Swedish national guidelines for diagnosis and management of acute appendicitis in adults and children

Introduction

Appendicitis is a common condition at emergency departments in Sweden. The disease mainly affects younger patients but is seen in all age groups. About 11 000 cases of appendicitis are seen each year in our country. Mortality rates are very low but morbidity rates can be high in cases of perforated appendicitis. Although appendicitis has been traditionally regarded as a progressive condition that always requires rapid diagnosis and surgical treatment, in more recent years different approaches to this disease have emerged. Specifically, two types of appendicitis have been identified: complicated appendicitis, which should be detected and treated without delay, and uncomplicated appendicitis, for which management is currently controversial. In the latter, spontaneous resolution is common and non-operative management based on observation and/or antibiotic treatment has been advocated as an alternative to surgery. This diversified view on appendicitis motivates structured management based on risk stratification (Fig. 1).

These national guidelines are aimed at healthcare professionals who manage patients with suspected or confirmed acute appendicitis. The main objectives of these guidelines are to ensure equal quality of care for patients with appendicitis regardless of where they seek treatment; reduce morbidity and mortality rates in acute appendicitis; provide up-to-date evidence for the diagnosis and management of acute appendicitis; and make appendicitis care more patient-centred and effective. A summary of the recommendations is listed in Table 1.

Triage and diagnostics

The decision whether the patient should be referred to an emergency department should be based primarily on history, clinical examination and CRP (⊕).

Scoring systems without acute blood tests seem promising to risk-stratify children in primary care for further management decisions (⊕).

When appendicitis is suspected, blood tests including leucocytes, neutrophils, and CRP should always be performed (⊕⊕⊕⊕).

An electrolyte panel should be made on admission, partly for possible correction before anaesthesia, and partly because hyponatraemia is a good marker of complicated disease, especially in children (⊕⊕).

Scoring systems provide objective support for assessing the likelihood of appendicitis and should always be used. They enable risk-stratified management for optimal resource utilization with fewer admissions, less use of imaging, and fewer operations (⊕⊕⊕⊕).

The AIR score has been shown in external validations to provide reproducible results for all ages and should be the first choice (⊕⊕⊕⊕).

Radiological diagnosis is particularly relevant in patients at intermediate risk of appendicitis (⊕⊕⊕⊕), where the diagnosis is unclear, or where other important differential diagnoses are likely (⊕⊕).

Ultrasound is the first choice, especially for examining children and pregnant women (⊕⊕).

Abdominal CT is the second choice, offering slightly higher specificity and sensitivity relative to ultrasound. However, it is associated with a small radiation risk, so there should be a clear indication for its use (⊕⊕).

Low-dose CT with contrast has similar accuracy as conventional CT (⊕⊕⊕⊕).

MRI has much lower availability and should only be used for pregnant women where ultrasound has been inconclusive (⊕⊕).

When appendicitis is suspected in pregnant women, blood tests including leucocytes, neutrophils, CRP, and a urine sample should always be taken (⊕⊕).

Ultrasound is the first choice in pregnant women (⊕), followed by MRI if available (⊕⊕⊕).

Observation with repeated blood tests and ultrasound in cases of suspected appendicitis is reasonable if the woman is not otherwise unwell. This does not appear to affect maternal or fetal outcome (⊕).

In pregnant women: if US is inconclusive or if US and MRI are not available or would significantly delay the diagnosis, CT may be indicated if there is a sufficiently strong suspicion of complicated appendicitis, unless the general condition is so affected that there is an indication for urgent surgery (⊕⊕).

Diagnostic laparoscopy seems safe in pregnant women when it comes to preterm birth and fetal loss at least in early pregnancy (<20 weeks). However, published evidence of the risks versus benefits is very limited and conflicting (⊕).

Treatment

A dose of broad-spectrum antibiotics should be given as prophylaxis for appendectomy (⊕⊕⊕⊕).

No postoperative antibiotics should be given in surgery for uncomplicated appendicitis (⊕⊕⊕⊕).

Postoperative antibiotics should be given after surgery for complicated appendicitis. The definitions of gangrenous and perforated appendicitis vary widely, making the studies difficult to interpret. There is probably no benefit for postoperative antibiotic treatment in gangrenous appendicitis (⊕⊕), but due to the uncertainty of the evidence, a 24-h postoperative treatment is recommended.

Postoperative antibiotics should be given after surgery for perforated appendicitis, especially if adequate source control has not been achieved. Start antibiotic treatment immediately upon suspicion and continue for 3–5 days after surgery (⊕⊕⊕⊕). Treatment can be switched to an oral option as soon as clinically feasible (⊕⊕⊕).

Thrombosis prophylaxis is not routinely recommended in surgery for acute appendicitis.

