New Perspectives in Inflammatory Bowel Disease
Moderators: Dr. Stanley Hamilton and Dr. Carolyn C. Compton
Section 3 -
Collagenous and Lymphocytic Colitis
Audrey J. Lazenby
Professor, Department of Pathology
University of Alabama School of Medicine
Collagenous colitis is a clinicopathologic syndrome characterized by:(1) chronic watery diarrhea and
crampy abdominal pain, and (2) distinctive colorectal histopathology that includes a subepithelial
collagen band, prominent chronic inflammation in the lamina propria, and increased intraepithelial
lymphocytes. Lindstrom described the first case in 1976, in a middle-aged Swedish woman, and coined the
term collagenous colitis because of the histopathologic similarity to
collagenous sprue, in which there is a subepithelial collagen deposit in jejunal mucosa .
Over the subsequent three decades, collagenous colitis has been increasingly recognized with a recent
reported incidence of 6.1 per 100,000 persons, in Orebo, Sweden . This disease is found
mainly in "Western" countries in Europe, Australia, and North America, but cases have been reported from
around the world including Africa .
Pathologic Features: As the name implies, there are two main histologic components to
collagenous colitis: (1) increased collagen deposition and (2) colitis. In normal colon, a delicate
basement membrane is visible just beneath the lumenal epithelium, measuring less than 3 microns in
thickness . In collagenous colitis, there is abnormal deposition of collagen immediately
beneath the basement membrane. This collagen forms a subepithelial band in the superficial lamina
propria, that is readily recognized on H&E stains. By immunohistochemical staining, this band
contains collagens type I, III, and VI as well as tenascin . Stains for basement membrane
components, such as type IV collagen and laminin, do not mark the collagen band, emphasizing that the
band is not a thick basement membrane but rather an abnormal deposit beneath the basement membrane.
Electron microscopic studies also emphasize that the collagen band is separate from and beneath the
basement membrane . By H&E stains however, one cannot distinguish between the basement
membrane and the collagen deposited beneath it. In collagenous colitis, the measured width of the band
is variable between studies and within studies, between patients. In individual patients, band thickness
can vary throughout the colon with the transverse colon usually having the thickest bands .
The rectum can lack a thick subepithelial collagen band in up to 33% of cases and in a small percentage,
the rectum can be histologically normal with no increase in inflammation . Consequently,
multiple biopsy specimens should be taken in areas proximal to the rectosigmoid to establish or exclude
the diagnosis of collagenous colitis. Rarely, collagenous gastritis is found , and functional
as well as histologic abnormalities of the small bowel have been noted in patients with collagenous
The increased subepithelial collagen has qualitative and quantitative changes from normal
colon. In normal colonic epithelium, the basement membrane has sharp, well-defined edges. In early
collagenous colitis, the increased collagen imparts a shaggy appearance to the lower border of the
basement membrane with tendrils of collagen extending down into the upper lamina propria, where
capillaries may be "entrapped" by the collagen. To delineate mild increases in subepithelial collagen, a
trichrome stain may be employed. German investigators have touted immunoperoxidase stains for tenascin
as a sensitive and specific marker for the subepithelial collagen band
Any increase in
subepithelial collagen, in the proper inflammatory and clinical context, is diagnostic of collagenous
colitis. Hence, measurement of the thickness of subepithelial collagen layer is not necessary to
diagnose collagenous colitis.
The second histologic component in collagenous colitis involves increases in inflammation both in the
lamina propria and within the epithelium. The lamina propria is expanded by a mixture of inflammatory
cells, including plasma cells, lymphocytes, eosinophils, and mast cells. Increased eosinophils can be
striking in some cases. Eosinophil granule component as well as TGF beta made by the eosinophils, may be
involved in the pathophysiology of the disease
Early, small studies noted the
occasional prominence of neutrophilic inflammation in some cases of collagenous colitis
and proposed that acutely inflamed cases represent an earlier stage of the disease. These "IBD-like"
features have been emphasized in larger, more recent studies. Ayata et al found small numbers of
neutrophils in 30% of cases, Paneth cell metaplasia in 44% and rare crypt distortion in 7.6% of
cases . Extensive neutrophils and pseudomembranes are rare but have been described in a few
cases, both with and without detectable C. difficile infection
occur in collagenous colitis, there is usually a second etiology such as NSAID usage .
