Sequential gastric and ileal perforations,a rare presentation in a man with sickle cell anemia: A case report

Abstract

The inheritance of the sickle gene (hemoglobin S) and another abnormal hemoglobin gene is described as sickle cell disease, and the homozygous form of the disease is hemoglobin SS. In sickle cell disease, abdominal pain is a common symptom attributed to circulatory stasis and vascular occlusion, along with chest and musculoskeletal pain for which nonsteroidal anti-inflammatory drugs are often prescribed. This report presents the case of a 21-year-old man with sequential gastric and ileal perforations related to nonsteroidal anti-inflammatory drug usage. Gastrointestinal perforation should be considered as a differential diagnosis in patients who present with abdominal pain accompanied with symptoms such as peritonitis, shock, or sepsis. Furthermore, perforation may be sequential with perforation of the stomach followed by that of the ileum. The use of nonsteroidal anti-inflammatory drugs in patients with sickle cell disease requires further revaluation.

Introduction

Sickle cell disease (SCD) is a condition caused by the inheritance of the sickle gene (hemoglobin (Hb) S) and another abnormal Hb gene. ¹ The homozygous form of the disease is HbSS, the most common SCD variant found in Africa. The other notable variant is Hb SCD.^1,2 SCD is an inherited disease caused by a point mutation in the triplet codon of the gene encoding the B-globin chain of Hb, altering the amino acid from glutamic acid to valine.^3,4 SCD is prevalent in the Middle East, Africa, and India. ² In Africa, it is the most common genetic condition with approximately 2% of children born with the condition in some sub-Saharan countries. ¹ Approximately 150,000 children are born with SCD every year in Nigeria. ¹ The main cause of gastroduodenal perforation (GDP) is peptic ulcer disease (PUD). ³ Nonsteroidal anti-inflammatory drugs (NSAIDs) with potent antipyretic, analgesic, and anti-inflammatory effects are used in clinical practice for gastrointestinal injury. ⁵ GDP is rarely caused by SCD. ² In sickle cell crisis, abdominal pain is a common symptom attributed to circulatory stasis and vascular occlusion.^3,6 Both SCD and NSAIDs can cause perforation, and the latter should be avoided in patients with SCD. Extraluminal free air on imaging is the most regular finding in GDP and may not be detected at the time of symptom onset. ³ An increasing number of children with SCD have been reported to survive till adulthood. ⁷ We present the case of a 21-year-old patient with SCD who had gastric and ileal perforations probably related to chronic NSAID usage. This report highlights the fact that although perforation in the gastroduodenal tract is rare in SCD patients, it should be considered as a differential diagnosis in patients who present with abdominal pain and shock or sepsis, especially those on NSAID treatment. Furthermore, perforation may be sequential, in line with our experience, wherein perforation of the stomach was followed by that of the ileum.

Case report

A 21-year-old man, a known patient with SCD, presented as a referral to the emergency department with a complaint of abdominal pain within the past 24 h. He also had been experiencing chest pain for the same duration. His sudden-onset abdominal pain was severe and limited to the upper abdomen. His pain worsened when he laid on his belly and was partially relieved when he laid on his sides. The pain was not localized to any part of the body. He had experienced three episodes of vomiting before presentation at our facility. The initial vomitus contained ingested meal; however, the later vomitus was greenish. There was associated constipation. Prior to this, he had recurrent episodes of chest and bone pain but did not report any history of recurrent abdominal pain. The patient did not admit to any history suggestive of hepatomegaly and splenomegaly but had previously undergone repeated blood transfusions. Furthermore, he had not received any vaccinations. He was managed by the hematologist with ibuprofen, diclofenac, and sometimes pentazocine for pain in addition to folic acid and astymin. The patient had taken the last dose of ibuprofen 4 h before the onset of abdominal pain. He also complained of a chronic wound on the ankle of the left leg within the past 16 months. The patient was not a known diabetic and had not undergone any surgery previously. There was no other SCD patient in his family. Prior to referral, he was managed by the hematologist with a diagnosis of abdominal vasoocclusive crisis and acute chest syndrome.

Examination revealed the following vital signs: (a) respiratory rate of 38 cycles/min; (b) pulse rate of 142 beats/min; (c) blood pressure of 90/60 mmHg; and (d) body temperature of 36°C. He had jaundice; he did not have pedal edema or peripheral lymphadenopathy. Chest examination was unremarkable. The abdomen was distended and moved with respiration (Figure 1). There was generalized tenderness, rebound tenderness, and guarding. Bowel sounds were absent. Digital rectal examination was unremarkable. A clinical diagnosis of peritonitis was established. There was an ulcer located on the medial aspect of the left ankle that measured 18 × 9 cm in the widest dimensions (Figure 2).

