Group A streptococcal pharyngitis associated with primary peritonitis

Abstract

Primary peritonitis, a bacterial infection within the peritoneal cavity that arises in the absence of an intraperitoneal source, is a rare entity in paediatrics. We describe the case of a previously healthy 11-year-old girl who presented with an acute abdomen and was found to have primary peritonitis due to Streptococcus pyogenes. She had an episode of pharyngitis with pharyngeal cultures positive for S. pyogenes in the month prior to presentation. We performed a review of the literature to better elucidate the risk factors, pathophysiology and presentation of peritonitis due to S. pyogenes and to draw attention to the potential association between group A streptococcal pharyngitis and peritonitis.

Background

Primary peritonitis is estimated to cause 1% to 3% of cases of acute abdomen in the paediatric population.¹ Patients typically present with the acute onset of abdominal pain, fever, vomiting and diarrhoea. Laboratory values may show leucocytosis and elevated acute phase reactants. In most cases, patients are diagnosed intra-operatively when laparotomy reveals free fluid in the abdomen without signs of appendicitis.^1–3 Streptococcus pneumoniae, gram negative organisms and Staphylococcal species are responsible for the majority of cases in the paediatric population.^4–7 Our patient’s peritoneal cultures grew Streptococcus pyogenes. While Lancefield group A beta-haemolytic streptococcus (GAS) is a well-documented cause of pharyngitis, impetigo, erysipelas, scarlet fever and streptococcal toxic shock syndrome, it can also cause primary peritonitis.⁸

Prior to the antibiotic era, primary peritonitis was commonly associated with a preceding pharyngitis (table 1).^{3 9–16} In their 1926 review of streptococcal and pneumococcal peritonitis cases, Lipshutz and Lowenburg noted that pharyngitis so frequently preceded primary peritonitis that its presence often helped confirm the diagnosis.⁹ In 1927, Schwartz described 14 cases of primary streptococcal peritonitis, half of which grew streptococcus on throat culture.¹³ Leopold described 11 cases of streptococcal peritonitis, five of which were preceded by pharyngitis, and noted that an intimate relationship between group A streptococcus pharyngitis and peritonitis.¹⁷ Ladd et al described 47 cases of paediatric streptococcus peritonitis, two of which were notable for pharyngeal cultures positive for streptococcus. In their review, a preceding upper respiratory tract infection, such as pharyngitis, was a key historical point in differentiating primary peritonitis from acute perforated appendicitis.³ The symptoms of pharyngitis proceeded the onset of peritonitis by 4 days to 3 weeks, with the majority of cases presenting with peritonitis approximately 1 week after developing pharyngitis.^{9 12}

Table 1.

Reported cases of group A streptococcal primary peritonitis in paediatric patients