A distinctive component of collagenous colitis is increased intraepithelial lymphocytes. An increase
in these cells is present in the majority, but not all, cases of collagenous colitis. Prominent diffuse
increases in intraepithelial lymphocytes are not a feature of other forms of colitis or enteritis except
for celiac disease and lymphocytic colitis. The intraepithelial lymphocytes of collagenous colitis are
predominantly CD8+ T cells and express the alpha beta form of the T cell receptor
Surface epithelial damage (flattening, detachment) may also be present.
Pitfalls In The Diagnosis Of Collagenous Colitis
Misdiagnosis of collagenous colitis can occur by focusing exclusively on the thickness of the
subepithelial collagen band. Collagenous colitis is an inflammatory
disorder of the colon, and thus increased mucosal inflammation is a prerequisite to the diagnosis. There
can be a mildly thickened subepithelial collagen layer/thick basement membrane in some non-inflammatory
conditions, such as hyperplastic polyps and diabetes mellitus
basement membrane can appear artificially increased in size especially from tangential sectioning. To
avoid misdiagnosis, remember that there are two words in the name of this condition – colitis as well as
collagenous, and both components must be present for a correct diagnosis. Also remember that the rectum
can lack the typical features of CC and thus more proximal biopsies are necessary to exclude CC.
Pathogenesis: The cause of collagenous colitis is unknown, and thus it can be considered a
type of chronic idiopathic IBD, albeit of a "gentler and more subtle form ." Hypotheses for
the etiology of collagenous colitis include (1) immune dysregulation, (2) abnormalities in pericryptal
fibroblasts, (3) intraluminal bacterial agents or toxins, (4) plasmatic vasculosis, and (5) drug induced
Some of the most intriguing recent findings relate to the possible role of infectious agents in
collagenous colitis. Swedish investigators found that diverting the fecal stream caused clinical and
histological remission in nine patients and that clinical symptoms and an abnormal collagen table
returned after ostomy takedown, which suggests that some lumenal agent or toxin is
involved . Other lines of evidence point to an infectious trigger including greater
frequency of antibodies against Yersinia virulence factors in collagenous colitis compared to control
patients , and scattered case reports of collagenous colitis developing after C. difficile
The pattern of inflammation, with increased intraepithelial lymphocytes,
suggests polarization of the immune system toward a luminal agent. One hypothesis is that a foreign
luminal agent, possibly bacteria, initiates colorectal inflammation that leads to an immunologic
cross-reactivity with an endogenous antigen in luminal epithelial cells leading to a self sustaining
On the other hand, collagenous colitis has been linked in rare cases to lansoprazole administration,
but the association is more common with lymphocytic colitis
In these cases, drug was
clearly associated with onset of symptoms and resolved with lansoprazole was stopped. NSAIDs have also
been linked to collagenous colitis by some but not all investigators .
The mechanisms of diarrhea are variable between patients. Fasting improves, but does not totally
abate the diarrhea in most patients, suggesting both an osmotic and a secretory component to the
diarrhea . Reduced Na and Cl absorption are the main mechanisms of diarrhea in collagenous
colitis, but there is also an active component of Cl secretion. Down regulation of tight junction
molecules, particularly occluding, is thought to contribute to the diarrhea . While the
diarrhea is felt to be mainly of colonic origin, some studies have also shown abnormal permeability in
the small bowel as well . A plethora of inflammatory mediators have been found to be
elevated in collagenous with the most recently investigated including basic fibroblast growth factor,
nitric oxide, and vascular endothelial growth factor
Clinical History: Collagenous colitis is a disease primarily of women with a female to male
ratio of 9:1 in recent Swedish studies
This disorder is seen primarily in middle-aged
patients in their 50's and 60's, but there is a wide age range of presentation.
Chronic watery diarrhea is the main symptom and in most patients has been present months to years.
Nocturnal diarrhea is not uncommon. The patients often also have crampy diffuse abdominal pain, symptoms
which cause misdiagnosis with irritable bowel syndrome. Enteropathic arthritis is seen in approximately
7% of collagenous colitis patients, with the arthritis being seronegative for rheumatoid factor and
nondestructive . A variety of other immunologic disorders have been noted in this patient
population, with 17%-40% of patients having coexistent autoimmune illnesses .
