- Email: [email protected]
26-Year-Old Man With New Abdominal Pain
RESIDENTS’ CLINIC
26-Year-Old Man With New Abdominal Pain Ali A. Alsaad, MBChB; Mark R. Waddle, MD; and Michael J. Maniaci, MD
A
26-year-old man presented to our emergency department at 6:00 AM with new onset of stabbing and burning upper left quadrant abdominal pain that had begun 2 hours previously. He indicated that the pain was an 8 on the visual analog pain scale (10 is the maximum score) with radiation to the epigastrium. He had taken 600 mg of ibuprofen 1 hour before presentation, but it failed to relieve the pain. The pain was associated with abdominal distention, nausea without vomiting, retching, and excessive flatulence. The patient had experienced both epigastric and abdominal discomfort (which he rated as 3) 5 to 6 times per year during the 2 years before presentation. This discomfort had become more frequent and more intense (rated as 5) in the 2 months before presentation to our emergency department. The patient reported that the consistency of his stools had become more loose and bulky without blood or melena over the previous 6 months. He had also noticed a 6.75-kg unintentional weight loss over the previous 3 months. His last bowel movement was the night before presentation and consisted of loose stool mixed with a small amount of bright red blood, which he had attributed to an anal fissure. His girlfriend had noticed an area of patchy hair loss on the occipital scalp, which had started 2 weeks before presentation and had progressively increased. He reported the recurrence of a painful aphthous ulceration 2 to 3 times per month that he treated with a triamcinolone topical solution prescribed by his primary care physician. Over the preceding 2 weeks, he noticed an increasing acidicbitter taste in his mouth and an irritated throat with globus sensation. The patient reported no fever, chills, night sweats, cough, anorexia, or vomiting. He had no recent sick contacts, dietary changes, or travel outside the United States. Six months before presentation, an anal fissure was diagnosed and treated topically with lidocaine and hydrocortisone cream.
His medical history was notable for gastroesophageal reflux disease (GERD) in the previous 2 years and chronic sinus congestion for which treatment failed to provide adequate symptomatic relief. His medications included ranitidine, nasal flunisolide, and loratadine. He had a false-positive result on routine human immunodeficiency virus (HIV) screening 2 months before presentation. Western blot and reverse transcriptionepolymerase chain reaction were both negative for HIV. He had a history of childhood asthma that resolved by the age of 6 years. His surgical history included a tonsillectomy at age 8 years. He had no history of upper endoscopy or colonoscopy. His family history included type 2 diabetes mellitus, hypertension, and vitiligo on his father’s side. No medical illnesses were noted from his mother’s side. He had a 1-year history of tobacco use of 1 pack per day starting at age 20 years and ending at age 21 years. He did not use alcohol or illicit drugs. Physical examination revealed a patient in moderate distress. He was alert and oriented to person, place, and time. His temperature was 36.8 C, heart rate was 117 beats/min, blood pressure was 130/85 mm Hg, and respiratory rate was 19 breaths/min. Pulse oximetry revealed an oxygen saturation of 99% while the patient breathed room air. There was no pallor or jaundice. He had no chest tenderness on palpation, and his lungs were clear on auscultation. Cardiac examination revealed a normal S1 and S2 without S3, S4, or murmur. No raised jugular vein distention was found on examination. Abdominal examination revealed epigastric tenderness to deep palpation with no rebound tenderness. He had a distended abdomen with hyperactive bowel sounds throughout all quadrants. No rigidity, palpable masses, or organomegaly were noted on superficial or deep palpation. On rectal examination, a small (1 1.5-cm) anal ulcer was noted at the 11-o’clock position, and he had positive results on a stool guaiac test. Ophthalmologic
Mayo Clin Proc. n XXX 2016;nn(n):e1-e6 n http://dx.doi.org/10.1016/j.mayocp.2016.03.010 www.mayoclinicproceedings.org n ª 2016 Mayo Foundation for Medical Education and Research
See end of article for correct answers to questions. Resident in Internal Medicine, Mayo School of Graduate Medical Education, Jacksonville, FL (A.A.A., M.R.W.); Advisor to residents and Consultant in Hospital Internal Medicine, Mayo Clinic, Jacksonville, FL (M.J.M.).
