*Department of Pediatric Gastroenterology
†Department of Pediatric Pathology
‡Department of Pediatric Surgery
§Department of Pediatric Rheumatology, Primary Children's Medical Center, University of Utah School of Medicine, Salt Lake City.
Address correspondence and reprint requests to John F. Pohl, MD, Department of Pediatric Gastroenterology, Primary Children's Medical Center, University of Utah, 100 N Mario Capecchi Dr, Suite 2650, Salt Lake City, UT 84113-1103 (e-mail: firstname.lastname@example.org).
Received 8 February, 2011
Accepted 21 April, 2011
Drs Pohl and Rollins have received funding for investigator-initiated funding from Eurand Pharmaceuticals (Yardley, PA). Dr Pohl has received investigator-initiated funding from Takeda Pharmaceuticals (Deerfield, IL). The other authors report no conflicts of interest.
Sclerosing mesenteritis (SM) is typically characterized as a rare, adult-onset disease with progressive inflammation involving the small intestinal mesentery leading to fibrosis and bowel obstruction (1,2). Most cases of SM are idiopathic, but the disease process has been described in concurrence with Henoch-Schönlein purpura, autoimmune disorders, abdominal trauma, and some medications (3,4). We present what we believe is the first described case of SM in a child with celiac disease.
An 8-year-old boy presented to our institution with a 1-month history of fatigue and diffuse abdominal pain. Two weeks before admission, the patient's parents noted that the child was developing abdominal distention with associated abdominal pain and fatigue. Before admission, he had developed recurrent high fevers up to 40°C for 4 weeks with associated bilious emesis and no stool output. Physical examination demonstrated that the patient was febrile, tachycardic, and hypotensive. He also had severe ascites and diffuse abdominal pain. Therefore, the patient was admitted into the hospital for a presumed bowel obstruction and a nasogastric tube was placed for decompression.
The child's medical history was significant only for constipation as a toddler. He had maintained normal growth parameters before this admission. Family history was noncontributory for gastrointestinal or autoimmune disease, and he was taking no medications.
Laboratory evaluation demonstrated a white blood cell count of 4800 cells/μL with a predominance of lymphocytes (53%), hemoglobin 12.6 g/dL, hematocrit 36.4%, and platelet count of 236,000 cells/μL. A hepatic panel revealed a normal serum glutamic-oxaloacetic transaminase and serum glutamic pyruvic transaminase of 45 and 38 U/L, respectively. A gamma-glutamyl transpeptidase was normal at 20 U/L. Serum albumin was low at 2.4 g/dL and serum protein was low at 4 g/dL, presumably secondary to ascites. C-reactive protein was elevated at 7.6 mg/dL. Serum amylase, lipase, lactate dehydrogenase, and uric acid levels were normal. A tissue transglutaminase immunoglobulin A (IgA) antibody titer (TTG IgA) was normal at 1 U. An anti-nuclear antibody IgG titer was normal. Paracentesis results were nondiagnostic, and flow cytometry of the ascitic fluid demonstrated no malignancy.
An abdominal ultrasound demonstrated moderate ascites with a normal Doppler flow of the portal system. An echocardiogram was normal. Computed tomography of the abdomen showed high-density ascites, suggesting hemorrhagic or proteinaceous fluid, small-bowel wall thickening with no evidence of obstruction, and a 2-cm rim-enhancing lesion adjacent to the ascending colon. Subsequent magnetic resonance imaging of the abdomen with gadolinium contrast demonstrated ascites, a matted appearance of the intestines with attachment to the retroperitoneum, and fibrous bands within the ascites (Fig. 1). Because the patient had unrelenting vomiting and no radiographic evidence of intestinal obstruction, the patient was started on parenteral nutrition, and an esophagogastroduodenoscopy (EGD) was performed. Although the mucosa appeared normal upon endoscopic visualization, biopsies of the duodenum (duodenal bulb and third portion of the duodenum) revealed increased intraepithelial lymphocytes, including at the villous tips, with significant villous blunting characteristic of celiac disease (Marsh type 3A) (Fig. 2).
The patient's clinical condition worsened, and he began to experience increased respiratory distress from the recurrent ascites, worsening bilious emesis, and abdominal pain. A subsequent exploratory laparotomy evacuated 2.5 L of straw-colored ascites, and the omentum was noted to be inflamed and matted. The entire small intestine was noted to be inflamed and fibrotic (Fig. 3). The retroperitoneal attachments of the colon also were inflamed, although the colon itself appeared normal. A frozen specimen of the omentum demonstrated spindle cell formation. Additional omentum biopsies revealed fibrosis, inflammation, fat necrosis, and spindle cell proliferation (Fig. 4). Biopsies of the inflammatory cyst adjacent to the right colon and the small intestine demonstrated chronic inflammation and fibrosis. Immunohistochemistry staining demonstrated that the spindle cells were positive for vimentin but were not positive for ALK-1, CD-117, caldesmin, or S-100, which excluded malignancies such as a smooth muscle tumor, inflammatory myofibroblastic tumor, or neural tumor. This staining was characteristic for a fibroinflammatory disorder, including SM (5).
