Prevalence of Different Types of Colitis in Patients with Chronic Diarrhea in Egypt; National Liver Institute, Single-Center Experience

Rewisha, Eman; Abdelgilil Elessawy, Mohamed; Sweed, Dina; Abdelsameea, Eman; Badr, Reda

doi:10.21608/aeji.2025.343488.1438

Prevalence of Different Types of Colitis in Patients with Chronic Diarrhea in Egypt; National Liver Institute, Single-Center Experience

Afro-Egyptian Journal of Infectious and Endemic Diseases

Article 10, Volume 15, Issue 2, June 2025, Page 193-204 PDF (616.24 K)

Document Type: Original Article

DOI: 10.21608/aeji.2025.343488.1438

View on SCiNiTO

Authors

Eman Rewisha¹; Mohamed Abdelgilil Elessawy

¹; Dina Sweed²; Eman Abdelsameea

¹; Reda Badr¹

¹Hepatology and gastroenterology department, National Liver Institute, Menoufia University, Shebein Elkom, Menoufia, Egypt.

²Pathology department, National Liver Institute, Menoufia University, Egypt

Abstract

Background and study aim: Chronic diarrhea is characterized by a predominant decrease in stool consistency for more than four weeks. Prevalence is (1% to 5%) of adult population. We aimed to evaluate the prevalence of different types of colitis, common presentation in Egyptian patients with chronic diarrhea, and single-center experience.
Patients and Methods: All patients who underwent lower endoscopy for chronic diarrhea of unexplained etiology from June 2015 to August 2023 were included.
Results: Among 200 patients with chronic diarrhea, non-specific inflammation was the most prevalent among various types of colitis, affecting 81 individuals (40.5%). There were 62 patients with inflammatory bowel disease (IBD) (31.0%), one of them had Crohn's disease. In addition, 41 patients (20.5%) were diagnosed with microscopic colitis (8 cases of collagenous and 33 cases of lymphocytic), and 16 patients had suspected eosinophilic colitis (8.0%). Weight loss, abdominal pain, duration of diarrhea, and number of daily defecations varied significantly among different types of colitis (P<0.05). However, there was no statistical difference regarding the impact of COVID-19 infection on demographic and clinical data (P > 0.05). Significant differences in hemoglobin and ESR levels were observed between IBD and other types of colitis. There were significant differences regarding histopathological parameters across different forms of colitis (P< 0.001).
Conclusion: Different types of colitis as ulcerative colitis, Crohn's disease, infectious colitis, and ischemic colitis vary in prevalence and are influenced by factors like age, gender, and underlying health conditions. Accurate diagnosis is crucial as management differs significantly among these types.

Highlights

Chronic diarrhea is characterized by a predominantly decrease in stool consistency for more than four weeks. Prevalence is 1% to 5% of adult population.
The prevalence of different types of colitis and common presentation in patients with chronic diarrhea need to be studied.
Accurate diagnosis is crucial, as management and treatment differ significantly among these types.

Keywords

chronic diarrhea; Crohn’s disease; colitis; inflammatory bowel disease

Full Text

INTRODUCTION

Chronic diarrhea is known as predominantly decreased stool consistency that persists for more than four weeks. The prevalence is (1% to 5%) of the adult population. Common causes include microscopic colitis, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) [1, 2]

Colitis is typically diagnosed by endoscopic and biochemical findings. There are numerous types of colitis involving ulcerative colitis (UC), Crohn’s disease (CD), diversion colitis, ischemic colitis, infection colitis, fulminant colitis, chemical colitis, collagenous colitis and lymphocytic colitis [3].

Nonspecific inflammatory bowel disease constitutes a group of diseases characterized by chronic inflammation of the gastrointestinal tract (GIT). For most of them, two clinical types are distinguished: CD and UC [4]. Continuous proactive monitoring is necessary to decide the most suitable treatment and follow-up strategy as IBD is a chronically relapsing disease. Gastrointestinal endoscopy with taking biopsies histological examination and contrast-enhanced imaging are necessary steps for diagnosis and evaluation the IBD activity [5].

Both UC and CD have different clinical manifestations. However, about 10 to 15% of patients with IBD do not present the manifestations of UC or CD such as (Behcet's disease, collagenous colitis, microscopic enteritis, and eosinophilic enteritis) are classified as indeterminate colitis (IC) [4, 6].

Microscopic colitis is diagnosed when the patient manifested by chronic watery non bloody diarrhea with normal colonoscopy. Microscopic colitis is diagnosed when the colonic biopsy shows pathological features of increased intra-epithelial lymphocytes (lymphocytic colitis) or thickened of basement membrane (collagenous colitis) [3].

