Crohn Disease: An Enigmatic Variant with Gastritis and Ileal Obstruction Abstract There are multiple atypical manifestations of Crohn disease which sometimes delay diagnosis or even more often result in complete misdiagnosis especially in poorly equipped facilities. This is a case of an elderly woman with Crohn disease who presented with gastritis and bowel obstruction. She had hitherto been wrongly managed for peptic ulcer disease based mainly on her symptoms. Further workup revealed the actual diagnosis, only after years of failed symptomatic management. This case aims to highlight the uncommon and easily misdiagnosed gastroduodenal presentation of Crohn disease, as well as clinical clues to correctly diagnosing the condition. Keywords: Crohn disease, gastritis, intestinal obstruction, constipation Introduction Crohn disease falls under the umbrella of inflammatory bowel disease and can involve any part of the gastrointestinal tract. It is many a time misdiagnosed or diagnosed late.1 This is even more so when health centres are not well equipped to appropriately investigate it, as is the case in many developing countries. Common presentations include abdominal pain, diarrhea, unintentional weight loss and haematochezia. It is more prevalent in young adults.2 There are however enigmatic variants that do not present with these tell-tale symptoms. These include those that manifest with obstructive symptoms, dyspeptic symptoms as well as those with more extra-intestinal than gastrointestinal symptoms such as arthritis, aphthous stomatitis and uveitis. Case Presentation This is the case of a 78-year old Ghanaian woman who was admitted on account of an acute exacerbation of Crohn disease. She was diagnosed about a year prior to the index presentation, through an investigation for incomplete intestinal obstruction. No treatment was started after diagnosis on the patient’s request. The index presentation was a week’s history of severe generalized abdominal pain graded 9/10, colicky in her lower abdomen and burning in her epigastric region. It was associated with constipation (hard, scanty, infrequent stools averaging once a week) and vomiting which was non-projectile, non-bilious and non-bloody. The symptoms waxed and waned and were worst at night. She also reported having anorexia, and unintentional weight loss but no pain related to eating or fasting. Antacids gave partial relief to the epigastric pain. There was no abdominal distension related with her symptoms and her constipation was not absolute, as she was able to pass flatus. There was no alternation of the constipation with diarrhea and no melena or hematochezia. Her other symptoms included borborygmi, lower back and bilateral knee pain. She had hypertension well-controlled with amlodipine. She had completed empirical triple therapy for peptic ulcer disease several years prior to this presentation, but without resolution of her occasional dyspeptic symptoms. There was no history of abdominal surgeries and she had never smoked nor consumed alcohol. The lower abdominal symptoms were identical to those from her admission a year ago. Her physical examination showed a soft, non-distended abdomen which moved with respiration. There was generalized tenderness which was worst at her lower abdomen. There were no palpable masses, percussion notes were tympanitic and bowel sounds were high pitched and frequent. Both knees were mildly tender on passive joint movement (worse on the left) but not swollen or warm, and there was mild tenderness at her lower back. All other examination findings were normal. Her renal and liver function tests were normal. She however had normocytic normochromic anaemia of 10.6g/dl on her complete blood count and low calcium and magnesium levels of 1.61mmol/L, 1.07mmol/L respectively. An erect and supine abdominal x-ray showed mildly dilated jejunum as well as gall stones. A contrast CT scan of the abdomen showed mild to moderate narrowing of the mid segment of the ileum with prestenotic dilatation of the ileum and jejunum. The dilated bowel measured 3.8cm-4.5cm. There were no masses