Download Functional asplenia and microscopic (collagenous) colitis

BRIEF COMMUNICATION
Functional asplenia and
microscopic (collagenous)
colitis
HUGH JAMES FREEMAN MD
HJ FREEMAN. Functional asplenia and microscopic (collagenous) colitis. Can J Gastroenterol 1996;10(7):443-446. A
54-year-old female presented with a pulmonary infection that resolved completely with antibiotic treatment. Peripheral blood
films showed features characteristic of splenic hypofunction, and
radiolabelling studies confirmed an absence of splenic reticuloendothelial cell activity, which is typical of functional asplenia.
The patient had a remote history of watery diarrhea but no clinical
and laboratory features of malabsorption. Extensive upper and
lower gastrointestinal tract biopsy studies revealed histopathological features of collagenous colitis without gastric or small
intestinal inflammatory changes or epithelial lymphocytosis. Hyposplenism has been associated with different gastrointestinal
disorders, particularly celiac disease. This is the first report of
functional asplenia and microscopic collagenous colitis.
Key Words: Celiac disease, Collagenous colitis, Functional asplenia,
Hyposplenism, Malabsorption syndrome, Microscopic colitis, Watery
diarrhea syndrome
I
mpaired splenic function has frequently been recognized
in several clinical disorders (1), including diseases causing
malabsorption, such as celiac disease (2-5), as well as tropical sprue (6), Whipple’s disease (7) and intestinal lymphangiectasia (8). Hyposplenism has been associated with
other chronic diarrheal disorders, usually involving the large
intestine, including both ulcerative colitis and Crohn’s disease (9-11). In some patients hyposplenism has been associated with more widespread atrophy of the lymphoreticular
system in celiac disease (12). In others it has been linked to
some rare disorders associated with celiac disease, including
cavitation necrosis of mesenteric lymph nodes (13,14) and
lymphoma-associated necrosis of hepatic, splenic and lymph
Asplénie sans anomalie organique et colite
microscopique (collagénique)
RÉSUMÉ : Unefemmede54ansaprésentéuneinfectionpulmonaire
qui est entièrement rentrée dans l’ordre après l’administration d’une
antibiothérapie. Les clichés de la circulation périphérique ont montré
des caractéristiques propres à une hypofonction splénique et les épreuves avec radiomarquage ont confirmé l’absence d’activité des cellules
réticulo-endothéliales spléniques typique de l’asplénie sans anomalie
organique. La patiente avait des antécédents lointains de diarrhée
mais aucun signe clinique ni résultats d’analyses de laboratoire évocateurs de malabsorption. Des biopsies du tractus digestif inférieur et
supérieur ont révélé la présence de signes de colite collagénique sans
inflammationdel’estomacnidugrêle,nilymphocytose épithéliale.
L’hyposplénie a été associée à différents troubles gastro-intestinaux,
en particulier à la maladie cœliaque. Il s’agit du premier rapport à faire
étatd’aspléniefonctionnelleetdecolitecollagéniquemicroscopique.
node tissues (15). Collagenous colitis was initially reported
in 1976 in two patients, one with celiac disease (16,17). It is
an unusual, but increasingly recognized, colonic mucosal inflammatory disease process usually occurring in middle-aged
to elderly females with a watery diarrhea syndrome. Colorectal biopsies typically reveal subepithelial collagencontaining deposits in the lamina propria. Some pathologists
have classified collagenous colitis and lymphocytic colitis as
types of microscopic colitis (18), and both occasionally may
be associated with celiac disease (19-22).
In the patient reported here, presentation with a pulmonary infection led to detection of hyposplenism. Because of
the frequent association of hyposplenism with specific gas-
Department of Medicine (Gastroenterology), University of British Columbia, Vancouver, British Columbia
Correspondence and reprints: Dr Hugh Freeman, ACU F-137, Gastroenterology, Vancouver Hospital (UBC Site), 2211 Wesbrook Mall,
Vancouver, British Columbia V6T 1W5. Telephone 604-822-7216, fax 604-822-7236
Received for publication September 29, 1995. Accepted February 5, 1996
CAN J GASTROENTEROL VOL 10 NO 7 NOVEMBER/DECEMBER 1996
443
Freeman
Figure 1) Peripheral blood smear showing characteristic features of hyposplenism, including Howell-Jolly bodies
Figure 3) Colonic mucosal biopsy showing features typical of collagenous colitis. A chronic inflammatory process is evident with the typical
eosinophilic subepithelial deposits that are trichrome-positive (hematoxylin and eosin, x55)
Figure 4) Higher power photomicrograph of Figure 3 showing subepithelial collagen-containing deposit (hematoxylin and eosin, x138)
Figure 2) Radiotagged technetium sulphur colloid liver and spleen scan.
