Abdominal pain is one of the most common presenting complaints and pediatric appendicitis remains the most common surgical diagnosis in children with a lifetime risk of 7-8%. Children typically present with fever, anorexia, migratory pain originating in the periumbilical region and moving to the RLQ. Laboratory findings can show a leukocytosis with a neutrophilic predominance that may support the diagnosis.

A variety of decision tools (PAS, CAS, pARC, APPE etc.) exist to help stratify the risk of appendicitis into mild, moderate, and severe categories (1,2,3). These tools are meant to be used alongside other clinical information and diagnostic testing to guide further imaging and workup. 

However similar abdominal symptoms can overlap with other more common diagnoses: influenza, strep pharyngitis, and infectious mononucleosis are examples of infectious illnesses that often present with abdominal symptoms. Oftentimes due to clinical uncertainty patients receive a RLQ ultrasound after already testing positive for these illnesses. But how frequent is the concurrent diagnosis of influenza, strep pharyngitis, or infectious mononucleosis AND appendicitis? Let’s look at the data.

Strep Pharyngitis

Strep pharyngitis can present with abdominal symptoms; one study by Igarashi et. al showed 5% of patients presenting to the emergency department with fever and abdominal pain were diagnosed with strep. They also found abdominal pain is more likely in children <6 years of age [positive likelihood ratio of 1.95 (95%CI = 0.98-3.88)] and more commonly seen in boys [(positive likelihood ratio of 2.41 (95%CI = 1.33-4.36)] (4). A meta analysis looking at patients aged 3-18 years diagnosed with strep found abdominal pain had a similar positive likelihood ratio of 1.18 (95% CI = 0.91-1.51) (5). Though neither study demonstrated statistical significance of abdominal pain in diagnosing GAS, both highlight that abdominal pain is a common presenting symptom in the pediatric population. 

There is, as expected, scant evidence about the risk of appendicitis when a patient already carries a diagnosis of strep pharyngitis. Upon review there is one case report citing strep pharyngitis associated with a complicated appendicitis (6). Nielsen et. al investigated 207 patients that received both GAS testing and an abdominal ultrasound in the emergency department. Of the 207 patients, 8 (<3%) patients had appendicitis and 35 (17%) tested positive for strep pharyngitis but importantly, no cases of concurrent strep pharyngitis and appendicitis were identified (7).

Influenza

Influenza can also present with similar abdominal manifestations. The prevalence of abdominal pain in influenza can vary from 10-31% with an odds ratio of 3.2 (95% CI = 1.2-8.2) (8,9). There does not appear to be a significant difference in abdominal pain between Influenza A and Influenza B (9). 

There have been only three case reports of appendicitis in association with influenza, all published during the swine flu (H1N1) epidemic. These three case reports describe a 16 year old, 15 year old, and 12 year old that all presented with influenza-like illness with some abdominal predominance and were subsequently found to have appendicitis. One patient had a previous history of appendicitis four years prior that was managed conservatively (10). Two patients were diagnosed on presentation, with one being diagnosed on hospital day three after demonstrating classic migratory pain (11). PCR testing of appendix tissue for the H1N1 virus was negative in one of the cases (12). 

The exact trigger for luminal obstruction in appendicitis remains unknown, with viral etiology thought to be a contributing factor. A study conducted by Alder et al. in 2010 attempted to elicit an epidemiologic reason for appendicitis. They found influenza and appendicitis have parallel incidence curves; both decreasing in prevalence from 1975-1990 and increasing since. However, given the discordance of appendicitis clustering in the summer and influenza in the winter they concluded the two were unlikely to be directly linked (13). 

Infectious Mononucleosis

Prevalence of abdominal symptoms in infectious mononucleosis is unclear, with different studies citing anywhere from 1% to 36% (14,15). However, abdominal pain concurrent with EVB is alarming given increased concern for splenomegaly and potential of splenic rupture. Pain from splenic rupture can be nonspecific and difficult to diagnose which can lead to delay in management and increased mortality (15). 

Though the association between infectious mononucleosis and splenic rupture is well understood, there is little data published on its association with appendicitis. One case report about their association in 1985 stated that “the time has come to look at the relationship between Epstein Barr virus to appendicitis” (16). Other case reports have described a variety of associations from incidental findings on CT scan done for splenic rupture to fatal peritonitis from appendicitis in an EBV positive patient (17, 18). Interestingly, testing appendix tissue for Epstein Barr nuclear antigen was negative similarly to influenza (19).

In summary, the jury is still out on if flu, strep, or infectious mononucleosis can occur at the same time as appendicitis. The strongest data is present in strep pharyngitis – showing no association in a single, small study. There is limited data in influenza, but the concurrent risk appears to be low and there does not seem to be a direct causality between the virus and appendicitis. Abdominal pain in infectious mononucleosis should be thought of more stringently. With an unclear symptom prevalence, and the risk of splenomegaly and splenic rupture, these patients should remain at a lower threshold to receive abdominal imaging. 

In patients who present with right lower quadrant abdominal pain better understanding the prevalence and individual likelihood of concurrent diagnoses can help save unnecessary work up. If the patient has strep or flu especially, the clinician may feel more comfortable deferring the RLQ U/S thus reducing cost and ED resource utilization. If you are going to send the child home without performing an ultrasound, strict return precautions (worsening pain, fever, emesis, pain when hopping) should be communicated. If the child has peritoneal signs a workup for a surgical abdomen is always warranted. Perhaps a large database, multicenter study could answer these questions more fully.

References

1. Kharbanda AB, Vazquez-Benitez G, Ballard DW, et al. Development and Validation of a Novel Pediatric Appendicitis Risk Calculator (pARC). Pediatrics. 2018;141(4):e20172699. doi:10.1542/peds.2017-2699

2. Boettcher M, Breil T, Günther P. The Heidelberg Appendicitis Score Simplifies Identification of Pediatric Appendicitis. Indian J Pediatr. 2016;83(10):1093–1097. doi:10.1007/s12098-016-2106-2

3. Lima M, Persichetti-Proietti D, Di Salvo N, et al. The APpendicitis PEdiatric (APPE) score: a new diagnostic tool in suspected pediatric acute appendicitis. Pediatr Med Chir. 2019;41(1):10.4081/pmc.2019.209. Published 2019 Apr 2. doi:10.4081/pmc.2019.209

4. Igarashi H, Nago N, Kiyokawa H, Fukushi M. Abdominal pain and nausea in the diagnosis of streptococcal pharyngitis in boys. Int J Gen Med. 2017;10:311–318. Published 2017 Sep 22. doi:10.2147/IJGM.S144310

5. Shaikh N, Swaminathan N, Hooper EG. Accuracy and precision of the signs and symptoms of streptococcal pharyngitis in children: a systematic review. J Pediatr. 2012;160(3):487–493.e3. doi:10.1016/j.jpeds.2011.09.011

6. Lê P, Zeiter AL, Ramaheriarison Y. Une angine à streptocoque associée à une appendicite compliquée [Association of streptococcal pharyngitis with complicated appendicitis]. Arch Pediatr. 2007;14(10):1199–1201. doi:10.1016/j.arcped.2007.06.032

7. Nielsen JW, Abel SA, Kenney B