortem diagnosis is difficult to establish. One of the first documented cases of aspergillosis as an unusual cause of perforated appendicitis was reported by Weingrad et al. in 1982. [10]

The lungs are well-known to be the portal of entry in invasive aspergillosis. [11] Infection in the lungs can spread to the blood stream and to the gastrointestinal system. There are very few cases that describe gastrointestinal aspergillosis with normal chest X-ray. However, the presence of such cases suggests that the bowel can be an initial portal of entry for Aspergillus. [11] One possible explanation for this would be that chemotherapeutic agents could alter the gastrointestinal mucosa leading to the entry of Aspergillus by disrupting mucosal barriers. [9] Eggimann et al. reviewed 23 cases of possible primary invasive aspergillosis of the digestive tract that were identified in the literature between 1960 and 2005. He presented details on ten patients. [12] By adding our case report, we will present details on 11 patients. All of them presented with acute hematological malignancy. AML in 8 (80%), 9 of them received cytarabine part of the chemotherapy. All of these developed typhlitis and required laparotomy with bowel resection, and 7 of them succumbed to death (68%). No report exists on the value of galactomannan test in these cases, the value of which would be worthwhile exploring in this context. It may potentially lead to early detection of aspergillosis infection and thus, early intervention with a proper antifungal therapy.

  Conclusion Top

Our case demonstrates the importance of early suspicion of primary invasive aspergillosis of the gut in neutropenic patients with abdominal symptoms. Hence, to consider the early introduction of antifungal therapy in similar condition and the value of galactomannan test in this context would also be worthwhile exploring.

  References Top

1.Shah SS, Birnbaum BA, Jacobs JE. Disseminated aspergillosis inciting intestinal ischaemia and obstruction. Br J Radiol 2001;74:1145-7.  Back to cited text no. 1
2.Watts JC, Chandler FW. Aspergillosis. In: Connor DH, Chandler FW, Schwartz DA, Manz HJ, Lack EE, editors. Pathology of Infectious Diseases. Standford, CT: Appleton and Lange; 1997. p. 933-41.  Back to cited text no. 2
3.Prescott RJ, Harris M, Banerjee SS. Fungal infections of the small and large intestine. J Clin Pathol 1992;45:806-11.  Back to cited text no. 3
4.Ouaïssi M, Moutardier V, Emungania O, Lelong B, Forel JM, Guiramand J, et al. Fatal bowel infarction due to aspergillosis after chemotherapy. Eur J Surg Oncol 2003;29:628.  Back to cited text no. 4
5.Tay MH, Balram C, Foo KF, Busmanis I, Raman S, Khoo KS. Unusual case of bowel infarction with invasive Aspergillus in an immunocompromised patient. Ann Acad Med Singapore 2003;32:122-5.  Back to cited text no. 5
6.Cohen R, Heffner JE. Bowel infarction as the initial manifestation of disseminated aspergillosis. Chest 1992;101:877-9.  Back to cited text no. 6
7.Trésallet C, Nguyen-Thanh Q, Aubriot-Lorton MH, Akakpo JP, Al Jijakli A, Cardot V, et al. Small-bowel infarction from disseminated aspergillosis. Dis Colon Rectum 2004;47:1515-8.  Back to cited text no. 7
8.Catalano L, Picardi M, Anzivino D, Insabato L, Notaro R, Rotoli B. Small bowel infarction by Aspergillus. Haematologica 1997;82:182-3.  Back to cited text no. 8
9.Young RC, Bennett JE, Vogel CL, Carbone PP, DeVita VT. Aspergillosis. The spectrum of the disease in 98 patients. Medicine (Baltimore) 1970;49:147-73.  Back to cited text no. 9
10.Weingrad DN, Knapper WH, Gold J, Mertelsmann R. Aspergillus peritonitis complicating perforated appendicitis in adult acute leukemia. J Surg Oncol 1982;19:5-8.  Back to cited text no. 10
11.Marterre WF Jr, Mong AT, Pulito AR. Locally invasive aspergillosis of the bowel. J Pediatr Surg 1992;27:1611-3.  Back to cited text no. 11
12.Eggimann P, Chevrolet JC, Starobinski M, Majno P, Totsch M, Chapuis B, et al. Primary invasive aspergillosis of the digestive tract: Report of two cases and review of the literature. Infection 2006;34:333-8.  Back to cited text no. 12


  [Figure 1], [Figure 2], [Figure 3]

This article has been cited by
1 Characteristic clinical features ofAspergillusappendicitis: Case report and literature review
Mihajlo Gjeorgjievski
World Journal of Gastroenterology. 2015; 21(44): 12713
[Pubmed] | [DOI]


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