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Case Communications

Isolated Severe Gastropathy – an Unusual Presentation of Crohn’s Disease in a Child

Roy Nattiv MD1, Gabriel Dinari MD1, Jacob Amir MD2 and Yaron Avitzur MD1,2

1Institute of Pediatric and Nutrition and 2Department of Pediatrics C, Schneider Children’s Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel

Key words: gastropathy, stomach, Crohn’s disease, infliximab, children IMAJ 2008;10:322–324

Crohn’s disease may involve any part of and therapeutic implications of such a the , but isolated presentation. Ultimately, the diagnosis was A involvement of the stomach is rare [1]. supported by suggestive endoscopic and In common presentations, the diagnosis histological findings and the presence of of Crohn’s disease is usually based on ASCA as a serological marker. Treatment a combination of typical clinical, labora- was refractory to steroids and treatment tory, endoscopic and pathological findings. with infliximab resulted in marked gross However, the diagnosis is difficult to clinical and endoscopic improvement. establish in cases of atypical presentation as in isolated gastroduodenal disease. In Patient Description such a scenario other possible etiologies A 13 year old girl was admitted with must be systematically ruled out in order symptoms of prominent epigastric pain, [A] Cobblestone appearance of the gastric body shown on gastroscopy. to establish the diagnosis. These may in- vomiting, bouts of both and clude Helicobacter pylori infection, tuberculo- , and anorexia with weight loss of sis, non-steroidal anti-inflammatory drugs, 5 kg. For 9 months prior to her admission eosinophilic , Menetrier’s disease, she was followed at an outside clinic for B gastrinoma, collagen , and symptoms of recurrent epigastric pain and lymphoma. Additional diagnostic strategy constipation. During that period erythro- in atypical cases of inflammatory bowel cyte sedimentation rate was elevated (54 disease is the use of anti-Saccharomyces mm/hour) while hemoglobin and albumin cervisia antibody. This serological marker were within normal limits. Gastroscopy 2 can be a helpful adjunctive tool in the months prior to her admission showed diagnostic process despite the test’s erythema and edema of the gastric mu- limitations. cosa, a single gastric , pseudopolyps Treatment regimens for gastric Crohn’s and a cobblestone appearance of the [B] Gastroscopy showing antral nodularity disease have been poorly studied. The mucosa. Chronic gastritis had been noted and pseudopolyps. routine treatment of inflammatory gastritis on corresponding biopsies; H. pylori had in Crohn’s disease includes the concomi- not been identified. Although the etiology tant use of acid-suppressive drugs and of these findings was unclear, an empiric 0.0–0.5), and normal ESR, complete blood immunomodulators such as ASA products, trial with prednisone was initiated but count, ferritin, iron, and liver function or steroids. In recent years infliximab was unsuccessful. In addition, one month tests. The lack of a definitive diagnosis (anti-tumor necrosis factor-alpha) has prior to the child’s referral she underwent prompted further endoscopic evaluation, become an important addition to the an appendectomy due to acute appendi- which revealed mild esophageal edema therapeutic options in Crohn’s disease. citis. Pathological findings demonstrated and erythema, severe gastritis [Figure A], The effectiveness of infliximab in isolated without granulomas. Her gastric pseudopolyps [Figure B], a single gastric Crohn’s disease is limited to only past medical history was otherwise antral ulcer and edema with erythema in a few case reports of adult patients and normal. the duodenal bulb. The second part of the the long-term outcome is unknown [2,3]. Physical examination on admission re- was normal. Colonoscopy was We present a child with isolated gastric vealed localized epigastric tenderness. The normal. Corresponding biopsies showed Crohn’s disease and discuss the diagnostic rest of the examination was normal. Initial chronic active gastritis with erosion and blood work showed mildly elevated C-re- ASCA = anti-Saccharomyces cervisia antibody active protein (2.230 mg/dl, normal value ESR = erythrocyte sedimentation rate