Routine laboratory studies are usually normal. However, antineutrophilic cytoplasmic antibodies have
been described . Importantly, gastrointestinal radiographic and endoscopic examinations
usually show normal mucosa. Thus, it is essential for clinicians to biopsy grossly normal mucosa to
establish this diagnosis.
Treatment: While collagenous colitis is usually a chronic process, patients can have
spontaneous remissions, thus complicating evaluation of drug effectiveness. While dietary modification
(elimination of caffeine, lactose, or NSAIDs) may help some individuals, most require medication of some
sort. In the past, first line therapy was with sulfasalazine or other 5-ASA derivatives .
If that therapy failed, patients were treated with steroids or even more potent immunosuppressives.
Currently, two main therapeutic regimens are being touted, either therapy with (budesonide) or high dose
bismuth preparations. Budesonide is a topically acting steroid with high first pass metabolism in the
liver, and so little systemic side effect. While patients usually respond to the above medications, it
is not infrequent for there to be flares of diarrhea after the medication is stopped
Lymphocytic colitis has similar clinical features to collagenous colitis. Watery diarrhea is the main
symptom with most individual also noting a mild, intermittent, crampy abdominal pain . Most
patients are middle-aged, but in contrast to collagenous colitis, there is less of a gender gap, with a
female:male ratio of 2.4:1. . The incidence of lymphocytic colitis is reported as 5.7/100,00
individuals, in Sweden from 1996-1998 . Routine hematologic tests are usually normal, but
occasionally the Westergren sedimentation is increased. Some patients have increased titers of
anti-nuclear antibodies, anti-parietal cell antibodies, and anti-microsomal antibodies
Lymphocytic colitis patients have an increased frequency of HLA A1 and of a diminished
frequency of HLA A3 compared to controls .
Pathologic Features: The main histologic feature of lymphocytic colitis is
increased intraepithelial lymphocytes. In a normal colon, the number of intraepithelial lymphocytes
(IELs) is approximately 5 per 100 epithelial cells, while in lymphocytic colitis, the median number of
IELs is 30 lymphocytes per 100 epithelial cells (range 10 to 50) . As in collagenous
colitis, the intraepithelial lymphocytes are CD8+ T lymphocytes, employing primarily alpha-beta forms of
the T cell receptor . Surface epithelial damage may be present and a mild increase in
chronic inflammation in the lamina propria is also seen. There is minimal to no increase in
intraepithelial neutrophils, and crypt distortion is generally absent, which sets these cases apart from
ulcerative colitis and Crohn's disease. In contrast to collagenous colitis, there is not a subepithelial
collagen band – the basement membrane has a sharp, discrete lower border
comparison to collagenous colitis, there are usually fewer eosinophils, and the amount of chronic
inflammation in the lamina propria is usually less.
Pathogenesis: While collagenous colitis is a tightly coherent clinicopathology entitiy,
lymphocytic colitis is a more a more amorphous condition occurring in varied clinical settings
While most of the cases are idiopathic and chronic, some are associated with celiac
disease and will resolve when the patients go on a gluten-free diet . A small group of cases
is also associated with particular drugs, including ticlopidine, carbamazepine, cimetidine, ranitidine,
simvastatin, and some drugs used primarily in France including veinotonics and vinburnine .
Finally, cases have been reported following certain infections, and thus may represent a slowly resolving
infection or perhaps and abnormal persistent immune response following an infectious
trigger . While most early studies describe chronic diarrhea, a more recent Swedish study
found a single attack in 63% of cases, with a chronic persistent or chronic intermittent course in the
remaining . In this same study, there was a family history of some type of intestinal
inflammatory disease in 12% of patients, suggesting a genetic underpinning in some .
The histology is slightly different between the cases of classical, idiopathic lymphocytic colitis and
those with known etiologies. Lymphocytic colitis that is associated with celiac disease, related to
certain medications, and post-infections seem to have less inflammation in the lamina propria and may
have mainly increased intraepithelial lymphocytes. Some prefer to diagnose these cases with known
etiologies as "colonic epithelial lymphocytosis". My practice is to lump all the cases together as
lymphocytic colitis and to always add a note as follows: "Lymphocytic colitis can be seen in varied
clinical settings including celiac disease, post-infectious, in association with certain medications and
as an idiopathic condition".
