The first endoscopy is of proven prognostic value for the future. How should the endoscopic severity be graded?
G.N.J. Tytgat (Amsterdam)
An adequate answer to the above question and statement will require consideration of various aspects of gastroesophageal reflux disease (GERD).
Role of initial endoscopy in the assessment of the natural history of GERD
The natural history of erosive reflux esophagitis is unclear and rather controversial. Some investigators feel that the degree of reflux induced mucosal damage unrelentingly progresses in time, from initial mild erosions to ultimate ulceration and stenosis, in the majority of the patients [1,2]. Others feel that the initial grade of severity (erosion, ulceration or stricture) determines, at large, the overall long-term severity of the disease. The esophagitis may improve or heal with or without medical or surgical therapy, but will usually not progress to a more severe grade of severity in the majority of the patients [3]. In real life, both pathways are presumably the most likely outcome. In 701 medically treated patients followed in Lausanne, 23% steadily progressed to more severe forms of esophagitis. In contrast, 31% relapsed to similar or milder degrees of mucosal damage, whereas the remaining 46% had no further episodes of esophagitis after the index episode had been healed [4]. It is unclear at
present which factors do influence the natural history of reflux esophagitis and the progressive or nonprogressive character of the disease.
The percentage of patients who develop complications, of ulceration or stricture after prior diagnosis of mild, moderate or severe erosive esophagitis, is small and amounts to 11-17% in the Lausanne study [4]. The majority of the patients with complications of ulceration or stricturing present "de novo", because usually no prior endoscopy has been performed despite the presence of occasionally long-standing typical symptoms.
Endoscopy as a predictor of treatment outcome
The presence and severity of esophagitis is the single best predictor of the lowest level of acid suppression which is needed for therapeutic success. There is a significant gradation of percentage esophageal acid exposure from GERD patients without esophageal mucosal damage to patients with severe confluent ulcerative esophagitis [5]. Therapeutic success is closely linked to correction of the esophageal acid exposure values, to within the normal range [6,7]. Many studies have shown that the endoscopic grade of severity is of decisive importance in predicting healing rates with antisecretory therapy, both with H2 receptor antagonists and proton pump inhibitors. The more severe the esophagitis, the greater and more prolonged is the acid suppressive effect needed to correct pathological esophageal acid exposure [8].
In healing therapy, severity of pretreatment esophagitis has been the most important determinant of success, regardless of the pharmaceutical principle used [9,10], The more severe the esophagitis, the lower the healing rate.
The endoscopic appearances in reflux disease also give guidance on the appropriate timing of acid suppression through the 24-h period. The contribution of nocturnal reflux to esophageal acid exposure is of minor importance in patients with mild erosive esophagitis or in the absence of mucosal damage [8,11,12]. In contrast, there is considerable nocturnal acid exposure in patients with severe erosive esophagitis or in patients with stricturing and columnar metaplasia [8]. Thus, the endoscopic grading gives an indication of the period of the 24-h cycle, during which acid suppression needs to be most effective.
Role of endoscopy in predicting future relapse
Studies on the natural history of GERD and reflux esophagitis are rare [4,13].
In general, the prevalence of reflux esophagitis ranges from 0.5-23% in the literature of patients referred for endoscopic examination [4]. The prevalence of GERD seems to be increasing [14,4]. There is a clear clinical impression that, in the majority of the patients with GERD, there is a chronically recurrent problem which is especially relentless in patients with more severe esophagitis [15].
The index endoscopy is important as an indicator of the degree of severity of mucosal damage, in case of future relapse. Moreover, the presence and severity of
endoscopic reflux esophagitis influences the relapse patterns, as patients who have more severe esophagitis appear to relapse earlier and in greater proportion after withdrawal of medical therapy [16,17], compared to patients with milder disease.
In patients with endoscopy negative reflux disease or only mild erosive esophagitis, it is usual for symptoms and macroscopic esophagitis to persist over periods of several years; although in a minority, symptoms and esophagitis may become intermittent [18]. In more severe esophagitis, there is substantial evidence of the unremitting nature of the reflux disease as spontaneous symptomatic and endoscopic remission is rare [9]. Moreover, medical therapy with limited/moderate acid suppression does not appear to prevent the formation of columnar metaplasia or dysplasia/cancer. Brossard et al. [19], in following 582 patients with recalcitrant esophagitis, noted that 93 of them went on to develop columnar metaplasia. McCallum et al. [20] have reported that almost 20% of patients with columnar metaplasia, initially free of dysplasia, developed dysplasia while on medical therapy and 1.3% developed malignancy.
Grading of reflux esophagitis
How reflux esophagitis should be graded is highly controversial. Over 100 grading systems have been presented in the literature [21]. The main problems encountered in evaluating the various grading schemes are summarized in Table 1.
To reconcile the various systems in a way which is useful to carry out clinical
Table 1. .Problems in endoscopic grading of esophagitis
* Very problematic is the large number of grading systems expressing lack of agreement on diagnostic criteria (>100 systems published).
* The main difference between the various grading systems is in the definition of grade I disease:
American systems accept erythema, color unevenness, fuzzy SCMJ and friability as
grade I.
