Published online Nov 21, 2020. doi: 10.3748/wjg.v26.i43.6891
Peer-review started: June 19, 2020
First decision: August 22, 2020
Revised: September 4, 2020
Accepted: October 20, 2020
Article in press: October 20, 2020
Published online: November 21, 2020
Crohn’s disease is a chronic gastrointestinal disease that has been recognized in the rapidly developing upper-middle income countries of East Asia, and South America. In contrast, previous systematic reviews of published literature have found few studies on either the prevalence or incidence of Crohn’s coming from the low- and lower-middle income countries (LLMICs). In the absence of primary population data regarding Crohn’s in these countries, there has been a perception that the burden of Crohn’s remains low among the global poor. As part of an effort to understand the non-communicable burden of disease among the world’s poorest, we have conducted a scoping review with broad inclusion criteria focused on the experience with Crohn’s in LLMICs.
The correct diagnosis of Crohn’s requires a complex chain of events beginning with patients seeking care and ending with colonoscopy and histology. A break in any part of this chain resulting from gaps in financing, education, equipment, or supplies on the part of the patient or provider can result in a missed diagnosis. Crohn’s may also have an impact on patients living in extreme poverty that is out of proportion with the disease prevalence. Follow-up care for Crohn’s, like many other chronic diseases, requires frequent visits to health facilities, a steady supply of medications (including biologics), and often surgery. The absence of the services could result in a high rates of disability and death among the poor affected by Crohn’s in LLMICs.
As part of an effort to understand the non-communicable burden of disease among the world’s poorest, we have conducted a scoping review with broad inclusion criteria focused on the experience with Crohn’s in LLMICs. Specifically, this review seeks to answer the following research questions: (1) What is the published evidence regarding the burden of Crohn’s disease in communities and health facilities in LLMICs? Is underdiagnosis a problem? (2) What is the diagnostic and treatment capacity for Crohn’s disease in LLMICs? What services, equipment, and medications are used to diagnose and manage Crohn’s in LLMICs? (3) What challenges and barriers are there to providers and patients with Crohn’s disease in LLMICs in terms of diagnosis, treatment, and long-term management? And (4) What is known from the published literature regarding the social and demographic characteristics of patients with Crohn’s disease in LLMICs?
The authors conducted a scoping review utilizing a full search strategy of studies that describe cases of individuals with Crohn’s disease in an LLMIC as defined by The World Bank that was developed and conducted in PubMed, Embase and World Health Organization Global Index Medicus. To capture possible undiagnosed or misdiagnosed cases of Crohn’s in LLMICs that do not have any published Crohn’s data, as well as to understand their diagnostic and treatment capacity for Crohn’s, studies that mention the use of diagnostics (i.e. colonoscopy, small bowel follow-through, stool calprotectin), findings (i.e. skip lesions, cobblestone, small bowel obstruction), and treatments (i.e. colectomy, small bowel resection, infliximab) utilized in managing Crohn’s disease were also included. Two independent reviewers screened the titles and abstracts of all of the publications found in this search, reviewed selected publications, and extracted relevant data, which underwent descriptive review and was analyzed in Excel.
The database search yielded 4486 publications, 216 of which were determined to be relevant to the research questions. Of all 79 LLMICs, only 21 (26.6%) have publications describing individuals with Crohn’s. The majority of Crohn’s studies identified are from India (49.5%), followed by Tunisia (19.0%), Egypt (8.3%), and Sri Lanka (5.1%). The mean number of Crohn’s patients reported per study is 56.84 and the median is 22, with a wide range from one to 980. Of the 21 LLMICs included in the review, only two countries (India and Sri Lanka) had studies estimating prevalence and only four countries (India, Indonesia, Sri Lanka and Philippines) had studies reporting incidence of Crohn’s disease with most of the data coming from one multi-country study.
Of the 216 studies included in the review, 112 discussed the utilization of diagnostic and treatment services, all of which include cases that were confirmed via both colonoscopy and histology. Of the 21 LLMICs included, all but Bolivia and Syria had at least one study discussing the utilization of Crohn’s diagnostic services: Blood testing, stool testing, TB testing, radiology/imaging, endoscopy, and pathology services. Corticosteroids, aminosalicyclates, and immunomodulators are the most frequently reported medications overall, while biologic agents are the least available. The most frequently discussed Crohn’s surgery overall is colectomy, followed closely by small bowel resection. Ileoanal pouches were not specifically described in any of the included studies, but several studies described other or unspecified anal surgery for Crohn’s disease. Of the 216 studies in 21 countries included in this review, only 29 studies in 11 countries discussed patient geographic, socioeconomic, or cost information.
