REVIEW ARTICLE

Classications of esophagitis: Who needs them?

Devjit S. Nayar, MD, Michael F. Vaezi, MD, PhD
Cleveland, Ohio

GERD is a common condition, one that aficts a substantial proportion of the American population. It is estimated that 40% to 45% of Americans have symptoms of GERD each month. The diagnosis of GERD often is established on the basis of symptoms of heartburn and regurgitation. EGD is an important modality for assessing esophageal damage caused by GERD; however, the assessment of the degree of esophageal injury (i.e., esophagitis) observed at EGD is often subjective. To make this assessment more objective, multiple classication schemes for esophagitis have been proposed (Table 1).1-8 An important goal behind the effort to establish an endoscopic classication of esophagitis is an objective gradation of disease severity that can serve as a benchmark when comparing studies of esophagitis. However, given the multiple schemes currently available and the varied utility of these classications, this effort has lead to more confusion than clarity. Furthermore, because GERD often is treated empirically, based on presenting symptoms, the value of any grading scheme appears academic at best. Given this confusion, it is timely to review the various classications for grading esophagitis. From the early part of the twentieth century, esophagoscopy was dominated by specialists who dealt with diseases of the ears, nose, and throat (ENT). Savary was professor and chairman of the Department of Otorhinolaryngology at the University of Lausanne Medical School, Switzerland, when his seminal work, The Esophagus: Handbook and Atlas of Endoscopy, was published.1 Initially, the rigid endoscope was the only technology available for esophagoscopy and ENT specialists were procient in using this instrument to examine the esophagus.
Current afliation: Department of Gastroenterology and Hepatology, Center for Swallowing and Esophageal Disorders, Cleveland Clinic Foundation, Cleveland, Ohio. Reprint requests: Michael F. Vaezi, MD, PhD, FACG, Department of Gastroenterology and Hepatology, Center for Swallowing and Esophageal Disorders, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195. Copyright 2004 by the American Society for Gastrointestinal Endoscopy 0016-5107/$30.00 PII: S0016-5107(04)01555-X VOLUME 60, NO. 2, 2004

By 1969, with the arrival of the beroptic endoscope, the gastroenterologist became even more closely involved in the evaluation of esophageal pathophysiology. In 1977, Savary and Miller (an academic gastroenterologist in Switzerland) collaborated in the creation of the Savary-Miller classication of esophagitis, which includes 4 grades of reux esophagitis (Table 2). Mild, and presumably early, esophagitis was graded 1 or 2, based on the presence of erosive lesions and their relationship to mucosal folds. Grade 3 included circumferential erosive lesions; grade 4 was reserved for chronic lesions: ulcer, stricture, columnar epithelium, and short esophagus. This classication was among the rst to describe the effects of gastroesophageal reux on the esophagus and was generally accepted through the 1980s. However, debate over the inclusion of complications of GERD, especially Barretts esophagus within grade 4, lead to the modied SavaryMiller classication (Table 2). The main distinction of this new classication was that the complication of columnar epithelium was transferred from grade 4 to a new grade 5.2 The Savary-Miller classication is still one of the most commonly used classication systems and is more popular in Europe than the United States. Hetzel et al.3 published the results of a study of the healing and relapse of reux esophagitis in response to treatment with omeprazole in 1988. Their classication of esophagitis (Hetzel-Dent) differed from the Savary-Miller classication in that it included mucosal changes such as erythema, friability, and hyperemia as grade 1 (Table 3). Unlike the Savary-Miller classication, the HetzelDent system graded the degree of injury, not by the number of lesions but by the surface area of injury, especially within the distal 5 cm of the esophageal squamous mucosa. A major criticism of this classication has been the subjective nature of grade 1 lesions and the inability of endoscopists to accurately and consistently label a mucosal lesion as red or friable. Given this subjectivity, interobserver reproducibility often is poor with the HetzelDent classication, especially for the lower grades of esophagitis.4 After its introduction, the Hetzel-Dent classication was commonly used in the United States and Australia. However, its use decreased markedly after introduction of the modied Los Angeles classication in 1999. Armstrong et al.5 proposed a new classication system for practicing clinicians and researchers in 1991. They criticized the prior classication schemes for using subtle mucosal changes as diagnostic criteria and because improvement in endoscopic grade was not associated with a corresponding
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Classications of esophagitis: who needs them?

