Современные подходы к дифференциальной диагностике острого аппендицита: стратификация риска и алгоритмизация

EDN:

Saransk, Russian Federation,

Национальный исследовательский Мордовский государственный университет, Саранск, Российская Федерация,

Acute appendicitis (AA) ranks first among acute surgical diseases of the abdominal cavity, accounting for up to 75% of all emergency hospitalizations for “acute abdomen”. Despite centuries of study, the differential diagnosis of AA remains highly challenging. According to modern meta-analyses, the rate of falsepositive diagnoses ranges from 5 to 15%, and in high-risk groups (women of reproductive age, children, obese patients) reaches 20–30%. On the other hand, delayed diagnosis with perforation of the appendix is observed in 25–30% of elderly patients and 15–20% of children, which directly increases the rate of postoperative complications and the duration of hospital stay [1].

Traditional clinical diagnosis, based on identifying the classic triad (epigastric pain with subsequent migration to the right iliac fossa, nausea, local tenderness), is possible in only 50–60% of patients. Atypical forms (retrocecal, subhepatic, pelvic location of the appendix), pregnancy, old age, obesity, as well as a wide range of diseases included in the differential diagnosis (terminal ileitis, Meckel's diverticulum, mesenteric lymphadenitis, gynecological and urological pathology), require a systematic approach to diagnosis [2].

Over the past decade, there has been a significant revision of diagnostic strategy: from relying solely on clinical symptoms to integrating validated clinical and laboratory scales, biomarkers, and imaging methods, followed by risk stratification of patients. It is important to note that more than 20–44% of appendectomy cases were erroneous. Although the percentage of postoperative complications, such as adhesive intestinal obstruction, hernias, etc., is low, they can lead to serious consequences [3; 4].

This article provides an overview of modern approaches to the differential diagnosis of AA, with an emphasis on algorithmization of the process and reduction of diagnostic errors.

The aim of this study is to improve modern approaches to the differential diagnosis of acute appendicitis in order to improve diagnostic accuracy and optimize treatment tactics.

MATERIALS AND METHODS

A narrative analysis of scientific papers on the diagnosis and treatment of AA has been carried out.

The standard search filtering criteria were publication type (clinical trials, cohort studies, meta-analyses, clinical recommendations), language (Russian, English), and accessibility (open access and full text).

The data obtained were statistically analyzed using Microsoft Excel 2013 and IBM SPSS Statistics 22.

RESULTS

Currently, a comprehensive examination, including clinical, biochemical, and radiation examinations, plays a role in the diagnosis of acute appendicitis [5].

There are no reviewers for this work for our purpose. When investigating the possibility of using structured diagnosis of acute abdominal pain, it was found that this type of diagnosis, including medical history, physical examination, laboratory, and instrumental studies, significantly increases the urgency of treatment and reduces morbidity and mortality [6].

Clinical and laboratory stratification: risk scales

The most studied and validated tool is the Alvarado scale (1986), which evaluates 8 parameters (migration of pain, anorexia, nausea/ vomiting, tenderness in the right iliac fossa, rebound tenderness, temperature >37.3°C, leukocytosis >10×109/L, shift to the left). With a threshold of ≥7 points, sensitivity is 75–85%, but specificity does not exceed 50–65%. The main limitations are the absence of C-reactive protein (CRP), overestimation of leukocytosis during pregnancy and pelvic inflammatory disease, and low specificity in women [7; 8].

The Spanish study evaluated the diagnostic value of the Alvarado scale in elderly people with AA. They found that the use of this scale in diagnosing elderly patients with AA is limited and requires caution [9].

A literature review on the achievements and contradictions in measures for the diagnosis and treatment of AA was described. It was noted that the early use of clinical scoring systems and visual methods in patients with AA significantly reduces the frequency of postoperative complications and the number of repeated operations [10].

120 patients with AA were examined in a retrospective cohort study to compare the diagnostic accuracy of the Alvarado scale with histopathological analysis. It was revealed that the sensitivity and specificity of the Alvarado scale were 83.3 and 41%, respectively, and the prognostic value of a positive result was 85% and a negative result was 41%. The number of erroneous appendectomies was 21% [11].

A retrospective comparison of the Alvarado score with ultrasound in the diagnosis of AA was performed. These methods have shown high sensitivity and specificity in diagnosis: for the Alvarado scale – 95 and 88%, and for ultrasound – 98 and 83%, respectively [12].