seen and the large bowel was normal. Both ESR and CRP were high (30mm/h and 147 respectively). Stool RE was normal and stool for occult blood and H. pylori antigen were negative. The final diagnosis was acute exacerbation of Crohn disease with partial ileal obstruction and gastroduodenal involvement. The noted Crohn disease associations were cholelithiasis, arthritis of both knees and sacroiliitis. Her calculated Crohn Disease Activity Index (CDAI) was 263, for moderate disease. She was hydrated with IV fluids, then put on hyoscine bromide for her crampy abdominal pains, IV omeprazole for her gastritis, IV metronidazole, SC enoxaparin for DVT prophylaxis and syrup lactulose for her constipation. After her vomiting subsided, she was switched to oral medications. Oral mesalazine 1g 6 hourly, oral prednisolone 30mg daily and oral paracetamol 1g 8 hourly were added to her medications. She showed improvement as well as reduced frequency of the flares and was finally discharged after 5 days on admission. Discussion Intestinal obstruction caused by strictures of Crohn disease widens the differential diagnoses for clinicians. These include intraluminal causes such as tumours, impacted feces and foreign bodies, intramural causes such as intussusception and extramural causes such as strangulated hernias, adhesions and volvulus.3-5 Most of these are purely surgical causes. It is no surprise this patient was managed by the general surgery team on her first admission. It is quite unusual that she had never experienced diarrhea at any point of the course of the disease because it is expected that before the strictures form, the preceding inflammation would irritative diarrheal symptoms.6 She also had peptic ulcer-like symptoms which had been treated unsuccessfully in the past. Because of the rareness of dyspepsia as a symptom of Crohn disease,7 it is unlikely to be the clue to the accurate diagnosis. Evidently, this patient had been managed empirically for peptic ulcer disease for a long time. It is common practice because of the low availability of endoscopy in the Central Region of the country. Her age of presentation is also unusual as it is usually diagnosed in the young. Intestinal strictures form part of the natural history of Crohn disease and will occur in up to 70% of patients over a 10-year period. 8 The strictures are classified as inflammatory, fibrotic, primary or anastomotic. 9 Inflammatory strictures result from edema of the intestinal lining while fibrotic ones are caused by chronic inflammation that results in accumulation of extracellular matrix and hyperproliferation of smooth muscle cells. 10 There are also mixed variants that have both mechanisms at play at the same time. Primary strictures are those that follow the natural history of the disease and anastomotic ones are those resulting from a surgical intervention; resection and anastomosis. This woman had a primary stricture which was most likely inflammatory because of the waxing and waning nature. Fibrotic strictures tend to produce a more constant type of obstruction. Medical management was her mainstay because of her advanced age and moderate disease severity (CDAI 263). Dietary modifications such as reducing fiber in diet is necessary for reducing obstructive symptoms by reducing stool bulk. Micronutrient supplementation may also be needed in cases where deficiencies such as hypocalcemia, hypomagnesemia and vitamin D are a concern due to malabsorption, as was in this patient. The deficiencies also result from anorexia caused by the abdominal pain (gastritis in this patient) and circulating inflammatory cytokines.11 Malabsorption is also the reason for formation of gallstones as in this patient (figure 1 and figure 2). The gallstones form as a result of failed reabsorption of bile acid and hence failed enterohepatic circulation, which in turn increases the concentration of cholesterol in the biliary system, precipitating the formation of cholesterol stones.12 It is usually asymptomatic and an incidental finding on radio imaging. Starting the patient on prednisolone and mesalazine resulted in a decline in symptoms by the 5th day of admission. 