The most common symptom is diarrhea which accounts for 96% of cases. Often abdominal cramping and nocturnal bowel movements are frequently observed (about 3-20 bowel movements per day). In 41 percent of cases, weight loss occurs while abdominal pain occurs in approximately 47% of the patients [7]. MC etiology remains unknown but several hypotheses have been put to explain the etiology such as some medication intake, gastrointestinal infections, autoimmune diseases, and bile acid malabsorption [8].

Studies comparing the prevalence of the disease between developing and developed countries may provide insight into the potential for a post-infectious etiology [8]. Most of the data on the incidence of microscopic colitis (MC) are from developed countries where it accounts for 4-13% of cases of chronic watery bloody diarrhea (CWND). There are only a few reports of microscopic colitis (MC) from developing countries [9]. This study aims to evaluate the prevalence of different types of colitis, common presentation in patients with chronic diarrhea at the National Liver Institute as a single center experience in Egypt.

PATIENTS AND METHODS

Study design and setting:

This study was carried out on patients who came to the gastroenterology endoscopic unit at the National Liver Institute (NLI), Menoufia University and underwent lower endoscopy for chronic diarrhea of unexplained etiology during the period of the study from June 2015 to December 2021. Also, a prospective part of the study was conducted from October 2021 till August 2023.

Patients’ criteria:

All patients who had presented with unexplained chronic diarrhea (three or more loose stools per day) during the period of the study were reviewed for detection of the cause of chronic diarrhea after the exclusion of parasitic infestation.

Patient’s diagnosis:

Patients who suffer from chronic diarrhea have loose or watery feces that occur three or more times per day and persist for four weeks or more. Although history and physical examination are essential components of diagnosis, they are generally nonspecific. The timing of diarrhea about ingestion should be the primary focus of history. All patients with chronic diarrhea require screening for acute kidney injury, electrolyte abnormalities, and malabsorption.

Patients’ evaluation:

Clinical information (including age, sex, and complaint) laboratory data, ultrasonographic data, and family history of the same condition were all obtained from the medical records. Detailed clinical history was taken from all patients including their age, medication intake, diarrhea duration, and other gastrointestinal symptoms including abdominal discomfort, abdominal pain, stool consistency, number of daily defecation, urgent need for bowel movement, and weight loss. For the retrospective study part, data was collected from patient files. Examination for general manifestations of dehydration due to chronic diarrhea was done (sunken eyes, dryness of mucous membrane, hypotension, and fever)

Laboratory investigations:

In the laboratory, the Sysmex XT 1800i (Sysmex Corporation, Kobe, Japan) system is used to measure hemoglobin (Hb), white blood cells (WBCs), and platelets during the complete blood count (CBC) test.

Endoscopic procedure:

The patient underwent a colonoscopy after good preparation by lying on his left side on an exam table and IV sedatives were given then a total colonoscopy was done up to terminal ileum intubation. Each segment of the colon and any abnormal-appearing areas were biopsied.

Histological evaluation

Samples:

After fixing the biopsy samples in neutral buffered formalin for 24 hours, they were embedded in paraffin blocks. Histological alterations were assessed by cutting, deparaffinizing drying, and staining Sections of 4-5 μm thickness with hematoxylin and eosin.

Histopathological criteria are evaluated for the diagnosis of possible etiologies. Lymphocytic colitis: >20 Intraepithelial Lymphocytes (IEL)/100 epithelial cells, and a mild to moderate increase in mononuclear inflammation in lamina propria. Collagenous colitis: Subepithelial collagen level >10 μ, and normal/ slightly increased intraepithelial lymphocytes [10]. Nonspecific inflammation: This is characterized by an increase in inflammatory cells that exceeds the normally present physiologically corresponding anatomical sites with lacking pathological features of other types of inflammation [11]. Eosinophilic colitis is characterized by >30 eosinophils/ HPF in the lamina propria and could be associated with eosinophil microabscesses, eosinophilic cryptitis, and eosinophil exocytosis [12]. Inflammatory bowel disease (IBD): The activity of IBD is characterized by the presence of neutrophils in the lamina propria, surface epithelium, cryptitis, or crypt abscess. Features of chronicity include basal plasmacytosis, crypt distortion, crypt atrophy, and irregular distribution of the crypts in the lamina propria. In addition, non-caseating epithelioid granulomas are regarded as a classical character of Crohn’s disease (CD) [13].