Dynamic serial images show hepatic, but not splenic, uptake of the radiopharmaceutical agent
CASE PRESENTATION
A 54-year-old female presented with malaise, anorexia,
cough, fever and chest pain for two days. Although physical
examination was normal, the normal hemoglobin value of
140 g/L appeared with a mild leukocytosis of 12,200/mm3
and chest radiograph revealed a left lower lobe pneumonic
infiltrate. Ampicillin was given and the symptoms resolved.
444
Follow-up radiographs of her chest confirmed resolution of
the pulmonary infiltrate.
During the initial evaluation hemogram (hemoglobin,
red blood cell indexes, white blood cell count and differential, and platelet count) was normal but peripheral blood
smear revealed irregular contracted cells with Howell-Jolly
bodies and large platelets, typical of hyposplenism (Figure 1).
An abdominal ultrasound showed a small spleen, estimated to be 8 cm. A liver-spleen scan with radiotagged technetium (99mTc) sulphur colloid (Figure 2) showed hepatic
extraction of the radiopharmaceutical but no splenic activity. SPECT imaging demonstrated an absence of functioning
splenic tissue, consistent with functional asplenia. Because
of the latter findings and her presentation with a respiratory
tract infection, she was administered polyvalent pneumococcal vaccine.
Additional history revealed no prior abdominal trauma,
skin rash or other symptoms suggestive of a collagen vascular
disease (23), hematological disorder, coagulopathy (24-26)
or prior surgery. There was a remote history of intermittent
CAN J GASTROENTEROL VOL 10 NO 7 NOVEMBER/DECEMBER 1996
Splenic function in collagenous colitis
watery, nonbloody diarrhea during the previous two decades
but this was never severe enough that the patient sought
medical assessment or used antidiarrheal medications.
Other laboratory investigations were normal including
urea nitrogen, red blood cell folate, serum creatinine, alkaline phosphatase, glucose, aspartate aminotransferase, alanine
aminotransferase, electrolytes, carotene, calcium, total proteins, albumin, immunoglobulins, thyroid-stimulating hormone, free thyroxine, cortisol, vitamin B12, iron and iron
binding capacity. Antinuclear antibodies, antineutrophilic
cytoplasmic antibodies and rheumatoid factor were negative. Urinalysis was normal.
Because of the reported association between celiac disease and inflammatory bowel disease, fibreoptic endoscopic
biopsies of the stomach, and the small and large bowel were
done. Colonic biopsies showed characteristic features of collagenous colitis (Figures 3,4) (16,17). Gastric biopsies were
normal, without epithelial lymphocytosis or collagen deposits (27, 28). Multiple small intestinal biopsies from different
sites in the proximal small intestine were also normal. Amyloid stains were negative (29).
DISCUSSION
This is the first description of functional asplenia associated with microscopic (collagenous) colitis. While this observation may only reflect the presence of two separate and
uncommon conditions in the same patient, the frequent association of both conditions with celiac disease and the occasional reports of hyposplenism in other forms of chronic
inflammatory bowel disease (ie, ulcerative colitis, Crohn’s
disease) (9-11) suggest that the two conditions are more directly related and that a more generalized – possibly immunologically related disorder – exists in the present patient.
At least three lines of evidence indicated that the patient’s splenic function was significantly impaired. First, the
splenic reticuloendothelial cells normally remove particulate matter and abnormal elements from the circulation, including damaged or abnormally shaped structures and
antibody-coated cells. In disorders such as celiac disease,
physiological or functional impairment of these splenic cells
may occur. This often results in a bizarre blood smear containing red blood cells with whole nuclei, nuclear fragments
(Howell-Jolly bodies), precipitated hemoglobin masses
(Heinz bodies) and pitted or distorted cell membranes, as occurred in our patient. Second, 99mTc, a radiopharmaceutical
agent normally removed from the circulation by reticuloendothelial cells, may be detected by abdominal scanning over
REFERENCES
1. Muller AF, Toghill PJ. Hyposplenism in gastrointestinal disease.
Gut 1995;36:165-7.
