Crohn's Disease

An email I received yesterday ask me if there was a tie in between lymphedema and Crohn's Disease. On the face of it, you would think not, however a closer examination of the two conditions reveals a distinct tie in.

I include a quote from renown British lymphedema expert Dr. Peter Mortimer in an article for Lymphovenous Canada:

"It is my belief that many of the types of edema that we see associated with treatment of cancer and other conditions such as Crohn's disease and some arthritic conditions, are in fact related to an underlying genetic weakness in lymph drainage which already exist. If you take Crohn's disease, for example, the pathology of Crohn's disease is effectively lymphedema of the gut. Gastroentologists don't call it that, but that is what it is."

There are two clinical features specifically of Crohn's that can lead to and are associated with lymhpedema.

First is granulomatous lymphangitis. Secondly is hyperplaysia of the lymphatics similar to that in lymphangiectasia. Both of these affet the lymphatics and subsequent have lymphedema presenting as an accompanying complication.

--------------------------

CROHN'S DISEASE

Background

This is one half of inflammatory bowel disease, its partner is ulcerative colitis. The presenting symptoms are varied including fever, mild diarrhea, and abdominal pain. The attacks may be episodic lasting weeks to months. Bleeding, especially in patients with colon involvement, may occur. Crohn's disease differs from ulcerative colitis in being able to involve the entire gastrointestinal tract from mouth to anus. In addition, a number of organ systems may be involved (see clinical presentations).

EPIDEMIOLOGIC ASSOCIATIONS CHARACTERIZATION

SYNONYMS Terminal ileitis, Regional enteritis, Granulomatous colitis, Crohn's colitis, inflammatory bowel disease

INCIDENCE 3/100,000 in USA

Clinical features of Crohn's disease: a clinical study of one hundred patients found in an unselected population.Kangas E, Matikainen M, Auvinen O, Harju E, Inkovaara J, Maki M.Int Surg 1986 Oct-Dec;71(4):256-9 Abstract quote

One hundred patients (mean age 34 years, range from 12 to 70 years) were treated at Tampere University Hospital during the thirteen year period, 1972-1984. Our hospital takes responsibility for the treatment of patients with Crohn's disease found in an unselected population of 400,000 inhabitants.

In 73% of cases Crohn's disease was diagnosed before the age of forty. The mean interval between the first clinical signs and the diagnosis was 3.3 years. In 57% of the patients the diagnosis was reached within one year. In nine patients the primary diagnosis was colitis ulcerosa. Most patient were anemic and were in the state of inflammation and/or catabolism suggested by low blood hemoglobin concentration and high ESR and CRP values on admission. Three percent of the patients had macroscopic Crohn's disease in all parts of the gastrointestinal tract, whereas 22% had it only in the small intestine and 18% only in the colon. Fifty of the hundred patients had lesions in the terminal ileum and 20% in the anus. The specific finding for the present series was a high frequency of rectal lesions, in 29% of the patients.

Histologically the condition was more often (P less than 0.001) revealed by the laparatomy specimen than the endoscopic biopsy, which gave a positive histology more often (P less than 0.001) in the lower than in the upper gastrointestinal tract. No gastrointestinal malignancies were found.

AGE-RANGE AND MEDIAN

Peak 2-3rd decadesMinor peak in 6-7th decades

SEX (MALE:FEMALE) Females slightly more common

GEOGRAPHIC DISTRIBUTION Whites:Nonwhites 2-5:1 Smoking Jewish et

DISEASE ASSOCIATIONS CHARACTERIZATION

CALCIPHYLAXIS

Calciphylaxis in a patient with Crohn's disease in the absence of end-stage renal disease.

Barri YM, Graves GS, Knochel JP.

Department of Medicine, Presbyterian Hospital of Dallas, TX 75231, USA

Am J Kidney Dis 1997 May;29(5):773-6 Abstract quote

Calciphylaxis is a rare and life-threatening condition of progressive cutaneous necrosis secondary to small and medium-sized vessel calcification previously described in patients with end-stage renal disease and hyperparathyroidism. Early diagnosis may be important in improving the poor outcome in these patients since early intervention may forestall the development of life-threatening complications.

