Pattern of Clinical Presentation and Management of Inﬂ ammatory Bowel Disease

Background: Inﬂ ammatory bowel disease (IBD) is characterized by non-speciﬁ c chronic relapsing inﬂ ammation of the gastrointestinal tract and extra-intestinal manifestations. It includes Crohn’s disease (CD) ulcerative colitis (UC) and unclassiﬁ ed colitis. Objective: To assess the clinical presentations and management of inﬂ ammatory bowel disease in Sudanese patients. Methodology: Prospective, cross-section hospital-based study was conducted at Soba University Hospital (SUH) and Ibn Sina Hospital, in a period from December 2016 to March 2017. Data was entered and analyzed with SPSS, an interview questionnaire containing demographic, clinical, type of IBD, treatment, and complications. Results: A total of 64 IBD patients were included, 50% were diagnosed with UC, 28.1% with CD and 21


Introduction
In lammatory bowel disease (IBD) is characterized by non-speci ic chronic relapsing in lammation of the gastrointestinal tract and extra-intestinal manifestations.The two main disease categories are Crohn's disease (CD) and ulcerative colitis (UC), which have both distinct and overlapping clinical and pathological features [1][2][3].https://doi.org/10.29328/journal.acgh.1001040[6], but the incidence of IBD is now rising in developing countries and is increasingly considered an emerging global disease [7].
Ulcerative colitis and Crohn's disease share many extraintestinal manifestations, although some of these tend to occur more commonly with either condition.Eye-skinmouth-joint extraintestinal manifestations (e.g., oral aphthae, erythema nodosum, large-joint arthritis, and episcleritis) re lect active disease, whereas pyoderma gangrenosum, primary sclerosing cholangitis (PSC), ankylosing spondylitis, uveitis, kidney stones, and gallstones may occur in quiescent disease [8,9].Systemic symptoms are common in IBD and include fever, sweats, malaise, and arthralgia [10,11].The rectum is always involved in ulcerative colitis, and the disease primarily involves continuous lesions of the mucosa and the submucosa.Both ulcerative colitis and Crohn's disease usually have waxing and waning intensity and severity.When the patient is symptomatic due to active in lammation, the disease is considered to be in an active stage (the patient is having a lare of the IBD) [12].

Materials and Methods
It was a descriptive, prospective, Hospital-based study conducted in a period from December 2016 to March 2017 at Soba University Hospital (SUH) and IbnSina Hospital which were referral hospitals from other States.Study populations included all patients diagnosed with In lammatory Bowel Disease at IbnSina Hospital and Soba Hospital.The inclusion criteria age above 18 years old and any patient diagnosed with in lammatory bowel disease within the study period.The study excluded ages below 18 years old and other comorbidities (chronic renal failure, chronic liver failure, and malignancies).
There were 64 patients included in this study.Data collection tools are used to collect different information.With direct Face-to-face questionnaire interviews at the referring clinic.Patients diagnosed with IBD were included after a written informed consent was taken, clinical presentation ascertained, the diagnosis based on colonoscopy and histopathology then the type of management received was written.All the recruited patients were under follow-up throughout the study period.The investigator and research assistants were included.
Every patient enrolled in this study had undergone a general physical examination.Study socio-demographic variables were age, gender, education level, residence, and occupation and dependent variables were clinical presentation, endoscopy indings, and histopathological test.
Data analysis was done using SPSS version 22.0 descriptive statistics in terms of frequency tables with percentages and graphs, bi-variable analysis to determine the associations between the main outcome variable and the other relevant factors with the Chi-square test (for categorical variables), p value of 0.05 or less is considered statistically signi icant, data represented after analysis in form of uni-variable tables, cross tabulation (bi variable tables), igures and narrative illustration.
Ethical considerations by written ethical clearance and approval for conducting this research was obtained from Sudan Medical Specialization Board Ethical Committee, written ethical clearance was obtained from Khartoum state MOH, written permission was obtained from the administrative authority of Soba and IbnSina hospitals, written informed consent was taken individually from all participants and study data/information was used for the research purposes only.The privacy issues were intentionally considered.