Statistical analysis

The statistical program of the social sciences was used to examine the results [14]. Two sorts of statistical analysis were carried out: Descriptive statistics: It includes estimates for summarizing the data as median (Med), and interquartile range (IQR) for not normally distributed quantitative data, and frequency with percentage (%) for qualitative data. Analytical or inferential statistics included Pearson Chi-square (χ2) test, Fisher's/monte Carlo Exact Test, Mann-Whitney test, Kruskal-Walli's test, Assumptions of normality in each group, and homogeneity of variances were verified using Shapiro-Wilk test and Levine's test and Post Hoc tests. P-values

RESULTS

A flowchart for the research population was illustrated. Of the 210 patients evaluated to determine the prevalence of different forms of colitis in patients with chronic diarrhea in Egypt at the National Liver Institute, Menoufia University, underwent lower endoscopy for chronic diarrhea of unknown origin. Ten people were eliminated from the study; four patients denied consent, and six did not match the eligibility requirements; 200 patients agreed to participate.

In the current study, non-specific inflammation showed the highest prevalence among different types of colitis (40.5%), followed by inflammatory bowel disease (31.0%), microscopic colitis (20.5%), and probable eosinophilic colitis (8.0%). (Table 1(

Abdominal pain, weight loss, duration of diarrhea, and the number of daily defecations were significantly different among the various types of colitis (P<0.05). However, there was no statistical difference regarding the impact of COVID-19 infection on the demographic and clinical data (P > 0.05). (Table 2(

Additionally, the laboratory data revealed statistical differences in Hb and ESR between IBD and other types of colitis (P=0.005 and P<0.001, respectively). (Table 3(

In terms of endoscopy's ability to predict the etiological diagnosis of colitis, the initial endoscopic results indicate the diagnosis of IBD in 50% of cases and microscopic colitis in 73.2% (P<0.001). IBD cases were significantly associated with multiple colonic sites affected and all over the colon affected compared to the other etiological diseases (P< 0.001). Regarding the mucosal findings, nearly half of IBD cases were presented significantly by ulceration compared to the other etiological diseases. On the other hand, microscopic colitis cases showed a significant normal endoscopic finding compared to the other diseases (P<0.001). (Table 4(

Histopathological findings distributed among different types of colitis with chronic diarrhea were explored. There were high statistical differences (P< 0.001) regarding the distributions of mucosal intra-epithelial lymphocytosis, and subepithelial collagen. The findings are characteristic in almost all patients with microscopic colitis. The eosinophil density and the grade of chronic inflammation are predominant in both IBD and probable eosinophilic colitis (P<0.001). Active inflammation (neutrophils) is a characteristic finding in IBD (P<0.001). (Table 5(

The distribution of histopathological findings according to mucosal findings was tested. The majority of patients showed increased mucosal intra-epithelial lymphocytosis, which was significantly associated endoscopically with free endoscopic findings or hyperemia (P=0.038). Eosinophil density is significantly related to ulceration or other endoscopic findings, not hyperemia or a free endoscope (P<0.001). Regarding the prevalence of active inflammation (neutrophils) and the grade of chronic inflammation, they were significantly higher in patients with ulcerations than in other mucosal findings categories (P<0.001).(Table 6)

Table 1: Prevalence of different types of colitis associated with chronic diarrhea.

Pathological Diagnosis (Types of colitis) n (%)	Colitis with chronic diarrhea (N=200)
Inflammatory bowel disease (IBD)	62 (31.0)
Crohn's disease	1 (0.5)
Ulcerative colitis	61 (30.5)
Microscopic colitis	41 (20.5)
Collagenous colitis	8 (4.0)
Lymphocytic colitis	33 (16.5)
Non-specific inflammation	81 (40.5)
Probable eosinophilic colitis	16 (8.0)
%: Percent within patients with colitis

Table 2: Comparisons of different types of colitis regarding demographic and clinical characteristics in colitis-associated chronic diarrhea patients.

Demographic and clinical characteristics

Types of colitis

Significance test

Pairwise comparisons^¥

IBD

(n=62)

Microscopic colitis

(n=41)

Non-specific inflammation

(n=81)

Probable eosinophilic colitis (n=16)

Age (year)

Median (IQR)

Range (min-max)

38.50 (26.30)

15.00 - 70.00

35.00 (19.50)

18.00 - 68.00

36.00 (17.50)

19.00 - 75.00

37.00 (17.50)

24.00 - 65.00

χ²= 1.35 ^a

P=0.718 ^NS

Sex

Male

Female

χ²=5.80 ^b

P=0.122 ^NS

51.6

48.4

41.5

58.5

56.8

43.2

75.0

25.0

Covid-19 infection

Yes

100.0

61.3

38.7

100.0

70.7

29.3

100.0

63.0

37.0

100.0

81.3

18.8

χ²=2.97 ^b

P=0.396 ^NS

Stool consistency, n (%))