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examination findings were unremarkable. A 3 4-cm area of hair loss with a fragile border was noted on the occipital scalp. There was no evidence of erythema, scaling, or discharge. In the emergency department, the patient received intravenous hydration with 0.9% sodium chloride, intravenous pantoprazole, and intravenous morphine. A complete blood cell count revealed a white blood cell count of 11.7 109/L, a hemoglobin level of 13.6 mg/dL, and a platelet count of 315 109/L. His venous lactate level was not elevated. Results of a complete metabolic panel including a lipase test and liver function test were all within normal limits. 1. At this time, which one of the following is the best diagnostic test? a. Abdominal ultrasonography b. Fluoroscopy with barium ingestion c. Computed tomography (CT) of the abdomen with contrast medium d. Magnetic resonance imaging (MRI) of the abdomen e. Explorative laparoscopy Although it is convenient because it is noninvasive and can be performed quickly at the bedside by a qualified physician, abdominal ultrasonography is not the optimal test to evaluate the bowel status. Its major limitation is low sensitivity and specificity in diagnosing most bowel disorders because of bowel gas interference, although it may be helpful in identifying acute bowel ischemia. Physicians who perform acute-care ultrasonography in patients with suspected mechanical small-bowel obstruction should be aware of the warning signs of an ischemic bowel loop, including the detection of intraperitoneal free fluid, thickening of the bowel wall to more than 4 mm, and an acute reduction of previously detected bowel hyperactivity.1 Historically, fluoroscopy was considered a good and readily available test to evaluate acute abdominal pain because of its superiority to abdominal radiography. Although fluoroscopy does have some value in evaluating upper gastrointestinal tract disease, it is no longer a first-line test because it is not as rapidly available as CT and it exposes the patient to more radiation, increasing risk to the patient. By contrast, CT with contrast medium is a fast e2
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and generally safe test with good sensitivity and specificity for acute abdominal disease. Although the role of MRI in the evaluation of inflammatory bowel diseases is expanding because it has high soft-tissue penetration and lack of radiation exposure,2 MRI of the abdomen should never be considered a firstline test in patients with no contraindications to CT because of the high cost and extended testing time associated with MRI. Explorative laparoscopy should not be considered without signs of an “acute surgical abdomen” (an acute abdominal condition requiring emergent surgical intervention). This procedure is often performed only after radiographic and diagnostic testing indicates that surgical treatment is needed. Our patient underwent contrast-enhanced abdominal CT, which revealed 2 sites of intussusception (telescoping) of the small bowel. The first was in the left upper quadrant and measured about 3.5 cm. The second was in the right upper quadrant and measured about 2.6 cm. Both areas were surrounded by nonspecific small lymph nodes. The bowel segments proximal to both intussusception sites were thickened, suggestive of chronic inflammation. No abdominal masses were seen. 2. On the basis of the CT findings, which one of the following is the most likely underlying cause of this patient’s intussusception? a. Multiple malignant bowel metastases b. Gluten-sensitivity enteropathy c. AIDS-related bowel intussusception d. Abdominal adhesions e. Intestinal lipoma Although the patient had experienced some weight loss, he had no other signs or symptoms of a neoplastic process, and CT identified no metastatic lesions in the abdomen. A chronic inflammatory process such as inflammatory bowel disease, Behçet disease, or gluten-sensitivity enteropathy (celiac disease) is the most likely cause of our patient’s intussusception because of the multiple sites of intussusception without distinct masses. AIDS-related small-bowel intussusception has been widely reported in HIV-infected patients with active AIDS. Our patient had negative results on a Western blot test and
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reverse-transcriptionepolymerase chain reaction for HIV just 2 months before presentation, making AIDS-related small-bowel intussusception unlikely. Abdominal adhesions are a common cause of small-bowel obstruction but rarely cause intussusception and occur almost exclusively in patients who have undergone an intra-abdominal operation previously.3 Our patient had no history of an intra-abdominal surgical procedure. Lipoma is a common cause of intussusception but usually occurs at a single point, and it is uncommon for it to occur in multiple areas of the bowel and result in multiple intussusceptions, as seen in our patient.3 Furthermore, intestinal lipomas can often be visualized on CT, and none were seen on our patient’s CT scan. The multiple sites of intussusception should raise suspicion for an inflammatory process, particularly celiac disease and inflammatory bowel diseases.3,4 The general surgery service was consulted about the case. They recommended a gastrointestinal radiographic series with barium followthrough study to better characterize the location of the intussusception and to define the level of obstruction, if any. The barium series revealed delayed emptying of contrast medium from the small to the large bowel, indicating a possible partial bowel obstruction. No areas of intussusception or intestinal masses were seen in the study. Normal results on barium follow-through study are classically found in most nonemass-related intussusceptions.5 3. Which one of the following is the best next step in the management of this patient’s intussusception? a. Pneumatic reduction b. Diatrizoic acid reduction c. Surgical reduction d. Surgical resection e. Conservative medical management In adult intussusception, unlike that in children, pneumatic or diatrizoic acid reduction is not recommended. The decision for surgical intervention is usually based on CT and clinical examination findings. Iodinated contrast-enhanced CT of the abdomen seems to be the most reliable radiographic imaging test for establishing a diagnosis in adults with intussusception before surgical intervention can be considered, especially for patients Mayo Clin Proc. n XXX 2016;nn(n):e1-e6 www.mayoclinicproceedings.org