2. Martin JB, Bell HE. The association of splenic atrophy and intestinal
malabsorption. Can Med Assoc J 1965;92:875-8.
3. Marsh GW, Stewart JS. Splenic function in adult coeliac disease.
Br J Haematol 1970;19:445-57.
4. Freeman HJ. Clinical spectrum of biopsy-defined celiac disease in the
elderly. Can J Gastroenterol 1994;9:42-6.
5. O’Grady JG, Stevens FM, Harding B, O’Gorman TA, McNicholl B,
McCarthy CF. Hyposplenism and gluten sensitive enteropathy.
Gastroenterology 1985;87:1326-31.
6. Suarez RM, Spies TD, Suarez RM Jr. The use of folic acid in sprue.
Ann Intern Med 1947;26:643-77.
CAN J GASTROENTEROL VOL 10 NO 7 NOVEMBER/DECEMBER 1996
the liver and spleen. In our patient, hepatic, but not splenic,
uptake was seen. Finally, clinical evidence of impaired
splenic function may result in susceptibility to bacterial infections, particularly pneumococcal infections. Initial presentation in our patient was due to clinical features of pneumonia. Although a reduction in splenic reticuloendothelial
cells may be present, a qualitative reduction in phagocytic
function may also develop. Although the mechanisms involved in or responsible for this functional impairment, such
as in celiac disease or ulcerative colitis, are very poorly understood, significant enteric loss of lymphocytes (30) and
raised levels of circulating immune complexes (31) have
been hypothesized to contribute to the splenic hypofunction
that appears to be very isolated, rather than a reflection of
a more generalized abnormality in lymphoreticular function (32).
CONCLUSIONS
The frequency of hyposplenism in patients with collagenous colitis is unknown but needs to be explored. Failure to
recognize this association may reflect, in part, the limited
sensitivity of the peripheral blood film for general assessment
of splenic function, particularly splenic reticuloendothelial
function. Other researchers, particularly those studying celiac disease patients, have used the clearance of isotopically
labelled heat-damaged red blood cells (3) or differential interference contrast microscopy to detect pits and craters in
the erythrocyte membrane (33). In a previous report on elderly celiac patients (4), for example, a review of peripheral
blood films led to the recognition of hyposplenism in 13%.
In contrast, studies using the clearance of isotopically labelled red blood cells or pitted red blood cell counts have
shown that up to 75% of patients with celiac disease may
have hyposplenism (5,34). Therefore, it can be predicted
that the frequency of hyposplenism in different colonic inflammatory bowel disorders, such as collagenous colitis, is
much greater than is appreciated.
The potential clinical significance of this association may
be more than academic, particularly for the typically elderly
individual with collagenous colitis, especially if this predisposes to a serious bacterial infection. Additional studies, possibly using more sensitive methods for the evaluation of
splenic function, are needed in patients with microscopic
forms of colitis.
7. Haeney MR, Ross IN. Whipple’s disease in a female with impaired cell
mediated immunity unresponsive to cotrimoxazole and levamisole
therapy. Postgrad Med J 1978;54:45-50.
8. Foster PN, Bullen AW, Robertson DAF, Chalmers AM, Losowsky
MS. Development of impaired splenic function in intestinal
lymphangiectasia. Gut 1985;26:861-4.
9. Ryan FP, Smart RC, Holdsworth CD, Preston FE. Hyposplenism in
inflammatory bowel disease. Gut 1978;19:50-5.
10. Palmer KR, Sherriff SB, Holdsworth CD, Ryan FP. Further experience
of hyposplenism in inflammatory bowel disease. Q J Med
1981;200:463-71.
11. Jewell DP, Berney JJ, Pettit JE. Splenic phagocytic function
in patients with inflammatory bowel disease. Pathology
1981;13:717-23.
443
Freeman
12. McCarthy CF, Fraser ID, Evans KT, Read AE. Lymphoreticular
dysfunction in idiopathic steatorrhea. Gut 1966;7:140-8.
