Recurrent intestinal perforations as a presentation of antiphospholipid syndrome

Antiphospholipid syndrome (APS) is a rare but important cause of thrombosis. It is suspected in patients who present with recurrent thrombosis or thrombosis in an unusual site. Gastrointestinal involvement is rare in this syndrome. Moreover, intestinal perforation in APS is very rare. We report a 19-year-old female patient who developed recurrent spontaneous intestinal perforations in which repeated laparotomies were undertaken and different diagnoses were entertained. The patient had received different treatments but without improvement. Antiphospholipid syndrome (APS) was suspected and diagnosed, and subsequently anticoagulant therapy was started. To our knowledge, this is a first report describing recurrent small intestinal perforation in a patient with APS. Case A 19-year-old single female patient was referred to the emergency room of King Abdulaziz University Hospital, in Jeddah, Saudi Arabia, complaining of generalized abdominal pain and vomiting of 2 days duration. The pain had started in the right lower quadrant, gradually increased in severity and became generalized. It was continuous, severe, aggravated by any movement, and associated with vomiting of whatever she ingested and a low-grade fever. There was no change in bowel habits and no history of previous similar pain. She gave a history of previous laparotomy in another hospital because of a ruptured ovarian cyst 4 years before presentation. There was no other significant medical history, she was not on any medication, and there was no significant familial disease apart from diabetes mellitus and hypertension in her mother. There was no family history of thrombosis or recurrent miscarriage. On examination, the patient was mildly dehydrated. Her temperature was 38 C, pulse rate 120/minute, and blood pressure 110/85 mm Hg. Her abdomen was tender all over with rigidity and sluggish bowel sounds. Examinations of other systems were unremarkable. The total leukocyte count was 17.3×103/μL, neutrophils were 88.5%, and Hb 9.7 g/dL. Other tests, including the platelet count, PT, PTT, urea, creatinine, electrolyte and liver function tests, stool and urine analyses, were within normal range. The chest x-ray was normal. An abdominal x-ray showed a dilated small intestine. A diagnosis of peritonitis, possibly secondary to perforated appendicitis, was made and the patient was operated on. The abdomen was opened through a previous lower midline incision, revealing a turbid fluid, mildly inflamed appendix, and a small perforation in the terminal ileum, while other abdominal organs were normal. Appendectomy was done with closure of the perforation. Postoperatively the patient improved and was discharged on the 5th postoperative day. Two days later, the patient presented to another hospital with the same complaint of abdominal pain. The patient was febrile and tachycardic. The abdomen was tender all over with rigidity and sluggish bowel sounds. The patient was operated upon, and the laparotomy showed multiple perforations in the terminal ileum. A segment of ileum that contained the perforations was resected and an end-to-end anastomosis was done (details of the histopathology were not available). The patient was referred once again to our hospital. During this admission, the patient had 15 laparotomies to close multiple small bowl perforations. Each time the patient developed abdominal pain with tachycardia and the abdomen was tender and rigid with absent bowel sounds. There were about 3 to 7 days between each laparotomy. The perforations developed over different sites and sometimes over the previous one. During the first laparotomy, biopsies were taken from the perforations in which the histopathology showed mucosal ulceration and transmural inflammation with a serosal reaction suggestive of Crohns disease. The patient was started on steroids, but there was no response and the patient developed multiple small bowl perforations during treatment. Serology for Salmonella typhi, S. paratyphi, Brucella, hepatitis B and C and HIV were negative. After the 7th laprotomy, tuberculosis was suspected and biopsy samples were taken from the perforations and sent for TB culture. The patient was started on empirical anti-TB therapy, but there was no response and the patient developed multiple perforations during the treatment. The TB culture was negative and, therefore, the anti-TB therapy was discontinued. During the 13th laprotomy, a segment of ileum was resected because it contained multiple perforations. The histopathology of the resected specimen showed infarction, thrombotic microangiopathy, thrombosis in some blood vessels and acute inflammatory cells, but there were no well-defined granuloma or a malignancy. The picture was highly suggestive of ischaemic bowel disease (Figures 1 and ​and2).2). Hypercoagulability syndrome was suspected, a blood sample was taken for hematological study and heparin was started. Protein C, protein S and antithrombin III were within normal ranges. Activated protein C was resistant and antinuclear antibodies were negative. Anticardiolipin was positive, IgG was 70 phospholipid (GPL) units/mL (negative <12.0 GPL units/mL), and IgM was 7 MPL units/mL (negative <6.0 MPL units/mL) measured by ELISA. Lupus anticoagulant was moderately positive. Both anticardiolipin antibodies and lupus anticoagulant were repeated six weeks later and remained positive. Measurement was carried on a BCS coagulation analyser (Dade Behring USA).