5-aminosalicylic acid derivatives such as mesalazine provide symptomatic relief for patients and remain the first line drugs for mild to moderate disease.13 Lactulose also improved her constipation by enabling her pass soft stools daily. Surgery is indicated in situations such as significant prestenotic dilatation, or presence of a fistula 8 ––none of which was present in this case. Gastroduodenal Crohn disease is not commonly symptomatic and seen in only about 4% of cases. 14 Its diagnosis is difficult as there are no specific or consistent pathological findings as well as the high prevalence of comorbidity with H. pylori gastritis. 15 Medical therapy is usually enough in most cases except for those with gastric outlet obstruction that may require surgery. 16 Conclusion Bowel obstruction from strictures in Crohn disease is a common complication which may not always be preceded by diarrhea in the early stages as was in this case. Gastroduodenal Crohn disease is uncommon but should be considered in all patients being worked up for Crohn disease who have dyspeptic symptoms. Negative H. pylori antigen tests or persistence of symptoms after eradication of H. pylori should increase suspicion for gastroduodenal Crohn disease. References 1. Card TR, Siffledeen J, Fleming, KM. Are IBD patients more likely to have a prior diagnosis of irritable bowel syndrome? Report of a case-control study in the General Practice Research Database. United European Gastroentrol J 2014 Dec; 2(6): 505-512. PMID: 25452846 2. Cheema YA, Munir M, Zainab K, Ogedegbe OJ. An Atypical Presentation of Crohn’s Disease: A Case Report. Cureus. 2022 Sep; 14(9): e29431. PMID: 36299929 3. Catena F, De Simone B, Coccolini F, Di Saverio S, Sartelli M, Ansaloni L. Bowel obstruction: a narrative review for all physicians. World J Emerg Surg. 2019 Apr; 20 (14) 4. Yeo HL, Lee SW. Colorectal emergencies: review and controversies in the management of large bowel obstruction. J Gastrointest Surg. 2013; 17(11): 2007-12 5. Roses RE, Folkert IW, Krouse RS. Malignant bowel obstruction: reappraising the value of surgery. Surg Oncol Clin N Am. 2018; 27(4): 705-15 6. Anbazhagan AN, Priyamvada S, Alrefai, WA, Dudeja PK. Pathophysiology of IBD associated diarrhea. Tissue Barriers. 2018; 6(2): e1463897. PMID: 29737913 7. Zhi TX, Hong GJ, Li T, Sun D, Yu XD, Chen QZ, Li T. Gastric Crohn’s Disease: A Rare Cause of Intermittent Abdominal Pain and Vomiting. Am J Med. 2017; 130 (5) 8. Lin X, Wang Y, Liu Z, Lin S, Tan J, He J, Hu F, Wu X, Ghosh S, Chen M, Liu F, Mao R. Intestinal Strictures in Crohn’s disease: a 2021 update 9. Ismail MS, Charabaty A. Management of Crohn’s stricture: medical, endoscopic and surgical therapies. Frontline Gastroenterology 2022; 13:524-530 10. Rieder F, Fiocchi C, Rogler G. Mechanisms, management and treatment of fibrosis in patients with inflammatory bowel diseases. Gastroenterology 2017; 152:340-50. PMID: 27720839 11. Naser SA, Abdelsalam A, Thanigachalam S, Naser SA, Alcedo K. Domino effect of hypomagnesemia on the innate immunity of Crohn’s disease patients. World J Diabetes. 2014 Aug; 5(4): 527-535. PMID: 25126398 12. Fevery, J. Pigment gallstones in Crohn’s disease. Gastroenterology. 1999; 116(6): 1492-1494 13. Iacucci M, de Silva S, Ghosh S. Mesalazine in inflammatory bowel disease: A trendy topic once again? Can J Gastroenterol. 2010 Feb; 24(20):127-133. PMID: 20151072 14. Steckstor M, Adam B, Pech O, Tannapfel A, Riphaus A. Gastroduodenal Crohn’s Disease. Video Journal and Encyclopedia of GI Endoscopy 2013; 1: 178-79 15. Ingle SB, Hinge CR, Dakhure S, Bhosale SS. Isolated gastric Crohn’s disease. World J Clin Cases. 2013; 1(2): 71-73. PMID: 3845940 16. Ibrahim SH, Smyrk TC, Faubion WA. Treatment of isolated gastric Crohn’s disease with inhaled corticosteroids. Case Re

