Acute Abdomen in Woman of Childbearing Age: Appendicitis or Pelvic Inflammatory Disease? A Systematic Review

Acute abdomen in women of childbearing age is a clinical presentation that requires emergency surgical treatment in many cases and rapid diagnosis is oftentimes essential. Most are the causes of acute abdomen: gynecological (ectopic pregnancy, ovarian torsion, ovarian cysts, endometriosis, pelvic inflammatory disease) and non-gynecological (appendicitis, Crohn’s disease, Meckel’s diverticulitis, sigmoid diverticulitis, perforated peptic ulcer, viral gastroenteritis, hernias, urological disease). Appendicitis and pelvic inflammatory disease (PID) are two of the most common causes of abdominal pain in women of childbearing age. This article is a systematic review of literature of the differential diagnosis between appendicitis and PID. The diagnosis is clinical, laboratory and radiological. When the sign and symptoms and the biochemical markers are non-specific abdominal ultrasound (US) is the first radiological test that is performed, but the computer tomography (CT) remains the best specific and sensible exam for the differential diagnosis. Nuclear Magnetic Resonance is performed when CT is contraindicated. Other test like transvaginal ultrasound is a relatively simple and inexpensive diagnostic test that could easily complement the classic abdominal US and be part of the routine diagnostic protocol of women with acute abdominal pain. Therefore, a careful management of the patient starting from the clinical examination and passing through the laboratory and radiological characteristics is necessary.

lower quadrant, classically more intense over McBurney's point.
The pain can be associated with fevers along with nausea, vomiting and anorexia, that classically occur after pain onset. Common laboratory abnormalities include leukocytosis (white blood cells WBS > 20.000 cells/mm 3 ) and an elevated C-reactive protein (CRP) level. Although appendicitis is a highly prevalent disease, especially in Western countries, diagnosis remains a challenge for the surgeon and requires a combination of medical history, laboratory tests, clinical and diagnostic imaging (ultrasound, CT and MRI). Several clinical and laboratory-based scoring systems have been devised to assist diagnosis and the most widely used are the Alvarado score, the AIR (Appendicitis Inflammatory Response) and the AAS (Adult Appendicitis Score). Table 1.

Non-Gynaecological Disease
Gynaecological Disease The last WSES guidelines [2] on appendicitis recommend the use of AIR score and AAS score as clinical predictors of acute appendicitis ( The aim of this article is to review the literature to identify the criteria to distinguish appendicitis from PID, to make an earliest possible diagnosis and treatment.

Material and Methods
We conducted a review of the PubMed database searching

Clinical Diagnosis
Abdominal pain in women of childbearing age can be difficult to diagnose. In attempting to differentiate appendicitis from PID, many aspects of history, physical examination and clinical data can help to clarify the diagnosis. However, some of the data historically used in differentiating appendicitis and PID have not proven to be useful in studies. Women of childbearing age who go to the emergency room for acute abdominal pain usually have various symptoms that can direct the diagnosis towards a gynecological or intestinal pathology.
It is usually difficult to distinguish acute appendicitis from PID just based on the patient's clinical examination during the first visit. Various studies have analyzed aspects of differential diagnosis between the two diseases. Charveriat, et al. [9] concluded that adnexal pain resulting from cervical motility is the most important clinical sign of PID (sensitivity 95-99%) and may be associated with other symptoms such as fever, leucorrhea and metrorrhagia that support the first diagnostic suspicion. Therefore, a patient with such symptoms should be directed to a gynecological consultation and a thorough pelvic examination.
Furthermore, a positive history for sexually transmitted diseases must be investigated to support the diagnosis of PID (with a specificity of 82%). Other authors [10] consider mandatory for a woman of childbearing age with non-specific abdominal symptoms to routinely perform both a complete abdominal examination and a pelvic-gynecological examination. Kruska [11] in 2010 summarized the symptoms of PID and acute appendicitis. Positive predictive values ratio for acute appendicitis were 8.4 for pain in the right iliac fossa, 3.6 for pain migrating from the periumbilical region to right iliac fossa, 3.2 for fever and psoas sign, and only 2.0 for positive Blumberg sign. Regarding PID, leucorrhea (positive predictive value 3,3) and bilateral pelvic abdominal pain (2,5) were very important, while fever and leukocytosis were less specific. Dahlberg, et al. [12] specifically analyzed the clinical presentations of the two diseases and documented that although cervical and uterine pain are more specific in PID, they are still present in 28% of women with acute appendicitis. Furthermore, almost 50% of the women who had an intraoperative diagnosis of acute appendicitis did not present the classic symptoms of the disease [13]. However, another study point out that cervical motion tenderness alone is not specific for PID; it is present in 25% of cases of appendicitis and 50% of ectopic pregnancies.
Morishita study in 2007 [14] is the most relevant on the clinical presentation of these two pathologies. In this retrospective study, analyzed the patient's number of pain episodes and their duration.
Typically, an acute onset pain is associated with appendicitis than PID. Acute appendicitis' pain usually lasts 24 to 36 hours, while the pain of PID can last for weeks or until treated. It is clear how the clinic itself can direct the surgeon towards a differential diagnosis between PID and acute appendicitis in women of childbearing age, but it must be accompanied by further laboratory and radiological investigations.