Year	Reference	n	Patient age	Sex	Preceding infection	Treatment
1926	* Lipshutz 9	9	3 mo to 6 yo	9 M	90% had nose or throat infection ‘antedating the onset of the abdominal symptom by 4 to 7 days’	80% of cases: laparotomy, drainage of peritoneal cavity, appendectomy; remaining 20% died prior to treatment and/or treatment not specified
1927	† Cohen 15	5	N/A	N/A	Pharyngitis in all five cases, symptom onset not specified	Laparotomy, drainage
1927	† Schwartz 13	14	N/A	5 M 9 F	Pharyngitis in 10 cases	Laparotomy, drainage of peritoneal cavity
1935	† Gordon 14	31	1 to 6 yo	N/A	Pharyngitis in 23 cases	Laparotomy, drainage of peritoneal cavity
1936	† Pollock 12	36	1 mo to 11 yo	15 M 21 F	Pharyngitis in 23 cases; ‘pharyngitis usually occurred within a week’ with a range from 3 weeks to 4 days prior to presentation	Laparotomy + ‘Intravenous injections of pooled antistreptococcus serum or mercurochrome’
1937	† Leopold 17	11	2 mo to 12 yo	5 M 6 F	Five associated with pharyngitis	Laparotomy, drainage of peritoneal cavity
1939	† Newell 16	25	<6 mo: 18 >6 mo: 7	15 M 10 F	Eight associated with erysipelas Five out of seven pharyngeal cultures positive for ‘beta streptococcus’	Laparotomy, drainage of peritoneal cavity
1939	† Ladd et al 3	47	<1 yo: 11 1 to 5 yo: 23 5 to 12 yo: 13	24 M 23 F	Two out of four pharyngeal cultures performed positive for ‘haemolytic streptococcus’	Incision and drainage of abdomen+/-sulfanilamide (7 out of 47 patients)
1953	† Gross 11	11	N/A	N/A	‘Frequent occurrence of an upper respiratory infection during or preceding the peritonitis’	Surgical treatment in all patients, specific treatment not specified
1957	Fowler 10	15	N/A	7 M 8 F	N/A	Laparotomy + antibiotics
1964	Fogel et al 27	1	8 yo	M	None	Laparotomy + antibiotics
1975	McDougal et al 28	5	N/A	N/A	Preceding upper respiratory infection	Antibiotics + laparotomy
1980	Goepel et al 29	1	15 yo	F	None	Antibiotics + laparotomy
1984	Freij et al 2	1	10 yo	M	N/A	Antibiotics + laparotomy
1988	Harnden 30	1	16 mo	M	Sore throat at presentation	Antibiotics + laparotomy
1992	Torres-Martínez et al 31	1	13 do	F	Diarrhoea, rash for 3 days	Antibiotics + laparotomy
1999	Watson 32	1	2 yo	F	Diarrhoea, vomiting for 2 days	Antibiotics + immune globulin + paracentesis
2002	Gillespie et al 20	1	3 yo	F	Patient’s mother had sore throat 1 week prior to presentation; patient had fever, vomiting, diarrhoea for 2 days with pharyngeal cultures positive for GAS	Antibiotics + laparotomy +  immune globulin
2002	Liang et al 33	1	5 yo	F	N/A	Antibiotics + laparotomy
2005	Dann et al 1	1	8 yo	F	None	Antibiotics + laparotomy
		1	6 yo	F	Sore throat, malaise, fevers 3 days prior to presentation; rapid strep positive	Antibiotics + laparoscopy
2009	Sewrey 5	1	7 mo	F	Decreased feeding, lethargy, vomiting (unclear time of symptom onset)	Antibiotics + laparotomy
2012	Demitrack 34	1	3 yo	F	Cough and fever for 1 week	Antibiotics + laparotomy
2012	Holden et al 35	1	14 yo	F	None	Antibiotics + laparotomy
2013	Patel et al 36	1	6 yo	F	Vomiting, abdominal pain, fever, diarrhoea for 5 days	Antibiotics + laparotomy
2014	Benidir 37	1	16 yo	F	None	Antibiotics + laparoscopy
2014	Filan38	1	7 yo	M	Peri-oral impetigo 3 weeks prior to presentation	Antibiotics + laparotomy
2016	Tapiainen39	7	N/A	N/A	Family member with recent streptococcal pharyngitis in 22 out of 151 cases‡	Antibiotics in all, 55% of 151 patients in this series underwent at least one surgical operation
2017	Chomton et al4	1	10 yo	F	Pharyngitis and fever for 3 days	Antibiotics + laparoscopy

*22 cases of streptococcal and pneumococcal peritonitis are presented without specific details of each case. Therefore the listed ages and culture results are of both the streptococcal and pneumococcal cases.

†We presume ‘haemolytic streptococcus’ and ‘beta streptococcus’ to be synonymous with group A streptococcus. We did not include cases of pneumococcal peritonitis in this table or in our review.

‡In this review of 151 cases of invasive GAS infections, seven cases were primary peritonitis. Of the 151 cases of invasive infection listed, 22 were characterised by a family member with a recent streptococcal pharyngitis. However, the literature does not specify whether these were the peritoneal peritonitis cases.

N/A, details not specified in report; n, number of cases; F, female; M, male; do, days old; mo, months old; yo, years old; GAS, group A streptococcus.