Despite the results of using the Alvarado scale in diagnosis, contradictory findings were noted. Therefore, other diagnostic scales were introduced [13]. The AIR (Appendicitis Inflammatory Response) scale (2008) includes 6 indicators: vomiting, pain in the right iliac fossa, rebound tenderness (assessed as mild or strong), temperature >38.5°C, CRP level (10–50 mg/L or >50 mg/L), and neutrophil proportion (70–84% or ≥85%). The total score allows patients to be divided into three groups: low risk (0–4 points) – AA frequency 2–5%; intermediate risk (5–8 points) – 20–35%; high risk (9–12 points) – 85–92% [14].

A meta-analysis of 11 prospective studies ( n = 3,856) showed that the area under the ROC curve for AIR was 0.91 (95% CI 0.88–0.94) versus 0.83 (95% CI 0.79–0.87) for Alvarado. The specificity of AIR reached 88% (95% CI 84–91%) with a sensitivity of 86% (95% CI 82–89%). Implementation of AIR in the emergency department reduced the rate of negative appendectomies (NA) from 18 to 6.8% in the intermediate-risk group and to 3.4% in the high-risk group [15].

Indian scientists compared the Alvarado score and the AIR score in the diagnosis of acute appendicitis. It was shown that the standardized AIR system was more reliable in diagnosing AA, reducing erroneous operations and improving patient treatment when compared with Alvarado [16].

The modern AA – RIPASA (Raja Isteri Pengi-ran Anak Saleha Appendicitis) diagnostic scale is also used in surgical practice; it is based on six additional clinical and individual patient parameters [17]. Italian scientists compared the capabilities of RIPASA and Alvarado in the diagnosis of this pathology. RIPASA results exceeded those of Alvarado in sensitivity (95% vs. 77%) and showed similar specificity (72% vs. 71%) [18].

A comparative assessment of the RIPASA and Alvarado scales in the diagnosis of AA was also carried out. The results showed that RIPASA's diagnostic capability was 51% and Alvarado's was 40% when compared with ultrasound (93%) and appendix histology (100%) results [19].

In 315 patients with AA, RIPASA and sonography were assessed. The results revealed that the sensitivity, specificity, and predictive value of RIPASA were 97, 31, and 94%, approaching the results of ultrasound – 95, 27, and 97%, respectively [20].

Laboratory markers

Traditional markers – leukocytosis (>10×109/L) and CRP (>10 mg/L) – retain diagnostic value, but their isolated use is insufficient. The combination of these two indicators increases specificity to 85–90%. CRP levels correlate with the severity of inflammation: in perforated appendicitis, they often exceed 50–100 mg/L [21].

Procalcitonin (PCT) has been considered an additional marker in recent years. In uncomplicated AA, PCT remains within normal limits (<0.5 ng/mL), whereas its elevation is characteristic of perforation or alternative infectious pathology (pyelonephritis, diverticulitis, chorioamnionitis). The sensitivity of PCT for perforated appendicitis reaches 75%, and specificity 85%. However, high cost and delayed results limit routine use [22].

Promising, but not yet implemented in routine practice, are multiplex biomarker panels (CRP + interleukin-6 + calprotectin), demonstrating an AUC of up to 0.94 [23].

Instrumental diagnostics

Modern clinical guidelines (WSES 2022) emphasize that imaging methods should not be used in all patients, but only in those with intermediate risk on the AIR scale (5–8 points) or in the presence of factors that complicate clinical assessment [24].

Ultrasound (US) is the first-line method in children, pregnant women, and adults with normal body weight. The sensitivity of US varies from 70 to 90%, and specificity reaches 95%, provided the appendix is visualized. The use of the graded compression technique, high-frequency transducers (5–12 MHz), and Doppler mapping improves detectability. The main limitations are operator dependence, low informativeness in obesity, retrocecal location, and marked flatulence [25; 26].

Computed tomography (CT) with intravenous contrast is considered the “gold standard” in adults: sensitivity 96–98%, specificity 95–97%. The introduction of low-dose CT protocols (effective dose 1–2 mSv) has preserved diagnostic accuracy while reducing radiation exposure. CT is indicated for non-informative US, in the intermediate-risk group according to AIR, and in elderly patients with a blurred clinical presentation [7].