We describe a patient with Crohn's disease complicated by short-bowel syndrome and modest renal insufficiency (not requiring renal replacement therapy) who developed calciphylaxis. It appears that longstanding Crohn's disease and the short-bowel syndrome accelerated the development of calciphylaxis as the chronic renal disease was not end stage. Considering the possibility of calciphylaxis in this setting may avoid delaying the diagnosis and its consequences.

LUPUS ERYTHEMATOSUS

Fatal evolution of systemic lupus erythematosus associated with Crohn's disease.

Chebli JM, Gaburri PD, de Souza AF, Dias KV, Cimino KO, de Carvalho-Filho RJ, Lucca FA.

Division of Gastroenterology, Department of Medicine, Juiz de Fora University, School of Medicine, Juiz de Fora, MG, BrazilA

rq Gastroenterol 2000 Oct-Dec;37(4):224-6 Abstract quote

The authors describe the case of a young Brazilian woman who was treated of ileocolonic Crohn's disease sparing rectum, as confirmed by colonoscopy and histopathological examination.

After a 4-year course of sulfasalazine treatment, she presented with skin facial lesions in vespertilio, fever, arthralgias and high titers of anti-ANA and LE cells. A sulfasalazine-induced lupus syndrome was diagnosed, because after sulfasalazine withdrawal and a short course of prednisone, the clinical symptoms disappeared and the laboratory tests returned to normal. Mesalazine 3 g/day was started and the patient remained well for the next 3 years, when she was again admitted with fever, weakness, arthralgias, diplopy, strabismus and hypoaesthesia in both hands and feet, microhematuria, haematic casts, hypocomplementemia and high titers of autoimmune antibodies.

A diagnosis of associated systemic lupus erythematosus was made. Although a pulsotherapy with methylprednisolone was started, no improvement was noticed. A cyclophosphamide trial was tried and again no positive results occurred. The patient evolved to severe clinical manifestations of general vasculitis affecting the central and peripheral nervous system and lungs, having a fatal evolution after 2 weeks.

Although uncommon, the association of both disease may occur, and the authors call attention to this possibility, making a brief review of literature

PSORIASIS

Connections between psoriasis and Crohn's disease.

Najarian DJ, Gottlieb AB.

University of Virginia School of Medicine, and the Clinical Research Center, University of Medicine and Dentistry of New Jersey-The Robert Wood Johnson Medical School.

J Am Acad Dermatol. 2003 Jun;48(6):805-21. Abstract quote The prevalence of psoriasis in patients with Crohn's disease (CD) is higher than chance would allow if they were mutually exclusive diseases. A close examination reveals genetic and pathologic connections between these diseases. An appreciation for the role of tumor necrosis factor-alpha in both diseases has proven very important.

Increased levels of this inflammatory cytokine have been measured in CD lesions, and in 1997 a clinical trial demonstrated the response of this disease to infliximab, a monoclonal antibody specific for tumor necrosis factor-alpha. A subsequent clinical trial evaluated infliximab in a patient with CD and psoriasis, another disease in which increased levels of tumor necrosis factor-alpha are seen in lesions.

Scientists noticed the marked skin improvement of this patient and later demonstrated the efficacy of infliximab for psoriasis in a randomized, double-blind, placebo-controlled trial. Thus, an appreciation for connections between psoriasis and CD can suggest novel therapeutic strategies with ensuing benefits to patients. This article reviews epidemiologic, genetic, and pathologic connections between psoriasis and CD and discusses pharmaceuticals targeting inflammatory mediators common to each disease. (J Am Acad Dermatol 2003;48:805-21.) Learning objective: At the completion of this learning activity, participants should understand how psoriasis and Crohn's disease are related at epidemiologic, genetic, and pathological levels and should appreciate how to use this knowledge to treat these diseases.