Crohn Disease: An Enigmatic Variant with Gastritis and Ileal ObstructionAbstractThere are multiple atypical manifestations of Crohn disease which sometimes delay diagnosis or even more often result in complete misdiagnosis especially in poorly equipped facilities. This is a case of an elderly woman with Crohn disease who presented with gastritis and bowel obstruction. She had hitherto been wrongly managed for peptic ulcer disease and functional constipation based mainly on her symptoms. Her diagnosis was made only after years of failed symptomatic management. This case aims to highlight the uncommon and easily misdiagnosed gastroduodenal presentation of Crohn disease, as well as clinical clues to correctly diagnosing the condition.Keywords: Crohn disease, gastritis, intestinal obstruction, constipationIntroductionCrohn disease falls under the umbrella of inflammatory bowel disease and can involve any part of the gastrointestinal tract. It is many a time misdiagnosed or diagnosed late.1 This is even more so when health centres are not well equipped to appropriately investigate it, as is the case in many developing countries. Common presentations include abdominal pain, diarrhea, unintentional weight loss and haematochezia. It is more prevalent in young adults.2There are however enigmatic variants that do not present with these tell-tale symptoms. These include those that manifest with obstructive symptoms, dyspeptic symptoms as well as those with more extra-intestinal than gastrointestinal symptoms such as arthritis, aphthous stomatitis and uveitis.Case PresentationThis is the case of a 78-year old Ghanaian woman who was admitted on account of an acute exacerbation of Crohn disease. She was diagnosed about a year prior to the index presentation, through an investigation for incomplete intestinal obstruction. No treatment was started after diagnosis as she declined medical interventions. The index presentation was a week’s history of severe generalized abdominal pain graded 9/10; colicky in her lower abdomen and burning in her epigastric region. It was associated with constipation (hard, scanty, infrequent stools averaging once a week) and vomiting which was non-projectile, non-bilious and non-bloody. The symptoms waxed and waned and were worst at night. She also reported having anorexia, and unintentional weight loss but no pain related to eating or fasting. Antacids gave partial relief to the epigastric pain. There was no abdominal distension related with her symptoms and her constipation was not absolute, as she was able to pass flatus. There was no alternation of the constipation with diarrhea and no melena or hematochezia. Her other symptoms included borborygmi, lower back and bilateral knee pain. She had hypertension well-controlled on amlodipine. She had completed empirical triple therapy for peptic ulcer disease several years prior to this presentation, but without resolution of her occasional dyspeptic symptoms. There was no history of abdominal surgeries and she had never smoked nor consumed alcohol.Her physical examination showed a soft, non-distended abdomen which moved with respiration. There was generalized tenderness which was worst at her lower abdomen. There were no palpable masses, percussion notes were tympanitic and bowel sounds were high pitched and frequent. Both knees were mildly tender on passive joint movement and worse on the left, without warmth or swelling, and there was mild tenderness at her lower back. All other examination findings were normal.Her renal and liver function tests were normal. She however had normocytic normochromic anaemia of 10.6g/dl on her complete blood count and low calcium and magnesium levels of 1.61mmol/L, 1.07mmol/L respectively. An erect and supine abdominal x-ray showed mildly dilated jejunum as well as gall stones. A contrast CT scan of the abdomen showed mild to moderate narrowing of the mid segment of the ileum with prestenotic dilatation of the ileum and jejunum. The dilated bowel measured 3.8cm-4.5cm. There were no masses seen and the large bowel was normal. Both ESR and CRP were high (30mm/h and 147mg/L respectively). Stool RE was normal and stool for occult blood and H. pylori antigen were negative.She was then managed for acute exacerbation of Crohn disease with partial ileal obstruction and gastroduodenal involvement. The noted Crohn disease