Magnetic resonance imaging (MRI) is the method of choice in pregnant women and when CT is contraindicated. Non-contrast protocols (T2-weighted images, STIR, DWI) provide sensitivity of 94–97% and specificity of 96–98%. Visualization of the appendix is possible in 96% of cases, even in the third trimester of pregnancy. MRI is also used in children as an alternative to CT to reduce radiation exposure [27].

Features of differential diagnosis in challenging groups

Women of reproductive age. The main mimicking conditions are ovarian apoplexy, ovarian cyst torsion, pelvic inflammatory disease, and ectopic pregnancy. The algorithm includes measurement of β-hCG, pelvic ultrasound, and stratification according to the AIR score. The use of this approach reduces the rate of NA from 20–25% to 8–10% [28; 29].

Pregnant women. Physiological leukocytosis (up to 15×10⁹/L) and displacement of abdominal organs complicate diagnosis. A two-step approach is recommended: US as a screening test; if non-informative, non-contrast MRI. CT is used only for absolute indications. Differential diagnosis is performed with premature placental abruption, pyelonephritis, and cholecystitis [30].

Elderly patients. Blunted symptoms, a high rate of perforation (up to 30%), and comorbidity require a low threshold for performing CT. The use of AIR in patients over 65 years of age requires caution: the absence of fever and leukocytosis may lower the score, so imaging is indicated even at 3–4 points [31].

Diagnostic laparoscopy

If suspicion of AA persists after non-invasive diagnostics, the method of choice is diagnostic laparoscopy. Its use in doubtful cases allows verification of pathology in 31.4% of cases and avoids unnecessary appendectomies. Laparoscopy also enables therapeutic intervention (appendectomy, adnexectomy, lavage) to be performed simultaneously. The complication rate of diagnostic laparoscopy does not exceed 2–3% [32].

Algorithm for differential diagnosis

Based on current data, the following stepwise approach is proposed [15; 33]:

• 1.    Clinical assessment with mandatory calculation of the AIR score.

• 2.    Laboratory tests: complete blood count with differential, CRP; in women – β-hCG.

• 3.    Stratification:

  – AIR 0–4 points: observation or outpatient workup (in the absence of peritoneal signs).

  – AIR 5–8 points: instrumental imaging (US; if non-informative – CT or MRI depending on the group).

  – AIR 9–12 points: emergency appendectomy without additional imaging (with typical clinical presentation).

• 4.    If the picture remains unclear after imaging – diagnostic laparoscopy.

According to multicenter studies, this algorithm reduces the rate of NA to 5–8% and shortens the time from admission to surgery by 1.5–2 h.

DISCUSSION

So, AA is considered one of the main causes of abdominal pain in emergency surgery [34]. The diagnosis of AA requires a structured approach with the inclusion of clinical (sensitivity is 39–74% and specificity is 57–84% [35]), laboratory (sensitivity is 70–85% and specificity is 75–85% [36]), and instrumental (sensitivity is 91–99% and specificity is 90–98% [37]) methods.

It is important to note that the accumulated data show that different forms (mild, severe, etc.) of AA cause difficulties in the diagnosis of this pathology, in the choice of treatment, and in the development of complications [37]. In this regard, different scales of AA diagnostics have been proposed, such as AIR, RIPASA, and Alvarado. According to the above data, it is noted that these systems have contradictory results. In our opinion, the diagnostic ability of RIPASA and AIR exceeded that of Alvarado in AA.

CONCLUSION

• 1.    The differential diagnosis of acute appendicitis in modern conditions requires abandoning isolated clinical assessment in favor of integrative algorithms based on risk stratification.

• 2.    The RIPASA and AIR scales have higher specificity compared to Alvarado, allowing a clear separation of patients into low, intermediate, and high-risk groups, which underlies the rational use of imaging methods.

• 3.    The combination of leukocytosis and CRP remains the mainstay of laboratory diagnostics; procalcitonin can be used as an additional marker when perforation is suspected.

• 4.    US is the first-line method in children, pregnant women, and adults with an uncomplicated course. Low-dose CT is the “gold standard” in adults; MRI is a safe alternative during pregnancy.

• 5.    The implementation of an algorithmic approach involving a multidisciplinary team (surgeons, gynecologists, urologists, radiologists) can

reduce the rate of negative appendectomies to 5–8% and improve treatment outcomes in patients with suspected acute appendicitis.