Review of the adult literature reveals fewer than 50 reported cases of primary peritonitis due to S. pyogenes.^{18 19} Primary peritonitis is especially uncommon in the healthy paediatric population, and GAS primary peritonitis is exceedingly rare. Review of the paediatric literature reveals only 28 reported cases since 1975 (table 1). Of these cases, S. pyogenes was isolated from both pharyngeal and peritoneal cultures in one report.²⁰ A second report described a case in which a rapid strep test was positive in addition to peritoneal cultures.¹ We describe an additional case of primary peritonitis associated with group A streptococcus pharyngitis infection in a paediatric patient.

Case presentation

An 11-year-old girl presented to the hospital with 1 day of fever, anorexia, vomiting and right lower quadrant abdominal pain. Her past medical history was notable only for an episode of pharyngitis 10 days prior to presentation that was positive for GAS and treated with a 10-day course of amoxicillin. She completed her antibiotics 4 days prior to presentation. The patient denied sexual activity or physical abuse. Her last period was 2 weeks prior to presentation; she did not use tampons or have an intrauterine device. There was no personal or family history of recurrent infections or gastrointestinal diseases.

Vital signs on presentation included a temperature of 38.9°C, heart rate of 134 beats per min and a blood pressure of 86/45. On examination, she was in significant distress. Her abdomen was soft, non-distended and diffusely tender to palpation. A pelvic examination was performed and was normal without cervical motion or adnexal tenderness. Rovsing, psoas and obturator signs were absent.

Investigations

Laboratory evaluation was significant for white blood cell count of 19.1×10⁹/L, with 84% neutrophils, 8% bands, 6% lymphocytes and 1% monocytes. Electrolytes, liver function tests and lipase levels were within normal limits for age. Urinalysis was negative for leucocytes, nitrites or leucocyte esterase. A urine pregnancy test was negative. CT scan of the abdomen demonstrated a minimally dilated appendix and a small amount of free fluid in the pelvis. Exploratory laparotomy was performed and cultures from peritoneal fluid demonstrated growth of S. pyogenes. Blood and urine cultures were negative. Review of the patient’s medical records confirmed a recent diagnosis of pharyngitis with throat cultures positive for S. pyogenes.

Differential diagnosis

The patient’s history of acute abdominal pain, vomiting, fever and anorexia with signs of inflammation on laboratory investigation was most concerning for appendicitis. The patient was taken to the operating room for surgical evaluation. Exploratory laparoscopy revealed a normal appendix without signs of inflammation.

Given that the patient was a girl of childbearing age, the differential diagnosis also included gynaecological organ pathologies such ectopic pregnancy, ruptured ovarian cyst, ovarian torsion, tubo-ovarian abscess and pelvic inflammatory disease. However, the patient denied a history of sexual activity and her pregnancy test was negative. She had no cervical motion tenderness or adnexal tenderness on pelvic examination. The uterus, fallopian tubes and ovaries were visualised during surgery and all appeared normal. Thus, the history, physical and surgical findings were not consistent with a gynaecological process.

In patients with undifferentiated acute abdominal pain, abdominal CT reliably excludes peritonitis secondary to intra-abdominal surgical pathologies.²¹ Our patient also underwent exploratory laparotomy, which visualised normal intra-abdominal and pelvic organs. The patient’s CT results in conjunction with these operative findings excluded a secondary cause of peritonitis. The diagnosis of primary peritonitis was confirmed when peritoneal fluid cultures grew S. pyogenes.

Treatment

During exploratory laparoscopy, the appendix was removed and the abdomen was copiously irrigated with saline. Initial gram stain of the patient’s peritoneal fluid revealed gram-positive cocci in chains. The patient was treated with piperacillin-tazobactam for 72 hours before being transitioned to oral antibiotics. It was impossible to determine whether the patient’s peritonitis was due to a persistent infection after her recent episode of Streptococcal pharyngitis, a recurrent episode or treatment failure. However, due to the possibility of persistent or recurrent infection, amoxicillin-clavulanate was chosen for treatment as it provides superior beta-lactamase stability compared with penicillin and amoxicillin.