Figure 1.

Clinical photograph showing a distended abdomen.

Figure 2.

Chronic left leg ulcer.

Preoperative workup confirmed HbSS on sickle cell solubility test and electrophoresis genotype test. Full blood count revealed the following: packed cell volume, 20.7% (35%–55%); white blood cell count, 18.47 × 10³/µL (4 × 10³ to 12 × 10³/µL); neutrophil count, 57% (50%–60%); lymphocyte count, 21.3% (25.0%–50.0%); monocyte count, 26.8% (2.0%–10.0%); eosinophil count, 0.1% (0.0%–5.0%); and basophil count, 0.8% (0.0%–2.0%). In addition, the urea level was 12.9 (2.5–6.7) mmol/L, Na⁺ level was 134 (132–145) mmol/L, K⁺ level was 4.9 (3.2–5.0) mmol/L, Cl⁻ level was 98 (96–108) mmol/L, HCO₃ level was 19 (22–28) mmol/L, and creatinine level was 138 (88.6–177.2) µmol/L. Hepatitis B antigen and hepatitis C virus were nonreactive. Total bilirubin level was 345.5 (2–17) µmol/L and conjugated bilirubin level was 290.5 (2–7) µmol/L. Total protein level was 57 (62–87) g/L, albumin level was 18 (36–52) g/L, and globulin level was 39 (18–36) g/L. Abdominal X-ray is shown in Figure 3(a) and (b). Figure 3(a) shows intraperitoneal gas (air under the diaphragm) and Figure 3(b) shows a dilated bowel. A preoperative diagnosis of perforated viscus with peritonitis was made.

Figure 3.

(a) Erect position showing bilateral subdiaphragmatic air and free intraperitoneal air and (b) Supine position showing the ileus and free intraperitoneal air.

He was resuscitated and underwent a laparotomy with the following findings: oval gastric perforation that measured 1.5 × 2 cm located in the body of the anterior gastric wall close to the greater curvature (Figure 4(a)). Two liters of bilious peritoneal fluid and fibrinous exudates were present. He underwent a biopsy of the edge of the perforation, and closure was performed with Graham’s patch (Figure 4(b)). There was no hepatomegaly or splenomegaly. The patient was admitted to the intensive care unit. The postoperative period was uneventful until postoperative day 4 when he developed abdominal distension and generalized abdominal tenderness. Abdominal ultrasonography showed echo-rich free intraperitoneal fluid with septations in the Morrison’s, splenorenal pouches including the right and left paracolic gutters consistent with intraperitoneal fluid with paralytic ileus. He underwent a repeat laparotomy with the following findings: bilious intraperitoneal fluid, distended bowel loops with a collapsed portion of the ileum, fibrinous exudates, 0.5 × 1 cm oval shaped perforation located at the mesenteric border about 50 cm from the ileocecal junction (Figure 5) and an intact Grahams patch from previous surgery. The edge of the perforation was biopsied, and the perforation was closed. The postoperative period was uneventful, and the patient was discharged to the outpatient department. Earlier, he was referred to the plastic surgery unit on account of the chronic leg ulcer and the hematologist for care.

Figure 4.

(a) Gastric perforation and (b) Graham’s patch.

Figure 5.

Ileal perforation located at the mesenteric border.

Discussion

Sickle cell abdominal crisis due to vaso-occlusion often results in acute abdominal pain due to ischemia or infarction. In total, 10% of SCD patients with acute abdominal pain are admitted to the hospital each year. ³ In patients with GDP, the lifetime risk is 10% with uncontrolled PUD; in about 30%–50% of the cases, perforations are associated with NSAIDs. Most perforated ulcers are present in the anterior wall of the duodenum or stomach. ⁸ GDP is a rare complication that causes abdominal pain in patients with SCD; however, only few cases are reported in the literature. ² Surprisingly, our patient did not admit to a history of previous recurrent abdominal pain but experienced frequent episodes of chest and musculoskeletal pain. This may suggest that the perforations were mainly attributable to the use of NSAIDs. The gastric perforation in our patient located in the body of the stomach was close to the greater curvature (blood supply). Similarly, ileal perforation occurred at the mesenteric border. These findings could suggest a combination vasoocclusive effect and adverse effects of NSAIDs. This subject warrants further investigation.

