Chronic Granulomatous Disease Colitis Research Articles

Recent topics and advanced therapies in chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by the inability of phagocytes to produce reactive oxygen species (ROS) owing to a defect in any of the five components (CYBB/gp91phox, CYBA/p22phox, NCF1/p47phox, NCF2/p67phox, and NCF4/p40phox) and a concomitant regulatory component of Rac1/2 and CYBC1/Eros of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Patients with CGD are at an increased risk of life-threatening infections caused by catalase-positive bacteria and fungi and of inflammatory complications such as CGD colitis. Antimicrobial and azole antifungal prophylaxes have considerably reduced the incidence and severity of bacterial and improved fungal infections and overall survival. CGD studies have revealed the precise epidemiology and role of NADPH oxidase in innate immunity which has led to a new understanding of the importance of phagocyte oxygen metabolism in various host-defense systems and the fields leading to cell death processes. Moreover, ROS plays central roles in the determination of cell fate as secondary messengers and by modifying of various signaling molecules. According to this increasing knowledge about the effects of ROS on the inflammasomal system, immunomodulatory treatments, such as IFN-γ and anti-IL-1 antibodies, have been established. This review covers the current topics in CGD and the relationship between ROS and ROS-mediated pathophysiological phenomena. In addition to the shirt summary of hematopoietic stem cell transplantation and gene therapy, we introduce a novel ROS-producing enzyme replacement therapy using PEG-fDAO to compensate for NADPH oxidase deficiency.

Safety and Efficacy of Ustekinumab in the Inflammatory Bowel Disease of Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by mutations encoding the NADPH oxidase complex.1 Those affected are at increased risk of bacterial and fungal infections and require antimicrobial prophylaxis. Dysregulated inflammation may cause inflammatory bowel disease (IBD), termed CGD-associated IBD or CGD colitis, a distinct entity from Crohn's disease (CD) or ulcerative colitis (UC).

P116 SMALL BOWEL INVOLVEMENT IN CHRONIC GRANULOMATOUS DISEASE COLITIS

Chronic granulomatous disease (CGD) is a rare disorder caused by genetic mutations of the nicotinamide adenine dinucleotide phosphate oxidase complex (NADPH), occurring in approximately 1/200,000 individuals. These mutations decrease residual reactive oxygen species (ROS) levels, leading to dysregulated inflammation. Inflammatory manifestations can be widespread, including severe and recurrent infections. The gastrointestinal tract is the most commonly affected organ with resultant inflammatory bowel disease, termed CGD colitis. Manifestations include abdominal pain, diarrhea with or without blood, nausea/vomiting, obstructions, and fistulas which can occur in a perianal distribution. Patients are often misdiagnosed with Crohn’s disease or ulcerative colitis, especially in the absence of extensive infectious history. We aimed to characterize the small bowel involvement in CGD.

A Review of Chronic Granulomatous Disease.

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defects in any of the five subunits of the NADPH oxidase complex responsible for the respiratory burst in phagocytic leukocytes. Patients with CGD are at increased risk of life-threatening infections with catalase-positive bacteria and fungi and inflammatory complications such as CGD colitis. The implementation of routine antimicrobial prophylaxis and the advent of azole antifungals has considerably improved overall survival. Nevertheless, life expectancy remains decreased compared to the general population. Inflammatory complications are a significant contributor to morbidity in CGD, and they are often refractory to standard therapies. At present, hematopoietic stem cell transplantation (HCT) is the only curative treatment, and transplantation outcomes have improved over the last few decades with overall survival rates now > 90% in children less than 14 years of age. However, there remains debate as to the optimal conditioning regimen, and there is question as to how to manage adolescent and adult patients. The current evidence suggests that myeloablative conditioning results is more durable myeloid engraftment but with increased toxicity and high rates of graft-versus-host disease. In recent years, gene therapy has been proposed as an alternative to HCT for patients without an HLA-matched donor. However, results to date have not been encouraging. with negligible long-term engraftment of gene-corrected hematopoietic stem cells and reports of myelodysplastic syndrome due to insertional mutagenesis. Multicenter trials are currently underway in the United States and Europe using a SIN-lentiviral vector under the control of a myeloid-specific promoter, and, should the trials be successful, gene therapy may be a viable option for patients with CGD in the future.