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with poorly localized nonspecific abdominal pain.6 If a lead point (like a mass) is suggested on CT, early surgical intervention is usually necessary. The findings of an acute surgical abdomen, elevated inflammatory markers, or increased lactate levels also indicate early surgical intervention. When surgical intervention is warranted, the decision for resection vs intraoperative reduction is controversial.6 If there are no indications for surgical intervention, conservative management can be done safely. Observation for suspected acute abdomen or intestinal obstruction has historically been indicated for 48 to 72 hours. Young patients with no comorbidities and improved or stabilized medical conditions could be discharged home to complete follow-up as an outpatient. Because our patient did not have an acute surgical abdomen, he was admitted to the hospital for observation and supportive management. No clinical deterioration or worsening of symptoms was reported in the next 72 hours, and the intussusception spontaneously resolved. He tolerated a liquid diet after passing a bowel movement. He was discharged home and had follow-up blood work and a gastroenterology clinic visit scheduled for 2 weeks after discharge. Laboratory testing performed before his return gastroenterology clinic visit revealed ferritin, vitamin B12, and vitamin D levels all within the lower limit of normal. Test results for HIV-1 and HIV-2 antibodies were negative. IgA and IgG antie tissue transglutaminase antibodies were present with elevated titers. 4. On the basis of these laboratory findings, which one of the following would be the best next step in this patient’s management? a. Colonoscopy with biopsy b. Repeated antietissue transglutaminase antibody serologic testing c. Antiegliadin antibody assay d. Esophagogastroduodenoscopy (EGD) with biopsy e. Oral iron and calcium supplementation and repeat laboratory tests in 4 to 6 weeks There is no indication to perform colonoscopy or repeat serologic studies at this point because neither would provide further
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diagnostic evidence. Antiegliadin antibody assays are not as sensitive and specific as IgA and IgG antietissue transglutaminase antibody tests and would not be helpful in this situation. Generally, after a serologic diagnosis of celiac disease with positive antibody results, it is crucial to perform an EGD with biopsy to confirm the diagnosis by histopathologic examination.7 Supplementation of calcium and iron is necessary in patients with celiac disease, but ruling out a malignant neoplasm is the best next step in managing this patient’s condition. The patient’s EGD revealed atrophic and erythematous duodenitis with loss of the general duodenal architecture. Biopsy results from the second part of the duodenum and duodenal bulb revealed areas of partial to complete villous atrophy, low goblet cell numbers with crypt/foveolar hyperplasia, and numerous lymphocytes in the lamina propria consistent with active celiac disease. No signs of lymphoma were seen on these biopsy specimens. There was concern that our patient’s multiple sites of intussusception might represent several areas of bowel affected by mucosal lymphoma, both because of this tumor’s propensity to occur in patients with celiac disease and because of the finding of multiple thickened bowel segments on CT.7 Because the patient did not meet the criteria for surgical exploration, the recommendation was to further investigate his bowel segments to conclusively rule out gut-related lymphoma. Capsule endoscopy to visualize the entire bowel and double-balloon enteroscopy (pushand-pull enteroscopy) were discussed with the patient as the proper next steps after EGD with biopsy to assess for lymphoma. The patient declined both procedures and agreed to repeating CT at 3-month intervals to confirm the resolution of the enlarged lymph nodes and thickened bowel segments near the intussusception sites. The final diagnosis was latent celiac disease with small-bowel intussusception. 5. Which one of the following treatment plans will help prevent recurrence of this patient’s intussusception and also treat his underlying illness? a. Gluten-free diet b. Immunosuppression with rituximab
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c. Three-week glucocorticoid burst and taper d. Small-bowel resection e. Observation The first-line treatment for celiac disease is a gluten-free diet. Strict adherence to a glutenfree diet has been found to be highly effective in eliminating symptoms, reducing the rate of complications in most cases, and reversing intestinal mucosal damage over time. Further, a gluten-free diet is readily available and more effective than alternative treatments and is not associated with the harmful adverse effects of other potential therapies such as immunosuppression and corticosteroids. Immunosuppression is not recommended for patients with celiac disease because it carries a high risk of adverse effects with shortand long-term complications. Rituximab and glucocorticoids should be avoided because they can cause profound B-lymphocyte dysfunction and may lead to the emergence of severe infections like tuberculosis. Also, no immunosuppression therapy has been found to be more effective than a gluten-free diet for patients with celiac disease. Unlike Crohn disease, celiac enteropathy rarely requires small-bowel resection. Unresolved intussusception and tumors represent the majority of those rare surgical indications. Adults infrequently achieve complete mucosal healing even if they adhere to a strict glutenfree diet. However, partial restoration of the mucosal architecture occurs after adopting a gluten-free diet in most patients with celiac disease.8 Observation is unacceptable in this situation. Continued ingestion of a glutencontaining diet in this patient may lead to persistent symptoms, recurrence of intussusception, and possible emergence of a malignant small-bowel mucosal-related lymphoma. A strict gluten-free diet was prescribed, and after 3 months, the patient had dramatic improvement with complete resolution of his abdominal pain and GERD. Repeated CT of the abdomen at that time confirmed resolution of the 2 areas of intussusception as well as the enlarged lymph nodes and small-bowel wall thickening. He also had great reduction in the bitter taste in his mouth, and his abdominal bloating had completely resolved. He