Soft

Watery

30.6

69.4

41.5

58.5

51.9

48.1

31.3

68.8

χ²=7.28 ^b

P=0.064 ^NS

No daily defecation

Median (IQR)

Range (min-max)

5.00 (5.00)

2.00 - 13.00

5.00 (4.50)

2.00 - 12.00

4.00 (2.00)

2.00 - 10.00

4.50 (1.00)

3.00 - 10.00

χ²= 9.33 ^a

P =0.025 ^S

p1=0.935 ^NS p2=0.012 ^S p3=0.893 ^NS p4=0.692 ^NS p5=1.000 ^NS p6=0.666 ^NS

Duration of diarrhea (week)

Median (IQR)

Range (min-max)

20.00 (12.00)

8.00 - 50.00

28.00 (34.00)

6.00 - 100.00

24.00 (19.00)

8.00 - 120.00

24.00 (26.00)

8.00 - 100.00

χ²= 11.05 ^a

P =0.011 ^S

p1=0.012 ^S p2=0.241 ^NS

p3=0.493 ^NS p4=0.378 ^NS p5=0.988 ^NS p6=0.998 ^NS

Abdominal cramps

Yes

9.7

90.3

2.4

97.6

11.1

88.9

0.0

100.0

χ²=3.70 ^c

P=0.258 ^NS

Abdominal pain

Yes

3.2

96.8

2.4

97.6

13.6

86.4

0.0

100.0

χ²=7.24 ^c

P=0.042 ^S

p1=1.000 ^NS p2=0.033 ^S p3=1.000 ^NS p4=0.059 ^NS p5=1.000 ^NS p6=0.202 ^NS

Weight loss

Yes

40.3

59.7

65.9

34.1

67.9

32.1

56.3

43.8

χ²=12.27 ^b

P=0.007 ^HS

p1=0.011 ^S p2=0.001 ^HS p3=0.252 ^NSp4=0.820 ^NS p5=0.499 ^NS p6=0.369 ^NS

Lost weight (kgs)

Median (IQR)

Range (min-max)

10.00 (3.00)

4.00 - 25.00

7.50 (4.30)

5.00 - 15.00

6.00 (5.00)

4.00 - 20.00

8.00 (5.00)

4.00 - 10.00

χ²= 5.07 ^a

P =0.166 ^NS

Manifestation of dehydration

Yes

66.1

33.9

82.9

17.1

80.2

19.8

81.3

18.8

χ²=5.48 ^b

P=0.140 ^NS

IBD: inflammatory bowel disease

Table 3: Comparisons of different types of colitis regarding laboratory data in colitis-associated chronic diarrhea patients.

Laboratory data

Types of colitis

Significance test

Pairwise comparisons^¥

IBD

(n=62)

Microscopic colitis

(n=41)

Non-specific inflammation

(n=81)

Probable eosinophilic colitis (n=16)

Hemoglobin (g/dL)

Median (IQR)

Range (min-max)

11.80 (2.90)

8.30 - 14.00

12.80 (1.60)

7.90 - 14.00

12.20 (2.00)

9.00 - 14.00

12.00 (1.90)

9.80 - 13.40

χ²= 12.7

P =0.005 ^HS

p1=0.006 ^HS

p2=0.151 ^NS

p3=0.868 ^NS p4=0.212 ^NS p5=0.413 ^NS p6=1.000 ^NS

WBCs(10³ cell/μL)

Median (IQR)

Range (min-max)

8.00 (4.60)

2.30 - 19.00

7.00 (2.00)

3.30 - 13.00

8.00 (4.00)

3.90 - 13.00

7.00 (6.00)

3.90 - 13.00

χ²= 4.99

P =0.172^NS

Platelets(10³cell/μL)

Median (IQR)

Range (min-max)

265.0 (131.0)

47.0 - 470.0

234.0 (110.0)

180.0 - 422.0

240.0 (100.5)

150.0 - 511.0

231.0 (26.3)

62.0 - 421.0

χ² 2.45

P =0.485^NS

ESR (mm/h)

Median (IQR)

Range (min-max)

65.00 (57.30)

12.00 - 123.00

23.00 (42.00)

8.00 - 94.00

33.00 (39.00)

7.00 - 125.00

33.00 (17.00)

12.00 - 108.00

χ²= 32.77

P <0.001^HS

p1HS p2HS p3=0.006 ^HS p4=0.958 ^NS p5=0.984 ^NS p6=1.000 ^NS

WBCs: white blood cells, ESR: erythrocyte sedimentation rate

Table 4: Comparisons of different types of colitis regarding endoscopic findings in colitis-associated chronic diarrhea patients.