P203 Thalidomide as an alternative therapy for steroid-refractory colitis in chronic granulomatous disease

P203 Thalidomide as an alternative therapy for steroid-refractory colitis in chronic granulomatous disease

Severe and Rapid Progression in Very Early-Onset Chronic Granulomatous Disease-Associated Colitis.

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease that leads to recurrent infection and hyper-inflammation, occasionally represented by CGD-associated colitis (CGD colitis). Although clinical symptoms of CGD colitis mimic those of ulcerative colitis (UC), there is no reliable standard measurement of disease activity or standard therapeutic strategy for CGD colitis. Here, we examined the clinical manifestation of CGD colitis based on severity using a noninvasive measure of disease activity, the Pediatric Ulcerative Colitis Activity Index (PUCAI), which has been validated and widely used for pediatric UC. Sixteen of 35 CGD patients, who were diagnosed with CGD colitis based on colonoscopic and histological findings, were examined using the PUCAI. Both the PUCAI and the physician global assessment (PGA) tool were retrospectively scored by reviewing medical records. Disease activity defined by PUCAI was correlated with PGA, and increased at diagnosis of CGD colitis, especially in patients who were younger than 6years of age (very early-onset CGD colitis: VEO-CGD colitis) when diagnosed with CGD colitis. All severe patients had a more progressive form of VEO-CGD colitis. Unlike mild and moderate patients, severe patients required multidrug therapy of corticosteroids and immunomodulator/immunosuppressants, and some were eventually treated with hematopoietic stem cell transplantation. Although the validation of PUCAI in CGD colitis should be considered for future use, our results indicate that noninvasive measures could be effective to measure disease activity and help to determine suitable treatment for CGD colitis. In patients with VEO-CGD colitis, multidrug therapy would need to be considered at an early stage on the basis of disease activity.

Recent advances in chronic granulomatous disease

Chronic Granulomatous Disease (CGD) is a primary immunodeficiency caused by abnormities in the NADPH Oxidase that is involved in the respiratory burst responsible for initiating the killing of microbes ingested by phagocytic cells. The hallmark of CGD is recurrent infection but the inflammatory complications can prove difficult to treat. New insights into the mechanisms responsible for the inflammatory complications have led to new therapies. The treatment of CGD colitis with an anti-tumour necrosis alpha agent has been shown to be successful but associated with significant infectious complications. Haematopoietic stem cell transplants offer the possibility of cure for those with ether a matched or unrelated donor transplant, with results of the latter improving significantly over recent years. Gene Therapy offers the promise of cure without the need for a transplant but better vectors are required.

Su1354 Factors Associated With Large Increases in Self-Reported Health Status in Infliximab-Treated IBD Patients

Introduction: Chronic granulomatous disease (CGD) is an immunodeficiency syndrome caused by a defective NADPH oxidase complex. Afflicted patients are unable to produce adequate reactive oxygen metabolites to neutralize microorganisms within macrophages. Approximately 50% of CGD patients develop gastrointestinal (GI) disease that shares features of both Crohn's disease and ulcerative colitis. In patients with pediatric-onset ulcerative colitis, the cumulative risk for colorectal cancer (CRC) is 2% at 10 years (yrs) and 8% at 20 yrs. While the increased risk of CRC among patients with longstanding inflammatory bowel disease (IBD) is well established, the incidence of CRC among CGD patients with longstanding colitis has not been described. Methods: Patients with CGD colitis were identified from a database comprised of 279 CGD patients seen at the NIH from 1972 to 2011. To allow for adequate endoscopic, pathologic, and clinical follow-up, 78 patients with evidence of CGD colitis seen between 1990 and 2010 were identified, and patients with disease duration >10 yrs were used for formal analysis. The clinical and endoscopic reports over the 10 year follow-up period were reviewed, and the colonic biopsies were reexamined when available. Demographic information, duration of disease, endoscopic findings, and treatment and surgical history were extracted from the electronic medical records. The primary endpoint was the evidence of dysplasia or development of CRC. Results: Of the 78 patients, 20 had disease for >10 yrs. Notably, no colonic dysplasia or CRC were seen at the time of the biopsies in any of these patients. Of the 20 patients with disease > 10 yrs, 8 had biopsies available for formal reexamination. On reexamination, no patients were found to have colonic dysplasia or CRC. For all 20 patients, the average age at diagnosis was 10 years, with the median duration of disease of 16.7 yrs. Polyps were noted in 5 of 20 patients, 3 of which were inflammatory, 1 hyperplastic and 1 normal mucosa. No patients were diagnosed with colorectal cancer during follow-up. Conclusions: Despite long-standing inflammation, there was no dysplasia or CRC among 20 patients with CGD after a median of 16.7 years of follow up. In addition, no cases of colonic dysplasia or CRC were found in any patients with CGD colitis. The incidence of CRC among patients with CGD colitis appears to be lower than the incidence among patients with IBD. In fact, there are no reported cases of malignant polyps, dysplasia, or any gastrointestinal cancers in the short term or long term data. Although limited by a retrospective study design, these data suggest that the development of CRC in the setting of chronic inflammation may be influenced by NADPH activity, suggesting superoxide metabolism as a possible target to prevent oncogenesis.