Table 1. Classications of esophagitis

Year 1977 Classication system Savary-Miller and Modied Savary-Miller (1989)
d

Strengths Contains: Degree of esophagitis Presence of stricture Presence of Barretts Radial extent is examined in more detail
d

Weaknesses Requires assessment of erosions and ulcers (depth of injury) Based on number of erosions Uses erythema and other minimal changes that are highly subjective ndings Must assess depth injury Limited to last 5 cm Few comparative studies Requires assessment of: Erosions and ulcers (depth of injury) Difcult to differentiate stricture from stenosis Lengthy Few comparative studies Does not incorporate presence/absence of Barretts Must assess length of mucosal break

1988

Hetzel-Dent

d d d

1991

MUSE

Contains: Degree of esophagitis Degree of stricture Degree of Barretts

d d

1996

Los Angeles and Modied Los Angeles (1999)

d d

Uses term mucosal break (no need to assess depth) More accurate assessment of radial extent Physiologically correlated Good comparative agreement studies

Table 2. Original (grades 1-4) and modied (grades 1-5) Savary-Miller classication
Grade 1 2 Lesion Single or isolated erosive lesion(s), oval or linear, but affecting only one longitudinal fold Multiple erosive lesions, non-circumferential, affecting more than one longitudinal fold, with or without conuence Circumferential erosive lesions Chronic lesions: ulcer(s), stricture(s) and/or short esophagus. Alone or associated with lesions of grades 1 to 3 Columnar epithelium in continuity with the Z line, non-circular, star-shaped, or circumferential. Alone or associated with lesions of grades 1 to 4 *Grade 5 was included in the original grade 4 classication.

Table 3. The Hetzel-Dent classication

Grade 0 1 2 Lesion No mucosal abnormalities No macroscopic erosions but erythema, hyperemia, or mucosal friability Supercial erosions involving <10% of the mucosal surface of the last 5 cm of esophageal squamous mucosa Supercial erosions or ulceration involving 10%-50% of the mucosal surface of last 5 cm of esophageal squamous mucosa Deep peptic ulceration anywhere in the esophagus or conuent erosion of >50% of the mucosal surface of the last 5 cm esophageal squamous mucosa

3 4

5*

improvement in symptoms. Their new system became known as the MUSE classication because it assessed the presence of columnar Metaplasia, mucosal Ulceration, Stricture formation, and Erosion(s) (Table 4). The severity of each type of lesion was subclassied by using 4 levels (0 = absent, 1 = mild, 2 = moderate, 3 = severe). The aim of Armstrong et al.5 was to create a classication for GERD that could be used in research and in clinical practice. However, because it is cumbersome, the MUSE classication has never been widely used. A more practical esophagitis classication system was introduced in 1996 at the meeting of the World Organization of Gastroenterology in Los Angeles.
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Called the Los Angeles (LA) classication, it used a grading scale from A through D (Table 5; Fig. 1).6 The goal of this classication was to reduce interpreter variability in the assessment of esophageal injury according to depth. Instead, the LA classication focuses on number, length, and location of mucosal breaks to determine the grade of esophageal injury. In the original study, good interobserver agreement was found for grades A and D, while that for grades B and C was poor. Thus, the LA classication was modied in 1999 by redening grade C as injury involving less than 75% of the circumference of the esophagus (Table 5).7 With this change, interobserver agreement for grades B and C improved. A review of major publications since 1980 (Table 6) shows that the Savary-Miller and the LA classiVOLUME 60, NO. 2, 2004

Classications of esophagitis: who needs them?

D Nayar, M Vaezi

Figure 1. Illustration depicting various grades of esophagitis according to the modied Los Angeles classication (1999).

Table 4. The MUSE classication

Grade* Metaplasia M1 M2 Ulcer U1 U2 Stricture S1 S2 Erosion E1 E2 Lesion Fingers +/ islands Circumferential 1 discrete ulcer $2 discrete conuent ulcers >9 mm (standard endoscope passes) #9 mm (standard endoscope does not pass) Only on peaks of folds Conuent: on and between folds

Table 5. The modied Los Angeles classication

Grade A B C Lesion One (or more) mucosal break on longer than 5 mm that does not extend between the tops of two mucosal folds One (or more) mucosal break more than 5-mm long that does not extent between the tops of two mucosal folds One (or more) mucosal break that is continuous between the tops of two or more mucosal folds but that involves less than 75% of the circumference One (or more) mucosal break that involves at least 75% of the esophageal circumference

*The degree was subscripted 0, absent; 1, mild; 2, moderate; and 3, severe, and later modied as above.