Laboratory Diagnosis
All women of childbearing age who present to the emergency room with acute abdominal pain undergo a blood sample for routine blood chemistry tests. These consist of blood counts with leukocyte formula, liver function tests, renal function tests and measurement of inflammation markers (for example erythrocyte sedimentation rate and CRP). Furthermore, if the painful symptoms affect the lower quadrants of the abdomen, a chemical-physical examination of the urine could be performed [15]. From the studies published on this topic, the simple execution of routine blood tests does not allow us to differentiate PID and acute appendicitis because an increase of inflammation indices (white blood cell counts and elevated CRP) is possible in both clinical conditions.
In case of prolonged observation of the patient, it may be useful to repeat the routine blood tests because a rapid worsening of the indexes of inflammation can highlight an acute appendicitis rather than a PID [12].
In patients of childbearing age with abdominal pain, a b-hcg test should be always done to exclude an unrecognized or ectopic pregnancy [12]. Second level examinations may be useful in patients with non-specific abdominal symptoms. Among these, certainly important is a cervical swab to diagnose genital infections specificities like those of cervical samples [12].
Newer evidence documents that microorganisms associated with bacterial vaginosis have been found in women with laparoscopically proven PID. However, it is important to realize that the sensitivity of the clinical diagnosis for PID based on a pelvic examination alone is only 60% to 70%. Considering additional biochemical markers that may aid in the differential diagnosis between PID and acute appendicitis, some authors have considered intrauterine nitric oxide measurement [16]. In this retrospective case-control study, intrauterine nitric oxide (NO) values were compared in women with a laparoscopic diagnosis of appendicitis or PID. In patients with PID, NO values were found much higher than those with appendicitis or compared to healthy controls.
Other biochemical markers of inflammation like interleukin-6, IL-8 and CD-64 have been associated with appendicitis compared with nonsurgical causes of acute abdominal pain [17]. On the contrary the plasma levels of LRG1 were not useful to differentiate between acute appendicitis and pelvic inflammatory disease [18].

Radiological Diagnosis
All women who come to the emergency room for acute abdominal pain undergo to first-level radiological investigations [19,20]. Among these, the first is abdominal ultrasound (US

Abdominal Ultrasound (US)
In the differential diagnosis between PID and acute appendicitis, abdominal ultrasound can guide the diagnosis but, in some cases, this is not diagnostic because both clinical conditions may have similar presentation (fluid in Douglas and ovaries, salpingi and appendix edematous and thickened) [21]. Therefore, in women of