If the patient is over 40 years old and the operation lasts longer than 60 min, thrombosis prophylaxis should be considered (⊕).

Thrombosis prophylaxis should be administered to patients with clear risk factors for thrombosis, including pregnancy (⊕).

In assumed complicated appendicitis (not abscess and phlegmon), patients should be optimized and operated within 6 (–8) hours for the sake of well-being and to reduce the risk of complications (⊕⊕).

In assumed uncomplicated appendicitis, the risk of complications is not increased by up to 24 h from arrival at the emergency department to surgery (⊕⊕⊕⊕).

Laparoscopic appendectomy is recommended as the first choice for all patient groups and for both uncomplicated and complicated appendicitis (not abscess and phlegmon) (⊕⊕⊕⊕).

The standard three-port technique for laparoscopic appendectomy is recommended for both adults and children (⊕⊕).

Open appendectomy may need to be used in late pregnancy and in case of contraindication to laparoscopy, but it is always a matter of judgement in each case.

In complicated appendicitis with free fluid in the abdomen, aspiration of the fluid is recommended but not peritoneal lavage (⊕⊕⊕).

Postoperative abdominal drain is not recommended (⊕⊕⊕⊕).

Patients with appendicitis abscess should be treated primarily with intravenous antibiotics and drainage. Phlegmon should be treated primarily with intravenous antibiotics (⊕⊕⊕⊕).

Planned interval appendectomy after a conservatively treated abscess or phlegmon is not routinely recommended except in cases where malignancy is suspected and/or unclear findings at follow-up remain (⊕⊕).

Patients who have been treated conservatively for appendicitis abscess or phlegmon should be followed up with CT or colonoscopy (sometimes a combination of both) as there may be an underlying malignancy

In two randomized trials, antibiotic treatment was not significantly better than placebo and therefore cannot be recommended for the treatment of uncomplicated appendicitis (⊕⊕⊕⊕).

The ERAS concept speeds up recovery, shortens hospitalization time, and seems to lead to fewer reoperations (⊕⊕⊕).

Children who have undergone laparoscopic appendectomy for uncomplicated appendicitis can be discharged from hospital on the same day (⊕⊕).

Urinary catheters and central access are not indicated in children with complicated appendicitis (⊕⊕).

Pain relief for children at home usually consists of paracetamol and NSAIDs.

Follow-up

PAD should be made routinely in all patients (⊕⊕). If the resources are scarce all appendices in patients >40 years of age should undergo PAD to avoid missing an alternative diagnosis. To evaluate the quality of the clinic, all consecutive appendectomy specimens should be analysed at least for a period of time.

Follow-up is not necessary if PAD shows acute appendicitis.

Children do not need follow-up.

People under 40 years of age do not require follow-up unless their medical history suggests a malignant genesis.

People over 40 years of age are recommended to have a CT colonography or colonoscopy after 6–8 weeks to rule out malignancy (⊕). The findings on the abdominal CT scan can guide the selection of the most appropriate test.

Elective surgery after non-operative successful treatment is not recommended with the following exceptions (⊕⊕):

The patient has recurrent appendicitis symptoms (relapse)

Malignancy is suspected during follow-up.

CRP, C-reactive protein; CT, computed tomography; AIR, appendicitis inflammatory response; MRI, magnetic resonance imaging; US, ultrasound; ERAS, enhanced recovery after surgery; NSAIDs, non-steroidal anti-inflammatory drugs; PAD, pathologic anatomic diagnosis.

Background and causes

Pathology and classification

The appendix is a true diverticulum, about 5–15 cm long, which originates from the first part of the large intestine (caecum). Acute appendicitis represents an acute inflammation of the appendix. The diagnosis can be made based on radiological, clinical, and intraoperative findings and the histopathological examination of the removed appendix. In most cases, several modalities are combined for diagnosis and there is no consensus.

The histopathological classification is considered the gold standard. However, pathologists apply different nomenclature and criteria, which may affect the assessment of the proportion of operated patients where the appendix is not inflamed (so-called negative appendectomy)^7–11. Uncomplicated phlegmonous appendicitis is characterized by invasion of inflammatory cells past the mucosa and submucosa into the muscularis propria (transmural inflammation). In complicated appendicitis there is necrosis of the appendix tissue (gangrenous appendicitis) which may lead to breakdown of the appendix wall and free passage of intestinal contents to the abdominal cavity (perforated appendicitis)¹¹. However, clinical (see Diagnosis) and radiological (see Imaging) signs of perforation may not always be detected on histopathological examination. A diagnosis of perforated appendicitis is therefore usually based on perioperative findings of pus in the abdomen, but free pus in the abdomen may also be caused by the inflammatory reaction per se and does not always contain bacteria.

