Simultaneous acute appendicitis in identical twin boys

Abstract

Acute appendicitis is one of the most common causes of abdominal pain in children but remains a diagnostic challenge, and insight into the aetiology of the condition is lacking. A case of simultaneous acute appendicitis in monozygotic twin boys is reported here. Familial aggregation in acute appendicitis has been described, but the underlying causes for this are not well understood. The patients reported here were both genetically identical and lived a mostly identical lifestyle. Their simultaneous presentation would be exceedingly rare if explained entirely by chance, suggesting a role for both genetic and environmental influences. Increased knowledge of this occurrence may assist in prompt diagnosis and reporting on the incidence and timing of appendicitis in monozygotic twins could better elucidate the genetic and environmental factors that predispose to this disease.

Background

Acute appendicitis is a common cause of abdominal pain in children, and the lifetime risk of appendicitis approaches 9% in men and 7% in women.¹ The pathophysiology of acute appendicitis is thought to be initiated by luminal obstruction of the appendix leading to distension, bacterial overgrowth and venous congestion. However, the precise inciting factors for this process are less well understood and both genetic and environmental influences have been implicated in increasing the risk of acute appendicitis.^{2 3}

To expand awareness of the potential aetiologies and risk factors for acute appendicitis, we present a case of simultaneous acute appendicitis in identical twin 8-year-old boys. From a clinical standpoint, increased knowledge of this occurrence may decrease delays in diagnosis and associated morbidity. More broadly, reporting on the incidence and timing of appendicitis in monozygotic twins could better elucidate the genetic and environmental factors that predispose to this disease.

Case presentation

Case 1

The first patient was an 8-year-old boy who presented to the emergency department with a several-hour history of generalised abdominal pain. On examination, he was afebrile with normal vital signs. Abdominal examination revealed right lower quadrant tenderness to palpation but no signs of generalised peritonitis. The patient was otherwise healthy with no recent sick contacts, and no family history of appendicitis. Abdominal ultrasound demonstrated a dilated appendix with periappendiceal stranding consistent with a diagnosis of acute appendicitis.

Case 2

The second patient was the identical twin brother of the first patient. He presented within hours of his brother, just as the first operation was completed. The presentation was similar, though the abdominal pain was more localised to the right lower quadrant. Abdominal examination was significant for tenderness in the right lower quadrant. Ultrasound was again consistent with acute appendicitis.

Differential diagnosis

The differential diagnosis in these young otherwise healthy twin brothers presenting with abdominal pain includes both infectious and inflammatory conditions. Infectious gastroenteritis is a common cause of abdominal pain in cohabitating young siblings. Meckel’s diverticulitis, urinary stones and inflammatory bowel disease can mimic acute appendicitis and have shown a familial predilection.^4–6 In women, ovarian pathology must also be considered.

In this case, diagnostic imaging in the form of abdominal ultrasound was able to ascertain a diagnosis of appendicitis preoperatively. Abdominal ultrasound in children has a diagnostic accuracy of 95.5% for acute appendicitis, with sensitivity and specificity of 97.1% and 94.8%, respectively.⁷

Treatment

Both patients underwent standard laparoscopic appendectomy with the same intraoperative findings and techniques. Briefly, laparoscopic access was gained using a Veress needle technique through the umbilicus, and two additional working ports were placed in the left lower quadrant and suprapubic positions, respectively. Diagnostic laparoscopy revealed an inflamed, non-perforated appendix (figure 1). After adequate exposure, a tunnel between the base of the appendix and its mesentery was created, and the mesoappendix was ligated with an endoscopic vascular stapler. The appendix was then resected using an endoscopic gastrointestinal stapler, and the specimen was placed in an endoscopic bag for subsequent removal through the umbilical incision.

Figure 1.

Intraoperative view of the inflamed appendix.

Outcome and follow-up

The twin brothers recovered without complication and were discharged on the first postoperative day. They were seen in follow-up together at 1 month and had fully recovered with return to baseline diet and activity level. Their incisions had healed, and their abdominal examination was normal (figure 2).

Figure 2.

Abdominal examination of twin brothers after appendectomy.

Final pathology revealed acute non-perforated appendicitis in both instances.

Discussion

Acute appendicitis represents one of the most common causes of an acute surgical abdomen in children.⁸ However, a clear understanding of the predisposing risk factors and causes of this condition are lacking. Additionally, though common, acute appendicitis remains a diagnostic challenge. In an effort to broaden awareness of the possible genetic and environmental factors leading to acute appendicitis, we describe the fourth-ever reported case of simultaneous acute appendicitis in monozygotic twins, and the first in the past decade.^9–11

Familial aggregation of acute appendicitis has been described in several institutional series and even national registries.^{2 12–17} These studies have shown that the relative risk of appendicitis increases with a family history of appendicitis,² and that this risk is inversely related to genetic distance.¹³ Furthermore, familial influence is more prominent at younger ages.¹⁸ However, as is a limitation in familial series, it is uncertain whether this predilection is explained by environmental factors, genetic predisposition or common exposure to infectious pathogens.

To better understand the role of genetic predisposition in acute appendicitis, researchers have employed analysis of twin studies. Using a large twin dataset from Australia, Oldmeadow et al found significant differences in the correlation between monozygotic and dizygotic female twins, but no such difference in male twins¹⁸; a finding that they attributed to small sample size and high sample variability. They estimated the heritability of appendicitis as 21% and the domesticity as 16%.¹⁸ Nearly 20 years later, Sadr Azodi et al found similar differences between female and male twins, with overall heritability estimated at 30%.³

The precise genetic variants associated with acute appendicitis are yet to be explained, but several modes of inheritance and candidate genes are proposed. Basta et al performed a comprehensive segregation analysis of 80 consecutive families affected by acute appendicitis that suggested a polygenic or multifactorial mode of inheritance with total heritability of 56%.¹³ More recently, two groups have discovered an association between appendicitis and a specific genetic variant close to the PITX2 gene, a locus responsible for levels of intestinal bacteria and colonic inflammation.^{19 20}

The patients reported here were both genetically identical and lived a mostly indistinguishable lifestyle, cohabitating in the same home with very similar environmental exposures and diet. They have no additional siblings and their adult parents had not experienced acute appendicitis. Their simultaneous presentation would be exceedingly rare if explained entirely by chance, suggesting a role for both genetic and environmental influences. For the clinician, knowledge of this phenomenon may lead to a more expeditious diagnosis, as one can imagine the diagnostic dilemma of twin brothers presenting with acute abdominal pain. And for the investigator, exploration of concurrent appendicitis in twins could further clarify the underlying causes of this common condition.

Patient’s perspective.

Both of our sons were quite strong before they headed to the surgery. After the surgery, they had some pain, but recovered quite well. We as parents were feeling very worried as to how they would recover from surgery at the same time, but they were totally fine. Everyone in the hospital was very helpful and supportive. We will always be indebted to our surgeon and the rest of the hospital staff for recognizing that they were both suffering from appendicitis at the same time, and for promptly performing the surgeries and bringing them back to health.

Learning points.

• Predisposition to acute appendicitis is both genetic and environmental.

• Family history of acute appendicitis is an important consideration in the evaluation of patients presenting with acute abdominal pain.

• Simultaneous acute appendicitis may occur in closely related and cohabitating individuals, and should be considered in the differential diagnosis of those presenting with concurrent abdominal pain.