PATHOGENESIS CHARACTERIZATION

GENERAL

Molecular Discoveries Alter Our View of Inflammatory Bowel Disease A Review From Scientific, Clinical, and Laboratory Perspectives

Eric B. Staros, MD

Am J Clin Pathol 2003;;119:524-539 Abstract quote Within the past decade, knowledge of the molecular basis of inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis, has advanced owing to the explosive growth of research involving the human genome.

Furthermore, a shared interest between molecular biologists and clinical researchers has contributed to an emerging understanding of IBD. Nucleotide-binding oligomerization domain 2 (NOD2) belongs to an apoptotic regulatory family of genes and has been linked to CD. In addition, research into nuclear factor kappa B (NF–kappa B), the proteasome, interleukins, and tumor necrosis factor alpha has improved our understanding of IBD. Our understanding of these molecules and other scientific discoveries offers hope for new diagnostic tests and therapeutic agents.

In the future, genetic markers will predict disease susceptibility, therapeutic responsiveness, and long-term sequelae of modern therapeutics. Also on the horizon, molecular markers promise to define disease heterogeneity, thereby providing a rational basis for patient-specific therapies. The molecular discoveries that are changing our views of IBD will affect the clinician, the laboratory professional, and the patient.

BACTERIAL 16S rRNA

Cutaneous manifestations of Crohn's disease, its spectrum, and its pathogenesis: intracellular consensus bacterial 16S rRNA is associated with the gastrointestinal but not the cutaneous manifestations of Crohn's disease.

Crowson AN, Nuovo GJ, Mihm MC Jr, Magro C. Central Medical Laboratories, Winnipeg, Manitoba, Canada

Hum Pathol. 2003 Nov;34(11):1185-92 Abstract quote.

The classic pathology of skin disease discontinuous from the inflamed gastrointestinal (GI) tract in patients with Crohn's disease (CD) includes pyoderma gangrenosum (PG), erythema nodosum (EN), and so-called metastatic Crohn's disease. The purpose of this study was two-fold: First, we explored the full spectrum of cutaneous lesions associated with Crohn's disease, and second, we sought to explore a potential molecular basis of the skin lesions in patients with CD.

In this regard, we analyzed skin and GI tract biopsies from affected patients for the consensus bacterial SrRNA to determine whether direct bacterial infection was associated with either condition. Formalin-fixed, paraffin-embedded sections were studied and correlated to clinical presentation and histories from 33 patients with CD. Consensus bacterial RNA sequences were analyzed using an RT in situ PCR assay on both skin biopsy and GI biopsy material. The GI tract material included biopsies from 3 patients who had skin lesions and from 7 patients in whom there were no known skin manifestations. There were 8 cases of neutrophilic dominant dermal infiltrates, including pyoderma gangrenosum, 6 cases of granuloma annulare/necrobiosis lipoidica-like lesions, 5 cases of sterile neutrophilic folliculitis, 5 cases of panniculitis, 4 cases of vasculitis, 2 cases of psoriasis, 2 cases of lichenoid and granulomatous inflammation, and 1 case of classic metastatic CD. Intracellular bacterial 16S rRNA was detected in 8 of 10 tissues of active CD in the GI tract, of which 3 of the cases tested were from patients who also developed skin lesions at some point in their clinical course; in contrast, none of the skin biopsies had detectable bacterial RNA.

The dermatopathological manifestations of CD discontiguous from the involved GI tract mucosa have in common a vascular injury syndrome, typically with a prominent extravascular neutrophilic and/or histiocytic dermal infiltrate. In addition, this study, the first to document in situ intracellular consensus bacterial SrRNA in the GI tract in CD, suggests that hematogenous dissemination of viable microbes is not associated with the cutaneous manifestations of this disease. Bacteria do, however, appear to play a role in bowel lesions of patients with CD.

CYTOKINES

Role of cytokines in the pathogenesis of inflammatory bowel disease.

Papadakis KA, Targan SR.

Division of Gastroenterology, Cedars-Sinai Medical Center, University of California, Los Angeles 90048, USA.