In SCD, the polymerization of deoxygenated HbS constitutes the primary event in the molecular pathogenesis that causes the distortion of erythrocyte shape and a marked decrease in its deformability. The resultant rigidity of the cells is responsible for the vasoocclusive phenomena that constitute the hallmark of the disease.^6,10 The release of “stress reticulocytes” arising prematurely from the marrow in anemic stress become adherent to the endothelium of the precapillary venules. This slows down blood flow thereby propagating irreversible sickling of the mature red blood cells (RBCs) which then occludes the micro vessels. Furthermore, leukocyte adhesion, neutrophil activation, and interaction with endothelial proteins such as fibronectin are believed to play contributory roles. Hydroxyurea, a drug of clinically proven benefit in SCD, is known to affect RBCs adhesive characteristics and decreases the frequency of vasoocclusive crises. ⁶

Abdominal painful crisis in SCD is thought to be due to mesenteric vasoocclusion; this may present with pain in other parts of the body. ² The index patient presented with recurrent chest and musculoskeletal pain. PUD may be caused by NSAIDs and Helicobacter pylori infection. Although rare, GDP can present as a complication from the ulcers and may occur in the absence of epigastric symptoms.^2,9 Vascular occlusion and injury arise from the distorted erythrocytes due to polymerized HbS under less oxygen tension. ³ The mucosal ischemia from this increases the incidence of PUD in SCD. ³ GDP is a rare cause of acute abdominal pain and can result in peritonitis and shock ¹¹ in line with this presentation. Gastrointestinal tract (GIT) injury induced by NSAID occurs more frequently in the small bowel than in the stomach. It can produce complications in the lower GIT, including the jejunum and the ileum. ¹² Park et al. reported multiple ileal perforations secondary to diclofenac use. ⁵ We report both gastric and ileal perforations. Regulation of GIT blood flow as well as other mucosal function depends on prostaglandins (PG). The NSAID-induced reduction in PG production is the primary cause of small bowel injuries.^5,13 Perforation results in the release of food and digestive enzymes into the peritoneal cavity. There is initial chemical peritonitis followed by secondary bacterial peritonitis. ⁸

Gastric perforations present with a sudden onset of severe upper abdominal pain, peritonitis, and abdominal rigidity due to the spasm of the rectus muscles and eventual sepsis. ⁸ Mehrabani et al. reported that the following symptoms were most common: abdominal pain (70%), vomiting (60%), and bone pain (45%), ² in line with the presentation of our patient. Clinically, it is difficult to distinguish abdominal vasoocclusive crisis from other causes of acute abdominal pain.^1,2 Acipiyan et al. reported duodenal perforation in the second part of the duodenum in a patient with SCD. ³ Johnson et al. described the perforation in the duodenum and pylorus in SCD induced by NSAID along with narcotics used for generalized pain. ⁹ Park et al. presented multiple ileal perforations caused by regular diclofenac injections in a non-SCD patient. ⁸ We report a rare presentation of sequential gastric and ileal perforations.

In GDP, the most common finding is extraluminal free air seen on abdominal X-ray (AXR) as subdiaphragmatic free air in the erect position. ² Pneumoperitoneum can also be detected on chest X-ray; however, in 20%–30% of cases, subdiaphragmatic free air may be absent. ⁹ Furthermore, free gas can be detected on AXR in the supine position in addition to that in the ileus. In 85.7% of patients with GDP, CT was able to identify the site of perforation. Other findings were free fluid in the abdominal cavity (89.4%), free air (76.6%), segmental wall thickening (48.9%), and wall discontinuity (25.5%). ¹⁰

Surgery is a necessary treatment.^2,3 Perforation may occasionally be sealed using a plug of omentum or other viscus prior to significant soiling and peritonitis. ⁸ Simple closure of the perforation by suture plication of the perforation and reinforcement using an omental patch is considered the treatment of choice. Routine drain insertion has not been proven as an effective treatment. ⁸ In patients with a history of <24 h of abdominal pain without evidence of hypovolemic shock with perforations <8–10 mm, laparoscopic surgery may be indicated. ⁸

Tissue biopsy of the edge of gastric perforation is indicated even in benign looking lesions in view of the risk of malignancy. ⁸ The indicators of poor prognosis associated with increased mortality are shock on admission or delayed surgery. ⁸

Conclusion

Gastrointestinal perforations are rare complications of SCD. This should be considered in patients with SCD who have abdominal pain and significant symptoms, such as peritonitis, shock, or sepsis. Gastric and ileal perforation result from the combined effects of abdominal vasoocclusive crisis, and the use of NSAIDs might be considered as a source of pneumoperitoneum with associated peritonitis. The use of NSAID in patients with SCD should be revaluated.