Correspondence

Regional Enteritis Associated with Enterovirus in a Patient with X-Linked Agammaglobulinemia

N Engl J Med 2000; 342:1611-1612May 25, 2000

Article

To the Editor:

X-linked agammaglobulinemia is characterized by a profound defect in the production of antibodies of all isotypes; the defect is related to impaired B-lymphocyte differentiation resulting from mutations in the gene for B tyrosine kinase.1 Immunity against viral infections is generally intact in patients with X-linked agammaglobulinemia, with the exception of an unusual susceptibility to enteroviral infection.1 Chronic intestinal inflammation mimicking Crohn's disease has been described in a few patients with X-linked agammaglobulinemia.2,3 Its origin, however, is unknown.

A 22-year-old man with X-linked agammaglobulinemia that had been diagnosed at the age of 9 was referred for chronic abdominal pain, diarrhea, and weight loss. Radiography of the small bowel and computed tomography of the abdomen revealed ileitis with multiple stenoses of the terminal ileum. Ileocecal resection of 60 cm of ileum was performed with an end-to-side anastomosis. Macroscopic examination of the resected ileum revealed irregular, mucosal, transmural ulcerations and marked thickening of the wall, with strictures and considerable narrowing of the lumen. Microscopical examination showed extensive mucosal ulceration, crypt abscesses, transmural inflammation, patchy epithelioid granulomas, and inflammatory lymph nodes in the omentum. Immunohistochemical studies showed that the intestinal mucosa contained no mature B cells, whereas the early B-cell marker CD22 was detected on a small number of cells. Virtually all the cells in the lamina propria were T cells; most (almost 80 percent) were CD8+, and the remainder expressed CD4. Cultures of intestinal tissues were negative for cytomegalovirus, herpesvirus, and enterovirus. The enterovirus genome was found with use of the polymerase chain reaction (PCR)4 in frozen sections of resected inflamed ileum and adjacent mesenteric lymph nodes but not in specimens of normal surrounding ileocolonic tissue (Figure 1Figure 1Detection of the Enterovirus Genome by the Polymerase Chain Reaction in Frozen Sections of Resected Inflamed Ileum and Adjacent Mesenteric Lymph Nodes, but Not in Specimens of Normal Surrounding Ileocolonic Tissue.). We amplified the highly conserved 5' noncoding region of enterovirus. We used primers localized between 164 and 184 bp and 516 and 530 bp. By using this combination, we obtained the 362-bp product.4

The patient was subsequently treated with intravenous injections of immune globulin (30 g per day) for three months. Two years later, the patient was symptom-free, had gained weight, and required only the previous, usual dose of intravenous immune globulin (25 g every three weeks). Retrograde push enteroscopy to explore 50 cm of ileum showed no macroscopically or histologically evident lesions. The results of PCR were negative for enterovirus.

Our patient meets the criteria for X-linked agammaglobulinemia associated with regional enteritis.2,3 The positive signal for enterovirus on PCR in specimens of resected inflamed ileum and adjacent mesenteric lymph nodes suggests that a reaction to enterovirus infection was responsible for the intestinal inflammation. The negative results on PCR in specimens of uninvolved intestine and in specimens of intestine from 10 patients with ileal Crohn's disease and normal immune function (data not shown) support the specificity of our finding. It was not possible to perform an immunohistochemical study with specific antibodies against enterovirus because we did not know the strain of virus. Moreover, the amount of virus might be very low and therefore not detectable by this technique.

Christophe Cellier, M.D., Ph.D.
Hôpital Européen Georges Pompidou, 75340 Paris CEDEX 07, France

Sophie Foray, M.D.
Laboratoire de Virologie, 69373 Lyons CEDEX 08, France

Olivier Hermine, M.D., Ph.D.
Hôpital Necker, 75015 Paris CEDEX 15, France

4 References

1. 1

   Ochs HD, Smith CI. X-linked agammaglobulinemia. Medicine (Baltimore) 1996;75:287-299
   CrossRef | Web of Science | Medline

2. 2

   Abramowsky CR, Sorensen RU. Regional enteritis-like enteropathy in a patient with agammaglobulinemia: histologic and immunocytologic studies. Hum Pathol 1988;19:483-486
   CrossRef | Web of Science | Medline

3. 3

   Washington K, Stenzel TT, Buckley RH, Gottfried MR. Gastrointestinal pathology in patients with common variable immunodeficiency and X-linked agammaglobulinemia. Am J Surg Pathol 1996;20:1240-1252
   CrossRef | Web of Science | Medline

4. 4

   Leparc I, Aymard M, Fuchs F. Acute, chronic and persistent enterovirus and poliovirus infections: detection of viral genome by seminested PCR amplification in culture-negative samples. Mol Cell Probes 1994;8:487-495
   CrossRef | Web of Science | Medline

Citing Articles (9)

Citing Articles

1. 1

   Annick A. J. M. Ven, David P. Hoytema van Konijnenburg, Annemarie M. J. Wensing, Joris M. Montfrans. (2011) The Role of Prolonged Viral Gastrointestinal Infections in the Development of Immunodeficiency-Related Enteropathy. Clinical Reviews in Allergy & Immunology
   CrossRef

2. 2

   Cary Qualia, Athos Bousvaros. 2011. Gastrointestinal Manifestations of Primary Immunodeficiency. , 435-446.
   CrossRef

3. 3

   Shradha Agarwal, Lloyd Mayer. (2009) Pathogenesis and treatment of gastrointestinal disease in antibody deficiency syndromes. Journal of Allergy and Clinical Immunology 124:4, 658-664
   CrossRef

4. 4

   ELIZABETH I. HARRIS, KAY WASHINGTON. 2009. Manifestations of Immunodeficiency in the GI Tract. , 81-96.
   CrossRef

5. 5

   Shradha Agarwal, Lloyd Mayer. (2009) Gastrointestinal manifestations in primary immune disorders. Inflammatory Bowel DiseasesNA-NA
   CrossRef

6. 6

   Vanessa Howard, Jeffrey M. Greene, Savita Pahwa, Jerry A. Winkelstein, John M. Boyle, Mehmet Kocak, Mary Ellen Conley. (2006) The health status and quality of life of adults with X-linked agammaglobulinemia. Clinical Immunology 118:2-3, 201-208
   CrossRef

7. 7

   Francisco A. Bonilla, I. Leonard Bernstein, David A. Khan, Zuhair K. Ballas, Javier Chinen, Michael M. Frank, Lisa J. Kobrynski, Arnold I. Levinson, Bruce Mazer, Robert P. Nelson, Jordan S. Orange, John M. Routes, William T. Shearer, Ricardo U. Sorensen. (2005) Practice parameter for the diagnosis and management of primary immunodeficiency. Annals of Allergy, Asthma & Immunology 94:5, S1-S63
   CrossRef

8. 8

   Christian Folwaczny, Jürgen Glas, Helga-Paula Török. (2003) Crohn's disease. European Journal of Gastroenterology & Hepatology 15:6, 621-626
   CrossRef

9. 9

   Robert P. McCabe. (2002) Gastrointestinal manifestations of non-AIDS immunodeficiency. Current Treatment Options in Gastroenterology 5:1, 17-25
   CrossRef