Lymph Folliculitis in Ulcerative Colitis
M. Chiba, H. Yamano, K. Fujiwara, T. Abe, M. Iizuka & S. WatanabeFirst Dept. of Internal Medicine, Akita University School of Medicine, Division of Gastroenterology,Akita Red Cross Hospital, and Division of Gastroenterology, Nakadori Hospital, Akita City, Japan,
Chiba M, Yamano H, Fujiwara K, Abe T, Iizuka M, Watanabe S. Lymph folliculitis in ulcerative colitis.Scand J Gastroenterol 2001;36:3326.
Preferential involvement of the appendix has recently been con rmed in ulcerative colitis. Since theappendix is an aggregate of lymph follicles, this new observation implies a critical role of the lymphfollicles, of both the large bowel and the appendix, in an etiopathogenesis of ulcerative colitis. This reportpresents two cases of ulcerative colitis in which lymph folliculitis and lymphoid hyperplasia wereobserved. Lymph folliculitis was observed endoscopically in a border between an established lesion andan uninvolved area. Case 1, proctitis type, relapsing remitting, mild in severity, showed lymph folliculitisin a proximal border of an established rectal lesion. Case 2, with left-sided colitis, mild in severity, had askip appendiceal ori ce in ammation. Lymph folliculitis was observed in the cecum surroundingestablished appendiceal ori ce in ammation. In both cases, lymphoid hyperplasia was observed in anuninvolved area with clear vascular patterns. These two cases clearly demonstrate the involvement of gutlymph follicles in ulcerative colitis. Lymph folliculitis and/or lymphoid hyperplasia was proposed to beearly lesions in ulcerative colitis. In addition, the need for microbiology targeting lymph follicles of thelarge bowel and appendix is stressed in order to disclose the casual microbial agents in ulcerative colitis.
Key words: Appendix; etiology; lymph follicle; lymphoid hyperplasia; microbiology; ulcerative colitis
Mitsuro Chiba, M.D., First Dept. of Internal Medicine, Akita University School of Medicine, 1-1-1,Hondo, Akita City 010-8543, Japan (fax. 81 18 831 1907)
Clinical, epidemiological, and animal model studieshave provided rm evidence for an associationbetween the appendix and ulcerative colitis. It has
been reported that the appendix is frequently affected inulcerative colitis either continuous with or discontinuous fromthe colonic lesion. This observation was rst made in surgicalspecimens (15) before it was reproduced by endoscopy (610). An advancement in colonoscopy made it easy for theendoscopist to observe the proximal area beyond the distallesion in ulcerative colitis. The discontinuous, skip appendi-ceal lesion is observed as in ammation of the appendicealori ce, either limited to the ori ce or extending to the areasurrounding it. It was called appendiceal ori ce in amma-tion (AOI) by Yang et al. (10), who con rmed that AOI wasnot an effect of treatment but that it could be observed in newulcerative colitis cases before treatment (10). The severity ofthe disease does not differ between cases with or without AOIprovided that the extent of the lesion is the same (9). One clearmessage in clinical practice is that skip AOI does not merelyimplicate Crohn disease, but is rather an accepted nding forulcerative colitis. It is therefore clear now that ulcerativecolitis has two preferred sites; the large bowel, especially thedistal colon, and the appendix. Epidemiological studiesconclude that appendectomy signi cantly protects against
the subsequent development of ulcerative colitis (1116). Inan animal model of T cell receptor-a mutant mice, thedevelopment of colitis is prevented by appendectomy (17).The mechanism as to how appendectomy protects subsequentdevelopment of colitis is not known (16, 17).
A well-known characteristic feature of the appendix isthe abundant lymph follicles. Involvement of the appendix inulcerative colitis indicates the importance of the lymphfollicles in ulcerative colitis. In an area where there is anestablished lesion, lymph follicles are not apparent endosco-pically and their structure is lost microscopically. Our aim inthis report is not to describe AOI, which has been con rmedin earlier studies (610), but rather to describe lymphfolliculitis and lymphoid hyperplasia in order to stress theinvolvement of lymph follicles in ulcerative colitis. Twocases in this report clearly demonstrated lymph folliculitis inareas close to established lesions: a distal lesion in case 1 andan AOI lesion in case 2.
In this case report, the term lymph folliculitis is usedfor in ammation of the lymph follicle including the lymphfollicle showing the red ring sign (18), central redness(erosion) or central coating and an aphthous ulcer (19, 20).Lymphoid hyperplasia is referred to as a swelling of lymphfollicle without central erosion or coating (21, 22).