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endoscopic findings, the exclusion of retrospective study of 230 pediatric Crohn’s C other possible etiologies, and a positive patients 30% of the children had lesions ASCA test. Treatment with of the , stomach or duodenum, and methylprednisolone (60 mg/day) was but only three of them had Crohn’s dis- started but a 2 week course of intravenous ease isolated to the upper gastrointestinal steroids achieved only minimal clinical tract [1]. Although histological changes improvement. Second gastroscopy and in the stomach and duodenum may be biopsies following the 2 week treatment seen in 20–40% of patients with Crohn’s were essentially similar to the previous disease, clinically symptomatic proximal gastroscopy. Due to the lack of response disease is only seen in 4% of patients [4]. to steroids, a course of infliximab at 0, 2 Even in patients who initially presented [C] Histopathological stain of gastric mucosa showing moderate chronic active gastritis and 6 weeks was started with concomitant with isolated gastroduodenal disease, with regenerative changes (hematoxylin & administration of azathioprine. Six weeks the majority will develop distal disease eosin stain, original magnification x400) after the first dose the patient showed over time. In a series of 72 patients with marked clinical and endoscopic improve- proximal Crohn’s disease diagnosed on ment. Gastroscopy demonstrated only histopathology, all but one were eventu- marked regenerative changes; no granulo- mild stomach wall nodularity with antral ally diagnosed with distal disease as mas were noted [Figure C]. Non-specific pseudopolyps. No or erythema were well [5]. Similarly, in another study 56% acute and chronic inflammatory changes seen. Gastric biopsies showed ameliora- of patients who presented initially with were seen in the duodenal bulb. Colonic tion of the chronic gastritis compared to isolated gastroduodenal disease developed biopsies were normal. the previous biopsies. Laboratory values distal disease at a median follow-up of Single-contrast barium follow-through showed normal ESR, normal hemoglobin, 11.7 years. showed non-specific findings isolated to normal albumin and a C-reactive protein To date there are only a few the stomach, namely small protrusions of 0.01 mg/dl. One year after the initia- documented case reports of adults with and collaring in the lesser curvature of tion of infliximab treatment the disease isolated gastric Crohn’s disease and no the stomach that may represent small fis- has not progressed to the remaining reports in the pediatric population. In one sures or ulcers and early cobblestoning. intestine and the child has resumed her case series, four adult patients with non- The remaining including normal daily activities. However, repeated healing gastric ulcers refractory to conven- the terminal was normal. Further infusions of infliximab were required due tional treatment were followed [2], and radiological investigation with computed to recurrent bouts of epigastric pain and in another report a 37 year old woman tomography of the abdomen showed appearance of extra-intestinal manifesta- with unusual gastric Crohn’s disease was widening of the stomach and thickened tions including erythema nodosum and described [3]. In all cases the diagnosis edematous mucosa in the region of monoarthritis of the right wrist. of Crohn’s disease was delayed for a long the pylorus without involvement of the time due to the non-specific presentation remaining gut. Comment of isolated gastropathy. The findings of non-specific gastropathy In most cases of Crohn’s disease the Normally, the diagnosis of Crohn’s without involvement of other parts of presentation, workup and diagnosis run disease is based on clinical presentation, the intestine and lack of inflammatory a familiar and substantiating course. radiological abnormalities of the small markers prompted a systematic workup to Sometimes, however, this disease can bowel, gastroscopy and colonoscopy find- rule out a number of possible etiologies manifest in an entirely non-specific and ings, and non-specific or typical patho- including H. pylori infection, tuberculosis, unusual manner. Uncommon presentations logical features. The abdominal pain and Zollinger-Ellison syndrome, collagen vas- of Crohn’s disease may manifest by a weight loss seen with our patient is by cular disease and lymphoma. Hence, the single symptom or sign, such as impair- far one of the most common modes of following tests were done and were found ment of linear growth, delayed puberty, presentation in Crohn’s patients, although to be within normal limits: Mantoux skin perianal disease, mouth ulcers, clubbing, it is non-specific. test, silver stain for H. pylori on gastric chronic iron deficiency anemia – or Radiology studies in gastroduodenal biopsies, serum levels, serology extra-intestinal manifestations preceding Crohn’s normally demonstrate similar for anti-neutrophil cytoplasmic antibody the gastrointestinal symptoms, mainly features to those found in more distal and antinuclear antibody, eye examination arthritis or arthralgia, primary sclerosing Crohn’s disease, such as thickened folds, for signs of uveitis, and blood films. The cholangitis, pyoderma gangrenosum, and ulcers, nodularity, stenosis and distorted only intriguing finding during this workup rarely osteoporosis. In such cases, the anatomy. Only mild ulceration of the was consistently elevated ASCA titers (63 diagnosis is challenging and can remain stomach was noted on a gastrointestinal U/ml, normal range < 10 U/ml). elusive for some time. follow-through in our patient with no A diagnosis of isolated gastric The stomach is rarely the sole or pathology found in the remaining gut. Crohn’s disease was made based on the predominant site of Crohn’s disease. In a Upper endoscopy in gastric Crohn’s

