C. Cuvelier

Histopathology of intestinal inflammation related to reactive arthritis.

This study has identified a group of patients with inflammatory chronic, or relapsing acute arthritis who even in the absence of gastrointestinal symptoms have histological evidence of ileocolitis. At colonoscopy simultaneous biopsies of the terminal ileum and colon were taken from 108 patients with reactive arthritis (n = 55) or ankylosing spondylitis (n = 53), 47 patients with other rheumatic diseases and 19 control patients suffering from colonic polyps, adenocarcinoma, or chronic constipation. All control patients and all but one patient with rheumatoid arthritis, juvenile chronic arthritis, systemic lupus erythematosus, lumbar back ache, and psoriatic arthritis did not have histological evidence of acute or chronic inflammatory bowel disease. In contrast, in 30 of 35 (56.6%) patients with ankylosing spondylitis, and in 37 of 55 (67%) patients with reactive arthritis, regardless of HLA B27 phenotype, there was histological evidence of inflammatory bowel disease with features either of acute enterocolitis, or early Crohns disease. Only 18 of 67 (27%) of the patients with histological gut inflammation, however, had intestinal symptoms.

Neutrophil‐Derived Metalloproteinase‐9 Predicts Healing Quality after Sinus Surgery

Background: In a recent study, we have shown that gelatinase‐B (metalloproteinase [MMP]‐9) in nasal secretions can have both monitoring and predictive value on the healing outcome after functional endoscopic sinus surgery (FESS) to treat chronic rhinosinusitis (CRS) and nasal polyposis (NP). In this work, we aimed to explore the source of MMP‐9 and the influence of inflammation on MMP‐9 expression and release in nasal tissue and secretions during airway remodelling after surgery.

Nasal biopsy is superior to nasal smear for finding eosinophils in nonallergic rhinitis

The presence of eosinophils was compared in nasal biopsy and smear. Thirty‐two nonallergic rhinitis patients, of whom six had nasal polyps, were included in the study. The specimens were studied light‐microscopically after staining with hematoxylin‐eosin. The association between the presence of polyps and the finding of eosinophils in the biopsy specimens proved to be significant. Ten normal subjects served as controls. It was far more simple to detect eosinophils in the biopsy samples than in the nasal smears. When we considered biopsies with at least four eosinophils in four fields as hypereosinophilic, our group of patients contained 25% nonallergic rhinitis with eosinophilia syndrome (NARES) patients.

Intestinal mucosal permeability in inflammatory rheumatic diseases

The gut must be considered an outside surface. Before material enters the body, it must traverse the mucosa either actively or passively. The gut acts as a selective barrier to the luminal material, consisting not only of nutrients, water and electrolytes but also of bacteria and antigens. Abnormalities in the gut membrane, e.g. inflammation or disturbed permeability, could lead to an enhanced uptake of antigens which can induce inflammatory responses in target organs.

Major histocompatibility complex class II antigen (HLA-DR) expression by ileal epithelial cells in patients with seronegative spondylarthropathy.

Major histocompatibility complex molecules act as non-specific receptors for antigenic proteins and present them to T-cells. Presented antigen together with class II molecules activates antigen specific T-helper cells and may trigger a cellular immune response. The expression of HLA-DR antigens by epithelial cells was examined with an indirect peroxidase technique in ileal biopsies from 38 patients with seronegative spondylarthropathy and features of acute or chronic gut inflammation on biopsy, 14 patients with chronic inflammatory bowel disease, 10 rheumatic and 10 non-rheumatic controls. In acute ileitis, there was more HLA-DR expression in villous and crypt epithelial cells than in non-inflamed controls (p less than 0.01). In chronic inflammation and in chronic inflammatory bowel disease, class II antigens were more expressed in villus (p less than 0.02) and crypt epithelium (p less than 0.01). Strong HLA-DR expression in crypt epithelial cells was connected with active inflammation (p less than 0.02). These findings suggest binding of unknown enterobacterial or nutritional luminal antigens to HLA-DR antigens normally present in enterocytes. The enterocytes act as antigen presenting cells causing a local increase of targets for activated T-cells and trigger the gut inflammation responsible for the clinical symptoms of the seronegative spondylarthropathy.

Immunoglobulin containing cells in terminal ileum and colorectum of patients with arthritis related gut inflammation.