Computer Tomography (CT)
When the clinical presentation is non-specific and the ultrasound is non-diagnostic, patients undergo abdomen computer tomography (CT) with contrast medium [19,20,22].  [20]. In Hentour's retrospective study of the role of CT in the differential diagnosis between PID and acute appendicitis, it was found that only two CT findings (appendiceal diameter and left tubal thickening) were very accurate in differentiating PID from acute appendicitis.
Consequently, the first step in interpreting abdominopelvic CT in non-appendectomised women of reproductive age with acute lower abdominal pain is to measure the appendiceal diameter.
If the appendiceal diameter is < 7 mm, appendicitis is very improbable and thus CT findings of PID should be investigated. If the appendiceal diameter is ≥ 7 mm, left tubal thickening should be analyzed, since a left tubal diameter ≥ 10 mm would indicate PID rather than appendicitis [22]. Conversely, it has been shown that in PID the most present CT radiological features are haziness of the pelvic fat, obscuration of the pelvic fascial planes, thickening of the uterosacral ligaments, abnormal endometrial enhancement with fluid in the endometrial cavity, enhancement and thickening of the fallopian tubes, and abnormal enhancement, enlargement, and reactive polycystic change of the ovaries [25]. Moreover, the presence of an appendicolith, cecal origin of the tubular structure, and the presence of cecal wall thickening ("cecal bar" sign) are helpful distinguishing features of appendicitis [22]. The sensitivity of CT in appendicitis is from 87% to 98%, higher than US o MRI.

Nuclear Magnetic Resonance (NMR)
In some centers, especially in the United States, the use in emergency of nuclear magnetic resonance (NMR) has become routine in the management of acute abdominal pain in women of childbearing age and in pregnant women [26,27]. Magnetic Resonance Image (MRI) is a valuable tool in the evaluation of suspected appendicitis, either as an adjunct to or a replacement for an initial right lower quadrant US. This is particularly true for pediatric and pregnant patients, in whom ionizing radiation must be avoided. Scan times have been decreased using protocols including as few as four sequences, which allow for diagnostic imaging of the abdomen and pelvis in almost 15 minutes [21]. MRI has sensitivity, specificity, and accuracy for diagnosis of appendicitis of 95%, 89%, and 93%, respectively. For diagnosis of appendiceal perforation, MRI imaging demonstrates slightly higher sensitivity (57%) than ultrasound with conditional CT (48% sensitivity) [22].
The inflammation will be depicted best on the fluid-sensitive T2weighted images; fat saturation allows the signal abnormality to be more readily apparent. Appendiceal wall thickening (>2mm) will show hypointense signal on T1-weighted images and hyperintensity on T2-weighted images, with the caliber of the appendix measuring greater than 6 mm.
Periappendiceal fat inflammation will manifest as hyperintense T2 signal, consistent with edema. In the nonpregnant patient, gadolinium contrast administration increases the sensitivity of MRI in diagnosing acute appendicitis where intense appendiceal wall enhancement is seen on the fat-suppressed postcontrast T1 images [28]. MRI imaging, given the lack of a radiation-associated risk and the relative safety of gadolinium-based contrast agents, is an attractive alternative to CT for the evaluation of pelvic inflammatory  On the other hand, transvaginal ultrasound is a relatively simple and inexpensive diagnostic test that could easily complement the classic abdominal US and be part of the routine diagnostic protocol of women with acute abdominal pain. This radiological test has good sensitivity and specificity to exclude acute appendicitis in those cases where the gynecological cause of pain is more likely. Certainly, new and further studies are needed to define the best diagnostic protocol in women of childbearing age with acute abdominal pain presenting in ED. Above all, prospective multicenter studies or randomized trials would be needed.

Conclusion
PID and acute appendicitis are two very frequent pathologies in women of childbearing age. A correct differential diagnosis may not always be easy, especially in not typically clinical presentation.
Therefore, a careful management of the patient starting from the clinical examination and passing through the laboratory and radiological characteristics is necessary. A correct diagnosis allows a better patient management and reduction of unnecessary surgeries.