Introduction: Chronic pancreatitis (CP) is characterised by pain, functional deficits, nutritional and mechanical complications. Frequently managed in out-patient settings, the clinical course is unpredictable and requires multi-disciplinary care. There remains substantial variation in management. In contrast to acute pancreatitis, there are no globally accepted classification or severity scores to predict the disease course or compare interventions. We conducted a systematic review to determine the scope and clinical use of existing scoring systems. Methods: A systematic search was developed with a medical librarian using the Embase, Medline and Cochrane databases. Original articles and conference abstracts describing an original or modified classification or scoring system in CP that stratified patients into clinical and/or severity categories were included. To assess clinical application/validation, studies using all or part of a score as a stratification tool to measure another parameter or outcome were selected. Studies reporting on diagnosis or aetiology only were excluded. Four authors performed the search in independent pairs and conflicts were resolved by a fifth author using CovidenceTM systematic review software. Results: Following screening 6,652 titles and 235 full-text reviews, 48 papers were analysed. Eleven described original scores and 6 described modifications of published scores. Many were comprehensive but limited in capturing the full spectrum of disease. In 31 studies, a score was used to categorise patients to compare or correlate various outcome measures. Exocrine and endocrine dysfunction and pain were included in 6, 5, and 4 scoring systems, respectively. No score included other nutrition parameters, such as bone health, malnutrition, or nutrient deficiency. Only one score has been objectively validated prospectively and independently for monitoring clinical progression and prognosis, but this had been applied to an in-patient population. Conclusion: Available systems and scores do not reflect recent advances and guidelines in CP and are not commonly used. A practical clinical classification and scoring system, validated prospectively for prognostication would be useful for the meaningful analysis in observational and interventional studies in CP.

Chronic pancreatitis (CP) is a heterogeneous, progressive inflammatory chronic disease. It is characterised by abdominal pain, irreversible pancreatic morphological changes, loss of exocrine and endocrine pancreatic function, nutritional and mechanical complications [1-5]. The overall incidence of CP in Europe is 5–10 per 100,000, and there are data to suggest that the incidence is increasing [6-8]. Whilst the majority of cases from western countries have been attributed to alcohol excess, it is now recognised to have a multifactorial aetiology [9]. The clinical manifestations demonstrate a wide spectrum of disease, and the clinical course and disease progression can be unpredictable. There have been significant developments in understanding the aetiology and substantial improvements in the diagnosis and treatment of this complex disease but there remains substantial variation in its management. In contrast to acute pancreatitis, there are no globally accepted or frequently used clinical classification or severity scoring systems for monitoring the clinical course or comparing interventions. Cambridge and Rosemont are widely known diagnostic classifications but are based on morphological changes only without clinical correlation, and the comprehensive TIGAR-O classification of aetiology does not stage the clinical manifestations [10-12].

Recently published evidence-based guidelines from the working group on “Harmonising diagnosis and treatment of CP across Europe” noted that there is no “preferred classification system for defining the aetiology of CP since the available classification systems need to be evaluated in randomised prospective trials” [6]. Contemporary clinical practice updates from North America also have not incorporated the use of clinical classification systems [13]. The Harmonising diagnosis and treatment of CP across Europe working group acknowledged that classification systems are of great importance for guiding the management of CP. Furthermore, treatment decisions should not be based solely on morphology, which is the limitation of the Cambridge system and various others using diagnostic imaging, but should incorporate clinical and functional complications of the disease. This is particularly important in areas with clinical equipoise such as selection of patients for surgery, choice of procedure, and timing of surgical interventions [14].

The aims of this systematic review were to (i) identify published clinical classification or severity scoring systems in CP, (ii) identify evidence of their use in clinical practice or research, and (iii) qualitatively assess if the studies reflected the full spectrum of disease incorporating aetiology and reflecting the modern understanding of disease complications across major categories of pain, functional loss (exocrine and endocrine), and pancreatic and extra-pancreatic mechanical complications.

Systematic Literature Search

A systematic search of the Embase, Medline and Cochrane databases for CP and “classification, scoring, prediction” systems was performed to include all articles from 1950 until May 5, 2018 (Appendix for MeSH terms). The search was restricted to studies in adult humans. In addition, major pancreatic meeting abstracts were reviewed for the years 2016 up to June 2018.

The studies selected based on the search strategy were uploaded into the online program CovidenceTM (Covidence systematic review software, Veritas Health Innovation, Melbourne, -Australia). Following title and abstract screening, full papers were retrieved to complete a full text review to determine the papers that were selected for analysis. When conference proceedings were available, the study was assessed if sufficient information was presented. If a score was reported more than once, the most recent publication was selected. Title screening and full text review were performed in duplicate by 2 pairs of authors and any conflicts were resolved by an independent 5th author. PRISMA guidelines for reporting were followed in systematic reviews.

Selection Criteria

Original articles or conference proceedings in English, which described any attempt to stratify patients with CP into a clinical and/or severity category, were included. To assess clinical application or validation, studies using all or part of a selected score as a stratification tool to measure another parameter or outcome were also included. Studies were excluded if (1) the scoring systems involved other conditions not specific to CP, (2) they stratified patients but did not categorise a clinical stage or correlate the scoring system to any other parameter (e.g., the classification had been used only for aetiology or diagnosis).