In 40 distal ileal and 40 colonic biopsies of arthritic patients mostly without gastrointestinal symptoms, but with histological evidence of acute or chronic inflammation of the gut, the number of immunoglobulin (Ig) containing plasma cells was studied morphometrically using a peroxidase antiperoxidase technique. Compared with controls, the ileal mucosal biopsies showed an increase of IgA and IgG in acute ileitis. In chronic ileitis there was an increase of IgA, IgG, and IgM similar to Crohns disease. In colonic biopsies there was a significant increase of all immunoglobulin classes in acute inflammation. In chronic inflamed mucosa there was also an increase of all three Ig classes. The Ig distribution, however, was significantly different in acute and chronic colitis. These findings give immunohistochemical evidence of the existence of two different types of inflammation related to reactive arthritis or the peripheral joint involvement of ankylosing spondylitis. The Ig pattern in acute colitis is similar to that found in infectious colitis, suggesting an enterobacterial origin of the arthritis in this group of patients although bacteriological and serological investigations were negative. In the chronic type of arthritis related ileocolitis, the pattern of Ig containing cells is similar to that found in Crohns disease but different from infectious and ulcerative colitis, which makes the hypothesis that a great number of these arthritis patients suffer from asymptomatic or subclinical Crohns disease acceptable.

A comparative phenotypical analysis of rheumatoid nodules and rheumatoid synovium with special reference to adhesion molecules and activation markers

OBJECTIVES (1)To analyse the in situ expression of adhesion molecules in rheumatoid nodules. (2) To compare the endothelial expression of adhesion molecules in synovial tissue and subcutaneous nodules obtained from the same patients. (3) To compare the expression of adhesion molecules and activation markers on T cell lines from nodules and synovium. METHODS (1) Immunohistochemical analysis by APAAP technique of E selectin, CD44, ICAM-1, PECAM-1, and VCAM-1 was performed on 10 rheumatoid nodules from seven patients with rheumatoid arthritis (RA); nodules and synovium were simultaneously analysed from three patients. (2) T cell lines were generated from RA nodules (n=7) and synovium (n=7) by interleukin 2 expansion, and subsequently characterised by flow cytometry for surface expression of αEβ7, α4β7, CD44, L selectin, LFA-1a, PECAM-1, and CD30. RESULTS (1) In rheumatoid nodules, the palisading layer strongly stains for ICAM-1 and PECAM-1, but less pronounced for CD44. VCAM-1 staining was usually negative. ICAM-1 is upregulated in the vessels surrounding the central zone of fibrinoid necrosis. The immunohistological picture in different nodules derived from the same patient was similar. (2) The endothelial expression of adhesion molecules is comparable in RA nodules and synovium on an individual level, except for E selectin, which is overexpressed in nodule endothelium. (3) T cell lines from nodules and synovium display similar adhesion molecule profiles. However, the expression of CD30, a T cell activation marker linked with Th2 subsets, is higher in nodules compared with synovium. CONCLUSION These data support a recirculation hypothesis of T cells between articular and extra-articular manifestations in RA, although the activation state of the T cells in each of these localisations may differ.

Natural history and clearance of HPV after treatment of precancerous cervical lesions

Aim:  To assess the clearance rate of human papillomavirus (HPV) after out‐patient treatment of cervical intraepithelial neoplasia (CIN).

Crohn's disease with adenocarcinoma and dysplasia. Macroscopical, histological, and immunohistochemical aspects of two cases

We present two cases of small-bowel adenocarcinoma and dysplasia in patients with longstanding Crohns disease. In one case, the dysplasia and cancer were exclusively located in the terminal ileum, whereas in the other case, several cancers were found from the ileum toward the transverse colon. In both cases, we found a clinically unsuspected Dukes C1 mucinous adenocarcinoma together with large foci of polypoid villous dysplasia or with multifocal high-grade dysplasia and intramucosal carcinoma. Immunohistochemical staining for carcinoembryonic antigen (CEA) revealed a different staining pattern in various diseased areas. The intensity of CEA staining paralleled the histologic degrees of dysplasia and neoplasia. Cytokeratin expression was disturbed in inflamed mucosa, and it was more pronounced in high-grade dysplasia and invasive carcinoma. We conclude that the presence of dysplasia in an intestinal biopsy of a patient with Crohns disease should arouse the pathologists suspicion of carcinoma and force him or her to take multiple sections from strictures and polypoid lesions, especially since the clinical symptoms of a carcinoma may be obscured by the symptoms of inflammatory bowel disease. Immunohistochemical staining with CEA and cytokeratin are useful in the objectivation of dysplasia.

Identification of the nasal mucosa as a new target for leptin action

Taildeman J, Demetter P, Rottiers I, Holtappels G, Bachert C, Cuvelier C A & Pérez‐Novo C A
(2010) Histopathology 56, 789–798
Identification of the nasal mucosa as a new target for leptin action