European systems require the presence of erosions for grade 1 disease. Inclusion of equivocal abnormalities increases the sensitivity, but markedly compromises the specificity.
* The term "confluence" is poorly defined. Distinction between nonconfluent and confluent erosions is vague.
* Defining circumferential erosion/ulceration is often difficult (does 95% involvement correspond to Savary grade II or III?).
* Diagnosing "circumferential" requires detailed inspection of the total circumference at the SCMJ, which is often difficult due to angulation at the cardia.
* Spots or patches of columnar mucosa may mimic erosions; such columnar islands may become apparent as inflammatory changes resolve.
* The widely accepted Savary-Miller system is often misinterpreted. Lumping all complications in Savary grade IV is a major drawback.
* Endoscopic abnormalities are regularly seen which do not readily fit within the prevailing grading schemes.
* The indistinct boundaries between the grades of esophagitis make the categorical rating more or less arbitrary; reflux mediated damage occurs as a continuous biologic phenomenon.
Table 2. .Grading of reflux esophagitis
|
Grade 0. |
No evidence of reflux-induced damage - crisp, sharply delineated SCMJ. No evidence of friability - smooth and shiny squamous mucosa in the distal esophagus. |
||
|
Grade I. |
Mild, patchy or more diffuse erythema at the level of the SCMJ; slight blurring of the SCMJ; minor friability; loss of shininess of the distal squamous mucosa. Such abnormalities are equivocal and cannot be interpreted as genuinely characteristic for reflux induced damage. There is no apparent break in the mucosa. |
||
|
Grade II. |
One or more discrete superficial erosions, seen as red dots or streaks, with or without adherent whitish exudate. Such linear erosions are usually small and often on top of the esophageal folds. They involve less than 10% of the mucosal surface of less than the distal 5 cm of the squamous segment of the esophagus above the gastroesophageal junction. |
||
|
Grade HI. |
Confluent but noncircumferential erosions seen as defects that merge either longitudinally or laterally. There may be an additional exudate covering the erosive defects or slough formation. Less than 50% of the overall mucosal surface of the distal 5 cm is involved. |
||
|
Grade IV. |
Circumferential erosions or exudative lesions at the level of the SCMJ, regardless of the extent along the distal esophagus. |
||
|
Grade V. |
Deep ulceration anywhere along the esophagus. |
||
|
Grade VI. |
Various degrees of stricturing, prohibiting passage of a standard (>9 mm) or small caliber (<9 mm) endoscope. |
||
Note: Grades I-VI can be present with/without a segment of columnar metaplasia.
trials and which is simple enough in routine clinical practice, the grading system proposed in Table 2 is presented. In essence, it retains the option of equivocal changes which may occasionally be the end-stage after healing of erosive esophagitis. The grading of erosive damage is rather straightforward and subdivided as mild, moderate and severe. The complications of ulceration and stricture have a separate grading number. All those abnormalities of the squamous mucosa can be diagnosed in the presence or in the absence of a segment of columnar metaplasia. In Table 3, a comparison is given of the currently most prevailing grading systems, the Savary-Miller system [21], the Hetzel grading system [22] used in many trials with proton pump inhibitors and the grading system presented in Table 2.
Concluding remarks
The only way to solve the highly confusing area of grading reflux esophagitis is to create a working party of experts experienced in the field, who should come up with a generally acceptable grading system. This is not a matter of semantics alone. Grading the degree of damage is of importance in selecting the appropriate therapy, estimating the degree of risk and predicting the future outcome. Indeed, the severity of reflux esophagitis is important as an indicator of responsiveness to therapy. Moreover, endoscopic severity is the best and the most practical indicator of disease severity and therefore the best guide to long-term management. Objective grading of the endoscopic appearances is therefore of immense importance.
Although GERD is basically a motor disorder, the symptoms and the degree of esophageal mucosa damage are primarily determined by the duration of esophageal
Table 3. .Comparison of commonly used grading schemes
|
|
Savary |
Hetzel |
Tytgat |
||
|
Normal |
grade 0 |
grade 0 |
grade 0 |
||
|
Equivocal changes |
|
grade I |
grade I |
||
|
Mild: nonconfluent erosions; <10% |
grade I |
grade II |
grade II |
||
|
Moderate: confluent erosions; 10-50% |
grade II |
grade III |
grade III |
||
|
Severe: circumferent erosions; >50% |
grade III |
grade IV |
grade IV |
||
|
Ulceration |
|
|
grade V |
||
|
Stricture |
|
|
grade VI |
||
mucosal exposure to gastric acid and pepsin. It is now evident that the more severe the esophageal acid exposure and the more severe the esophagitis, the greater the level of acid suppression required for normalization of esophageal acid exposure values and for healing of esophagitis, if the motor abnormality cannot be corrected. The alternative approach is to attempt to improve the disordered motor pattern thereby decreasing the esophageal acid exposure.
References
1. Palmer ED. The hiatus hernia-oesophagitis-esophageal stricture complex. Am J Med 1968;44:566-579.