cations are currently the most popular systems in use.7-33 There appears to be a geographic variation with respect to the use of these two classications. Before 1999, 8 of 12 (67%) studies, predominantly from Europe, used the Savary-Miller classication. After its introduction, the LA scheme was used in 13 of 19 (68%) studies. In Japan and in the United States, the LA classication appears to predominate (Table 6). The ideal endoscopic grading system for esophagitis must be accurate and reproducible, as well as easy to remember and interpret. There are few comparative studies of the LA and Savary-Miller classications. However, it appears that the LA classication may have two advantages. First, observer agreement is good across the various grades of esophagitis.
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In one study, 325 endoscopic photographs were randomly graded twice by 9 endoscopists.8 The intraobserver and the interobserver agreements were good (k = 0.545 and k = 0.556, respectively). Moreover, these agreements were independent of the level of reviewer expertise.6-8 The Savary-Miller classication does not perform as well when used by less experienced interpreters or for lower grades of esophagitis.4 In contrast, the reproducibility for grade A in the LA classication is acceptable (k = 0.65).7 Second, the LA classication may be the only classication in which grades of esophagitis correlate directly with the severity of esophageal acid exposure.7 Esophageal acid exposure was found to increase signicantly (p < 0.01) in a stepwise fashion across the LA esophagitis grading scale (percentage of time pH < 4: grade A, 9.3%; grade D, 19.1%).7 In addition, there was a graded healing response to acid
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Classications of esophagitis: who needs them?

Table 6. Studies with endoscopic grade of esophagitis From 1980 to 2004

Investigator Okamoto et al. Shibuya et al.10 Inamori et al.11 Defreitas et al.12 Pandolno et al.8 Manabe et al.13 Dupas et al.14 Adachi et al.15 Sugiura et al.16 Lukas et al.17 Ishikawa et al.18 Deprez et al.19 Lundell et al.7 Fujimoto et al.20* Furukawa et al.21* and Soga et al.22 Kusano et al.23 Vcev et al.24 Watson et al.25 Armstrong et al.6 Csendes et al.26 Omura et al.27 Koop et al.28 Bytzer et al.4 Sciume et al.29 Mitov et al.30 Hetzel et al.3 Tytgat 31 Simon et al.32 Siewert et al.33
9

Publication year 2003 2003 2003 2002 2002 2002 2001 2001 2001 2000 2000 1999 1999 2003 1999 1999 1999 1999 1997 1996 1996 1995 1995 1993 1989 1989 1988 1987 1987 1986

Country Japan Japan Japan Brazil USA Japan France Japan Japan Czech Japan Belgium Worldwide Japan Japan Japan Croatia Australia Worldwide Chile Japan Germany Denmark Italy Bulgaria Australia Netherlands Germany Germany

Study type Cross sectional Retrospective cohort Cross sectional Prospective cohort Agreement Prospective cohort RCT Cross sectional Prospective cohort Retrospective cohort Prospective cohort Prospective cohort Prospective comparative Cross sectional RCT Prospective comparative RCT Prospective cohort Prospective comparative Cross sectional Prospective cohort RCT Prospective comparative Retrospective cohort Retrospective cohort RCT RCT RCT Prospective cohort

No. patients 1199 53 392 89 325 105 461 57 76 65 22 19 22 901 71 20 120 231 143 430 15 249 150 121 436 132 42 49 323

Classication system Los Angeles Los Angeles Los Angeles Savary-Miller Los Angeles and Hetzel-Dent Los Angeles Savary-Miller Los Angeles Los Angeles Savary-Miller Los Angeles Savary-Miller Los Angeles Los Angeles Los Angeles Los Angeles Savary-Miller Savary-Miller Los Angeles Savary-Miller AFP Savary-Miller Savary-Miller modied Savary-Miller Pluoke Hetzel-Dent Savary-Miller Savary-Miller Savary-Miller

RCT, Randomized controlled trial; AFP, anatomic-functional-pathologic classication. *Two studies different outcome measures from one patient population.

suppression: after 4 weeks of treatment with omeprazole (10 mg daily), complete healing was achieved in 77% of patients with grade A esophagitis, 50% of those with grade B, and only 20% of patients with grade C esophagitis. A classication of esophagitis is essential in clinical research and for trials of pharmacotherapy, because classication imposes consistency and provides an objective evaluation of response to therapy. For these purposes, the LA classication may be the most appropriate candidate. However, grading systems for esophagitis may have limited relevance in clinical practice. The majority of patients with GERD currently are treated empirically, without prior endoscopic evaluation. Although studies have shown that patients with advanced grades of esophagitis require chronic acid suppression, this level of severity often can be determined clinically based on symptom relapse when treatment is tapered.7 For practical purposes, classication of endoscopic ndings as normal, erosive or ulcerative esophagitis, and Barretts esophagus appears to be
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reproducible and easy to communicate. In addition, because endoscopic photodocumentation has become routine, a picture is worth a thousand words.
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