Annu Rev Med 2000;51:289-98 Abstract quote

Recent advances in the drug treatment of inflammatory bowel disease (IBD) have paralleled our understanding of the pathophysiology of ulcerative colitis and Crohn's disease.

Several proinflammatory and immune-regulatory cytokines are upregulated in the mucosa of patients with IBD, and differences and similarities in the cytokine profiles of ulcerative colitis and Crohn's disease have been elucidated. Several clinical trials involving a chimeric anti-TNF-alpha (tumor necrosis factor-alpha) antibody have shown marked clinical benefit in the majority of patients with Crohn's disease, verifying the importance of TNF-alpha in the pathogenesis of Crohn's disease.

In preliminary studies, treatment with recombinant human interleukin-10 has been beneficial in Crohn's disease but not in ulcerative colitis.

Future treatment of IBD may include combination or sequential cytokine and anticytokine administration in defined groups of patients based on their mucosal cytokine profiles

.....

Comparative Studies of the Colonic In Situ Expression of Intercellular Adhesion Molecules (ICAM-1, -2, and -3), 2 Integrins (LFA-1, Mac-1, and p150,95), and PECAM-1 in Ulcerative Colitis and Crohn's Disease

Ben Vainer, M.D.; Ole Haagen Nielsen, M.D., D.M.Sc.; Thomas Horn, M.D., D.M.Sc.

From the Department of Medicine M (B.V., O.H.N.), Division of Gastroenterology, Glostrup Hospital; and the Department of Pathology (T.H.), Herlev Hospital, University of Copenhagen, Denmark.

Am J Surg Pathol 2000;24:1115-1124 Abstract quote

A dysregulated local immune defense with a constant influx of leukocytes provides a basis for continuous intestinal inflammation in ulcerative colitis (UC) and Crohn's disease (CD). Cell adhesion molecules are pivotal for the migration of leukocytes from the circulation toward the colonic epithelium.

A study quantifying the cells expressing intercellular adhesion molecules (ICAMs), 2 integrins, and platelet–endothelial cell adhesion molecule-1 (PECAM-1) in the colon was performed to illustrate the leukocyte migration pathway in inflammatory bowel disease.

Serial colonic sections (10 UC, 10 CD, and 10 controls) were stained immunohistochemically for ICAM-1, ICAM-2, ICAM-3, CD11a, CD11b, CD18, and PECAM-1. Cell adhesion molecule expression was evaluated quantitatively with reference to topographic localization. In UC, polymorphonuclear leukocytes (PMNs) in contact with the crypt epithelium and in crypt abscesses expressed CD11b. CD tissue was characterized by CD11a-, CD11c-, and ICAM-1-expressing cells. ICAM-1 was detected on endothelial cells, leukocytes, and apical parts of epithelial membranes, whereas ICAM-2 was expressed on basal epithelial membranes. Most infiltrating leukocytes expressed ICAM-3, whereas perivascular mononuclear cells expressed PECAM-1. Interestingly, the epithelial basement membrane in UC stained for CD18.

In conclusion, CD11b, CD18, and ICAM-2 seem to be important for PMN transepithelial migration in UC, whereas CD11a, CD11c, ICAM-1, and ICAM-3 seem central in leukocyte locomotion and aggregation in CD. Differentiated upregulation of cell adhesion molecules is suggested to be essential for the diversities between UC and CD.

MYCOBACTERIUM

Absence of Mycobacterium avium subsp. paratuberculosis in the microdissected granulomas of Crohn's disease.

Baksh FK, Finkelstein SD, Ariyanayagam-Baksh SM, Swalsky PA, Klein EC, Dunn JC.

1Department of Pathology, Lancaster General Hospital, Lancaster, PA, USA

Mod Pathol. 2004 Oct;17(10):1289-94. Abstract quote

The etiology of Crohn's disease remains unknown with inflammatory, infectious, and/or genetic causes suspected. Granulomatous inflammation is a characteristic feature of the disorder, resembling the tissue response to mycobacterium. Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent in Johne's disease, a chronic ulcerative intestinal condition in cattle, and has been implicated as a likely candidate.