Results
This is a cross-sectional study covering 64 patients who were diagnosed with in lammatory bowel disease at Soba and IbnSina hospitals in 2017, 50% were diagnosed with UC, 28.1% with CD and 21.9% remained unclassi ied.The mean age in UC was 43.3, while it was 34.3 in CD and 47.4 in the unclassi ied type (Figure 1).
Regarding the residences, 35(54.7%) of the study participants live in urban areas while 29(45.3%) of them live in rural areas and the majority of our study participants were nonsmokers 93.8% while the smokers were 4 (6.2%).
Regarding the occurrence of complications, the perianal istula occurred in 1 (3.1%) patient with UC and 2(11.1%)patients with CD.While the abdominal abscess occurred in 1 (3.1%) patient with UC.There were no complications in the study participants with the unclassi ied type disease.
The lare-up during the last year occurred in 11 (17.2%)patients of the study participants, they were 6 (18.8%) patients of UC patients 4 (22.2%)CD patients, and 1(7.1%) of the unclassi ied type patients.Figure 6.

Discussion
This is a cross-sectional study that covered 64 patients who were diagnosed with in lammatory bowel disease recruited during the study period at Soba and IbnSina hospitals in 2017.
Half of the study participants 50% were diagnosed with ulcerative colitis, 18 (28.1%)with Crohn's disease, and 14 (21.9%)diagnosed as unclassi ied type.UC is more common than CD, this is like most of the world studies [13][14][15], This is also like Ibrahim M.'s study concerning In lammatory Bowel Disease in Sudanese Patients: in 2011 [16], We also keeping with him in having a signi icant number of patients diagnosed with the unclassi ied type, this could be due to the lack of effective communication between clinicians and pathologists and the lack of effective clinical data that enable the pathologists to make a clear diagnosis.
This study found that the most frequent age group in ulcerative colitis patients was 41 -50 years in 11(34.4%), in Crohn's disease was 31-40 years in 7 (38.9%),and for the unclassi ied type was 51 -70 years 8 (57.2%), this is almost in keeping with Ibrahim M. study [16].Within the context of the participant's age, a study of In lammatory Bowel Disease: An Expanding Global Health Problem by M'Koma AE [17] claimed that IBD is now affecting a much younger population presents an additional concern.Meta-analyses conducted on patients acquiring IBD at a young age also reveal a trend for their increased risk of developing colorectal cancer (CRC) [17].
Our study found the overall male-to-female ratio was (1.46:1), 38 (59.4%) of all the study participants were males while the females were 26(40.6%).According to IBD subtypes, the males are more than the females in UC, while in CD the females are more than the males.These results are like some world studies [18,19] but unlike the Egyptian study by Esmat S, et al. [9], the researchers found that the males were less frequent than females in UC and the reverse for CD.
Our study found that there is a signi icant relation between the residence and the IBD subtype (p = 0.01).Urbanization was more associated with UC while rural residency was more found with CD, which is like Ibrahim M.'s study [12], in that seventy percent of his cases were residing in central relatively more urbanized areas of the country.The urban population were 54.7% compared with rural 45.3% this variation is explained by migration to urban in recent years where several factors may be involved in these increased risks, including population density, education, lifestyle changes, and potentially, exposure to industrial agents, exposure to SO2 and NO2 may increase the risk of early onset UC and CD, respectively, these data lend support to the hypothesis that components of industrialization, such as pollution, may play a role in the development and course of IBD.These indings further argue that factors associated with an urban lifestyle in luence one's risk of IBD.It is unclear whether the relationship occurs due to the environment itself or in combination with one's genetic predisposition to the disease [20].
Living in an urban setting has been associated with an increased risk for IBD through a series of studies conducted in the last six decades.In a systematic review published in 2012, living in an urban setting was associated with an increased risk of both UC and CD [21].
Smoking among study populations, the majority of our study participants were nonsmokers, 93.8% while the smokers were 6.2%, which is the most widely and longest Thirteen studies examined the relationship between UC and smoking, whereas 9 examined the relationship between CD and smoking.We found evidence of an association between current smoking and CD (OR, 1.76; 95% con idence interval [CI], 1.40-2.22)and former smoking and UC (OR, 1.79; 95% CI, 1.37-2.34).Current smoking had a protective effect on the development of UC when compared with controls (OR, 0.58; 95% CI, 0.45-0.75)[22].
In this study the most frequent symptom was diarrhea in 55 (85.9%) of overall study participants, with a higher occurrence among UC than CD, there was signi icant variation with diarrhea (p = 0.01), which is like most of the world studies [23,24].
The most frequent symptoms in overall study participants were diarrhea, rectal bleeding, abdominal pain, rectal pain in and tenesmus this is like a study in Libya by Ahmaida AI et about In lammatory Bowel Disease in Libya: Epidemiological and Clinical features [23].