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gained 2.25 kg during the 3 months and reported no more anal pain. At the 3-month follow-up visit, the only remaining symptom was the alopecia areata. The size of the scalp lesion had grown to about 10 8 cm. His response to local triamcinolone injection was minimal after the first visit. The patient was advised to have additional visits for injections. DISCUSSION The final diagnosis for our patient’s abdominal pain was celiac diseaseeinduced small-bowel intussusceptions. Intussusception is defined as the invagination of one portion of the bowel into an immediately adjacent portion.9 The intussusception lead point can be 1 of 3 main types: mucosal, intramural, or extraintestinal. The lead point can be the nidus that pulls the proximal portion of the intestine into the distal part, resulting in telescoping.1,9 Intussusception is rare in adults,4 and its diagnosis can be challenging. Diagnosing intussusception preoperatively can be difficult, and thus, many cases are diagnosed during laparotomy9 or laparoscopy. However, the more frequent use of CT has increased the rate of preoperative detection.4 Nevertheless, only half of adult intussusception cases can be diagnosed preoperatively by CT or abdominal ultrasonography.3 More frequent use of CT in patients with undiagnosed abdominal pain increases the pick-up rate.10 The hallmark radiographic feature of intussusception on both CT and abdominal ultrasonography is the target sign.5,6 Idiopathic intussusception of the small bowel accounts for 8% to 20% of all cases of intussusception.5 Adult intussusception can have benign or malignant causes. Benign causes include inflammatory bowel diseases such as Crohn disease and celiac disease, lipoma, and trauma. Malignant causes include small intestinal lymphoma, adenocarcinoma, neuroendocrine tumors, and malignant metastases to the bowel.5 Adult intussusceptions have been categorized according to the site of origin: enteric, ileocolic, ileocecal, and colonic.11 Because our patient had 2 sites of enteric intussusception, we suspected an inflammatory process, which could affect multiple areas. Intussusception has been found as a rare but noted complication of celiac disease. It can be the initial presentation of celiac disease Mayo Clin Proc. n XXX 2016;nn(n):e1-e6 www.mayoclinicproceedings.org
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and is often associated with symptoms of vague, frequent, poorly localized abdominal pain. Bowel lymphoma should be excluded in this group of patients.4 Celiac disease should be suspected in adults when intussusception is detected radiographically or surgically.9 Most patients do not experience recurrence of their symptoms when they adhere to a gluten-free diet. The trigger in our case was chronic mucosal inflammation and irritation, with the possible enlargement of underlying Peyer patches. These factors led to the telescoping of the proximal small intestinal loop through the distal loop. The reactive mesenteric lymphadenopathy could be an initiating trigger of the intussusception as well. The mucosal chronic irritation and inflammation likely improved after gluten was removed from the patient’s diet. Other causes of intussusception include Crohn disease, intestinal polyps, lymphadenopathy, and benign or malignant tumors. Intussusception in adults can cause complete or partial bowel obstruction, which may not necessarily present as “currant jelly” stool as it does in pediatric patients. Intussusception represents only 1% of bowel obstruction causes for adults in the United States; it is rare for patients with celiac disease to have it as the initial presentation. Our patient had intussusceptions of 3.5 cm and 2.6 cm, both of which resolved spontaneously. This outcome is consistent with findings in the study by Lvoff et al,12 which examined features of self-limiting adult small-bowel intussusception and those that required surgical correction based on radiologic findings. They found that intussusceptions detected by CT of the abdomen that are shorter than 3.5 cm have a high likelihood of resolving spontaneously and would not require surgical intervention.12 The patient’s other symptoms can be explained by celiac disease. GERD can occur in 7% to 17% of patients with celiac disease. However, GERD is probably no more common in celiac disease than in the general population. A recent cohort study to evaluate the cost-effectiveness of routine duodenal biopsy for celiac disease during endoscopy in patients with GERD revealed that it is not cost-effective to perform biopsy analysis to detect celiac
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disease in patients undergoing EGD for refractory GERD, with the exception of patients from geographic areas with a high prevalence of celiac disease (1.8% or greater).8 Aphthous stomatitis occurs frequently in this group of patients. About 18% of patients with celiac disease may experience aphthous stomatitis.7,13 Alopecia areata is linked to many autoimmune diseases and has been reported to occur with celiac disease.13 Celiac disease is common in Western societies. Its association with adult intussusception is rare but well reported. Intussusception in adults with celiac disease can resolve spontaneously after adoption of a gluten-free diet. Surgical intervention may be required in more complicated cases. Correspondence: Address to Michael J. Maniaci, MD, Division of Hospital Internal Medicine, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224 ([email protected]).
REFERENCES 1. Hefny AF, Corr P, Abu-Zidan FM. The role of ultrasound in the management of intestinal obstruction. J Emerg Trauma Shock. 2012;5(1):84-86. 2. Gee MS, Harisinghani MG. MRI in patients with inflammatory bowel disease. J Magn Reson Imaging. 2011;33(3):527-534.
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3. Marinis A, Yiallourou A, Samanides L, et al. Intussusception of the bowel in adults: a review. World J Gastroenterol. 2009;15(4): 407-411. 4. Gonda TA, Khan SU, Cheng J, Lewis SK, Rubin M, Green PH. Association of intussusception and celiac disease in adults. Dig Dis Sci. 2010;55(10):2899-2903. 5. Azar T, Berger DL. Adult intussusception. Ann Surg. 1997; 226(2):134-138. 6. Gayer G, Zissin R, Apter S, Papa M, Hertz M. Pictorial review: adult intussusceptionda CT diagnosis. Br J Radiol. 2002; 75(890):185-190. 7. Volta U, Caio G, Stanghellini V, De Giorgio R. The changing clinical profile of celiac disease: a 15-year experience (1998-2012) in an Italian referral center. BMC Gastroenterol. 2014;14:194. 8. Yang JJ, Thanataveerat A, Green PH, Lebwohl B. Cost effectiveness of routine duodenal biopsy analysis for celiac disease during endoscopy for gastroesophageal reflux. Clin Gastroenterol Hepatol. 2015;13(8):1437-1443. 9. Ilias EJ, Kassab P, Castro OA. Intestinal intussusception. Rev Assoc Med Bras. 2012;58(4):404-405. 10. Yalamarthi S, Smith RC. Adult intussusception: case reports and review of literature. Postgrad Med J. 2005;81(953):174-177. 11. Weilbaecher D, Bolin JA, Hearn D, Ogden W II. Intussusception in adults: review of 160 cases. Am J Surg. 1971;121(5): 531-535. 12. Lvoff N, Breiman RS, Coakley FV, Lu Y, Warren RS. Distinguishing features of self-limiting adult small-bowel intussusception identified at CT. Radiology. 2003;227(1):68-72. 13. Denham JM, Hill ID. Celiac disease and autoimmunity: review and controversies. Curr Allergy Asthma Rep. 2013;13(4): 347-353.