We carefully microdissected the granulomas from the paraffin-embedded resection specimens of 18 patients with well-established Crohn's disease. The DNA obtained was PCR amplified for the IS900 and IS1311 repeat elements of MAP, PCR product size maintained at 101 and 124 base pairs, respectively. Archival tissue from bovine Johne's disease was used as a positive control. MAP-specific DNA, confirmed by sequencing and comparison with prototype strain sequence, was appropriately amplified from the positive control.

None of the Crohn's disease cases yielded a positive amplification product, failing to support a role for the organism in the pathogenesis of this illness.

NOD2 GENE

The Nod2 gene in Crohn's disease: implications for future research into the genetics and immunology of Crohn's disease.

Cho JH. Department of Medicine (GI), University of Chicago Hospitals, Illinois 60637, USA.

Inflamm Bowel Dis 2001 Aug;7(3):271-5 Abstract quote

The association of the Nod2 gene on chromosome 16 with increased susceptibility to Crohn's disease holds the promise of catalyzing fundamental genetic and therapeutic advances.

Coding region variants in the leucine-rich repeat region of Nod2 may affect host interactions with bacterial lipopolysaccharide. Genetic differences in pattern-recognition proteins (such as Nod2) of the innate immune system represent an increasingly important paradigm for understanding host-environment interactions. The central problem for complex disease gene identification through genome-wide searches has been that of locus heterogeneity; it is hoped that this heterogeneity will recede with the identification of Nod2, as the first pieces of a puzzle accelerate placement of subsequent pieces.

The potential for genetic approaches to positively impact the treatment of Crohn's disease and ulcerative colitis is unparalleled among complex, multigenic disorders

YERSINIA

Pathogenic yersinia DNA is detected in bowel and mesenteric lymph nodes from patients with Crohn's disease.

Lamps LW, Madhusudhan KT, Havens JM, Greenson JK, Bronner MP, Chiles MC, Dean PJ, Scott MA.

Am J Surg Pathol 2003 Feb;27(2):220-7 Abstract quote Previously, we detected pathogenic (invasive) DNA in the appendices of two patients who later developed Crohn's disease (CD).

This subsequent investigation is the first to evaluate a series of specimens from CD patients for the presence of pathogenic DNA. A total of 54 intestinal resection specimens from 52 patients with confirmed CD were evaluated.

Lesional tissue was tested by polymerase chain reaction analysis for the presence of genes occurring only in pathogenic Primer pairs are specific for each species, with no known cross reactions with other bacteria. Forty normal bowel specimens, 30 cases of acute appendicitis, and 50 cases of various active colitides served as disease controls. Medical records were reviewed following polymerase chain reaction and histologic evaluation. A total of 17 of 54 resections (31%) contained DNA by polymerase chain reaction. Mesenteric lymph nodes were also positive in eight of these cases.

All controls were negative. -positive patients had carried the diagnosis of CD for a median of 10 years before resection (range 1 month to 40 years).

We report the first documentation of DNA in a series of CD cases. Further studies are needed, including serial study, over time, of -positive CD patients, as well as prospective studies of newly diagnosed CD patients for evidence of infection. Like previous studies associating infectious organisms with CD, much work remains to elucidate whether the presence of DNA is an epiphenomenon or actually a factor in the pathogenesis of CD.

LABORATORY/ RADIOLOGIC/ OTHER TESTS CHARACTERIZATION

Barium enema-radiology

String sign-characteristic narrowing of the small bowel lumen

Perinuclear antineutrophil cytoplasmic antibodies in patients with Crohn's disease define a clinical subgroup.

Vasiliauskas EA, Plevy SE, Landers CJ, Binder SW, Ferguson DM, Yang H, Rotter JI, Vidrich A, Targan SR.

Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.Gastroenterology 1996 Jun;110(6):1810-9 Abstract quote

BACKGROUND & AIMS: Antineutrophil cytoplasmic antibodies (ANCA) have been consistently detected in a subgroup of patients with Crohn's disease (CD). This study was designed to determine whether serum ANCA expression in patients with CD characterizes an identifiable clinical subgroup.

