Pattern of presentation of gastroesophageal reflux disease among patients with dyspepsia in Kano, Nigeria.

BACKGROUND: Dyspepsia is a symptom complex rather than a specific disease entity. It can be caused by both organic and functional gastrointestinal (GI) disorders. Gastroesophageal reflux disease (GORD) though a common digestive disorder worldwide is scarcely reported in Nigeria. The aim of this study is to determine the pattern of presentation of GORD among patients with dyspepsia.
METHODS: One hundred and seventy dyspeptic patients were recruited consecutively as they were referred to the Gastroenterology Unit of Aminu Kano Teaching Hospital for upper GI endoscopy. A prepared questionnaire on relevant demographic and clinical history relating to GORD was administered. Upper GI endoscopy was then performed on each patient.
RESULTS: The prevalence of GORD was 24.1%, with a M:F ratio of 1:1.1. Endoscopy-positive variant accounted for 16 cases (9.4%), while endoscopy-negative variant accounted for 25 cases (14.7%), with of the total GORD patients, 26(63.4%) were males while 15(36.6%) were females. Los Angeles Grade A (37.5%) was the predominant endoscopic esophageal mucosal injury found in 6 cases. Barrett's esophagus and esophageal adenocarcinoma accounted 4.9% each and were considered to be rare. Extra-esophageal manifestations were also rare.
CONCLUSIONS: Endoscopy-negative variant still remains the predominant endoscopic finding in GORD patients.

INTRODUCTION

Dyspepsia is defined as the presence of chronic/recurrent symptoms centered in the upper abdomen.[1] It is a very common complaint among patients in both general and gastroenterology practice in Nigeria. Its prevalence ranges between 26% in the United States and 40% in England.[2]

Functional dyspepsia and gastroesophageal reflux disease (GORD) now account for a majority of upper gastrointestinal (GI) symptoms in Western societies.[34] However, robust clinical definitions for dyspepsia remain evasive, and this term and its various qualifiers have been interpreted differently by both physicians and patients alike for years.

GORD is a clinical manifestation of excessive reflux of gastric contents into the esophagus, causing various degrees of symptomatic irritation to the esophageal mucosa. Typical symptoms of GORD include heartburn, regurgitation, and dysphagia. Atypical manifestations include laryngo-pharyngeal (chronic sore throat, pharyngitis, laryngitis, globus sensation), pulmonary (chronic cough or asthma), or cardiac (noncardiac chest pain) symptoms.

GORD is a very common disorder. Based on hospitalization and death rates, the prevalence of GORD has increased while that of peptic ulcer disease has been decreasing.[5] The pathophysiology of GORD is complex and results from an imbalance between defensive factors protecting the esophagus (anti-reflux barriers, esophageal acid clearance, tissue resistance), and aggressive factors from the stomach contents (gastric acidity and volume and duodenal contents).

There is no gold standard investigation for the diagnosis of GORD; however, upper GI endoscopy allows direct visualization of the esophageal mucosa. The sensitivity of endoscopy for GORD is 60% as compared to 24-h pH monitoring, but it has excellent specificity at 90%–95%.[6] Endoscopy allows for grading of the severity of the disease. Other modes of investigation with higher sensitivity such as 24-h pH monitoring, esophageal manometry, and impedance studies are not readily available in Nigeria.

A limited number of hospital-based studies have been reported on GORD and its complications in African countries, but there are few population-based studies describing the prevalence of GORD. A study among 105 Sudanese patients with symptoms of heartburn showed erosive esophagitis in 45% and Barrett's esophagus in 10.6% of the patients.[7] In a recent study from Johannesburg, South Africa, of the 216 consecutive Barrett's patients, only 5% were negroes despite the ratio of blacks to caucasians in the city being 5:1.[8] The data indicate that Barrett's esophagus is rare in sub-Saharan African countries (South Africa, Ethiopia, Nigeria, Kenya, Zimbabwe, and Uganda).

GORD though a common digestive disorder worldwide is scarcely reported in Nigeria. A search of the literature also revealed a dearth of information on this condition and its complications among Black Africans. The rising prevalence of GORD in Western population and the growing population of patients presenting with dyspepsia to our health facility are challenges that call for us to establish the pattern of presentation of the disease.

METHODS

This study was carried out at Aminu Kano Teaching Hospital (AKTH), Kano, Nigeria. Approval to conduct the study was obtained from the Ethics and Research committee of AKTH. One hundred and seventy consecutive adult patients (>18 years) referred to the Endoscopy Unit of AKTH for upper GI endoscopy with dyspeptic symptoms were recruited, but those with previous endoscopic diagnosis were excluded from the study. Each consenting patient was administered a structured questionnaire on relevant demographic, clinical, social, and drug history associated with dyspepsia. Height and weight were measured, and body mass index was calculated (weight [kg]/height [m2]). Drugs such as antacids, histamine-2-receptor antagonists (H2 RAs), proton pump inhibitors (PPIs), prokinetic agents, and herbal medications used a month before endoscopy were recorded.

