Colonic diverticular disease: medical treatments for acute diverticulitis

Abstract

Introduction

Diverticula (mucosal outpouchings through the wall of the colon) are rare before the age of 40 years, after which prevalence increases steadily and reaches over 25% by 60 years. However, only 10% to 25% of affected people will develop symptoms such as lower abdominal pain. Recurrent symptoms are common, and 5% of people with diverticula eventually develop complications such as perforation, obstruction, haemorrhage, fistulae, or abscesses.

Methods and outcomes

We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of medical treatments for acute diverticulitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2014 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).

Results

At this update, searching of electronic databases retrieved 193 studies. After deduplication and removal of conference abstracts, 75 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 37 studies and the further review of 38 full publications. Of the 38 full articles evaluated, four systematic reviews and one RCT were added at this update. We performed a GRADE evaluation for two PICO combinations

Conclusions

In this systematic overview, we categorised the efficacy for one comparison based on information about the effectiveness and safety of medical treatment (mesalazine, antibiotics [any] only) versus placebo or no treatment.

Key Points

Diverticula (mucosal outpouchings through the wall of the colon) are rare before the age of 40 years, after which prevalence increases steadily and reaches over 25% by 60 years and older. However, only 10% to 25% of affected people will develop symptoms such as lower abdominal pain.

• Recurrent symptoms are common, and 5% of people with diverticula eventually develop complications such as perforation, obstruction, haemorrhage, fistulae, or abscesses.

• Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and opiate analgesics have been associated with an increased risk of perforation of diverticula, while calcium antagonists may protect against these complications.

• At this update we have focused on medical treatments for acute diverticulitis, the most commonly occurring complication.

We searched for RCTs and systematic reviews of RCTs on the effects of medical treatments (mesalazine, antibiotics) versus placebo or no treatment.

• We found few RCTs. There is a need for further RCTs to inform the evidence base.

Recent evidence suggests that those people with CT-proven uncomplicated acute diverticulitis may not benefit from treatment with intravenous antibiotics.

• This evidence comes from a single RCT, which may have excluded people with severe sepsis, and which had a large percentage of people included in the study with prior episodes of acute diverticulitis.

• However, the results of the study are promising and suggest that, in mild disease, antibiotic treatment may not be beneficial in those with simple CT-proven uncomplicated acute diverticulitis.

As suggested by one systematic review on the subject, further evidence will be required to change clinical practice.

We found no RCTs on the effects of antibiotics in people with complicated acute diverticulitis, or on the effects of mesalazine.

Clinical context

General background

Colonic diverticular disease is a common condition, and its complications cause significant morbidity, mortality, and health care costs. The treatment of its most commonly occurring complication, acute diverticulitis, is changing as evidence from RCTs has started to be published.

Focus of the review

For this update we have focused on the issue of medical treatment (either mesalazine or antibiotics) for acute diverticulitis.

Comments on evidence

We found four systematic reviews, which identified one RCT of relevance on the use of antibiotics.

Search and appraisal summary

The update literature search for this overview was carried out from the date of the last search, May 2010, to August 2014. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the overview, please see the Methods section. Searching of electronic databases retrieved 193 studies. After deduplication and removal of conference abstracts, 75 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 37 studies and the further review of 38 full publications. Of the 38 full articles evaluated, four systematic reviews and one RCT were added at this update.

About this condition

Definition

Colonic diverticula are mucosal outpouchings through the large bowel wall. They are often accompanied by structural changes (elastosis of the taenia coli, muscular thickening, and mucosal folding). They are usually multiple, and occur most frequently in the sigmoid colon. Most people with colonic diverticula are asymptomatic, with little to find on clinical examination, while 20% develop symptoms at some point.[1] If diverticula are associated with symptoms, then this is termed diverticular disease. If asymptomatic, then the condition is known as diverticulosis. People who go on to develop complications associated with diverticula (inflammation, perforation, fistulae, abscess formation, obstruction, or haemorrhage) are referred to as having complicated diverticular disease. People with uncomplicated diverticular disease may report abdominal pain (principally colicky left iliac fossa pain), bloating, and altered bowel habit, and may have mild left iliac fossa tenderness on examination. Acute diverticulitis occurs when a diverticulum becomes acutely inflamed. People with acute diverticulitis typically present with severe left iliac fossa pain and tenderness associated with fever, tachycardia, malaise, and altered bowel habit.