Endoscopic findings

Types of colitis

Significance test

Pairwise comparisons^¥

IBD

(n=62)

Microscopic colitis

(n=41)

Non-specific inflammation

(n=81)

Probable eosinophilic colitis (n=16)

Endoscopic diagnosis

Normal colonoscopic picture

Acute inflammation

Chronic inflammation

Suggestive IBD

χ²=62.02 ^a

PHS

p1HS

p2HS

p3=0.208 ^NS

p4=0.487 ^NS

p5=0.008 ^HS

p6=0.047 ^S

21.0

24.2

4.8

50.0

73.2

24.4

0.0

2.4

64.2

24.7

4.9

6.2

37.5

0.0

25.0

Affected site multiplicity

None

Single site

Multiple sites

All over colon

21.0

25.8

32.3

21.0

73.2

14.6

9.8

2.4

64.2

14.8

16.0

4.9

37.5

6.3

31.3

25.0

χ²=44.93 ^a

PHS

p1HS p2HS p3=0.278 ^NS p4=0.758 ^NS p5=0.005 ^HS p6=0.017 ^S

Mucosal findings categories

Free

Hyperemia

Ulceration

Others

21.0

25.8

46.8

6.5

73.2

19.5

2.4

4.9

64.2

22.2

4.9

8.6

37.5

31.3

18.8

12.5

χ²=59.82 ^a

PHS

p1HS p2HS p3=0.138 ^NS p4=0.714 ^NS p5=0.030 ^S p6=0.084 ^NS

IBD: - inflammatory bowel disease

Table 5: Comparisons of different types of colitis regarding histopathological findings in colitis-associated chronic diarrhea patients.

Pathological findings

Types of colitis

Significance test

Pairwise comparisons^¥

IBD

(n=62)

Microscopic colitis

(n=41)

Non-specific inflammation

(n=81)

Probable eosinophilic colitis (n=16)

Mucosal intra-epithelial lymphocytosis

Normal

Increased

χ²=115.15 ^b

PHS

p1HS p2=0.101 ^NS p3=0.112 ^NS p4HS p5HS p6=0.585 ^NS

83.9

16.1

7.3

92.7

92.6

7.4

100.0

0.0

Eosinophil’s density [30/HPF]

Less

71.0

29.0

87.8

12.2

97.5

2.5

0.0

100.0

χ²=82.71 ^b

PHS

p1=0.045 ^S p2HS p3HS p4=0.042 ^S p5HS p6HS

Active inflammation (Neutrophils)

Absent

Present

1.6

98.4

97.6

2.4

90.1

9.9

75.0

25.0

χ²=147.79 ^b

PHS

p1HS p2HS p3HS p4=0.270 ^NS p5=0.019 ^S p6=0.108 ^NS

Grade of chronic inflammation

Mild

Moderate

Marked

11.3

58.1

30.6

46.3

53.7

0.0

66.7

33.3

0.0

12.5

81.3

6.3

χ²=77.34 ^b

PHS

p1HS p2HS p3=0.107 ^NS p4=0.031 ^S p5=0.012 ^S p6HS

Subepithelial collagen

Normal

Increased

100.0

0.0

85.4

14.6

100.0

0.0

100.0

0.0

χ²=15.02 ^c

PHS

p1=0.003 ^HS

p4=0.001 ^HS p5=0.170 ^NS

HPF: high power field

Table 6: Comparisons of mucosal findings screened by endoscopy regarding histopathological findings in colitis-associated chronic diarrhea patients.

Pathological findings

Mucosal findings (endoscopic)

Significance test

Pairwise comparisons^¥

Free

(n= 101)

Hyperemia

(n= 47)

Ulceration

(n= 37)

Others*

(n= 15)

Mucosal intra-epithelial lymphocytosis

Normal

Increased

χ²=8.40 ^b

P=0.038 ^S

p1=1.000 ^NS

p2=0.030 ^S

p3=1.000 ^NS

p4=0.047 ^S

p5=1.000 ^NS

p6=0.680 ^NS

68.3

31.7

68.1

31.9

91.9

8.1

73.3

26.7

Eosinophils density (30/HPF)

Less

87.1

12.9

83.0

17.0

51.4

48.6

86.7

13.3

χ²=22.42 ^b

P≤0.001 ^HS

p1=0.985 ^NS

p2≤0.001 ^HS

p3=1.000 ^NS

p4=0.024 ^S

p5=1.000 ^NS

p6=0.103 ^NS

Active inflammation (Neutrophils)