CORRECT ANSWERS: 1. c. 2. b. 3. e. 4. d. 5. a
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26-Year-Old Man With New Abdominal Pain Ali A. Alsaad, MBChB; Mark R. Waddle, MD; and Michael J. Maniaci, MD
A
26-year-old man presented to our emergency department at 6:00 AM with new onset of stabbing and burning upper left quadrant abdominal pain that had begun 2 hours previously. He indicated that the pain was an 8 on the visual analog pain scale (10 is the maximum score) with radiation to the epigastrium. He had taken 600 mg of ibuprofen 1 hour before presentation, but it failed to relieve the pain. The pain was associated with abdominal distention, nausea without vomiting, retching, and excessive flatulence. The patient had experienced both epigastric and abdominal discomfort (which he rated as 3) 5 to 6 times per year during the 2 years before presentation. This discomfort had become more frequent and more intense (rated as 5) in the 2 months before presentation to our emergency department. The patient reported that the consistency of his stools had become more loose and bulky without blood or melena over the previous 6 months. He had also noticed a 6.75-kg unintentional weight loss over the previous 3 months. His last bowel movement was the night before presentation and consisted of loose stool mixed with a small amount of bright red blood, which he had attributed to an anal fissure. His girlfriend had noticed an area of patchy hair loss on the occipital scalp, which had started 2 weeks before presentation and had progressively increased. He reported the recurrence of a painful aphthous ulceration 2 to 3 times per month that he treated with a triamcinolone topical solution prescribed by his primary care physician. Over the preceding 2 weeks, he noticed an increasing acidicbitter taste in his mouth and an irritated throat with globus sensation. The patient reported no fever, chills, night sweats, cough, anorexia, or vomiting. He had no recent sick contacts, dietary changes, or travel outside the United States. Six months before presentation, an anal fissure was diagnosed and treated topically with lidocaine and hydrocortisone cream.
His medical history was notable for gastroesophageal reflux disease (GERD) in the previous 2 years and chronic sinus congestion for which treatment failed to provide adequate symptomatic relief. His medications included ranitidine, nasal flunisolide, and loratadine. He had a false-positive result on routine human immunodeficiency virus (HIV) screening 2 months before presentation. Western blot and reverse transcriptionepolymerase chain reaction were both negative for HIV. He had a history of childhood asthma that resolved by the age of 6 years. His surgical history included a tonsillectomy at age 8 years. He had no history of upper endoscopy or colonoscopy. His family history included type 2 diabetes mellitus, hypertension, and vitiligo on his father’s side. No medical illnesses were noted from his mother’s side. He had a 1-year history of tobacco use of 1 pack per day starting at age 20 years and ending at age 21 years. He did not use alcohol or illicit drugs. Physical examination revealed a patient in moderate distress. He was alert and oriented to person, place, and time. His temperature was 36.8 C, heart rate was 117 beats/min, blood pressure was 130/85 mm Hg, and respiratory rate was 19 breaths/min. Pulse oximetry revealed an oxygen saturation of 99% while the patient breathed room air. There was no pallor or jaundice. He had no chest tenderness on palpation, and his lungs were clear on auscultation. Cardiac examination revealed a normal S1 and S2 without S3, S4, or murmur. No raised jugular vein distention was found on examination. Abdominal examination revealed epigastric tenderness to deep palpation with no rebound tenderness. He had a distended abdomen with hyperactive bowel sounds throughout all quadrants. No rigidity, palpable masses, or organomegaly were noted on superficial or deep palpation. On rectal examination, a small (1 1.5-cm) anal ulcer was noted at the 11-o’clock position, and he had positive results on a stool guaiac test. Ophthalmologic
Mayo Clin Proc. n XXX 2016;nn(n):e1-e6 n http://dx.doi.org/10.1016/j.mayocp.2016.03.010 www.mayoclinicproceedings.org n ª 2016 Mayo Foundation for Medical Education and Research
See end of article for correct answers to questions. Resident in Internal Medicine, Mayo School of Graduate Medical Education, Jacksonville, FL (A.A.A., M.R.W.); Advisor to residents and Consultant in Hospital Internal Medicine, Mayo Clinic, Jacksonville, FL (M.J.M.).