Incidence/ Prevalence

In the UK, the incidence of diverticulosis increases with age; about 5% of people are affected in their fifth decade of life, 25% aged 60 years, and about 50% by their ninth decade.[2] Diverticulosis is common in resource-rich countries, although there is a lower prevalence of diverticulosis in Western vegetarians consuming a diet high in fibre.[3] Diverticulosis was almost unknown in rural Africa and Asia but is becoming more common as these countries industrialise.[4]

Aetiology/ Risk factors

There is an association between low-fibre diets and diverticulosis of the colon, although recent cross-sectional observations challenge this link.[4] [5] A prospective cohort study reported that consuming a vegetarian diet and a high intake of dietary fibre were associated with a lower risk of admission to hospital or death from diverticular disease.[6] High meat intake is also a risk factor for developing diverticular disease.[7] Prospective observational studies have found that both physical activity and a high-fibre diet are associated with a lower risk of developing diverticular disease.[7] [8] The risk of developing diverticulitis or diverticular bleeding has been shown to be associated with regular use of aspirin and NSAIDs.[9] Case-control studies have found an association between perforated diverticular disease and use of NSAIDs, corticosteroids, and opiate analgesics, and have found that calcium antagonists have a protective effect.[10] [11] [12] [13] [14] People in Japan, Singapore, and Thailand develop diverticula that affect mainly the right side of the colon.[15] Observational studies have reported an increased risk of diverticular bleeding and diverticulitis in people with a BMI greater than or equal to 30 kg/m² compared with those who have a BMI less than 21 kg/m².[16] A population-based study of women reported a 23% increased risk (RR 1.23, 95% CI 0.99 to 1.52) of symptomatic diverticular disease in current smokers compared with non-smokers when accounting for other confounding factors, with a greater risk of developing a perforation or abscess than non-smokers (RR 1.89, 1.15 to 3.10).[17] However, further evidence on this association is required as other studies have not found such a relationship.[17] [18]

Prognosis

Inflammation will develop in 10% to 25% of people with diverticula at some point.[2] It is unclear why some people develop symptoms and some do not. Even after successful medical treatment of acute diverticulitis, almost two-thirds of people suffer recurrent pain in the lower abdomen.[19] Recurrent diverticulitis is observed in 7% to 42% of people with diverticular disease, and after recovery from the initial attack the calculated yearly risk of suffering a further episode is 3%.[20] About 50% of recurrences occur within 1 year of the initial episode, and 90% occur within 5 years.[21] The largest of these retrospective series reported data on 2366 medically treated patients, with a median follow-up of 8.9 years and with a recurrence rate of 13.3%.[22] Complications of diverticular disease (perforation, obstruction, haemorrhage, and fistula formation) are each seen in about 5% of people with colonic diverticula when followed up for 10 to 30 years.[23] In the UK, the incidence of perforation is 2 to 4 cases per 100,000 people a year, leading to approximately 2000 cases annually.[24] [25] Intra-abdominal abscess formation is also a recognised complication.

Aims of intervention

To reduce mortality, symptoms, and complications, with minimal adverse effects.

Outcomes

Mortality from complications of diverticulitis; symptom relief (includes subjective gastrointestinal symptoms assessed by the use of questionnaires and cure rates; admission and readmission rates as a result of diverticular disease and its complications); recurrence incidence of diverticulitis, haemorrhage, perforation, abscess, fistula formation; adverse effects. Stool weight and transit time are surrogate outcomes and are not reported in this overview.