Pitfalls In The Diagnosis Of Lymphocytic Colitis
Compared to biopsies from classical, idiopathic inflammatory bowel disease, such as ulcerative
colitis, the histologic changes in lymphocytic colitis are relatively mild and subtle. But, all mild and
subtle changes from "normal" are not synonymous with lymphocytic colitis. Regional variations in normal
histology and focal changes may lead to an over-diagnosis of lymphocytic colitis. In different regions
of the large intestine, there is a variation in histologic "normalcy". Compared to the rest of the
colon, the cecum normally displays more crypt mitotic figures, decreased epithelial mucin, slightly more
plasma cells and eosinophils and lamina propria, and slightly more intraepithelial lymphocytes. Thus, be
aware that biopsies from the cecum are normally "busy". Also, some cases of Crohn's disease, in addition
to the normal histologic features, have focal increases in intraepithelial lymphocytes
Lymphocytic colitis is characterized by a diffuse increase in intraepithelial lymphocytes,
usually with more chronic inflammation of the lamina propria. Thus, pay attention to the location of the
biopsy and look for diffuse changes to insure a correct diagnosis.
Microscopic colitis is a term introduced by Read et al  to describe a group of patients
with chronic diarrhea that had normal endoscopy , but abnormal histology (thus disease diagnosed by a
microscope). Subsequent review of those cases showed them to be primarily collagenous colitis but to
also include lymphocytic colitis. While microscopic colitis is a good clinical "umbrella" term, it would
seem preferable to have pathologists give a specific diagnosis. A microscope is how we make our
diagnosis – not a diagnostic entity.
- Lindstrom CG. 'Collagenous colitis' with watery diarrhoea--a new entity? Pathol Eur 11:87-89, 1976.
- Olesen M, Eriksson S, Bohr J, et al. Microscopic colitis: a common diarrhoeal disease. An epidemiological study in Orebro, Sweden, 1993-1998. Gut 53:346-50,2004.
- Otegbayo JA, Oluwasola AO, Akang EE. Collagenous colitis in an adult patient with chronic diarrhoea: case report. East Afr Med J 78:272-274, 2001.
- Jessurun J, Yardley JH, Giardiello FM, et al. Chronic colitis with thickening of the subepithelial collagen layer (collagenous colitis): histopathologic findings in 15 patients. Hum Pathol 18:839-848, 1987.
- Aigner T, Neureiter D, Muller S, et al. Extracellular matrix composition and gene expression in collagenous colitis. Gastroenterol113:136-143, 1997.
- Widgren S, Jlidi R, Cox JN. Collagenous colitis: Histologic, morphometric, immunohistochemical and ultrastructural studies. Report of 21 cases. Virchows Arch A Pathol Anat Histopathol 413:287-296, 1988.
- Offner FA, Jao RV, Lewin KJ, et al. Collagenous colitis: a study of the distribution of morphological abnormalities and their histological detection. Hum Pathol 30:451-457, 1999.?
- Lagorce-Pages C, Fabiani B, Bouvier R: Collagenous gastritis: A report of six cases: Am J Surg Pathol 25:1174-9,2001.
- Sapp H, Ithamukkala S, Bien TP. The terminal ileum is affected in lymphocytic and collagenous colitis: Am J Surg Pathol 26:1484-92, 2002.
- Moayyedi P, O'Mahony S, Jackson P, et al. Small intestine in lymphocytic and collagenous colitis: mucosal morphology, permeability, and secretory immunity to gliadin. J Clin Pathol 50:527-529, 1997.
- Muller S, Neureiter D, Stolte M, et al. Tenascin: a sensitive and specific diagnostic marker of minimal collagenous colitis. Virchows Arch 438:435-441, 2001.
- Ulrich S, Wagner U and Wegmann W. Tenascin: A simple tool in the diagnosis of collagenous colitis. Schweiz Med Wochenschr 129:1363-1367, 1999
- Levy AM, Yamazaki K, Van Keulen VP, et al. Increased eosinophil infiltration and degranulation in colonic tissue from patients with collagenous colitis. Am J Gastroenterol 96:1522-1528, 2001.
- Taha Y, Carlson M, Thorn M, et al. Evidence of local eosinophil activation and altered mucosal permeability in collagenous colitis. Dig Dis Sci 46:888-897, 2001.
- Stahle-Backdahl M, Maim J, Veress B, et al. Increased presence of eosinophilic granulocytes expressing transforming growth factor-beta1 in collagenous colitis. Scand J Gastroenterol 35:742-746, 2000.