Search Results

The search yielded 6,652 titles. Following title and abstract screening, 235 full-text reviews were conducted and 48 papers were ultimately included in the systematic review (Fig. 1 for complete search results).

Fig. 1.

PRISMA flow diagram for search strategy used in the systematic review of chronic pancreatitis (CP) classification and scoring systems.

Fig. 1.

PRISMA flow diagram for search strategy used in the systematic review of chronic pancreatitis (CP) classification and scoring systems.

Close modal

Original Scoring Systems [10, 14-23]

Eleven studies described original scores that collected patient parameters to classify patients into severity groups or clinical stages (or to assign a score for severity). The studies included a minimum of 2 parameters (Table 1). Pancreatic morphology and peri-pancreatic complications (including biliary stricture, duodenal stenosis, and portal vein thrombosis) were the most commonly used feature (included in 7 of 11 papers). Exocrine and endocrine dysfunctions and pain were also commonly used and were included in 6, 5, and 4 scoring systems, respectively. Three systems included interventions as a parameter (Table 1). Aetiology was generally not correlated to clinical severity, but definitions of aetiology were classified in 4 studies. No systems included indices of nutritional status, such as malnutrition, nutrient deficiency or bone health.

Table 1.

Original clinical classification or severity scoring systems

Original clinical classification or severity scoring systems
Original clinical classification or severity scoring systems

Modified Scoring Systems [24-29]

The search yielded 6 studies, which applied substantial modification to an original CP scoring system (Table 2). The Cambridge classification was the most frequently adapted system despite not being originally designed as a clinical severity score. The most common modification involved the addition of other parameters to broaden the clinical scope of the system such as, including exocrine dysfunction or aetiological risk factors. These modified scoring systems were typically used to form comparator groupings within each study without specific proposals for further application.

Table 2.

Modified scoring systems

Modified scoring systems
Modified scoring systems

Validation Studies of Existing Scoring Systems [30-60]

An application or validation of an original scoring system was reported in 31 studies (Table 3). The Cambridge classification (either in its original form applied to endoscopic retrograde cholangiopancreatography or adapted for other imaging modalities such as computed tomography) featured in 16 papers. The M-ANNHEIM classification was partially applied in eleven studies. As the Cambridge classification was designed as a diagnostic tool without intent for scoring clinical severity, it did not fit our inclusion criteria as an original scoring system. However, many studies adopted the Cambridge classification. The most common application, both with the Cambridge score and overall, was the use of imaging to stratify patients into groups for comparison or correlation of a single functional measurement, for example, exocrine dysfunction. The degree of correlation reported between imaging findings and other clinical or functional parameters was highly variable.

Table 3.

Studies applying or validating scoring systems

Studies applying or validating scoring systems
Studies applying or validating scoring systems

The M-ANNHEIM classification has been applied to predict the clinical course and need for operative intervention. The majority of studies utilized only a single component of the M-ANNHEIM system instead of the full tool as was originally presented.

This systematic review identified various classification systems for CP, but there is limited evidence of their application in clinical practice or clinical studies. This is in contrast to the situation in acute pancreatitis where scoring systems such as Glasgow and Ranson are routinely applied in patient management as part of best practice and also as a covariate in clinical studies [61, 62]. Furthermore, in other chronic diseases that require medical and surgical interventions such as colitis, the Mayo score is frequently applied in therapeutic guidance or escalation of care [63]. To improve the clinical management of CP and to reflect the advances in understanding of genetic, aetiological, and functional characteristics of the disease, a classification system based on the key clinical aspects is desirable. Any severity score derived from such a classification should be simple to apply, objective, and accurate for observing progression of disease or comparing interventions.

The Cambridge classification established discrete categories of severity based on morphological changes. It has been adapted for computed tomography for wider application [10]. More recently, the Rosemont criteria has been described using EUS technology for diagnostic classification [11]. While they are important for diagnosis, there is limited correlation between morphology and clinical symptoms or functional deficits. Studies have indicated that patients with similar imaging findings can exhibit a wide variation of pain severity and patterns [64]. The TIGAR-O system includes all major aspects of aetiology, including genetic and auto-immune, but it does not describe clinical stages or severity [12]. Categorising patients by aetiology is clinically important and could be used to predict the clinical course of CP if incorporated into a system, for example, that included clinical complications.

The ABC, Manchester, and Heidelberg systems classify patients based on discrete clinical features into 3 severity stages. They are designed to be easy to use in clinical practice and reflected the advances in knowledge at the time of their development. The Manchester and ABC systems are similar and have been applied retrospectively to show some correlation with disease progression. The staging proposed by Büchler et al. [14] has been used to demonstrate which clinical stages and complications were most likely to have been associated with surgical intervention. These systems do not facilitate classification of the full spectrum of clinical presentation. Also they classify patients with exocrine insufficiency as severe or end-stage, and it has become apparent that exocrine dysfunction can occur much earlier in the course of CP than previously considered, in particular in patients in whom CP develops following acute severe AP [65, 66]. Furthermore, these systems do not account for the clinically important sequelae of mild or moderate pancreatic exocrine insufficiency, such as fat-soluble vitamin malabsorption and osteopathy [6].

