Article Text
Summary
Gross and histopathological examination of a resected segment of ileum in a 72-year-old man with the preoperative diagnosis of small intestinal perforation peritonitis revealed the first-ever diagnosed case of Crohn Disease (CD) at the B P Koirala Institute of Health Sciences, Dharan, Nepal. In view of the recent reports on rising incidence of CD in neighbouring Asian countries, it was decided to perform an exhaustive literature search to find out the documented prevalence of CD in Nepal. It was surprising to find only a single case of CD from Nepal, occurring in the year 1980, to be documented in English literature. Further, the index case of CD presenting with acute abdomen is of interest since only about 100 cases of CD with small intestinal perforation have been so far reported worldwide.
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BACKGROUND
The first case of regional ileitis or Crohn Disease (CD) was reported in 1932 in the USA.1 Although traditionally it has been held that the incidence of CD is lower in Asian countries as compared with the West, a rising incidence of CD is being increasingly reported from most Asian countries, including India, China, Japan, Hong Kong and Taiwan.2–4 In this perspective, we made an attempt to find out the prevalence of CD in Nepal as documented in the existing literature. The immediate stimulus for such a quest was a recent encounter with the first-ever diagnosed case of CD at the B P Koirala Institute of Health Sciences, Dharan, Nepal. We decided to write up this case in order to (1) document the occurrence of an additional case of CD in Nepal, 27 years after the documented first case occurring in the year 1980, and (2) to report that CD can rarely present with symptoms of ileal perforation.
CASE PRESENTATION
A 72-year-old man was admitted to the emergency medicine ward with the complaint of acute abdominal pain and an episode of vomiting. History revealed complaint of intermittent bloody diarrhoea for the last 3 months. There was no significant past medical history. On examination, there was generalised abdominal tenderness. x Ray of the abdomen revealed pneumoperitoneum. A preoperative diagnosis of “small bowel perforation peritonitis, unknown cause” was made and the patient underwent an exploratory laparotomy. The unhealthy segment of the terminal ileum, approximately 6 cm proximal to the ileocaecal valve, was resected and sent for detailed pathological examination.
PATHOLOGICAL EXAMINATION
A resected segment of ileum measuring 26.5 cm in length was received. On gross examination, a single stricture was identified 4 cm away from one of the resected ends. The mucosal aspect showed segmental areas of ulceration with intervening normal appearing mucosa (“skip areas”) (fig 1). There was thickening of the involved bowel wall and mesentery. Although a site of perforation could not be clearly identified, features of acute serositis were present. Microscopical examination from the ulcerated segment revealed transmural chronic inflammation (fig 2) along with presence of fissures. The fissures were arranged perpendicular to the mucosa extending deeply into the oedematous submucosa and muscularis externa (fig 3). Lymphoid aggregates (fig 4) and submucosal fibrosis were also seen at the site of stricture. There were submucosal oedema and acute serositis in the non-ulcerated segment (fig 5). However, caseating and/or non-caseating granulomas were not identified in any of the extensively sampled tissue sections. Stain for acid-fast bacillus, performed on tissue sections from ulcerated and strictured ileal segment, proved to be negative. In the light of the above-mentioned gross and histological findings, a diagnosis of Crohn ileitis was entertained.
Gross specimen of the resected segment of ileum showing a site of stricture along with sharply delineated segmental areas of ulceration with intervening normal appearing mucosa (“skip areas”).
(A) Photomicrograph showing transmural chronic inflammation (×2); note the presence of lymphoid aggregates (arrows). (B) Photomicrograph showing transmural chronic inflammation (×10).
(A) Photomicrograph of fissure extending from the mucosa and burrowing through muscularis propria (×2). (B) Photomicrograph of fissure extending from the mucosa and burrowing through muscularis propria (×10).
Photomicrograph showing lymphoid aggregates (×20).
Photomicrograph showing acute serositis (×20).
INVESTIGATIONS
x Ray of abdomen in erect posture revealed presence of pneumoperitoneum. Routine pre-operative chest x ray did not reveal any abnormality.
DIFFERENTIAL DIAGNOSIS
The most important differential diagnosis taken into consideration was tuberculosis. However histological features did not support this diagnosis, despite extensive sampling of tissue from the specimen.
TREATMENT
The patient underwent emergency laparotomy with resection of a segment of ileum under general anaesthesia.
OUTCOME AND FOLLOW-UP
The postoperative course was uneventful. The patient is asymptomatic at the end of 4 months of postoperative follow-up.