Absent

Present

82.2

17.8

57.4

42.6

18.9

81.1

60.0

40.0

χ²=47.46 ^b

P≤0.001 ^HS

p1=0.006 ^HS

p2≤0.001 ^HS

p3=0.398 ^NS

p4≤0.001 ^HS

p5=1.000 ^NS

p6=0.041 ^S

Grade of chronic inflammation

Mild

Moderate

Marked

47.5

51.5

1.0

48.9

42.6

8.5

10.8

51.4

37.8

46.7

6.7

χ²=42.54 ^c

P≤0.001 ^HS

p1=0.310 ^NS

p2≤0.001 ^NS

p3=0.898 ^NS

p4≤0.001 ^NS

p5=1.000 ^NS

p6=0.041 ^S

Subepithelial collagen

Normal

Increased

94.1

5.9

100.0

0.0

100.0

0.0

100.0

0.0

χ²=3.96 ^c

P=0.217 ^NS

HPF: high power field

Table 7: Comparisons of COVID-19 infection regarding histopathological findings in colitis-associated chronic diarrhea patients

Pathological findings	Covid-19 infection		Significance test	P-value
Pathological findings	Negative (n= 131)	Positive (n= 69)	Significance test	P-value
Pathological Diagnosis (Type of colitis), n (%)			χ²=5.14 ^a	0.549 ^NS
*IBD*
Ulcerative colitis	37 (28.2)	24 (34.8)
Crohn's disease	1 (0.8)	0 (0.0)
Ischemic type colitis/mucosal injury	2 (1.5)	0 (0.0)
*Microscopic colitis*
Collagenous colitis	6 (4.6)	2 (2.9)
Lymphocytic colitis	23 (17.6)	10 (14.5)
*Non-specific inflammation*	51 (38.9)	30 (43.5)
*Probable eosinophilic colitis*	13 (9.9)	3 (4.3)
Mucosal intra-epithelial lymphocytosis, n (%)
Normal	97 (74.0)	49 (71.0)	χ²=0.21 ^b	0.646 ^NS
Increased	34 (26.0)	20 (29.0)
Eosinophils density [30/HPF], n (%)			χ²=2.33 ^b	0.127 ^NS
Less	100 (76.3)	59 (85.5)
More	31 (23.7)	10 (14.5)
Active inflammation (Neutrophils), n (%)			χ²=0.02 ^b	0.885 ^NS
Absent	83 (63.4)	43 (62.3)
Present	48 (36.6)	26 (37.7)
Grade of chronic inflammation, n (%)			χ²=4.71 ^b	0.095 ^NS
Mild	58 (44.3)	24 (34.8)
Marked	9 (6.9)	11 (15.9)
Moderate	64 (48.9)	34 (49.3)
Subepithelial collagen, n (%)			χ²=0.00 ^a	1.000 ^NS
Normal	127 (96.9)	67 (97.1)
Increased	4 (3.1)	2 (2.9)

HPF: high power field , IBD : inflammatory power disease

DISCUSSION

The inflammatory diseases of the colon are characterized by chronic watery diarrhea (CWD) which is a significant reason why patients visit the emergency room and primary care physicians. The most frequent cause of chronic diarrhea is microscopic colitis (MC), presented by normal colonoscopy findings. Yearly, the prevalence of MC is 262 cases/100,000 persons, with the highest incidence among older women [15]. The quality of life is significantly impacted by MC [16]. As a subtype of IBD, ulcerative colitis (UC) is characterized by chronic nonspecific inflammation of the colorectal mucosa. UC has multifactorial etiopathogenesis: genetic, microbial, and environmental factors that have not been completely Known [17,18].

This study's goal is to evaluate different types of colitis prevalence and its common presentation in patients with chronic diarrhea in Egypt. To elevate that goal, a retrospective and prospective study was carried out on patients who came to the gastroenterology endoscopic unit at the National Liver Institute (NLI), Menoufia University and underwent lower endoscopy for chronic diarrhea of unexplained etiology.

Our study showed the prevalence of different types of colitis among 200 cases with chronic diarrhea. Non-specific inflammation showed the highest prevalence among different types of colitis followed by IBD, microscopic colitis, and probable eosinophilic colitis. In the same line, colonoscopy findings were normal in all patients (130 cases). From all the cases, there were 7 (5.4%) cases of microscopic colitis, 5 (3.8%) had lymphocytic colitis and 2(1.5%) had collagenous colitis. LC is diagnosed When crypts architecture is not affected and intraepithelial lymphocytic count is raised to at least >20 lymphocytes per 100 cells. CC is diagnosed histologically when more than a 10-m collagen band is identified in the subepithelial layer [19].