Of the 21 LLMICs included in this review, 14 hypothesized at least one specific diagnostic, management, access, or financial challenge or barrier to individuals with Crohn’s disease and providers. The most commonly reported provider challenge is differentiating between Crohn’s and intestinal tuberculosis (ITB), due to the high prevalence of TB in LLMICs and its overlap of symptoms and endoscopic features. This can result in long delays in disease diagnosis and thus appropriate treatment. This was followed by diagnostic delays due to perceived rarity of IBD and lack of clinical awareness among providers, which was mentioned in 17 studies from eight countries, and lack of quality diagnostic facilities, which was mentioned in 14 studies from eight countries. The most frequently reported patient barrier was the cost of Crohn’s surgeries and medications, particularly biologics. Lack of access to high quality health care facilities was another common patient barrier, with nine studies describing access to care as a patient barrier.
A lack of published data has contributed to a perceived rarity of Crohn’s by gastroenterologists in LLMICs, reducing their awareness of the disease and thus likelihood of accurately diagnosing it. It is critical to study and publish data on Crohn’s in LLMICs, even if they are single facility-based or case-studies, and to set up clinical data registries so that population-based epidemiologic research can shed light on the true burden of Crohn’s in these settings.
This scoping review has shown that Crohn’s disease does indeed exist in LLMICs in South Asia, the Middle East and North Africa, sub-Saharan Africa, East Asia and Pacific, and Latin America and the Caribbean, sometimes in large numbers.
This scoping review demonstrates that although there is a lack of rigorous epidemiologic data on Crohn’s disease in LLMICs, it actually does exist, sometimes in large numbers, in these settings and presents unique challenges that need to be addressed to advance non-communicable diseases care in low resource settings.
There is a pressing need to study the population epidemiology of Crohns’ disease in LLMICs to fully understand the burden of Crohn’s disease among the world’s poorest people. This is particularly important in those countries where it has not been studied at all, and in rural areas, where there is likely the most significant underdiagnosis and lack of access to medical care.
Patients with Crohn’s disease do indeed exist in low resource settings and there are existing models of service delivery that could be learned from and adapted to meet the unique challenges of management. For example, this study has found that one of the primary diagnostic challenges facing Crohn’s disease providers in LLMIC are: difficulty differentiating between Crohn’s and ITB. Crohn’s and ITB overlap substantially in terms of their clinical symptoms, as well as their endoscopic, pathologic, and radiologic findings, but have entirely different treatment methods. Many providers in LLMICs treat TB empirically before even considering Crohn’s disease, which can delay diagnosis by months or years.
Decentralizing Crohn’s care by training providers at lower-level care facilities in endoscopy and colonoscopy can potentially reduce underdiagnosis of Crohn’s in these areas. This may also be an opportunity to utilize telemedicine and telepathology technologies.
This study utilized broad inclusion criteria to map the landscape of studies showing where and how services for the management of Crohn’s disease are provided and organized.
If there are existing models of service delivery for patients with Crohn’s disease in low resource settings, there can also be valuable lessons in how these models can be adapted and translated to similar areas still in need of services.
This review seeks to answer the following research questions: (1) What is the published evidence regarding the burden of Crohn’s disease in communities and health facilities in LLMICs? Is underdiagnosis a problem? (2) What is the diagnostic and treatment capacity for Crohn’s disease in LLMICs? What services, equipment, and medications are used to diagnose and manage Crohn’s in LLMICs? (3) What challenges and barriers are there to providers and patients with Crohn’s disease in LLMICs in terms of diagnosis, treatment, and long-term management? And (4) What is known from the published literature regarding the social and demographic characteristics of patients with Crohn’s disease in LLMICs?
Education of both gastroenterologists and other providers in LLMICs about the symptoms and findings of Crohn’s, especially at rural lower-level facilities, is essential to improving disease awareness among providers and thus accurate diagnosis. Decentralizing Crohn’s care by training providers at lower-level care facilities in endoscopy and colonoscopy can potentially reduce underdiagnosis of Crohn’s in these areas. This may also be an opportunity to utilize telemedicine and telepathology technologies.
Crohn’s disease research in general is very important in LLMICs, especially in those countries where there is no or very little data. What little data is published from LLMICs is generated primarily from large tertiary hospitals and likely does not reflect the status of Crohn’s in the rest of the country.
It is critical to study and publish data on Crohn’s in LLMICs, even if they are single facility-based or case-studies, and to set up clinical data registries so that population-based epidemiologic research can shed light on the true burden of Crohn’s in these settings.
A survey of gastroenterology providers in LLMICs, including in-depth interviews, would also be useful to more comprehensively capture the nuances of diagnosing and treating Crohn’s disease in low resource settings. Future studies should also collect and report data on the geography of where patients’ reside, as well as socioeconomic information such as income-level or employment. In addition, algorithms for accurately diagnosing Crohn’s and TB is an important area of gastroenterology research in LLMICs.