Su1353 Longstanding Chronic Granulomatous Disease Colitis Does Not Increase the Risk of Colorectal Cancer

Introduction: Chronic granulomatous disease (CGD) is an immunodeficiency syndrome caused by a defective NADPH oxidase complex. Afflicted patients are unable to produce adequate reactive oxygen metabolites to neutralize microorganisms within macrophages. Approximately 50% of CGD patients develop gastrointestinal (GI) disease that shares features of both Crohn's disease and ulcerative colitis. In patients with pediatric-onset ulcerative colitis, the cumulative risk for colorectal cancer (CRC) is 2% at 10 years (yrs) and 8% at 20 yrs. While the increased risk of CRC among patients with longstanding inflammatory bowel disease (IBD) is well established, the incidence of CRC among CGD patients with longstanding colitis has not been described. Methods: Patients with CGD colitis were identified from a database comprised of 279 CGD patients seen at the NIH from 1972 to 2011. To allow for adequate endoscopic, pathologic, and clinical follow-up, 78 patients with evidence of CGD colitis seen between 1990 and 2010 were identified, and patients with disease duration >10 yrs were used for formal analysis. The clinical and endoscopic reports over the 10 year follow-up period were reviewed, and the colonic biopsies were reexamined when available. Demographic information, duration of disease, endoscopic findings, and treatment and surgical history were extracted from the electronic medical records. The primary endpoint was the evidence of dysplasia or development of CRC. Results: Of the 78 patients, 20 had disease for >10 yrs. Notably, no colonic dysplasia or CRC were seen at the time of the biopsies in any of these patients. Of the 20 patients with disease > 10 yrs, 8 had biopsies available for formal reexamination. On reexamination, no patients were found to have colonic dysplasia or CRC. For all 20 patients, the average age at diagnosis was 10 years, with the median duration of disease of 16.7 yrs. Polyps were noted in 5 of 20 patients, 3 of which were inflammatory, 1 hyperplastic and 1 normal mucosa. No patients were diagnosed with colorectal cancer during follow-up. Conclusions: Despite long-standing inflammation, there was no dysplasia or CRC among 20 patients with CGD after a median of 16.7 years of follow up. In addition, no cases of colonic dysplasia or CRC were found in any patients with CGD colitis. The incidence of CRC among patients with CGD colitis appears to be lower than the incidence among patients with IBD. In fact, there are no reported cases of malignant polyps, dysplasia, or any gastrointestinal cancers in the short term or long term data. Although limited by a retrospective study design, these data suggest that the development of CRC in the setting of chronic inflammation may be influenced by NADPH activity, suggesting superoxide metabolism as a possible target to prevent oncogenesis.

A Case of Macrophage Activation Syndrome Developing in a Patient With Chronic Granulomatous Disease-associated Colitis

Although macrophage activation syndrome (MAS) develops in some patients with chronic granulomatous disease (CGD), all of the reported cases have been associated with pathogenic microbial infections. We report a 2-year-old boy with CGD-associated colitis who suffered from MAS without any clinical signs of a microbial infection. He was treated with 1 course of methylprednisolone pulse therapy and the clinical symptoms improved; however, the colitis was difficult to control even with immunosuppressive drugs, and he eventually required hematopoietic stem cell transplantation 1 year after the onset of MAS. It is likely that MAS develops in patients with CGD colitis independent of microbial infections.

The role of surgery in the management of patients with refractory chronic granulomatous disease colitis.