Moreover, results showed that among MC patients, 39.1% (95% CI: 22.9–56.6%) had bowel dysfunction; this percentage was not signiﬁcantly higher for patients with lymphocytic colitis (40.7%; 95% CI: 8.2–78.9) than for those with collagenous colitis (28.4%; 95% CI: 8.4–54.5%) (P = 0.58) [20]. When the study was applied to patients presented by IBS-D, it was found to be present in 32.5% (95% CI: 18.1–48.8%) of patients with MC. Also, there are no signiﬁcant differences between the prevalence of diagnostic criteria for IBS-D in patients with lymphocytic colitis (24%; 95% CI: 4–53.7%) and those with collagenous colitis (22.5%; 95% CI: 5.8–45.9%). There were overlapped manifestations among patients with MC and functional diarrhea. (22.8%, 95% CI: 0.6–63%) [20].

Our study showed statistical differences between types of colitis regarding the number of daily defecations, duration of diarrhea, abdominal pain, and weight loss. In the same line, studies showed that 88 patients were recruited from July 2017 to December 2019. The study enrolled all CWND patients who were at least 15 years old and had normal colonoscopy findings [15]. The age of the studied patients ranged from 15-72 y with a mean of 38.03±12.67. Regarding gender, the study included 46 males representing (52.3%) and 42 females representing (47.7%), regarding the duration of diarrhea in months a median of 9 (7-15) in the range (of 3-9) months, 18 patients represent chronic diarrhea less than 6months and 70 patients represent it more than 6 months. Also, by a range of 3-12 bowel motions frequency in the included patient's study [15]. Regarding weight loss, nocturnal diarrhea, and abdominal pain, there is a substantial statistical difference between the two groups (p values of 0.009, 0.001, and 0.001, respectively). Additionally, fever has a statistically significant p-value of 0.039 [15].

As per the categories of chronic diarrhea-in summary- the number of patients was 3503 participants were as follows: (1527 men and 1976 women). The participants had an average age of 46.9 ± 12.6 years. Rural areas comprised 1433 participants (40.91%) of the total, while the urban areas comprised 2070 participants (59.09 %). Among the chronic diarrhea was diagnosed in 502 participants, (237 men and 265 women), which comprises 14.33% of 3503 participants (total population). The average BMI was 24.7 ± 4.6 kg/m2. Overweight participants comprised the entirety of participants with 35.17% (1232/3503) and 16.13% (565/3503) falling into the obese category [18]. Regarding BMI, marital status, smoking, alcohol intake, milk and dairy products, and fat intake - there was a significant difference between the group presented by chronic diarrhea and control groups ( P > 0.001) [18].

Additionally, across most age categories, there was a statistically positive correlation between the increase in body weight and the increase in the prevalence of chronic diarrhea (P > 0.05). Comorbid obesity with diarrhea is found in 2.89%of the population (4.36% for men and 1.69% for females) [18]. Furthermore, studies demonstrated that the parameters of intestinal permeability in obese people show a positive correlation with anthropometric and metabolic factors. The gut microbiota might have an essential role in this association. People with Bacteroide-dominant gut microbiota are better able to absorb nutrients from meals and have shorter intestinal transient time. Multiple studies have found that obesity is associated with a greater ratio of firmicutes to Bacteroides ratio. Metabolites of the gastrointestinal microbiota such as short-chain fatty acids may play an important role in obesity and diarrhea. Nevertheless, additional human investigations are required to confirm the diagnosis. Furthermore, this association may be influenced by intestinal inflammation and disturbances in bile acid metabolism [18]. Also, a study relieved a Total - 130 individuals - were enrolled, with age ranging from 28-55 years. There were 67 females (51.5% of the total) [19].

Our study showed that there was a statistical difference in Hemoglobin (Hb) and erythrocyte sedimentation rate (ESR) between IBD and other types of colitis.

the white blood cell (WBCs) count, C- reactive protein (CRP) and ESR are the commonest inflammatory markers used in clinical practice for the assessment of the activity of UC but they do not role on the case of intestinal inflammation as they are not enough sensitive or specific . So other tests are needed [21].

Furthermore, the sum of endoscopic and histological scores was reported to be correlated with CRP, ESR, and WBC counts furthermore they discovered that the activity of proximal colonic lesions was significantly correlated with CRP and ESR, but not with distal lesions. For determining the activity of UC, It is important to consider the use of CRP and other lab markers as a complement to clinical manifestations and physical examination rather than as a substitute. By incorporating these markers with a colonoscopy, their significance in detecting UC activity will be significantly increased [22].