13. Matuchansky C, Colin R, Hemet J, et al. Cavitation of mesenteric
lymph nodes, splenic atrophy, and a flat small intestinal mucosa.
Gastroenterology 1984;87:606-14.
14. Freeman HJ, Chiu BK. Small bowel malignant lymphoma
complicating celiac sprue and the mesenteric lymph node cavitation
syndrome. Gastroenterology 1986;90:2008-12.
15. Freeman HJ. Fulminant liver failure with necrotizing foci in the liver,
spleen and lymph nodes in celiac disease due to malignant lymphoma.
Can J Gastroenterol 1996;10:225-9.
16. Freeman HJ, Weinstein WM, Shnitka TK, Wensel R, Sartor V.
Watery diarrhea syndrome associated with a lesion of the colonic
basement membrane-lamina propria interface. Ann R Coll
Phys Surg Can 1976;9:45.
17. Freeman HJ. Collagenous inflammatory mucosal disease
of the gastrointestinal tract. Can J Gastroenterol
1990;4:196-200.
18. Yardley JH, Lazenby AJ, Giardiello FM, Bayless TM. Collagenous,
‘microscopic’, lymphocytic and other gentler and more subtle
forms of colitis. Hum Pathol 1990;21:1089-91.
19. Wolber R, Owen D, Freeman HJ. Colonic lymphocytosis in patients
with celiac sprue. Hum Pathol 1990;21:1092-6.
20. Hamilton I, Sanders S, Hopwood D, Bouchier IAD. Collagenous
colitis associated with small intestinal villous atrophy. Gut
1986;27:1394-8.
21. Breen EG, Farren C, Connolly CE, McCarthy CF. Collagenous colitis
and coeliac disease. Gut 1986;28:364.
22. Breen EG, Coughlan G, Connolly CE, Stevens FM, McCarthy CF.
Coeliac proctitis. Scand J Gastroenterol 1987;22:471-7.
444
23. Dillon AM, Stein HB, English RA. Splenic atrophy in systemic lupus
erythematosis. Ann Intern Med 1982;96:40-3.
24. Pearson HA, Spencer RP, Cornelius EA. Functional asplenia in sickle
cell anemia. N Engl J Med 1969;281:923-6.
25. Joshpe G, Rothenberg SP, Baum S. Transient functional asplenism in
sickle cell C disease. Am J Med 1973;55:720-2.
26. Coleman CN, McDougall IR, Dailey MO, Ager P, Bush S, Kaplan HS.
Functional hyposplenia after splenic irradiation for Hodgkin’s disease.
Ann Intern Med 1982;96:44-7.
27. Wolber R, Owen D, DelBuono L, Appelman H, Freeman HJ.
Lymphocytic gastritis in patients with celiac sprue or sprue-like
intestinal disease. Gastroenterology 1990;98:310-5.
28. Freeman HJ, Piercey JRA, Raine RJ. Collagenous gastritis. Can J
Gastroenterol 1989;3:171-4.
29. Gertz MA, Kyle RA, Greipp PR. Hyposplenism in primary systemic
amyloidosis. Ann Intern Med 1983;98:475-7.
30. Douglas AP, Weetman AP, Haggith JW. The distribution and enteric
loss of 51Cr-labelled lymphocytes in normal subjects and in patients
with coeliac disease and other disorders of the small intestine.
Digestion 1976;14:29-43.
31. Doe WF, Booth CC, Brown DL. Evidence for complement-binding
immune complexes in adult coeliac disease, Crohn’s disease and
ulcerative colitis. Lancet 1973;i:402-3.
32. Palmer KR, Barber DC, Sherriff SB, Holdsworth CD.
Reticuloendothelial function in coeliac disease and ulcerative colitis.
Gut 1983;24:384-8.
33. Corazza GR, Bullen AW, Hall R, Losowsky MS. A simple method of
assessing splenic function in coeliac disease. Clin Sci 1981;60:109-13.
34. Corazza GR, Lazzari R, Frisoni M, Gasbarrini G. Splenic function in
childhood coeliac disease. Gut 1982;23:415-6.
CAN J GASTROENTEROL VOL 10 NO 7 NOVEMBER/DECEMBER 1996
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