Chronic granulomatous disease is a rare immunodeficiency complicated by dysregulated inflammation and granulomatous complications of the GI tract. The management of chronic granulomatous disease colitis presents the dilemma of an immunocompromised host requiring immunosuppressive therapy which can potentiate fatal infections. The aim of this study was to identify the types of GI surgery performed in patients and determine the role of surgery in the management of refractory colitis. A retrospective single-institution chart review was performed. Of 268 patients with chronic granulomatous disease treated at the National Institutes of Health between 1985 and 2011, 98 (37%) were identified as having colitis; 27 (10%) had a history of GI luminal surgery. Patient characteristics, type of GI surgery, and clinical outcomes were documented. A total of 62 GI luminal surgeries were performed in 27 patients with chronic granulomatous disease and colitis. All 27 had a history of perineal disease requiring intervention. Four (15%) had additional surgery performed for reasons other than colitis. Otherwise, 12 (44%) had surgery limited to the perineum, 2 (7%) had a segmental resection, and 13 (48%) underwent fecal diversion with ileostomy or colostomy. Despite local procedures, 7 (58%) patients in the perineal-only group remained symptomatic. Both patients with a segmental resection had persistent perineal disease, and 1 had a recurrent colovesicular fistula. Of the 13 ostomy patients, 11 initially received a diverting ostomy. Eight (73%) of these ultimately required additional procedures for refractory disease, and 4 (36%) developed peristomal pyoderma gangrenosum. Four patients who underwent proctocolectomy with end ileostomy, either initially (2) or as a definitive procedure (2), experienced resolution of colitis and perineal disease. This study is limited by its retrospective design, small sample size, and highly selected patient population. Proctocolectomy with end ileostomy may offer a definitive treatment in a patient with refractory chronic granulomatous disease colitis given current therapeutic limitations.

Thalidomide attenuates excessive inflammation without interrupting lipopolysaccharide-driven inflammatory cytokine production in chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare inherited disorder characterized by an inability to produce reactive oxygen species, resulting in recurrent life-threatening infections. Curiously, half of the patients with CGD suffer from aseptic bowel inflammation (CGD colitis) due to dysregulated inflammation induced by TNF-α and IL-1β. Thus, developing therapies that regulate excessive inflammatory responses without interrupting antimicrobial immunity would benefit CGD colitis patients. Here, we show that thalidomide suppressed TNF-α-induced NF-κB activation and ATP-induced IL-1β secretion, but did not interrupt the production of IL-1β, IL-6, IL-8, and TNF-α in response to lipopolysaccharide in CGD monocytes. We report on a CGD colitis patient that showed decreased bowel inflammation characterized by reduced serum levels of inflammatory cytokines without evidence of progression of fungal and bacterial infections present at initiation of thalidomide therapy. Our results suggest that thalidomide could be an efficacious therapeutic option for patients with CGD colitis suffering from serious infections.

High levels of Crohn's disease-associated anti-microbial antibodies are present and independent of colitis in chronic granulomatous disease.

Chronic granulomatous disease (CGD) and inflammatory bowel disease (IBD) have overlapping gastrointestinal manifestations. Serum antibodies to intestinal microbial antigens in IBD are thought to reflect a loss of tolerance in the setting of genetically encoded innate immune defects. CGD subjects studied here, with or without colitis, had considerably higher levels of ASCA IgA, ASCA IgG, anti-OmpC, anti-I2, and anti-CBir1, but absent to low pANCA, compared to IBD-predictive cutoffs. Higher antibody levels were not associated with a history of colitis. Except for higher ASCA IgG in subjects <18 years, antibody levels were not age-dependent. In comparison, 7 HIES subjects expressed negative to low antibody levels to all of these antigens; none had colitis. Our results suggest that markedly elevated levels of antimicrobial antibodies in CGD do not correlate with a history of colitis but may reflect a specific defect in innate immunity in the face of chronic antigenic stimulation.

Microbial Antigen Sensitization and Colitis in Chronic Granulomatous Disease and Hyper IgE Syndrome

RATIONALE: Subjects with Chronic Granulomatous Disease (CGD) and Hyper IgE Syndrome (HIES) experience chronic bacterial and fungal infections. A number of CGD subjects have colitis which presents similarly to inflammatory bowel disease (IBD), thus we sought to compare the prevalence of sensitization to IBD-associated microbial antigens in these primary immunodeficiencies.