Following 8 h of fasting, each patient had upper GI endoscopy performed using a forward-viewing fiber-optic Olympus GIF-Q40 gastroscope and the endoscopic findings were recorded. GORD was defined as symptoms of heartburn and/or regurgitation lasting longer than 6 months with or without positive endoscopic finding. Those with endoscopy findings of esophageal erosion, Barrett's esophagus, esophageal peptic stricture, ulcer, or adenocarcinoma on endoscopy were classified as endoscopy-positive GORD patients, while those with symptoms of heartburn or regurgitation but with normal esophageal mucosa were classified as endoscopy-negative GORD cases. The Los Angeles Classification of oesophagitis was used to grade reflux findings at endoscopy. Data were analyzed using computer-based Statistical Packages for Social Sciences version 20.0 (IBM SPSS Statistics) Amonk, NY, IBM Corp. USA. Quantitative variables were summarized using range, mean, and standard deviation while qualitative variables were summarized using ratios, proportions, and percentages.

RESULTS

Of the 170 dyspeptic patients studied, 41 (24.1%) were found to have GORD, of which 26 (63.4%) were males while 15 (36.4%) were females with a M: F ratio of 1.1:1. The ages of the patients ranged from 18 to 60 years, with a mean of 36.5 ± 11.2 years. The age range of 40–49 years had the highest frequency with 14 cases (34.1%) [Table 1].

Table 1

Age and sex distribution of study patients with gastro-esophageal reflux disease

Age group (years)	Male (%)	Female (%)	Total (%)
10-19	1 (2.4)	1 (2.4)	2 (4.8)
20-29	7 (17.1)	5 (12.2)	12 (29.3)
30-39	2 (4.9)	6 (14.6)	8 (19.5)
40-49	13 (31.7)	1 (2.4)	14 (34.1)
50-59	3 (7.3)	1 (2.4)	4 (9.8)
>60	0 (0)	1 (2.4)	1 (2.4)
Total	26 (63.4)	15 (36.6)	41 (100)

There was no significant difference in gender distribution of the study patients.

There was no statistically significant difference in symptoms of heartburn (χ2 = 0.64, df = 3, P = 0.43) and regurgitation (χ2 = 0.02, df = 3, P = 0.90) between males and females [Table 2]. In addition, asthma was observed in two patients (1.2%), a female and a male aged 29 and 58 years, respectively. Both had heartburn and regurgitation and accounted for 4.9% of patients with GORD. They both also had erosive esophagitis (12.5%). The female patient has been having asthmatic symptoms since childhood and has a family history of asthma. The male patient had symptoms dating back to 4 years.

Table 2

Gender distribution of symptoms of gastro-esophageal reflux disease among study patients

Symptoms	Heartburn		Regurgitation
	Yes	No	Yes	No
Male, n (%)	19 (11.2)	69 (40.6)	33 (19.4)	55 (32.3)
Female, n (%)	22 (12.9)	60 (35.3)	30 (17.7)	52 (30.6)
Total	41 (24.1)	129 (75.9)	63 (37.1)	107 (62.9)
	χ2=0.64, df=3, P=0.43		χ2=0.02, df=3, P=0.90

Twenty-five (61%) patients with the symptoms of GORD had normal endoscopic findings and were classified as having nonerosive reflux disease (NERD), with a female predominance, i.e., 15 patients (60%) [Table 3].

Table 3

Endoscopic distribution of gastro-esophageal reflux disease among study patients

Endoscopic finding	Male (%)	Female (%)	Total (%)
Endoscopy-positive patients	9 (22.0)	7 (17.0)	16 (39.0)
Endoscopy-negative patients	10 (24.4)	15 (36.6)	25 (61.0)
Total	19 (46.4)	22 (53.6)	41 (100)

Endoscopy-positive patients=Endoscopic findings of esophageal erosion, Barrett’s esophagus, esophageal peptic stricture, or adenocarcinoma with symptoms of heartburn or regurgitation. Endoscopy-negative patients=Those with symptoms of heartburn or regurgitation but with normal esophageal mucosa

Los Angeles Grade A in 6 cases (37.5%) was the predominant endoscopy-positive finding [Table 4].

Table 4

Los Angeles Classification of Erosive Esophagitis (endoscopy positive) in study patients

Grade	Male (%)	Female (%)	Total (%)
A	3 (18.8)	3 (18.8)	6 (37.5)
B	3 (18.8)	3 (18.8)	4 (25)
C	1 (6.3)	1 (6.3)	2 (12.5)
D	2 (12.5)	2 (12.5)	4 (25)
Total	9 (56.3)	7 (43.9)	16 (100)

A=One or more mucosal breaks no longer than 5 mm, none of which extend between the tops of the mucosal folds; B=One or more mucosal breaks more than 5 mm long, none of which extend between the tops of two mucosal folds; C=Mucosal breaks that extend between the tops of two or more mucosal folds but which involve <75% of the esophageal circumference; D=Mucosal breaks which involve at least 75% of the esophageal circumference

In addition, Barrett's esophagus was observed in two (4.9%) patients with GORD (Los Angeles Grade C and D), with a mean age of 58 years. Two (4.9%) GORD patients had esophageal adenocarcinoma and both were classified as Los Angeles Grade C and D. The mean age of patients with adenocarcinoma was 65 years.