• Vol 10 • April 2008 Isolated Gastropathy due to Crohn’s Disease 323 Case Communications may be grossly normal, or it may reveal highlights the relatively good specificity others described suggest an important various combinations of edema, erythema, but poor sensitivity of ASCA as a marker role for infliximab in steroid-resistant ulcers, nodularity and cobblestone ap- for Crohn’s disease. pANCA on the other gastric Crohn’s disease. pearance. The antrum is most frequently hand is more specific to ulcerative , In summary, we describe a young girl involved, while the proximal stomach is and the combination of a positive ASCA with atypical presentation of isolated often spared. Gastric biopsies have poor test with a negative pANCA test has a gastric Crohn’s disease. In atypical cases specificity and the changes of non-specific positive predictive value of 96% and a with non-conclusive clinical, endoscopic gastritis may be seen in other conditions specificity of 97% for Crohn’s disease. and pathological findings, the ASCA test such as H. pylori infection. Discovery of In addition, some NOD2/CARD15 gene could be helpful in the diagnostic process. granulomatous gastritis might help nar- polymorphisms, particularly L1007P Infliximab may be an effective treatment row the differential diagnosis to Crohn’s homozygocity, were found to be associ- in cases of severe isolated gastropathy disease, tuberculosis, malignancy, and ated with gastroduodenal Crohn’s disease due to Crohn’s disease. collagen vascular disease. Interestingly, and with younger age at diagnosis. It is however, granulomas are only identified in possible that these genes might also help References 3–24% of the biopsies and repeat biopsies to support the diagnosis in the atypical 1. Lenaerts C, Roy CC, Vaillancourt M, do not result in higher rates of granuloma presentation of Crohn’s disease in the Weber AM, Morin CL, Seidman E. High discovery [5]. It is no surprise, therefore, future. incidence of upper gastrointestinal tract that granulomas were absent on repeated Infliximab, a monoclonal antibody to involvement in children with Crohn’s disease. Pediatrics 1989;83:777–81. biopsies in our patient. However, the TNFα, is often used in cases of steroid 2. Grubel P, Choi Y, Schneider D, Knox TA, marked edematous, inflamed and ulcerated refractory Crohn’s disease. The role of Cave DR. Severe isolated Crohn’s-like regions with cobblestone appearance and infliximab in treating patients with gas- disease of the gastroduodenal tract. Dig inflammatory pseudopolyps found mainly tric Crohn’s disease has scarcely been Dis Sci 2003;48:1360–5. in the antrum on endoscopy are at least studied. In one case series, infliximab 3. Firth MG, Prather CM. Unusual gastric Crohn’s disease treated with infliximab suggestive of Crohn’s disease. was effective in healing ulcers in two pa- – a case report. Am J Gastroenterol 2002;97 In the absence of any other source tients [2], but the development of chest (Suppl 1):S190. of disease and in the presence of non- in one and surgery in the other 4. Akbulut S, Yavuz B, Koseoglu T, Gokoz A, specific upper endoscopy and histological necessitated stopping the treatment. In Saritas U. Crohn’s disease with isolated findings, serological testing can play a another case study the symptoms in a esophagus and gastric involvement. Turk J Gastroenterol 2004;15:196–200. larger role in the diagnosis of atypical patient with diffuse mucosal thickening 5. Wagtmans MJ, Verspaget HW, Lamers Crohn’s disease. Recent studies have and ulceration throughout the antrum CB, van Hogezand RA. Clinical aspects suggested that pANCA and ASCA may be and duodenum continued despite of Crohn’s disease of the upper gastro- used as additional diagnostic tools for pa- prednisone and a twice-daily dose of a intestinal tract: a comparison with distal tients with suspected inflammatory bowel proton pump inhibitor. Treatment with Crohn’s disease. Am J Gastroenterol 1997; 92:1467–71. disease and to help differentiate between infliximab led to marked improvement Crohn’s disease and . within one week [3]. Similarly, in our Correspondence: Dr. Y. Avitzur, Institute of Indeed, ASCA is detected in 55–60% of patient infliximab was effective in both Pediatric Gastroenterology, Nutrition and children and adults with Crohn’s disease controlling the symptoms and healing Liver Diseases, Schneider Children’s Medi- and only 5–10% of controls with other gastric ulceration. The effect was tem- cal Center of Israel, Petah Tikva 49202, gastrointestinal disorders. This finding porary and repeated administration of Israel. infliximab was needed. Our case and the Phone: (972-3) 925-3673 pANCA = perinuclear anti-neutrophil cytoplas- Fax: (972-3) 925-3401 mic antibody TNFα = tumor necrosis factor-alpha email: [email protected]

Capsule Peripheral immune response An immune response to infection begins within the mentally reactivated in transplanted nervous tissue in secondary lymphoid tissues, where foreign antigen is combination with adoptively transferred T cells. Fresh T presented to T cells by dendritic cells. Activated T cells cell activation was detected at these sites, and as happens then migrate to the infected peripheral tissues. Wakim in lymph nodes, this process required dendritic cells and et al. present evidence that may revise the view that the help of CD4+ T cells. peripheral sites are simply arenas for the end stages of Science 2008;319:198 combat. A pathogen (herpes simplex virus) was experi- Eitan Israeli

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