The M-ANNHEIM system appears to be the most comprehensive tool available. It incorporates detailed diagnostic criteria, appropriately includes a multifactorial risk factor classification, and presents a severity score for grading of the clinical stage. Although expansive, the scoring system does not account for important sequelae of functional pancreatic insufficiency such as malnutrition, reduced bone mineral density, and type 3c diabetes [67, 68]. It has been applied retrospectively to demonstrate that patients with an earlier stage had a better outcome from endoscopic therapy for pain control [54]. The highly detailed format arguably limits application to routine clinical practice, and it has not been validated prospectively for use in predicting important clinical outcomes.

The most recently published score, CP Prognosis Score, has been prospectively validated to be able to predict important outcomes [23]. During the development of CP Prognosis Score, an array of biochemical and clinical parameters were analysed in patients with an unequivocal diagnosis of CP [23]. Bivariate correlations were determined and the resulting system accurately discriminated patients into stages of disease severity from low to high and predicted risk for hospitalisation and length of stay. The system was also validated in an independent external cohort. Although this scoring system was developed prospectively, it was applied almost exclusively to hospitalised patients. As -patients with CP are often managed in the outpatient clinic setting, the predictive value may therefore be most relevant to patients at the extreme end of the severity spectrum. It is certainly a useful prediction model and has parallels with the Child-Pugh score for decompensated liver disease, but it does not -incorporate a descriptive staging based on clinical characteristics.

The aforementioned scoring systems assist in the categorisation of CP patients, however, each having individual deficiencies. A comprehensive scoring system will allow for patients to be categorised according to disease severity, and therefore allow for appropriate treatment designations. In relation to pain, the patient’s score should reflect if the patient has required pain-specialist intervention or is refractory to medical therapy including opiates and other adjuncts such as nerve blocks. Studies have indicated that majority of the patients with CP will require surgery for the disease, however, surgery is not indicated in most centres until there is significant increase in pain [69, 70]. A scoring system which is clinically relevant should accurately stratify patients into disease severity and could be applied to randomised trials or prospective studies looking to answer areas of equipoise such as optimal surgery or timing of surgical interventions to limit disease progression and improve quality of life [71, 72].

To improve the clinical management of CP and reflect up to date advances in the understanding of aetiological and functional sequelae, a classification system based on the key clinical aspects such as pain, pancreatic functional status (exocrine and endocrine), and imaging modalities are desirable [6, 73]. An effective scoring system would be able to classify and characterise all presentations of CP complications across relevant categories of pain, function (including endocrine function, exocrine function, nutritional status, and bone health) and mechanical (including pancreatic and extra-pancreatic complications) while incorporating explicit aetiological and diagnostic classifications. Complementary to this would be an easy-to-calculate but accurate score, to determine disease severity in meaningful observational or interventional studies as well as to determine patient treatment plans in regular clinical practice.

We would like to thank Trinity College Dublin for providing the support necessary to make this research initiative a success.

The authors have no ethical conflicts to disclose.

The authors have no conflicts of interest to declare.

This study was supported by an unrestricted grant from the Meath Foundation, Tallaght University Hospital, Dublin 24, -Ireland.

A.R. and D.B.O.: participated in the conception and design of the study, analysis and interpretation of data, drafting the article, revised it critically for important intellectual content, and approved the final version of the article. Y.B.: participated in drafting the article, revised it critically for important intellectual content, and approved the final version of the article. F.G., S.K., and J.G.: participated in the analysis and interpretation of data, drafting the article, and approved the final version of the article. D.M. and R.M.: participated in the conception and design of the study, and approved the final version of the article. S.N.D.: participated in revising the article critically for important intellectual content, and approved the final version of the article. K.C.C.: was the supervising co-coordinator for the project and participated in revising the article critically for important intellectual content, and approved the final version of the article.

Search Strategy

1. “Chronic pancreatitis”/exp

2. ([Chronic] NEAR/2 pancreatitis):ti,ab

3. #1 OR #2

4. “Disease severity assessment”/exp OR “disease severity”/exp OR “scoring system”/exp OR “diagnosis”/exp OR “diagnostic approach route”/exp

5. (“Chronic pancreatitis” NEAR/5 [severity OR assess* OR Scale* OR score* OR scoring OR degree OR index OR assess* OR predict* OR diagnos* OR grading]):ti,ab

6. #4 OR #5

7. “Diagnostic accuracy”/exp OR “diagnostic value”/exp OR “predictive value”/exp OR “prediction”/exp OR “sensitivity and specificity”/exp

8. (Compar* OR evaluat* OR valid* OR reliab* OR accurac* OR value OR predict* OR sensitivity OR specificity):ti,ab

9. #7 OR #8

10. #3 AND #6 AND #

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A.R. and D.B.O.C. contributed equally to the manuscript.

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