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examination findings were unremarkable. A 3 4-cm area of hair loss with a fragile border was noted on the occipital scalp. There was no evidence of erythema, scaling, or discharge. In the emergency department, the patient received intravenous hydration with 0.9% sodium chloride, intravenous pantoprazole, and intravenous morphine. A complete blood cell count revealed a white blood cell count of 11.7 109/L, a hemoglobin level of 13.6 mg/dL, and a platelet count of 315 109/L. His venous lactate level was not elevated. Results of a complete metabolic panel including a lipase test and liver function test were all within normal limits. 1. At this time, which one of the following is the best diagnostic test? a. Abdominal ultrasonography b. Fluoroscopy with barium ingestion c. Computed tomography (CT) of the abdomen with contrast medium d. Magnetic resonance imaging (MRI) of the abdomen e. Explorative laparoscopy Although it is convenient because it is noninvasive and can be performed quickly at the bedside by a qualified physician, abdominal ultrasonography is not the optimal test to evaluate the bowel status. Its major limitation is low sensitivity and specificity in diagnosing most bowel disorders because of bowel gas interference, although it may be helpful in identifying acute bowel ischemia. Physicians who perform acute-care ultrasonography in patients with suspected mechanical small-bowel obstruction should be aware of the warning signs of an ischemic bowel loop, including the detection of intraperitoneal free fluid, thickening of the bowel wall to more than 4 mm, and an acute reduction of previously detected bowel hyperactivity.1 Historically, fluoroscopy was considered a good and readily available test to evaluate acute abdominal pain because of its superiority to abdominal radiography. Although fluoroscopy does have some value in evaluating upper gastrointestinal tract disease, it is no longer a first-line test because it is not as rapidly available as CT and it exposes the patient to more radiation, increasing risk to the patient. By contrast, CT with contrast medium is a fast e2
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and generally safe test with good sensitivity and specificity for acute abdominal disease. Although the role of MRI in the evaluation of inflammatory bowel diseases is expanding because it has high soft-tissue penetration and lack of radiation exposure,2 MRI of the abdomen should never be considered a firstline test in patients with no contraindications to CT because of the high cost and extended testing time associated with MRI. Explorative laparoscopy should not be considered without signs of an “acute surgical abdomen” (an acute abdominal condition requiring emergent surgical intervention). This procedure is often performed only after radiographic and diagnostic testing indicates that surgical treatment is needed. Our patient underwent contrast-enhanced abdominal CT, which revealed 2 sites of intussusception (telescoping) of the small bowel. The first was in the left upper quadrant and measured about 3.5 cm. The second was in the right upper quadrant and measured about 2.6 cm. Both areas were surrounded by nonspecific small lymph nodes. The bowel segments proximal to both intussusception sites were thickened, suggestive of chronic inflammation. No abdominal masses were seen. 2. On the basis of the CT findings, which one of the following is the most likely underlying cause of this patient’s intussusception? a. Multiple malignant bowel metastases b. Gluten-sensitivity enteropathy c. AIDS-related bowel intussusception d. Abdominal adhesions e. Intestinal lipoma Although the patient had experienced some weight loss, he had no other signs or symptoms of a neoplastic process, and CT identified no metastatic lesions in the abdomen. A chronic inflammatory process such as inflammatory bowel disease, Behçet disease, or gluten-sensitivity enteropathy (celiac disease) is the most likely cause of our patient’s intussusception because of the multiple sites of intussusception without distinct masses. AIDS-related small-bowel intussusception has been widely reported in HIV-infected patients with active AIDS. Our patient had negative results on a Western blot test and
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reverse-transcriptionepolymerase chain reaction for HIV just 2 months before presentation, making AIDS-related small-bowel intussusception unlikely. Abdominal adhesions are a common cause of small-bowel obstruction but rarely cause intussusception and occur almost exclusively in patients who have undergone an intra-abdominal operation previously.3 Our patient had no history of an intra-abdominal surgical procedure. Lipoma is a common cause of intussusception but usually occurs at a single point, and it is uncommon for it to occur in multiple areas of the bowel and result in multiple intussusceptions, as seen in our patient.3 Furthermore, intestinal lipomas can often be visualized on CT, and none were seen on our patient’s CT scan. The multiple sites of intussusception should raise suspicion for an inflammatory process, particularly celiac disease and inflammatory bowel diseases.3,4 The general surgery service was consulted about the case. They recommended a gastrointestinal radiographic series with barium followthrough study to better characterize the location of the intussusception and to define the level of obstruction, if any. The barium series revealed delayed emptying of contrast medium from the small to the large bowel, indicating a possible partial bowel obstruction. No areas of intussusception or intestinal masses were seen in the study. Normal results on barium follow-through study are classically found in most nonemass-related intussusceptions.5 3. Which one of the following is the best next step in the management of this patient’s intussusception? a. Pneumatic reduction b. Diatrizoic acid reduction c. Surgical reduction d. Surgical resection e. Conservative medical management In adult intussusception, unlike that in children, pneumatic or diatrizoic acid reduction is not recommended. The decision for surgical intervention is usually based on CT and clinical examination findings. Iodinated contrast-enhanced CT of the abdomen seems to be the most reliable radiographic imaging test for establishing a diagnosis in adults with intussusception before surgical intervention can be considered, especially for patients Mayo Clin Proc. n XXX 2016;nn(n):e1-e6 www.mayoclinicproceedings.org