The distribution of extra intestinal manifestations among the study participants were as follows, In UC were arthropathy in 13(40.6%),cutaneous manifestations in 4 (12.5%), and ocular manifestations in 4 (12.5%).In CD were arthropathy in 2 (11.1%), cutaneous manifestations in 1(5.6%), and ocular manifestations in 1(5.6%).In the unclassi ied type, there was just 2 (14.3%) had arthropathy, while the complications, the perianal istula occurred in 1 (3.1%) patient with UC and 2(11.1%)patients with CD, and the abdominal abscess occurred in 1 (3.1%) patient with UC.There were no complications in the study participants with the unclassi ied type disease.The minimal occurrence of extra intestinal manifestations and complications is probably due to the relatively few number of study participants which is similar to [9].
Regarding the endoscopic extent of the disease at the index colonoscopy, this study found that Pancolitis was the most common type, indicating that IBD presented in the most severe form in our study participants, and there was a signi icant variation with Pancolitis (p = 0.03).
In this study the terminal ileum disease occurred exclusively in CD in 4(22.2%),p-value <.05, this signi ies the importance of reaching and carefully visualizing the ileum during an endoscopic procedure.Our study found that there was no signi icant variation in perianal, rectal, or terminal ileum with colitis with IBD subtypes (p values > 0.05), while there was a signi icant variation with distal colitis (p < 0.05), These results are like the study of in lammatory bowel disease in India--changing paradigms.By Ray G1 [25], the researchers found that Sixty-ive percent of their UC patients presented with Pancolitis, and the majority had severe clinical, endoscopic, and histological disease, like a study done in China by Xia B, et al. [24,26,27].
Unlike most of the IBD treatment guidelines which recommended steroids for acute disease and lare up only [28][29][30], there was relatively excessive usage of steroids among our study participants 42(65.6%)p -value (> 0.05), this is most probably due to unavailability and expensive price of immune modi ier drugs and the biological agents in Sudan, while the steroid are readily available.Regarding the use of azathioprine, the study found a signi icant variation according to IBD subtypes (p < 0.05) but not with the use of biological agents (p < 0.669).Immunosuppressants, such as azathioprine, that require several weeks to achieve their therapeutic effect have a limited role in the acute setting but are preferred for long-term management [31].Immunosuppressant drugs can be an invaluable adjunct therapy for the treatment of patients with intractable in lammatory bowel disease or complex, inoperable perianal disease.Although immunosuppressant agents have signi icant side effects, they are safer and better tolerated than long-term corticosteroid therapy.Should not be used in young patients who are candidates for surgery or in patients who are non-compliant and refuse to return for periodic monitoring [32].
In this study, participants received oral 5 aminosalicylic acids were 54(84.4%),While the study participants received topical 5 aminsalicylic acids were 4(6.2%).Of the Study participants who received oral steroid 41 (64.1%), while the intra venous steroid was received by 3(4.7%) of the IBD study participants.Although the topical form of 5 aminosalicylic and steroid importance was proved [28], they were minimally used by our study participants, this is likely because they are expensive and not covered by insurance companies.5-ASA is the active therapeutic moiety, absorbed in the upper gastrointestinal tract, the ef icacy of 5-ASA preparations (e.g., sulfasalazine) in CD is less striking, with a modest bene it at best in controlled trials [33].
Although not statistically signi icant (p -value > 0.05), most of the study participants' disease remained quiescent during the last year, and the lare-up during the last year occurred in 11 (17.2%)patients of the study participants.https://doi.org/10.29328/journal.acgh.1001040 When we go through our indings with a similar Sudanese context in Sudan, the research of SE Khalifa, et al. [34], we have agreement and con lict, the majority of their patients with UC improved with medical treatment.They concluded that IBD is not a rare disease in Sudan, with UC being more common than CD.The disease tends to be more common in men in both UC and CD.
Study participants who received oral steroids were 41 (64.1%), according to the IBD subtype they were 35.9% in UC patients, 23.3% in CD patients and 4.7% in unclassi ied type patients, while the intra venous steroids were received by 4.7% of the IBD study participants, they are 3.1% of patients with UC, and 1 patient with CD, in contrast with the study [39], which CD patients were more likely than UC patients to have disease judged as moderate/severely active at the time of clinic visit (23.8% vs. 17.6%.While steroids remain the cornerstone of inducing remission in IBD, their longer-term or repeated use is discouraged because of a lack of long-term ef icacy and an unacceptable level of side effects.Avoiding excess steroid use is therefore a key aim for clinicians and patients [40,41]. The rapid induction and maintenance of remission are the main principles of treatment for UC.Corticosteroids, 5-aminosalicylates (5-ASA), immunomodulators, biologics, and small molecules are the foundation of UC treatment.The most cost-effective immunomodulators, such as azathioprine (AZA), have been used to treat UC for many decades, primarily to maintain remission [42].
This study had some limitations.The relatively few number of study participants only 64 may affect negatively the probability of inding signi icant relationships between different factors or variables with the IBD subtypes.Another limitation, some outcomes may need to be followed over more time.So, a cohort follow-up design may be useful for a more detailed description of the outcome among IBD patients.Also, this study was conducted in two centers so, the results may not be generalized, highlighting the need for a multicenter trial with the uniform assessment protocol.