The patient had continued abdominal pain, nausea, fever, and bilious emesis, and he was started on intravenous methylprednisone at 2 mg · kg−1 · day−1 and intramuscular methotrexate at 15 mg daily. Intravenous immunoglobulin also was given, because the patient had low serum immunoglobulin levels, including IgA, presumed secondary to the large amount of ascites. On this regimen, the ascites and fever resolved; however, the child had recalcitrant bilious emesis and nausea. Therefore, after 7 days of therapy, the patient was started on intravenous infliximab (Remicade, Centocor Ortho Biotech Inc, Horsham, PA) at 5 mg·kg−1·dose−1. Within 48 hours of the first infliximab infusion, the bilious emesis had resolved, and the patient began to have bowel movements. The patient was eventually weaned from parenteral nutrition and was able to tolerate full oral feeds using a gluten-free diet.
A repeat EGD performed 8 months after the child was placed on a gluten-free diet demonstrated normal villous formation. The family then wished to challenge the child with gluten to determine whether there was any clinical change. Within 6 weeks of starting a gluten-containing diet, the patient began to complain of abdominal pain. Repeat duodenal biopsies demonstrated ulcerations with mild villous lymphocytic infiltration. Subsequently, the family maintained the child on a strict gluten-free diet, and he has had no recurrence of symptoms except for constipation. Repeat TTG IgA levels have been normal, and his total serum IgA level has normalized, with resolution of ascites.
The patient is currently maintained on weekly intramuscular methotrexate and every-8-week intravenous infliximab. A repeat magnetic resonance image of the abdomen has revealed no ascites and a normal appearance of the intestines.
This case describes the presentation of SM in a child with celiac disease. Celiac disease is a gastrointestinal disease affecting 0.5% to 1% of the population in many countries (6). Celiac disease is defined as a T-cell-mediated immune response to the gluten protein found in wheat. When genetically at-risk individuals are exposed to gluten, major histocompatibility complex class I–related proteins expressed on enterocytes lead to enterocyte death by a dysregulated immune response (7). Celiac disease is associated with concomitant autoimmune diseases including type 1 diabetes mellitus and autoimmune thyroiditis (8). Additionally, the incidence of other autoimmune disorders occurring in patients with celiac disease is 3- to 10-fold higher than in the general population (9).
The incidence of SM (and related disorders such as retroperitoneal fibrosis and mesenteric panniculitis) peaks between 40 and 60 years of age, with men affected more often than women. It is a rare disease in children (5,10). Although the pathogenesis of SM is poorly understood, autoantibodies such as the anti-nuclear antibody are found in up to 60% of cases, and anti–smooth muscle antibodies and rheumatoid factor also can be seen, suggesting that there is an autoimmune component to this disease (5). Infiltrating plasma cells expressing IgG4 have been described in the inflammatory infiltrate of some patients with SM (11). Treatment of SM typically is aimed at surgically relieving anatomic obstructions where present and using anti-inflammatory therapy such as glucocorticoids as the primary medical treatment for disease regression (12). Other immunosuppressive treatments have been used, including mycophenolate mofetil, cyclophosphamide, azathioprine, and methotrexate (5,13). Little is known about the efficacy of infliximab in the treatment of SM; however, it has been used for similar sclerosing diseases, and our patient experienced dramatic improvement in symptoms once inflixmab was introduced (14).
It is well established that patients with celiac disease improve their gastrointestinal symptoms while adhering to a gluten-free diet. Indeed, screening serum antibody tests such as TTG IgA and duodenal biopsies obtained by EGD (which reveal villous atrophy and intraepithelial lymphocyte infiltration) normalize on a gluten-free diet (15). During the initial presentation, our patient experienced no elevation of TTG IgA levels presumably secondary to hypogammaglobulinemia from ascites (16). It is known that patients with celiac disease can have IgA deficiency leading to normal TTG IgA levels, despite clinical findings of celiac disease on duodenal biopsy (17). Additionally, low-level villous atrophy (similar to what was seen during this child's final endoscopy) can be associated with false-negative TTG IgA levels (18). The use of a TTG IgG titer can be helpful in diagnosing celiac disease in patients with potential false-negative TTG IgA levels (15). Unfortunately, no TTG IgG level was obtained during the workup of the patient, and the diagnosis of celiac disease was made by serial EGDs. Case reports of adult patients with mesenteric panniculitis and retroperitoneal fibrosis (fibroinflammatory disorders similar to SM) associated with celiac disease have been described, although no pediatric cases have been reported until this case (19,20).
Celiac disease is associated with other autoimmune diseases, and the present report suggests that SM also may be associated with celiac disease. We suggest that any pediatric patient who presents with SM be evaluated for celiac disease as a potential modifier of the disease.
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