Scand J Gastroenterol 2001 (3)
Case 1A 31-year-old medical student (male) noticed a mu-
cobloody stool in May 1999 and presented to NakadoriHospital on 21 June. He was taking no medication before theonset of symptoms. His family and medical histories werenoncontributory. Physical examination was unremarkable.Laboratory data, including C-reactive protein (CRP), ery-throcyte sedimentation rate (ESR), serum total protein,albumin, and complete blood count, were normal. Nopathogenic bacteria were found by stool culture. Colonoscopyrevealed a diffuse rough mucosa with loss of vascular patternsand with numerous white spots in the rectum (Fig. 1A). In anarea of transition to an uninvolved area in the sigmoid colon,there were numerous aphthous ulcers surrounded by rednessforming a group of aphthous ulcers (Fig. 1B). Proximal to thegroup of aphthous ulcers, lymph follicles with a centralcoating surrounded by redness were scattered (Fig. 1B). In anuninvolved area cephalad, numerous whitish round nodules,namely lymphoid hyperplasia, were observed with clearvascular patterns in the background (Fig. 1C). No in amma-tion was observed in the cecum including an appendicealori ce. Biopsy specimens from the rectum showed diffusesevere mononuclear cell in ltration extending to the muscu-laris mucosa, diffuse goblet cell depletion, cryptitis, milddistortion of the gland tubular pattern, and lymph follicles.Specimens from aphthous ulcers showed a similar picture ofin ammation with less intensity and lymph follicles (Fig.1D). A diagnosis of ulcerative colitis, proctitis type, the rstattack, mild by severity (23), was made, and 1.5 gm/day of 5-aminosalicylic acid (mesalazine, Pentasa1, Nisshin, Tokyo)was started on 16 July. The mucobloody stool disappeared butappeared again when he ceased taking medicine duringsummer vacation in his home town. Readministration ofmesalazine decreased eight instances of mucobloody stool aday to four. He was referred to Akita University Hospital on 8September 1999. Two grams of betamethasone (Rinderon1,Shionogi, Osaka, Japan) suppository in two divided doses wasadded, resulting in the disappearance of mucobloody stool. Acolonoscopy performed on 4 October showed loss of vascularpatterns only in the lower portion of the rectum. Since then, hehas been in remission (April, 2000).
Case 2A 23-year-old pharmacist (male) had noticed bloody
diarrhea since 21 July 1998 and presented at the Akita RedCross Hospital on 27 July. He was taking no medicationbefore the onset of symptoms. His family and medicalhistories were noncontributory. Physical examination wasunremarkable. Laboratory data, including CRP, ESR, serumtotal protein, albumin, and complete blood count, werenormal. No pathogenic bacteria were found by stool culture.Colonoscopy revealed a diffuse, continuous in ammationwith loss of vascular patterns from the rectum to the splenic
exure (Fig. 2A). Discontinuous, skip AOI with numerouswhite spots was observed (Fig. 2B). In an area of transitionfrom the appendiceal ori ce to an uninvolved area, there werenumerous lymph follicles with the red ring sign (18) (Fig.2B). Indigo carmine dye spraying (18) to the same siterevealed prominent lymphoid hyperplasia in an area showingvascular patterns but not in an area of established AOI (Fig.2C). In uninvolved areas in the transverse colon wherevascular patterns were clear, lymphoid hyperplasia wasevident by dye spraying (Figs. 2D, E). Biopsy specimensfrom the rectum showed diffuse severe mononuclear cellin ltration extending to the muscularis mucosa, diffuse gobletcell depletion and distortion of the gland tubular pattern.Those from an appendiceal ori ce showed diffuse moderatemononuclear cell in ltration extending to the muscularismucosa and distortion of the gland tubular pattern. Thosefrom the border between AOI and an uninvolved area showeda similar picture of in ammation with less intensity andlymph follicles (Fig. 2F). A biopsy from lymphoid hyperpla-sia in the uninvolved area showed a lymph follicle withoutin ammation or sequela to in ammation in surroundingmucosa. A diagnosis of ulcerative colitis, left-sided colitis,the rst attack, mild by severity (23), was made, and 1.5 gm/day of mesalazine was given. The symptom graduallydisappeared. Since then, he has been in remission up to thepresent (April, 2000). Despite stable clinical remission, thelast colonoscopy performed on 14 January 2000 showedcloudiness of mucosa and insuf cient recovery of vascularpatterns in the distal colon. The AOI was decreased in sizeand white spots were no longer observed. He was referred toAkita University Hospital due to his transfer on 7 March2000.