DISCUSSION
A literature search revealed almost nil information on CD in Nepal, except for a single case that was documented in a survey conducted on patients with inflammatory bowel disease (IBD) attending Mission hospitals in the rural Indian subcontinent in the year of 1980. In that study, of the 18 cases of CD, 14 cases were from India, three were from Pakistan, and a single case was from Nepal. There were no cases diagnosed from Bhutan or Bangladesh. The small number of hospitals studied in Nepal, Bangladesh and Bhutan was considered as a limiting factor for the study.5
One of the current views focusing on IBD in Asia is an actual increase in the occurrence of CD. In our neighbouring countries, such as India and China, CD followed ulcerative colitis (UC) after a gap of approximately 60 years.6–8 This was similar to the trend of disease in the West where there had been a time lag of approximately 40 years.7 IBD, like many other diseases, is considered to result from an interaction between genetic and environmental factors. However, genetic factors are assumed to play a more dominant role in CD than UC, leading to an abnormal immune response of the intestinal mucosa to intraluminal antigens for development of the disease.9 Since hereditary factors do not change in a few decades and hence can not account for the increasing incidence, the emergence and rising incidence of CD have usually been ascribed to the environmental factors related to improving sanitation and hygiene in a given country.
In India, CD was considered non-existent until 1986. Recent reports however describe 3–10 patients per year, indicating an increase in the incidence of CD during the last decade. The earliest report of a high prevalence of CD from the state of Kerala in India, which has comparatively better sanitation and hygiene, also emphasises the importance of this environmental factor.7 The earlier appearance of CD in developed rather than in developing countries, in urban rather than rural populations, in higher rather than lower socioeconomic groups, and in whites rather than in native populations, indicates that improved sanitation–hygiene factor plays an important role in the aetiopathogenesis of IBD.10 A systematic review of CD in the mainland of China during a span of 50 years also revealed a rising incidence of CD in the economically well-developed eastern and southern areas.11 Further, it has been observed that the persons belonging to populations with a low incidence of IBD develop a higher incidence of the disease on migration to developed countries.12
Although the crucial role of environmental factors for development of CD is well documented, it is however often overlooked that the reported incidence and prevalence of a disease is also dependant on the following two factors. First is the awareness and belief of the presence of a disease in a particular country. For example, although it was believed until recently that coeliac disease is not common in North America, subsequent well-designed epidemiological studies have demonstrated that its prevalence in North America is almost equal to that in Europe.13 The second important factor is the availability of quality healthcare facilities with high professional standards in order to be able to diagnose a disease that is not commonly encountered in routine practice. The above two factors assume particular significance, especially in the context of a developing country such as Nepal, for documentation of the true prevalence of CD.
The task of an accurate diagnosis of CD in developing countries is further complicated because of a high prevalence of intestinal tuberculosis. In a given clinical situation, if the diagnosis of CD or intestinal tuberculosis can not be clearly established, it is often presumed to be tuberculosis and the patient is treated accordingly. A response to antituberculous treatment in such patients helps in the differential diagnosis, but offers no scope of definitive diagnosis of CD in non-responsive patients. Lack of specific symptoms and a diagnostic test with high sensitivity and specificity for CD seem to be the reasons for diagnostic failure. Such a situation is especially true for Nepal, which is a high-burden country for tuberculosis. About 45% of the total population is infected with tuberculosis and an estimated 20 000 new infectious cases are reported to occur each year.14 The estimated annual incidence rate for all types of tuberculous disease is 187 per 100 000 population, and the annual incidence of new smear positive cases is 83.5 per 100 000 population.15
In conclusion, it is hypothesised that since Nepal is not isolated from the neighbouring Asian countries in its share of environmental factors and lifestyle, the apparent rarity of CD is likely to be a false perception because of lack of awareness and quality medical diagnostic facilities for the large majority of the population.
Last, the index case of CD had an unusual presentation of ileal perforation. Though the perforation was not evident on gross examination, microscopical evidence of acute serositis was indicative of a healed perforation. Small intestinal perforation is a rare presenting feature of CD with an incidence of 1–3% in western countries. So far, approximately 100 cases have been reported in the English literature.16,17
LEARNING POINTS
It is possible that Crohn disease is truly of rare occurrence in Nepal.
An alternative and favoured possibility is that such rarity is a false perception ascribable to following factors: (1) underdiagnosis because of lack of clinical awareness and histopathological facilities, (2) misdiagnosis in favour of tuberculosis, and (3) inaccessibility of quality medical care for large majority of population.
REFERENCES
Footnotes
Competing interests: none.
Patient consent: Patient/guardian consent was obtained for publication.