- Rams H, Roger AI, Ghandur-Mnaymneh L. Collagenous colitis. Ann Intern Med 106: 108-113, 1987.
- Teglbjaerg PS, Thaysen EH, Jensen HH. Development of collagenous colitis in sequential biopsy specimens. Gastroenterol 87:703-709, 1984
- Ayata G, Ithamukkala S, Sapp H, et al. Prevalence and significance of inflammatory bowel disease-like morphologic features in collagenous and lymphocytic colitis. Am J Surg Pathol 26 11:1414-1423, 2002.
- Giardiello FM, Hansen FC, 3rd, Lazenby AJ, et al. Collagenous colitis in setting of nonsteroidal antiinflammatory drugs and antibiotics. Dig Dis Sci 35:257-260, 1990.
- Yuan S, Reyes V, Bronner MP. Pseudomembranous collagenous colitis. Am J Surg Pathol 27:1375-1379, 2003.
- Treanor D, Gibbons D, O'Donoghn DP, Sheahan K. Pseudomembranes in collagenous colitis: Histopathology 38:83-4, 2001.
- Khan MA, Brunt EM, Presti ME: Persistent Clostridium difficile colitis, a possible etiology for the development of collagenous colitis: Dig Dis Sci 45 998-1001, 2000.
- Kakar S, Pardi DS, Burgart LJ. Colonic Ulcers Accompanying Collagenous Colitis: Implication of Nonsteroidal anti-inflammatory Drugs. Am J Gastroenterol 98:1834-1837, 2003.
- Lazenby AJ, Alianiello RG, Fox WM, et al: T cell receptors in collagenous and lymphocytic colitis. Gastroenterol 98: A459, 1990 (Abstract).
- Mosnier JF, Larvol L, Barge J et al: Lymphocytic and collagenous colitis: an immuohistochemical study: Am J Gastroenterol; 91:709-13. 1996.
- Flejou, JF, Grimaud, JA, Molas G, Baviera, Potet, F: Collagenous Colitis. Ultrastructural study and sollagen Immunotyping in four cases. Arch Pathol Lab Med 108: 977-982, 1984.
- Kandemir O, Utas C, Goren O, et al: Colonic subepithelial collagenous thickening in diabetic patients: Dis Colon Rectum 38:1097-100, 1995.
- Yardley JH, Lazenby AJ, Giardiello FM et al. Collagenous, "microscopic," lymphocytic, and other gentler and more subtle forms of colitis. Hum Pathol 21:1089-1091, 1990.
- Jarnerot G, Tysk C, Bohr J, et al. Collagenous colitis and fecal stream diversion. Gastroenterology 109:449-455, 1995.
- Bohr J, Nordfelth R, Jarnerot G et al. Yersinia species in collagenous colitis: a serologic study. Scand J Gastroenterol 37:711-714, 2002.
- Wilcox GM, Mattia A. Collagenous colitis associated with lansoprazole. J Clin Gastroenterol 34:164-166, 2002.
- Thomson RD, Lestina LS, Bensen SP, et al. Lansoprazole-associated microscopic colitis: a case series. Am J Gastroenterol 97:2908-2913, 2002.
- Riddell RH, Tanaka M, Mazzoleni G. Non-steroidal anti-inflammatory drugs as a possible cause of collagenous colitis: a case-control study. Gut 33:683-686, 1992
- Bohr J, Jarnerot G, Tysk C, et al. Effect of fasting on diarrhoea in collagenous colitis. Digestion 65:30-34, 2002.
- Burgel N, Bojarski C, Mankertz J, et al. Mechanisms of diarrhea in collagenous colitis. Gastroenterology 123:433-443, 2002.
- Giardiello FM, Bayless TM, Jessurun J, et al. Collagenous colitis: physiologic and histopathologic studies in seven patients. Ann Intern Med 106:46-49, 1987.
- Taha Y, Raab Y, Larsson A: Mucosal secretion and expression of basic fibroblast growth factor in patients with collagenous colitis. Am J Gastroenterol 09:2011-7, 2003
- Olesen M, Middleveld R. Bohr J: Luminal nitric oxide and epithelial expression of inducible and endothelial nitric oxide synthase in collagenous and lymphocytic colitis. Scand J Gasteroenterol 38:66-72, 2003.