According to the Swedish Society of Pathology, a histopathological report should always include information on granulocyte infiltration in the different layers including transmural inflammation. Wall necrosis should be indicated. Perforation can sometimes be demonstrated, but intestinal contents on serosal surfaces are usually accepted as indirect evidence. Perforation or not should be commented on.

Acute appendicitis may be covered by omentum, fibrin, or other tissue, which prevents free perforation to the peritoneal cavity and creates a palpable appendiceal mass. Based on radiological findings, this mass is classified as appendicitis abscess if it contains fluid/pus, or appendicitis phlegmon if it contains only inflamed tissue.

Chronic appendicitis is a rare and controversial condition, clinically characterized by persistent, mild abdominal pain that can last for an extended period although inflammatory markers often remain within normal ranges^12–14. In retrospective studies, about three-quarters of these patients become pain-free after appendectomy. Histopathological examination may reveal granulomatous inflammation with fibrosis, and sometimes crypt abscesses. However, these changes can also be observed in appendix specimens from asymptomatic patients^7,11,13. In a randomized trial including patients with persistent or recurrent right lower-quadrant abdominal pain, laparoscopic appendectomy was associated with reduced pain at 6 months after surgery compared to laparoscopic inspection only. However, no association was found between freedom from symptoms and histology¹⁴.

Diagnosis codes

Administrative health records use diagnosis codes according to the International Classification of Diseases (ICD) coding system. Several versions have been published and the definitions have varied over time, which has affected the interpretation of longitudinal comparisons. Especially after the latest revision in 2010, very large variations have arisen between reporting hospitals¹⁵. See further under Quality registers and quality indicators.

Current ICD-10 codes for appendicitis are: C35.2 Acute appendicitis with generalized peritonitis, C35.3 Acute appendicitis with localized peritonitis, C35.8 Other and unspecified acute appendicitis, C36.9 Other appendicitis, and K37.9 Unspecified appendicitis.

Epidemiology

In Sweden, the incidence of diagnosed appendicitis is about 120/100 000 inhabitants/year, with a higher incidence in men. Appendicitis is relatively uncommon in children under 5 years of age, peaking in adolescence and then declining (Fig. 2).

The incidence of complicated and uncomplicated appendicitis shows different patterns in many studies. The lockdown period during the coronavirus disease-2019 (COVID-19) epidemic was associated with large variations in the incidence of uncomplicated appendicitis in relation to age, geographical areas, and over time, in contrast to complicated appendicitis, which remained almost the same regardless of these factors^16–22.

In Sweden, the incidence has developed differently for children and adults. In children, a declining incidence is seen, mainly of uncomplicated appendicitis¹⁹. In adults, a corresponding declining incidence has been seen up to a lowest level of 85/100 000 inhabitants in 2004, after which, unlike in children, it has risen and plateaued at around 120/100 000 inhabitants. The reason for these variations is unclear. There are also geographical variations in incidence within Sweden, which most likely reflect differences in the management of patients with suspected appendicitis (Fig. 3).

The mortality rate from appendicitis is very low in high-income countries (0.09–0.24%) compared to low-income countries (1–4%)²³. According to the National Board of Health and Welfare, 12 patients died due to appendicitis in 2020 in Sweden (0.12/100 000 inhabitants), all of whom were over 65 years of age. The same number of annual deaths was seen in a chart review of patients who died in Sweden within 30 days of appendectomy between 1987 and 1996²⁴. Co-morbidities and age are crucial contributors to mortality, not least in the case of negative appendectomy, as the patient is exposed to an unnecessary burden and the underlying diagnosis may be missed²⁵. Mortality is present in all stages of disease but is doubled in perforated compared to non-perforated appendicitis and in negative appendectomy (likely due to the underlying undetected morbidity). Mortality rate is low in younger patients but increases in those over 75 years of age^24–26. In pregnant women, mortality from appendicitis is extremely rare but not absent²⁷.

Aetiology and heredity

The aetiology of appendicitis is not completely understood. Complicated and uncomplicated appendicitis have different associations with multiple factors. Uncomplicated appendicitis varies geographically, between different ages and different ethnicities, and over time. This pattern is not seen for complicated appendicitis¹⁷. There are also differences in association with genetic factors^28–31. This suggests that these represent two different entities.

Several factors are involved in the pathogenesis¹¹. Obstruction of the appendix lumen, usually due to a calcified faecal stone, may be the cause especially in cases where a perforation develops^32–34. However, faecal stones can be seen in healthy people without symptoms³⁵. Large faecal stones are associated with complicated appendicitis³⁶. Local outbreaks, space–time clusters and seasonal variation may suggest an infectious genesis, but no specific agents have been identified^37–39.