METHODS: The study population consisted of 69 consecutive patients with an established diagnosis of CD as determined by a combination of characteristic clinical, radiographic, endoscopic, and histopathologic criteria. Sera from the patients were analyzed for the presence of ANCAs using the fixed neutrophil enzyme-linked immunosorbent assay (ELISA) assay. Perinuclear ANCA (pANCA)-positive and cytoplasmic ANCA (cANCA)-positive results by ELISA were confirmed by indirect immunofluorescence staining. Clinical profiles of the ANCA-positive patients with CD were compared with those of patients with CD not expressing ANCA (ANCA-negative).

RESULTS: pANCA-positive patients with CD have endoscopically and/or histopathologically documented left-sided colitis and symptoms of left-sided colonic inflammation, clinically reflected by rectal bleeding and mucus discharge, urgency, and treatment with topical agents. One hundred percent of patients with CD expressing pANCA had "UC-like" features.

CONCLUSIONS: In patients with CD, serum pANCA expression characterizes a UC-like clinical phenotype. Stratification of CD by serum pANCA provides evidence of heterogeneity within CD and suggests a common intestinal mucosal inflammatory process among a definable subgroup of patients with CD and UC expressing this marker

.....

Tumor necrosis factor-alpha in serum of patients with inflammatory bowel disease as measured by a highly sensitive immuno-PCR.

Komatsu M, Kobayashi D, Saito K, Furuya D, Yagihashi A, Araake H, Tsuji N, Sakamaki S, Niitsu Y, Watanabe N.

Division of Laboratory Diagnosis, Department of Clinical Laboratory Medicine, Sapporo Medical University, School of Medicine, South-I, West-16, Chuo-ku, Sapporo 060-8543, Japan.

Clin Chem 2001;47(7):1297-301 Abstract quote

GROSS APPEARANCE/CLINICAL VARIANTS CHARACTERIZATION The significance of serum concentrations of tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of inflammatory bowel disease (IBD) is uncertain. We measured TNF-alpha in serum from IBD patients by immuno-PCR to analyze the relationship between TNF-alpha and pathophysiologic state in IBD.

METHODS: Serum samples were collected from 54 healthy blood donors, 29 patients with ulcerative colitis (UC; 46 samples), and 7 patients with Crohn disease (CD; 8 samples). DNA label was generated by PCR amplification using biotinylated primer and was bound with streptavidin to biotinylated third antibody. TNF-alpha sandwiched by antibodies was detected by PCR amplification of the DNA label.

RESULTS: TNF-alpha could be measured in all samples. The median serum concentration in IBD patients overall was approximately 390-fold higher than in healthy donors (median increase, 380-fold for UC, 640-fold for CD). The median serum TNF-alpha concentration was 1.7-fold higher in the active stage of UC than in the inactive stage (P <0.05),

CONCLUSIONS: Sensitive measurement of serum TNF-alpha could provide an important pathophysiologic marker for the presence and activity of IBD.

GROSS APPEARANCE/CLINICAL VARIANTS CHARACTERIZATION

Site of involvement

Small intestine alone 40%

Small and large intestine 30%

Colon alone 30%

GASTROINTESTINAL TRACT

Characteristic skip lesions with diseased segments of bowel interspersed with normal segments, leading to cobblestone mucosa

Mesenteric fat wraps around bowel forming creeping fat

Intestinal wall is thickened and rubbery with narrowing of the lumen

Aphthous ulcers, focal mucosal ulcers, in early disease, leading to linear ulcers

Numerous fissures and sinus tract formation

.....

Prospective evaluation of upper gastrointestinal mucosal lesions in children with ulcerative colitis and Crohn's disease.

Ruuska T, Vaajalahti P, Arajarvi P, Maki M.

Department of Clinical Medicine, University of Tampere, Finland.