Methods

Search strategy BMJ Clinical Evidence search and appraisal date August 2014. Databases used to identify studies for this systematic overview include: Medline 1966 to August 2014, Embase 1980 to August 2014, The Cochrane Database of Systematic Reviews 2014 issue 8 (1966 to date of issue), the Database of Abstracts of Reviews of Effects (DARE), and the Health Technology Assessment (HTA) database. Inclusion criteria Study design criteria for inclusion in this systematic overview were systematic reviews and RCTs published in English, including trials described as 'open' or 'open label', and containing more than 20 individuals, of whom more than 80% were followed up. There was no minimum length of follow-up. BMJ Clinical Evidence does not necessarily report every study found (e.g., every systematic review). Rather, we report the most recent, relevant, and comprehensive studies identified through an agreed process involving our evidence team, editorial team, and expert contributors. Evidence evaluation A systematic literature search was conducted by our evidence team, who then assessed titles and abstracts, and finally selected articles for full text appraisal against inclusion and exclusion criteria agreed a priori with our expert contributors. In consultation with the expert contributors, studies were selected for inclusion and all data relevant to this overview extracted into the benefits and harms section of the overview. In addition, information that did not meet our pre-defined criteria for inclusion in the benefits and harms section may have been reported in the 'Further information on studies' or 'Comment' section. Adverse effects All serious adverse effects, or those adverse effects reported as statistically significant, were included in the harms section of the overview. Pre-specified adverse effects identified as being clinically important were also reported, even if the results were not statistically significant. Although BMJ Clinical Evidence presents data on selected adverse effects reported in included studies, it is not meant to be, and cannot be, a comprehensive list of all adverse effects, contraindications, or interactions of included drugs or interventions. A reliable national or local drug database must be consulted for this information. Comment and Clinical guide sections In the Comment section of each intervention, our expert contributors may have provided additional comment and analysis of the evidence, which may include additional studies (over and above those identified via our systematic search) by way of background data or supporting information. As BMJ Clinical Evidence does not systematically search for studies reported in the Comment section, we cannot guarantee the completeness of the studies listed there or the robustness of methods. Our expert contributors add clinical context and interpretation to the Clinical guide sections where appropriate. Structural changes this update We have removed two questions included in the previous version of this systematic overview: What are the effects of treatments for uncomplicated diverticular disease? What are the effects of treatments to prevent complications of diverticular disease? At this update we have added one new option: medical treatment (mesalazine, antibiotics only) versus placebo or no treatment, in people with acute diverticulitis. Data and quality To aid readability of the numerical data in our overviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). BMJ Clinical Evidence does not report all methodological details of included studies. Rather, it reports by exception any methodological issue or more general issue that may affect the weight a reader may put on an individual study, or the generalisability of the result. These issues may be reflected in the overall GRADE analysis. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for Colonic diverticular disease: medical treatments for acute diverticulitis.

Important outcomes	Mortality, Recurrence, Symptom relief
Studies (Participants)	Outcome	Comparison	Type of evidence	Quality	Consistency	Directness	Effect size	GRADE	Comment
What are the effects of medical treatments for acute diverticulitis?
1 (623)	Symptom relief	Medical treatment (mesalazine, antibiotics) versus placebo or no treatment	4	–2	0	–1	0	Very low	Quality points deducted for incomplete reporting of results and weak methods (lack of blinding, baseline differences); directness point deducted for selected population limiting generalisability (sepsis excluded so may be bias towards mild disease, complicated diverticulitis excluded, 40% with recurrent disease)
1 (623)	Recurrence	Medical treatment (mesalazine, antibiotics) versus placebo or no treatment	4	–1	0	–1	0	Low	Quality point deducted for lack of blinding; directness point deducted for selected population limiting generalisability (sepsis excluded so may be bias towards mild disease, complicated diverticulitis excluded, 40% with recurrent disease)

We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

Glossary

Acute diverticulitis

A condition that occurs when a diverticulum becomes acutely inflamed. There may be general symptoms and signs of infection (including fever and rapid heart rate) with or without local symptoms and signs (pain and localised tenderness, usually in the lower left abdomen, sometimes with a mass that can be felt on abdominal or rectal examination).

Diverticular disease

Association of diverticula with any symptoms. Symptoms commonly include abdominal pain and alteration in bowel habit. Diverticular disease may be complicated by abscess formation, fistulae, perforation, obstruction, or haemorrhage.

Diverticulosis

The presence of diverticula that are asymptomatic. Most people with sigmoid colonic diverticula have no symptoms.

Low-quality evidence

Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Very low-quality evidence

Any estimate of effect is very uncertain.

Disclaimer

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