- Griga T, Trenor A. Schmiegal, W: Collagenous colitis implication for the role of vascular endothelial growth factor in repair mechanisms: Eur J Gastroenterol 16:397-402, 2004
- Bohr J, Tysk C, Eriksson S et al. Collagenous colitis in Orebro, Sweden, an epidemiological study 1984-1993. Gut 37:394-397, 1995.
- Roubenoff R, Ratain J, Giardiello F, et al. Collagenous colitis, enteropathic arthritis, and autoimmune diseases: results of a patient survey. J Rheumatol 16:1229-1232, 1989.
- Giardiello FM, Lazenby AJ: The atypical colitides. Gastroenterology Clinics of North America 28:479-490, 1999.
- Duerr, R, Giardiello F, Landers C, et al. Neutrophil autoantibodies in patients with collagesol and lymphocytic colitis: Gasteroenterol 102:A618, 1992, abstract
- Cruz-Correa M, Giardiello FM. Lymphocytic and Collagenous Colitis. Curr Treat Options Gastroenterol 3:243-248, 2000.
- Baert F, Schmit A, D'Haens G, et al. Budesonide in collagenous colitis: a double-blind placebo-controlled trial with histologic follow-up. Gastroenterol 122:20-25, 200
- Bonderup OK, Hansen JB, Birket-Smith L, et al. Budesonide treatment of collagenous colitis: a randomised, double blind, placebo controlled trial with morphometric analysis. Gut 52:248-251, 2003.
- Chande N, McDonald JD, MacDonald MA. Interventions for Treating Collagenous Colitis: A Cochrane Inflammatory Bowel Disease Group Systematic Review of Randomized Trials. Am J Gastroenterol 99:2459-2465, 2004.
- Giardiello FM, Lazenby AJ, Bayless TM, et al. Lymphocytic (microscopic) colitis. Clinicopathologic study of 18 patients and comparison to collagenous colitis. Dig Dis Sci 34:1730-1738, 1989.
- Oleson J, Ericksson, S, Bohr J, et al. Lymphocytic colitis in retrospective clinical study of 199 Swedish patients. Gut 53:536-541, 2004.
- Pardi DS, Ramnath VR, Loftus EV, Tremaine WJ, Sanborn WJ. Lymphocytic colitis: clinical features, treatment and outcomes: Am J Gastroenterol, 77:2829-2833, 2002.
- Giardiello FM, Lazenby AJ, Yardley JH, et al. Increased HLA A1 and diminished HLA A3 in lymphocytic colitis compared to controls and patients with collagenous colitis. Dig Dis Sci 37:496-499, 1992.
- Lazenby AJ, Yardley JH, Giardiello FM, et al. Lymphocytic ("microscopic") colitis: a comparative histopathologic study with particular reference to collagenous colitis. Hum Pathol 20:18-28, 1989
- Lazenby AJ, Yardley JH, Giardiello FM et al. Pitfalls in the diagnosis of collagenous colitis: experience with 75 cases from a registry of collagenous colitis at the Johns Hopkins Hospital . Hum Pathol 21:905-910, 1990.
- Matteoni CA, Goldblum JR, Wang N, et al. Celiac disease is highly prevalent in lymphocytic colitis. J Clin Gasterenterol. 32:225-7, 2001.
- Wang N, Dumot JA, Achkar E, et al. Colonic epithethial lymphocytosis without a thickened subepithelial collagen table: a clinicopathelogic study of 40 cases supporting a heterogenous entitiy. Am J Surg Pathol 24:755-6, 200.
- Wolber R, Owen D, Freeman H: Colonic lymphocytosis in patient with celiac sprue. Human Pathol. 1990 Nov; 21(11): 1092-6, 1990.
- Bryant DA, Mintz ED, Purh ND, et al. Colonic epithelial lymphocytosis associated with an epidemic of diarrhea. Am J Surg Pathol 20: 1102-9, 1996
- Goldstein NS , Gyorfi T. Focal lymphocytic colitis and collagenous colitis. Patterns of Crohn's colitis. Am J Surgical Pathol.23 (9): 1075-1083, 1999.
- Lamps LW and Lazenby AJ. Colonic epithelial lymphocytosis and lymphocytic colitis: Descriptive histopathology vs. distinct clinicopathologic entities. Advances in Anatomic Pathol 7:201-213, 2000.
- Read NW, Krejs GJ, Read MG et al. chronic diarrhea of unknown origin. Gastroenterol 78:264-71, 1980.