Conclusion
The study found that the most frequent symptoms in overall study participants were diarrhea, rectal bleeding, abdominal pain, rectal pain, tenesmus, and fatigue.Also, the study found that pancreatitis was the most common type at the index colonoscopy.Most of the study participants received 5 aminosalicylic acids, and steroids, especially in the oral formulation but there is minimal usage of topical forms, also there is minimal use of azathioprine, and biological agents.There is age variation in IBD subtypes and higher proportions of females in Crohn's disease more males in Ulcerative colitis disease.
The unavailability and the expensive price of immune modi ier drugs and biological agents in Sudan should be urgently addressed and further studies are recommended with a larger sample size for a more in-depth investigation of relevant factors and patient characteristics and treatment effectiveness.

Figure 5 :
Figure 5: Medical management received by the study participants according to IBD subtypes (n = 64).

Table 1 :
Symptoms according to IBD subtypes among the study participants (n = 64).

Table 2 :
Medical treatment according to IBD subtypes among the study participants (n = 64).To date, it has been observed that smoking has a varying impact on CD and UC, contributing to an increased risk for individuals with CD and a protective role in individuals with UC.
Yes No Figure 6: The incidence of Flare-ups during the Last Year according to IBD subtypes among the study participants (n = 64).https://doi.org/10.29328/journal.acgh.1001040studied environmental exposure associated with IBD.