DISCUSSION

GORD is a chronic disorder that is associated with a huge economic burden in the Western countries and significantly decreased quality of life with typical symptoms. It has been suggested that there is an increasing trend in the prevalence over the last two decades.[9] Traditionally, GORD has been viewed as a disease of the Western world and thought to be uncommon in Africans. In Asia, the prevalence was <5%.[10] A study showed a prevalence of 26.34% among Nigerian medical students,[11] suggesting that GORD is a disease with a rising prevalence even in Blacks. The prevalence of GORD in this study was 24.1% among dyspeptic patients referred for upper GI endoscopy. This study further suggests that GORD is actually common and not rare in Blacks as was previously thought. All the GORD patients presented with the typical presentation of heartburn and regurgitation. Although several studies have suggested that the prevalence of GORD increases with increasing age,[12] this has not been confirmed in most cross-sectional studies[13] as was also found in this study.

Although the association between GORD and asthma has been well accepted,[1415] whether GORD plays a causative role in asthma has been controversial. In this study, two (4.9%) patients were found to have asthmatic symptoms. The younger patient (29-year-old female) had symptoms dating back to childhood, with a well-documented family history of asthma and atopy. The second patient (58-year-old male) had reflux symptoms dating back to 4 years, with endoscopic finding of erosive esophagitis. It may well be that GORD symptoms predisposed the patient to asthma-like symptoms either by micro-aspiration of gastric refluxate into the lung parenchyma or by vagally mediated esophago-bronchial reflex mechanisms. Cough may be the sole manifestation of GORD, with many patients denying heartburn and/or regurgitation. In this study, no patient was found to have chronic cough, nausea, or noncardiac chest pain. Though these manifestations are relatively uncommon in GORD[16] patients, extra-esophageal manifestations are likely to end up in other specialty clinics except for a high index of suspicion by the attending physician. In clinical practice, endoscopic esophagitis is seen in <50% of patients with typical GORD symptoms.[5] Esophageal erosions, therefore, represent the most common consequence or esophageal injury rather than the principal manifestation of GORD. Endoscopy-positive GORD (characterized by erosive esophagitis, Barrett's esophagus, or esophageal adenocarcinoma) accounted for 16 (9.4%) while endoscopy-negative, i.e., NERD (normal endoscopic finding) accounted for 25 (14.7%) dyspeptic patients. However, 16 (39%) GORD patients were endoscopy positive while 25 (61%) accounted for endoscopy-negative GORD with Los Angeles Grade A being the predominant finding in 6 cases (37.5%). In a similar study in Nigeria, 25.6% of patients presented with varying degrees of esophagitis in patients with GORD, with Los Angeles Grade A being the predominant endoscopic finding.[17] In a study among patients with dyspepsia referred for upper GI endoscopy in Egypt, 24% had endoscopically confirmed esophagitis.[18] There is no correlation between the severity of GORD symptoms and the presence of esophagitis. The severity of heartburn and regurgitation does not differ between patients with normal mucosa and varying degrees of esophagitis. There are studies in the literature reporting that over 50% of patients presenting with reflux symptoms in primary care settings have negative endoscopy,[19] with even a more recent European study showing a rate as high as 75%.[20] This study showed a similar pattern of presentation despite the lack of application of 24 h pH monitoring. Los Angeles Grade A represented the highest frequency of endoscopy-positive patients. Some of these patients may have been falsely labeled as endoscopy negative as majority of the patients were likely to have been treated for their symptoms in primary or secondary health-care settings. Esophageal mucosal breaks are likely to heal by previous use of PPIs or H2 RAs, although there is evidence that in most patients symptoms will persist despite treatment.[21] PPIs or H2 RAs are over-the-counter medications and are easily accessible in Nigeria. What has remained incontrovertible is the observation that Barrett's esophagus occurs commonly in men, and is uncommon in persons of African descent in North America[22] and Africa,[23] resulting in an equally low prevalence of adenocarcinoma of the lower esophagus. Barrett's esophagus and esophageal adenocarcinoma continue to be rare in Blacks and Africans. A limited number of studies have elucidated ethnic differences in GORD in multi-racial populations. Whether the pathophysiology of GORD differs among different populations remains to be answered satisfactorily. These differences could be artifactual (differences in definitions, referral patterns, diagnostic practices, etc.) or rather due to environmental and genetic factors.

Limitations of the study

Twenty 4-h pH monitoring and impedance studies could not be undertaken in this study which were the limitations of this study.

CONCLUSIONS

The present study indicated that GORD may not be rare as was previously thought and serves as a common clinical presentation for referrals for upper GI endoscopy. Extra-esophageal manifestations and complications of GORD, i.e., Barrett's esophagus and esophageal adenocarcinoma, are still relatively uncommon. There is a need for population-based studies involving larger sample sizes in the various geo-political zones of the country to establish the true prevalence rate and pattern of presentation of GORD since endoscopic facilities are beginning to be readily available in Nigeria. Un-investigated dyspepsia that may have an organic cause needs to be clearly differentiated from functional dyspepsia as GORD can present with either a normal or pathologic mucosa.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.