Outcome and follow-up

Postoperatively, the patient defervesced and had no further episodes of abdominal pain or vomiting. No source of infection, from the genitourinary tract or abdomen, was identified. The patient was discharged from the hospital on postoperative day 4. She completed a 10-day course of on amoxicillin-clavulanate after discharge and was doing well at a 2 week follow-up visit.

Discussion

Our patient’s group A streptococcal pharyngitis and subsequent streptococcal peritonitis without any underlying risk factors for primary peritonitis, may have been the result of inadequate therapy, the presence of a carrier state, reinfection or coincidental. While it is impossible to prove causality, our case, in addition to previously reported cases, suggests a potential association between her pharyngeal and her peritoneal infections (table 1). Inadequate or insufficient treatment of a GAS throat infection creates a similar scenario to those reported cases of GAS peritonitis in the early 1900’s, before the use of antibiotics. Without source control, the infection may be able to persist and spread to the abdominal cavity through the bloodstream.

The reports of GAS peritonitis and associated GAS pharyngitis were most frequent prior to the development of antibiotics in the 1940’s (table 1). Prior to the 1940’s, cases of GAS peritonitis was treated with laparotomy, incision and drainage and a variety of supportive measures such as gentian violet and antistreptococcic serum.3 9 12–17 As antibiotic use became widespread and the incidence of untreated GAS pharyngitis decreased, reports of pharyngitis associated with peritonitis also became less frequent. Our review of the paediatric literature revealed only two reports of primary peritonitis associated with streptococcal pharyngitis since 1975. Gillespie et al described a 3-year-old girl who presented with an acute abdomen; S. pyogenes was isolated from both pharyngeal and peritoneal fluid cultures. In contrast to our case, the patient did not have symptoms of pharyngitis; her positive pharyngeal culture was an incidental finding.²⁰ Dann et al described a 6-year-old girl who presented with 1 day of vomiting, low-grade fevers, crampy abdominal pain, sore throat and malaise. A rapid strep test was positive and peritoneal cultures grew S. pyogenes.¹ We describe the third paediatric case in recent history in which both peritoneal and pharyngeal cultures were positive for group A streptococcus.

To our knowledge, there is only one reported case in the English literature in which an adult patient had primary GAS peritonitis with culture-positive pharyngitis.²² However, there are four reported cases of GAS primary peritonitis in which children of adult patients had a recent group A streptococcal pharyngitis.^23–26 It is possible that these cases may have been caused by an asymptomatic throat colonisation and transient asymptomatic bacteraemia, resulting in GAS seeding the peritoneum.²¹ These cases are notable because they provide a possible explanation for how S. pyogenes in the pharynx may be transmitted to the peritoneum, although more research is needed to examine the pathogenesis of GAS peritonitis and consider the mode of transmission of these infections.

In recent years, invasive GAS infections have increased in frequency and severity.²¹ This trend is reflected in the increased frequency of case reports of GAS primary peritonitis in the paediatric literature (table 1). Although primary peritonitis is a rare, it carries a high morbidity and mortality. The increased incidence of invasive streptococcal infections implies that peritonitis due to S. pyogenes may also become more common. Thus, a thorough medical history, including recent upper respiratory and dermatological infections, may provide clues to the underlying diagnosis in a paediatric patient presenting with acute abdominal symptoms.

Recognition of the potential association between group A streptococcal pharyngitis and peritonitis may expedite diagnosis and initiation of appropriate antimicrobial therapy. Further research is needed to investigate the relationship between prior infections, particularly streptococcal pharyngitis and subsequent group A streptococcal peritonitis.

Learning points.

• Primary group A streptococcus peritonitis is a rare entity in paediatrics and it should be included in the differential diagnosis of patients presenting with an acute abdomen.

• This case highlights and provides historical content to the potential association between pharyngitis and group A beta-haemolytic streptococcus primary peritonitis.

• Clinicians should be aware of the potential association between pharyngitis and peritonitis as this recognition may result in earlier diagnosis and treatment.