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with poorly localized nonspecific abdominal pain.6 If a lead point (like a mass) is suggested on CT, early surgical intervention is usually necessary. The findings of an acute surgical abdomen, elevated inflammatory markers, or increased lactate levels also indicate early surgical intervention. When surgical intervention is warranted, the decision for resection vs intraoperative reduction is controversial.6 If there are no indications for surgical intervention, conservative management can be done safely. Observation for suspected acute abdomen or intestinal obstruction has historically been indicated for 48 to 72 hours. Young patients with no comorbidities and improved or stabilized medical conditions could be discharged home to complete follow-up as an outpatient. Because our patient did not have an acute surgical abdomen, he was admitted to the hospital for observation and supportive management. No clinical deterioration or worsening of symptoms was reported in the next 72 hours, and the intussusception spontaneously resolved. He tolerated a liquid diet after passing a bowel movement. He was discharged home and had follow-up blood work and a gastroenterology clinic visit scheduled for 2 weeks after discharge. Laboratory testing performed before his return gastroenterology clinic visit revealed ferritin, vitamin B12, and vitamin D levels all within the lower limit of normal. Test results for HIV-1 and HIV-2 antibodies were negative. IgA and IgG antie tissue transglutaminase antibodies were present with elevated titers. 4. On the basis of these laboratory findings, which one of the following would be the best next step in this patient’s management? a. Colonoscopy with biopsy b. Repeated antietissue transglutaminase antibody serologic testing c. Antiegliadin antibody assay d. Esophagogastroduodenoscopy (EGD) with biopsy e. Oral iron and calcium supplementation and repeat laboratory tests in 4 to 6 weeks There is no indication to perform colonoscopy or repeat serologic studies at this point because neither would provide further
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diagnostic evidence. Antiegliadin antibody assays are not as sensitive and specific as IgA and IgG antietissue transglutaminase antibody tests and would not be helpful in this situation. Generally, after a serologic diagnosis of celiac disease with positive antibody results, it is crucial to perform an EGD with biopsy to confirm the diagnosis by histopathologic examination.7 Supplementation of calcium and iron is necessary in patients with celiac disease, but ruling out a malignant neoplasm is the best next step in managing this patient’s condition. The patient’s EGD revealed atrophic and erythematous duodenitis with loss of the general duodenal architecture. Biopsy results from the second part of the duodenum and duodenal bulb revealed areas of partial to complete villous atrophy, low goblet cell numbers with crypt/foveolar hyperplasia, and numerous lymphocytes in the lamina propria consistent with active celiac disease. No signs of lymphoma were seen on these biopsy specimens. There was concern that our patient’s multiple sites of intussusception might represent several areas of bowel affected by mucosal lymphoma, both because of this tumor’s propensity to occur in patients with celiac disease and because of the finding of multiple thickened bowel segments on CT.7 Because the patient did not meet the criteria for surgical exploration, the recommendation was to further investigate his bowel segments to conclusively rule out gut-related lymphoma. Capsule endoscopy to visualize the entire bowel and double-balloon enteroscopy (pushand-pull enteroscopy) were discussed with the patient as the proper next steps after EGD with biopsy to assess for lymphoma. The patient declined both procedures and agreed to repeating CT at 3-month intervals to confirm the resolution of the enlarged lymph nodes and thickened bowel segments near the intussusception sites. The final diagnosis was latent celiac disease with small-bowel intussusception. 5. Which one of the following treatment plans will help prevent recurrence of this patient’s intussusception and also treat his underlying illness? a. Gluten-free diet b. Immunosuppression with rituximab
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c. Three-week glucocorticoid burst and taper d. Small-bowel resection e. Observation The first-line treatment for celiac disease is a gluten-free diet. Strict adherence to a glutenfree diet has been found to be highly effective in eliminating symptoms, reducing the rate of complications in most cases, and reversing intestinal mucosal damage over time. Further, a gluten-free diet is readily available and more effective than alternative treatments and is not associated with the harmful adverse effects of other potential therapies such as immunosuppression and corticosteroids. Immunosuppression is not recommended for patients with celiac disease because it carries a high risk of adverse effects with shortand long-term complications. Rituximab and glucocorticoids should be avoided because they can cause profound B-lymphocyte dysfunction and may lead to the emergence of severe infections like tuberculosis. Also, no immunosuppression therapy has been found to be more effective than a gluten-free diet for patients with celiac disease. Unlike Crohn disease, celiac enteropathy rarely requires small-bowel resection. Unresolved intussusception and tumors represent the majority of those rare surgical indications. Adults infrequently achieve complete mucosal healing even if they adhere to a strict glutenfree diet. However, partial restoration of the mucosal architecture occurs after adopting a gluten-free diet in most patients with celiac disease.8 Observation is unacceptable in this situation. Continued ingestion of a glutencontaining diet in this patient may lead to persistent symptoms, recurrence of intussusception, and possible emergence of a malignant small-bowel mucosal-related lymphoma. A strict gluten-free diet was prescribed, and after 3 months, the patient had dramatic improvement with complete resolution of his abdominal pain and GERD. Repeated CT of the abdomen at that time confirmed resolution of the 2 areas of intussusception as well as the enlarged lymph nodes and small-bowel wall thickening. He also had great reduction in the bitter taste in his mouth, and his abdominal bloating had completely resolved. He