J Pediatr Gastroenterol Nutr 1994 Aug;19(2):181-6 Abstract quote Eighty-eight consecutive children with inflammatory bowel disease were studied, and upper gastrointestinal endoscopy was performed in 80 of them as one of the initial investigations before commencing medical or nutritional treatment.

Forty-one children were found to have Crohn's disease and 47, ulcerative colitis. Upper gastrointestinal endoscopy revealed pathology in 32 (80%) cases of Crohn's disease, esophagitis in 16, and esophageal ulcer in two, nonspecific gastritis in 22, duodenitis or duodenal ulcer in 18, and Helicobacter pylori infection in two cases. Granulomas were detected in 10 patients in the upper gastrointestinal tract: one esophageal, eight gastric, and three duodenal. Of the ulcerative colitis patients, seven had esophagitis, one had esophageal ulcer, 17 had nonspecific gastritis, two had gastric ulcers, two had duodenal ulcers, and five had H. pylori infection; altogether 30 (75%) yielded pathological findings. Radiological studies using barium meal revealed pathology in only eight of all inflammatory bowel disease cases. Symptoms at admission were not conclusive for definite diagnosis because 63% of patients with Crohn's disease had signs of colitis (such as diarrhea, bloody diarrhea) compared to 94% of ulcerative colitis patients.

Upper gastrointestinal endoscopy may be used to achieve a specific diagnosis, thus being helpful when planning treatment. Also a considerable incidence of nonspecific gastritis, duodenitis, and esophagitis with or without concomitant H. pylori infection may be anticipated in children suffering from both ulcerative colitis and Crohn's disease.

EXTRAGASTROINTESTINAL

EYE

Uveitis

JOINTS

Migratory polyarthritis

Sacroiliitis

Ankylosing spondylitis

LIVER

Hepatic sclerosing cholangitis

Noninfectious lung pathology in patients with Crohn's disease.

Casey MB, Tazelaar HD, Myers JL, Hunninghake GW, Kakar S, Kalra SX, Ashton R, Colby TV.

Am J Surg Pathol 2003 Feb;27(2):213-9 Abstract quote Lung involvement in Crohn's disease is not well characterized. We reviewed our experience with 11 lung biopsies (seven wedge and four transbronchial) from patients with Crohn's disease to study this association further. Negative cultures, special stains for organisms Gomori-methenamine-silver [GMS], acid fast), and polymerase chain reaction for (four cases) were required for inclusion. The group included five women and six men with a mean age of 47 years (range 13-84 years).

A diagnosis of Crohn's disease preceded the lung disease in nine patients. In two patients the diagnosis of Crohn's disease followed the diagnosis of their pulmonary disease 1 and 15 months later. Radiologically, eight patients had diffuse infiltrates, two had bilateral nodular infiltrates, and one had a mass. Chronic bronchiolitis with nonnecrotizing granulomatous inflammation was present in four patients, one of whom was taking mesalamine. Two patients had an acute bronchiolitis associated with a neutrophil-rich bronchopneumonia with suppuration and vague granulomatous features. One patient on mesalamine had cellular interstitial pneumonia with rare giant cells. Four patients demonstrated organizing pneumonia with focal granulomatous features, two of whom were taking mesalamine, and one of these two responded to infliximab (anti-tumor necrosis factor) monoclonal antibody therapy.

Noninfectious pulmonary disease in patients with Crohn's disease has variable histologic appearances, including granulomatous inflammation and airway-centered disease resembling that seen in patients with ulcerative colitis. Drugs may contribute to pulmonary disease in some patients.

GROSS APPEARANCE/CLINICAL VARIANTS CHARACTERIZATION Site of involvement Small intestine alone 40%Small and large intestine 30%Colon alone 30%

GASTROINTESTINAL TRACT Characteristic skip lesions with diseased segments of bowel interspersed with normal segments, leading to cobblestone mucosa

Mesenteric fat wraps around bowel forming creeping fat

Intestinal wall is thickened and rubbery with narrowing of the lumen

Aphthous ulcers, focal mucosal ulcers, in early disease, leading to linear ulcers

Numerous fissures and sinus tract formation

See complete page:

Lymphedema People