Chronic Granulomatous Disease Colitis: A Therapeutic Approach to a Rare Condition

Purpose: Introduction: Chronic Granulomatous Disease (CGD) refers to a group of inherited disorders in which phagocytes are deficient in the ability to generate reactive oxygen intermediates. This predisposes patients to recurrent infections and granuloma formation, commonly involving the gastrointestinal system. CGD colitis mimics Crohn's colitis, however, the treatment approaches are distinct given the concern of further immunosuppression in an immunocompromised patient. Case Description: We describe the case of a 15 year old male with CGD colitis and the systematic therapeutic approach to refractory disease including 5-ASA compounds, steroids, prophylactic trimethoprim-sulfamethoxazole, interferon gamma, and a sustained course of azathioprine. The use of azathioprine for 35 months, the longest course described in a patient with CGD colitis, led to a dramatic improvement in symptoms and endoscopic disease activity, without infectious complications. Discussion: The therapeutic approach to CGD colitis is not well described. We will review the literature on treatment modalities and suggest a systematic therapeutic approach for CGD colitis. Our case also supports the use of azathioprine as an agent to treat CGD colitis without the risk of infection described in other therapies although more research is needed.

Is TNFα a Potential Target for the Treatment of Colitis in Chronic Granulomatous Disease?

Background: Chronic granulomatous disease (CGD) is an immmunodeficiency and hyperinflammation disorder. Sterile hyperinflammation in the colon, CGD colitis, contributes significantly to the morbidity of patients. Presently available treatment options for CGD colitis include corticosteroids and interferon γ. Overshooting tumor necrosis factor α (TNFα) production in CGD phagocytes has been proposed as a mechanism contributing to hyperinflammation. In this study, we have investigated whether a deletion or suppression of TNFα resulted in a diminution of the hyperinflammation in a murine CGD model. Methods: For genetic deletion experiments, wild-type (N = 6), CGD (=Nox 2 [gp91phox]-deficient, N = 6), and CGD/TNFα–deficient mice (N = 6) were injected intradermally with β-glucan to induce hyperinflammation. For pharmacological experiments, CGD mice were treated with the TNFα scavenger sTNFR2-Fc (Ethanercept) before β-glucan injection. Seven days later, the severity of inflammation was assessed on hematoxylin and eosin–stained slides of ear sections by a histological score (from 0 to 4, with 4 being the most severe inflammation). Results: The β-glucan generated a mild inflammatory score in the wild-type mice (mean score 1.5 ± 0.5), whereas CGD mice showed severe inflammation (mean 3.5 ± 0.2). Genetic deletion or pharmacological inhibition of TNFα did not decrease the severity of inflammation in CGD mice: histological scores for CGD/TNFα-deficient mice and for sTNFR2-Fc-treated CGD mice were 3.7 ± 0.3, and 3.7 ± 0.4, respectively. In both TNFα suppressed mice, a hyperinflammatory syndrome associated with necrotic lesions was observed. Conclusions: Neither genetic deletion of TNFα nor treatment with a TNFα scavenger prevented skin hyperinflammation in CGD mice. Thus, unlike as previously suggested, TNFα probably does not represent a potential target for the treatment of CGD hyperinflammation. However, our results were obtained in skin hyperinflammation and future research will have to investigate the similarities and differences between hyperinflammation in the skin and the colon. The authors report no conflicts of interest.

TRICHOSPORON PULLULANS AS A COMPLICATION OF CHRONIC GRANULOMATOUS DISEASE IN A PATIENT UNDERGOING IMMUNOSUPPRESSIVE THERAPY FOR INFLAMMATORY BOWEL DISEASE

We describe a patient with chronic granulomatous disease and receiving immunosuppressive therapy for refractory granulomatous colitis who developed fatal fulminant pneumonia, with Trichosporon pullulans isolated from multiple sites. This case highlights potential difficulties in treating chronic granulomatous disease colitis with high dose immunosuppressants and suggests that T. pullulans may represent an opportunistic organism with high morbidity and mortality in such patients.