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gained 2.25 kg during the 3 months and reported no more anal pain. At the 3-month follow-up visit, the only remaining symptom was the alopecia areata. The size of the scalp lesion had grown to about 10 8 cm. His response to local triamcinolone injection was minimal after the first visit. The patient was advised to have additional visits for injections. DISCUSSION The final diagnosis for our patient’s abdominal pain was celiac diseaseeinduced small-bowel intussusceptions. Intussusception is defined as the invagination of one portion of the bowel into an immediately adjacent portion.9 The intussusception lead point can be 1 of 3 main types: mucosal, intramural, or extraintestinal. The lead point can be the nidus that pulls the proximal portion of the intestine into the distal part, resulting in telescoping.1,9 Intussusception is rare in adults,4 and its diagnosis can be challenging. Diagnosing intussusception preoperatively can be difficult, and thus, many cases are diagnosed during laparotomy9 or laparoscopy. However, the more frequent use of CT has increased the rate of preoperative detection.4 Nevertheless, only half of adult intussusception cases can be diagnosed preoperatively by CT or abdominal ultrasonography.3 More frequent use of CT in patients with undiagnosed abdominal pain increases the pick-up rate.10 The hallmark radiographic feature of intussusception on both CT and abdominal ultrasonography is the target sign.5,6 Idiopathic intussusception of the small bowel accounts for 8% to 20% of all cases of intussusception.5 Adult intussusception can have benign or malignant causes. Benign causes include inflammatory bowel diseases such as Crohn disease and celiac disease, lipoma, and trauma. Malignant causes include small intestinal lymphoma, adenocarcinoma, neuroendocrine tumors, and malignant metastases to the bowel.5 Adult intussusceptions have been categorized according to the site of origin: enteric, ileocolic, ileocecal, and colonic.11 Because our patient had 2 sites of enteric intussusception, we suspected an inflammatory process, which could affect multiple areas. Intussusception has been found as a rare but noted complication of celiac disease. It can be the initial presentation of celiac disease Mayo Clin Proc. n XXX 2016;nn(n):e1-e6 www.mayoclinicproceedings.org
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and is often associated with symptoms of vague, frequent, poorly localized abdominal pain. Bowel lymphoma should be excluded in this group of patients.4 Celiac disease should be suspected in adults when intussusception is detected radiographically or surgically.9 Most patients do not experience recurrence of their symptoms when they adhere to a gluten-free diet. The trigger in our case was chronic mucosal inflammation and irritation, with the possible enlargement of underlying Peyer patches. These factors led to the telescoping of the proximal small intestinal loop through the distal loop. The reactive mesenteric lymphadenopathy could be an initiating trigger of the intussusception as well. The mucosal chronic irritation and inflammation likely improved after gluten was removed from the patient’s diet. Other causes of intussusception include Crohn disease, intestinal polyps, lymphadenopathy, and benign or malignant tumors. Intussusception in adults can cause complete or partial bowel obstruction, which may not necessarily present as “currant jelly” stool as it does in pediatric patients. Intussusception represents only 1% of bowel obstruction causes for adults in the United States; it is rare for patients with celiac disease to have it as the initial presentation. Our patient had intussusceptions of 3.5 cm and 2.6 cm, both of which resolved spontaneously. This outcome is consistent with findings in the study by Lvoff et al,12 which examined features of self-limiting adult small-bowel intussusception and those that required surgical correction based on radiologic findings. They found that intussusceptions detected by CT of the abdomen that are shorter than 3.5 cm have a high likelihood of resolving spontaneously and would not require surgical intervention.12 The patient’s other symptoms can be explained by celiac disease. GERD can occur in 7% to 17% of patients with celiac disease. However, GERD is probably no more common in celiac disease than in the general population. A recent cohort study to evaluate the cost-effectiveness of routine duodenal biopsy for celiac disease during endoscopy in patients with GERD revealed that it is not cost-effective to perform biopsy analysis to detect celiac
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disease in patients undergoing EGD for refractory GERD, with the exception of patients from geographic areas with a high prevalence of celiac disease (1.8% or greater).8 Aphthous stomatitis occurs frequently in this group of patients. About 18% of patients with celiac disease may experience aphthous stomatitis.7,13 Alopecia areata is linked to many autoimmune diseases and has been reported to occur with celiac disease.13 Celiac disease is common in Western societies. Its association with adult intussusception is rare but well reported. Intussusception in adults with celiac disease can resolve spontaneously after adoption of a gluten-free diet. Surgical intervention may be required in more complicated cases. Correspondence: Address to Michael J. Maniaci, MD, Division of Hospital Internal Medicine, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224 ([email protected]).
REFERENCES 1. Hefny AF, Corr P, Abu-Zidan FM. The role of ultrasound in the management of intestinal obstruction. J Emerg Trauma Shock. 2012;5(1):84-86. 2. Gee MS, Harisinghani MG. MRI in patients with inflammatory bowel disease. J Magn Reson Imaging. 2011;33(3):527-534.
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3. Marinis A, Yiallourou A, Samanides L, et al. Intussusception of the bowel in adults: a review. World J Gastroenterol. 2009;15(4): 407-411. 4. Gonda TA, Khan SU, Cheng J, Lewis SK, Rubin M, Green PH. Association of intussusception and celiac disease in adults. Dig Dis Sci. 2010;55(10):2899-2903. 5. Azar T, Berger DL. Adult intussusception. Ann Surg. 1997; 226(2):134-138. 6. Gayer G, Zissin R, Apter S, Papa M, Hertz M. Pictorial review: adult intussusceptionda CT diagnosis. Br J Radiol. 2002; 75(890):185-190. 7. Volta U, Caio G, Stanghellini V, De Giorgio R. The changing clinical profile of celiac disease: a 15-year experience (1998-2012) in an Italian referral center. BMC Gastroenterol. 2014;14:194. 8. Yang JJ, Thanataveerat A, Green PH, Lebwohl B. Cost effectiveness of routine duodenal biopsy analysis for celiac disease during endoscopy for gastroesophageal reflux. Clin Gastroenterol Hepatol. 2015;13(8):1437-1443. 9. Ilias EJ, Kassab P, Castro OA. Intestinal intussusception. Rev Assoc Med Bras. 2012;58(4):404-405. 10. Yalamarthi S, Smith RC. Adult intussusception: case reports and review of literature. Postgrad Med J. 2005;81(953):174-177. 11. Weilbaecher D, Bolin JA, Hearn D, Ogden W II. Intussusception in adults: review of 160 cases. Am J Surg. 1971;121(5): 531-535. 12. Lvoff N, Breiman RS, Coakley FV, Lu Y, Warren RS. Distinguishing features of self-limiting adult small-bowel intussusception identified at CT. Radiology. 2003;227(1):68-72. 13. Denham JM, Hill ID. Celiac disease and autoimmunity: review and controversies. Curr Allergy Asthma Rep. 2013;13(4): 347-353.
CORRECT ANSWERS: 1. c. 2. b. 3. e. 4. d. 5. a
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