Our study showed that there were highly statistical differences regarding the distributions of mucosal intra-epithelial lymphocytosis, eosinophils density, active inflammation (neutrophils), grade of chronic inflammation, and subepithelial collagen among different types of colitis but without specific pattern or trend. However, subepithelial collagen was normal in almost all patients but for 6 patients with microscopic colitis who displayed increased subepithelial collagen in histopathological findings.

A histopathological examination was performed on biopsied samples collected during colonoscopy to determine the occurrence rate of (MC) among persons experiencing (CWND). The presence of (MC) was pathologically established in eight patients, accounting for 9.1% of the total sample. All these cases were identified as lymphocytic colitis. (NSC) was observed in 54 patients, representing 61.4% of the sample. Normal histology was found in 21 patients (23.9%), while incomplete microscopic colitis (IMC) was present in 3 patients (3.4%). Eosinophilic colitis was identified in one patient (1.1%), and inflammatory bowel disease (IBD) was diagnosed in another patient (1.1%) [15].

The diagnosis of MC was made in 9.5% to 14% of cases presented by chronic diarrhea with normal colonoscopy. Typical histological abnormalities findings in the case of MC include intraepithelial lymphocytosis, the lamina propria are infiltrated by inflammatory cells, and in CC, thickening of the subepithelial collagen band [23].

Furthermore, the histopathological abnormalities were diffusely distributed throughout the colon in ten patients (77%) with lymphocytic colitis, while the inflammatory changes were exclusively located in the transverse colon and ascending colon in three patients (23%), one of them had collagenous colitis. In these three patients (23%) the diagnosis could be missed if only sigmoidoscopy had been done [24].

Our study showed that regarding prevalence of active inflammation (neutrophils), was higher in patients who had ulcerations (81.1%) than in other mucosal findings categories revealing a statistical difference. Furthermore, the distribution of grade of chronic inflammation differed significantly among mucosal findings categories but without specific patterns. On the contrary, subepithelial collagen was normal in almost all patients. However, six patients with no mucosal findings during endoscopy displayed increased subepithelial collagen in histopathological findings causing significant differences.

In the same line, the pathology investigation included 255 patients, of whom 199 had CC and 56 LC [25].

The lamina propria was inflamed in the majority of biopsies from the entire colon of patients diagnosed with CC. In comparison to all other segments, the rectum was the sole segment in which cases were almost exclusively restricted, to the absence of inflammation (p < 0.05). The inflammation was more pronounced in the proximal colon (moderate and severe) than in the distal colon [25].

Although a significantly higher proportion of patients were classified as having little or mild inflammation in the rectum than any other section, it was discovered that this was less apparent in LC. LC patients exhibited more evident inflammation (moderate to severe) in all segments compared to CC, with the rectum and sigmoid colon exhibiting the most significant differences [25].

The thickness of the subepithelial collagenous band CC patients varied. In the proximal colon, it exhibits higher values. Additionally, the ratio of patients with a collagen band thickness exceeding > 10 μm in the rectum was significantly lower in the rectum compared with all other segments and in sigmoid compared with the descending and cecum/ascending colon, respectively. The average thickness of the collagenous band in patients with LC varied from 3.6 μm in the cecum/ascending colon to 3.9 μm in the transverse and descending colon [25].

CONCLUSION

Different types of colitis as ulcerative colitis, Crohn's disease, infectious colitis, and ischemic colitis vary in prevalence and are influenced by factors like age, gender, and underlying health conditions. Accurate diagnosis is crucial, as the management and treatment differ significantly among these types. Understanding the epidemiology of colitis types in chronic diarrhea patients can aid clinicians in making informed decisions, more effective interventions, and improved patient outcomes.

Ethics approval and consent to participate:

After receiving a brief and detailed description of the study's goals, the participant's legal guardian signed informed consent. The 1964 Declaration of Helsinki and its subsequent amendments or equivalent ethical standards, as well as the ethical standards established by the institutional and/or national research committee, were followed in all processes. The protocol of the current study was approved by the local Ethics Committee at the National Liver Institute (NLI) (IRB approval ID: (00642/2024) and obtained signed informed consent from all patients who were prospectively included.

Consent for publication: all authors have read and revised well for the manuscript and agree to publish.

Availability of data and material: All data supporting the study are presented in the manuscript or available upon request.

Competing interests: There is no conflict of interest.

Funding: The author received no financial support for this article's research, authorship, and publication.

Author contribution: We declare that all listed authors have made substantial contributions to all of the following three parts of the manuscript:

- Research design, acquisition, analysis, or interpretation of data.

- Drafting the paper or revising it critically.

- Approving the submitted version.

We also declare that no one who qualifies for authorship has been excluded from the list of authors.

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