associations were cholelithiasis, arthritis of both knees and sacroiliitis. Her calculated Crohn Disease Activity Index (CDAI) was 263, for moderate disease. She was hydrated with IV fluids, then put on hyoscine bromide for her crampy abdominal pains, IV omeprazole for her gastritis, SC enoxaparin for DVT prophylaxis and syrup lactulose for her constipation. After her vomiting subsided, she was switched to oral medications. Oral mesalazine 1g 6 hourly, oral prednisolone 30mg daily and oral paracetamol 1g 8 hourly were added to these medications. She had dietary interventions such as reducing meal fiber as well. She improved and had a significantly reduced frequency of the flares and was finally discharged after 5 days on admission.DiscussionIntestinal obstruction caused by strictures of Crohn disease widens the differential diagnoses for clinicians. These include intraluminal causes such as tumours, impacted feces and foreign bodies, intramural causes such as intussusception and extramural causes such as strangulated hernias, adhesions and volvulus.3-5 Most of these are purely surgical causes. It is no surprise this patient was managed by the general surgery team on her first admission. It is quite unusual that she had never experienced diarrhea at any point of the course of the disease because it is expected that before the strictures form, the preceding inflammation would cause irritative diarrheal symptoms.6 She also had peptic ulcer-like symptoms which had been treated unsuccessfully in the past. That she was managed empirically for peptic ulcer disease for a long period is because of the low availability of endoscopy in the Central Region of the country. Lack of these investigative facilities and low socioeconomic status result in the frequent use of mainly clinical impressions to make diagnoses in smaller facilities. Since dyspeptic symptoms are rare in Crohn disease,7 they are unlikely to be the clinical clue to the accurate diagnosis, which unfortunately was the case in this patient for several years. Her age of presentation was also unusual as Crohn disease is usually diagnosed in the young.Intestinal strictures form part of the natural history of Crohn disease and will occur in up to 70% of patients over a 10-year period.8 The strictures are classified as inflammatory, fibrotic, primary or anastomotic. 9 Inflammatory strictures result from edema of the intestinal lining while fibrotic ones are caused by chronic inflammation that results in accumulation of extracellular matrix and hyperproliferation of smooth muscle cells.10 There are also mixed variants that have both mechanisms at play at the same time. Primary strictures are those that follow the natural history of the disease and anastomotic ones are those resulting from a surgical intervention; resection and anastomosis. This woman had a primary stricture which was most likely mixed inflammatory and fibrotic because of the waxing and waning nature of her baseline constipation associated with the flares. Fibrotic strictures tend to produce a more constant type of obstruction while inflammatory ones occur in waves.Medical management was her mainstay because of her advanced age and moderate disease severity (CDAI 263). Dietary modifications such as reducing fiber in diet is necessary for reducing obstructive symptoms by reducing stool bulk to enable it bypass strictures.9Micronutrient supplementation may also be needed in cases where deficiencies such as hypocalcemia, hypomagnesemia and vitamin D are a concern due to malabsorption, as was in this patient. The deficiencies also result from anorexia caused by the abdominal pain (gastritis in this patient) and circulating inflammatory cytokines.11 Malabsorption is also the reason for formation of gallstones as in this patient (figure 1 and figure 2). The gallstones form as a result of failed reabsorption of bile acid and hence failed enterohepatic circulation, which in turn increases the concentration of cholesterol in the biliary system, precipitating the formation of cholesterol stones.12 It is usually asymptomatic and an incidental finding on radio imaging.Starting the patient on prednisolone and mesalazine resulted in a decline in symptoms by the 5th day of admission. 