The inflammatory response of the immune system seems to be important. Children who develop allergy have a lower risk of later developing complicated appendicitis compared to non-allergic children^40–42. Patients who have had surgery for appendicitis before the age of 20 are less likely to develop ulcerative colitis^43,44. This relationship is also seen within families, suggesting that appendicitis and ulcerative colitis have common, but opposite, underlying genetic factors⁴⁵. Pregnancy has a protective effect during the first and especially the third trimester⁴⁶.

Several reports have shown an increased risk of appendicitis within families and among relatives, suggesting genetic factors^31,47–55. However, several of these studies have methodological weaknesses, especially because they often study the risk of appendectomy, which may be influenced by social factors^56,57. Speculatively, it is possible that parents who have experienced appendicitis themselves may be more likely to seek medical care for their children if they develop abdominal pain, leading to biased care-seeking behaviour. In addition, data in the studies above have often been collected retrospectively through questionnaires, which can cause recall bias. A twin study, using data from the Swedish Patient Registry and the Swedish Twin Registry, could not identify a genetic effect, but found a significant influence of environmental factors⁵¹. However, some studies have shown association with specific genes^31,55,58.

In summary, appendicitis has a complex aetiology, where infection, obstruction, environment, gender, age, and genetic and immunological factors are involved.

Natural history

Knowing its natural history is of great importance for the optimal management of a disease. Indirect evidence suggests that complicated and uncomplicated appendicitis represent two different types of disease with different natural history—a type that can rapidly progress to gangrene and perforation, or circumscribed abscess, and a type that is spontaneously resolving and possibly recurrent⁵⁹.

The spontaneous resolving form can often go undiagnosed. A meta-analysis of four studies that randomized patients with acute non-specific abdominal pain to laparoscopy or observation showed a six-fold higher rate of diagnosed appendicitis in the laparoscopy group suggesting spontaneous resolution in the other^60–64. A systematic review and meta-analysis of the impact of reduced access to healthcare during the COVID-19 pandemic in 63 reports showed a reduced incidence of uncomplicated appendicitis during the pandemic but no impact on complicated appendicitis²². In two placebo-controlled trials of patients with presumed uncomplicated appendicitis, over 90% and 80% healed, respectively, irrespective of whether they received antibiotics or placebo, showing that spontaneous resolution is common in uncomplicated appendicitis^65,66. More than 60% of 182 patients with ultrasound-verified low-grade appendicitis who received supportive care only were still cured after 9 years of follow-up⁶⁷. Increased use of imaging is associated with an increased incidence of diagnosed and treated appendicitis. In two studies that randomized patients to CT or observation, there was a significantly higher number of patients diagnosed with appendicitis in the CT group^68,69.

There is a clear correlation between the duration of symptoms before arrival at the hospital and the proportion of perforations, with a higher proportion of perforations when the duration of symptoms is long^70–72. However, there is no increase in the proportion of perforations when treatment is delayed for up to 24 h after arrival at the hospital^73–80. This may indicate that perforation in most cases has already occurred when the patient seeks care or may occur shortly after arrival at the hospital for patients with a short duration of symptoms. Due to spontaneous resolution of uncomplicated appendicitis, increasing duration of symptoms on arrival will result in the selection of those with complicated disease. Selection due to spontaneous resolution may therefore be a possible explanation for the increasing proportion of complicated disease with increasing duration of symptoms^16,59.

The proportion of perforations is a composite measure that is dependent on both the number of perforations (numerator) and the total number of appendicitis cases (denominator). Many studies comment only on changes in the proportion of perforations after an intervention, although the change is often only seen in the number of appendicitis cases (denominator) whereas the number of perforated appendicitis cases in the numerator may be unchanged. An increased proportion of perforations can therefore often be seen in association with a decreased total number of appendicitis cases.

For example, the introduction of CT diagnostics showed a sharp decrease in the rate of perforation⁸¹, but careful analysis shows that this is explained by an increase in the number of patients treated for non-perforated appendicitis.

The optimal pace of management of patients with suspected appendicitis depends on the nature of the underlying disease. The focus in the past has been to prevent perforation by prompt surgery in all patients with suspected appendicitis, even if associated with a high rate of negative appendectomies. If perforation typically occurs before hospital arrival, the focus should be on promptly diagnosing and surgically treating patients with progressive or complicated appendicitis. In contrast, the need for rapid diagnosis and treatment is less urgent for patients with suspected uncomplicated appendicitis. This does not mean that these patients may not require equally rapid assessment for symptomatic treatment, such as analgesia. There are currently no reliable ways to predict the prognosis of patients with suspected uncomplicated appendicitis⁸². Many will resolve, but some will not heal spontaneously and may finally require surgical treatment.

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