P0892 PRESENTING FEATURES OF COLITIS IN CHRONIC GRANULOMATOUS DISEASE PATIENTS IN THE UK AND IRELAND

Introduction: Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency due to a defective phagocytic cell oxidative burst, rendering patients suspectible to severe recurrent infections and chronic inflammatory process. The objective of this study was to describe the presenting features of colitis in CGD patients within the United Kingdom and Ireland. Methods: A national survey of CGD patients was undertaken. Consenting patients were identified and clinical data on epidemiology and morbidity was abstracted from their hospital notes. Results: 94 CGD patients were identified-68 (72%)with X-linked (XL) disease and 16 (17%) with Auto-recessive (AR) disease. Mode of inheritance was unknown (U) in 10 patients (11%).35 CGD patients (37%) had macroscopic or histological appearance of large bowel colitis-26 XL,7 AR, 2 U. Barium studies of the small bowel were normal in 21 of 23 patients, 1 patient having midileal abnormalities, the other a stricture in the terminal ileum. Symptoms at presentation: diarrhoea 74%, bloody stools 68%, abdominal pain 47%. In pathology reports, granulomas were reported in 63%, pigmented macrophages in 26% and eosinophilic infiltrate in 20%. 15 (43%)patients presented with colitis before being diagnosed with CGD- 11 XL,3 AR,1 U. Initial diagnosis was Crohns disease in 5 (33%) and Cows milk protein intolerance in 3 (20%). Mean age of presentation in this subgroup of 15 was 2.86 years in XL (range 0.1–7.1) and 8.93 years in AR (Range 5–14.1). Conclusion: CGD colitis is significant problem and often presents before CGD is diagnosed. There are no consistent pathognomnic features. It is primarily a large bowel disease. CGD should be considered in all children presenting with colitis. Assessment of the oxidative burst should be undertaken, particular in children under the age of 5 or with a unusual history of infections.

The nature of colitis in chronic granulomatous disease.

Patients with chronic granulomatous disease (CGD) may have gastrointestinal manifestations, commonly colitis. The etiology, prevalence, and inflammatory process of CGD colitis are unclear. To characterize the inflammatory process of CGD colitis and to compare it with other inflammatory bowel disorders. Colonic mucosal biopsies from 8 CGD patients were immunostained for eosinophils, neutrophils, macrophages, and adhesion molecules (ICAM; VCAM, E-selectin) and compared with normal and diseased controls (allergic colitis, ulcerative colitis, and melanosis coli). Cell types were counted and expressed as cell/mm2. The inflammatory infiltrate in CGD colitis differed from the normal controls by an increase in eosinophils (110; 48-176 [median and range] versus 14.5; 3-30; P < 0.005) and macrophages (291.5; 203-480 versus 38.5; 27-64; P < 0.005). There was a paucity of neutrophils compared to ulcerative colitis (10; 0-101 versus 315.5; 78-688; P < 0.005). Expression of HLA-DR was increased in the epithelium and vascular endothelium in CGD compared with normal controls. Patterns of expression of the adhesion molecules differed significantly in CGD from those in other inflammatory bowel diseases: intracellular adhesion molecule-1 was more strongly expressed in the lamina propria, vascular adhesion molecule-1 was more patchily expressed, and E-selectin was present only in the small vessels. The mechanism of inflammation and profile of inflammatory mediators in CGD colitis differs from that in other inflammatory bowel diseases.

The Nature of Colitis in Chronic Granulomatous Disease

ABSTRACTBackgroundPatients with chronic granulomatous disease (CGD) may have gastrointestinal manifestations, commonly colitis. The etiology, prevalence, and inflammatory process of CGD colitis are unclear.ObjectivesTo characterize the inflammatory process of CGD colitis and to compare it with other inflammatory bowel disorders.MethodsColonic mucosal biopsies from 8 CGD patients were immunostained for eosinophils, neutrophils, macrophages, and adhesion molecules (ICAM; VCAM, E‐selectin) and compared with normal and diseased controls (allergic colitis, ulcerative colitis, and melanosis coli). Cell types were counted and expressed as cell/mm2ResultsThe inflammatory infiltrate in CGD colitis differed from the normal controls by an increase in eosinophils (110; 48–176 [median and range] versus 14.5; 3–30;P &lt; 0.005) and macrophages (291.5; 203–480 versus 38.5; 27–64;P &lt; 0.005). There was a paucity of neutrophils compared to ulcerative colitis (10; 0–101 versus 315.5; 78–688;P &lt; 0.005). Expression of HLA‐DR was increased in the epithelium and vascular endothelium in CGD compared with normal controls. Patterns of expression of the adhesion molecules differed significantly in CGD from those in other inflammatory bowel diseases: intracellular adhesion molecule‐1 was more strongly expressed in the lamina propria, vascular adhesion molecule‐1 was more patchily expressed, and E‐selectin was present only in the small vessels.ConclusionsThe mechanism of inflammation and profile of inflammatory mediators in CGD colitis differs from that in other inflammatory bowel diseases.