5-aminosalicylic acid derivatives such as mesalazine provide symptomatic relief for patients and remain the first line drugs for mild to moderate disease.13 Lactulose also improved her constipation by enabling her pass soft stools daily.Surgery is indicated in situations such as significant prestenotic dilatation, or presence of a fistula 8 —-none of which was present in this case.Gastroduodenal Crohn disease is not commonly symptomatic and seen in only about 4% of cases. 14 Its diagnosis is difficult because there are no specific or consistent pathological findings as well as the high prevalence of comorbidity with H. pylori gastritis.15 Medical therapy is usually enough in most cases except for those with gastric outlet obstruction that may require surgery. 16ConclusionBowel obstruction from strictures in Crohn disease is a common complication which may not always be preceded by diarrhea in the early stages as was in this case. Gastroduodenal Crohn disease is uncommon but should be considered in all patients being worked up for Crohn disease who have dyspeptic symptoms. Negative H. pylori antigen tests or persistence of symptoms after eradication of H. pylori should increase suspicion for gastroduodenal Crohn disease. These clinical clues are necessary not only for poorly equipped facilities, but also those that have all the investigative capacity in order to prioritize investigations and intervene as soon as possible.ReferencesCard TR, Siffledeen J, Fleming, KM. Are IBD patients more likely to have a prior diagnosis of irritable bowel syndrome? Report of a case-control study in the General Practice Research Database. United European Gastroentrol J 2014 Dec; 2(6): 505-512. PMID: 25452846Cheema YA, Munir M, Zainab K, Ogedegbe OJ. An Atypical Presentation of Crohn’s Disease: A Case Report. Cureus. 2022 Sep; 14(9): e29431. PMID: 36299929Catena F, De Simone B, Coccolini F, Di Saverio S, Sartelli M, Ansaloni L. Bowel obstruction: a narrative review for all physicians. World J Emerg Surg. 2019 Apr; 20 (14)Yeo HL, Lee SW. Colorectal emergencies: review and controversies in the management of large bowel obstruction. J Gastrointest Surg. 2013; 17(11): 2007-12Roses RE, Folkert IW, Krouse RS. Malignant bowel obstruction: reappraising the value of surgery. Surg Oncol Clin N Am. 2018; 27(4): 705-15Anbazhagan AN, Priyamvada S, Alrefai, WA, Dudeja PK. Pathophysiology of IBD associated diarrhea. Tissue Barriers. 2018; 6(2): e1463897. PMID: 29737913Zhi TX, Hong GJ, Li T, Sun D, Yu XD, Chen QZ, Li T. Gastric Crohn’s Disease: A Rare Cause of Intermittent Abdominal Pain and Vomiting. Am J Med. 2017; 130 (5)Lin X, Wang Y, Liu Z, Lin S, Tan J, He J, Hu F, Wu X, Ghosh S, Chen M, Liu F, Mao R. Intestinal Strictures in Crohn’s disease: a 2021 updateIsmail MS, Charabaty A. Management of Crohn’s stricture: medical, endoscopic and surgical therapies. Frontline Gastroenterology 2022; 13:524-530Rieder F, Fiocchi C, Rogler G. Mechanisms, management and treatment of fibrosis in patients with inflammatory bowel diseases. Gastroenterology 2017; 152:340-50. PMID: 27720839Naser SA, Abdelsalam A, Thanigachalam S, Naser SA, Alcedo K. Domino effect of hypomagnesemia on the innate immunity of Crohn’s disease patients. World J Diabetes. 2014 Aug; 5(4): 527-535. PMID: 25126398Fevery, J. Pigment gallstones in Crohn’s disease. Gastroenterology. 1999; 116(6): 1492-1494Iacucci M, de Silva S, Ghosh S. Mesalazine in inflammatory bowel disease: A trendy topic once again? Can J Gastroenterol. 2010 Feb; 24(20):127-133. PMID: 20151072Steckstor M, Adam B, Pech O, Tannapfel A, Riphaus A. Gastroduodenal Crohn’s Disease. Video Journal and Encyclopedia of GI Endoscopy 2013; 1: 178-79Ingle SB, Hinge CR, Dakhure S, Bhosale SS. Isolated gastric Crohn’s disease. World J Clin Cases. 2013; 1(2): 71-73. PMID: 3845940Ibrahim SH, Smyrk TC, Faubion WA. Treatment of isolated gastric Crohn’s disease with inhaled corticosteroids. Case Rep Gastroenterol. 2008 Nov 5; 2(3): 363-8. PMID: PMC3075198