q Birkhäuser Verlag, Basel, 1998
Inflamm. res. 47, Supplement 1 (1998) S64–S65
1023-3830/98/010S64-02 $ 1.50+0.20/0
Evidence for mast cell activation in collagenous colitis
D. Schwab, M. Raithel and E. G. Hahn
Medical Department I, University Hospital of Erlangen-Nürnberg, Functional Tissue Diagnostics, Krankenhausstr. 12, D-91054 Erlangen, Germany,
Fax +49 9131 85 6909, e-mail: Dieter.Schwab@med1.med.uni-erlangen.de
Introduction
Collagenous colitis is a disease characterised by cramping
abdominal pain and a secretory watery diarrhoea, while
endoscopical-macroscopical findings reveal almost unre-
markable colonic mucosa. The diagnostic–histological
finding consists of a subepithelial collagenous layer of 10–
100 mm. Although its aetiology is unknown, several results
suggest a relevant immunological mechanism: (1) The
demonstration of increased quantities of faecal leukocytes
[1]; (2) the effectiveness of immunomodulatory drugs like
corticosteroids, 5-aminosalicylic acid or histamine-1-recep-
tor antagonists [2, 3]; and (3) an inflammatory infiltrate of
the lamina propia of the colon consisting of lymphocytes,
mast cells [3] and activated eosinophilic granulocytes [4]. To
further clarify their role in collagenous colitis, we investi-
gated typical and specific mast cell mediators in blood and
urine of patients with this disease for evidence of systemic
activity.
Materials and methods
Patients with typical clinical, endoscopic and histological findings of
collagenous colitis were investigated for histamine, its main metabolite,
n-methylhistamine and the mast cell-specific mediator tryptase [5].
Plasma samples were drawn for histamine and serum samples for
tryptase at 8.00 a.m.. Histamine and n-methylhistamine were measured
in urine collected over a 12-h period after the addition of hydrochloric
acid (10%). Patients received a non-restricted diet until 2.00 p.m.
During the following fasting period, the urine-collection was performed
overnight, from 6.00 p.m.–6.00 a.m. Only urine samples with pH values
between 1 and 2 were analysed. Histamine (Coulter-Immunotech,
Marseille, France), n-methylhistamine (Pharmacia-Upjohn, Freiburg,
Germany) and tryptase (Pharmacia-Upjohn) were measured by radio-
immuno-assay.
For statistical analysis, the Mann-Whitney-U-test with a two-tailed
p-value was used.
Results and discussion
Eight patients (age: 47.7 6 10.9 years, range 34–64 years;
male to female ratio: 1:1, duration of disease: 1–15 years,
Correspondence to: D. Schwab
m
Inflammation Research
mean: 4 years) took part in this investigation. Twenty-four
plasma and serum samples and 30 urine samples were
obtained. One hundred and fifty healthy subjects with no
underlying atopic or gastrointestinal disease served as
controls.
Plasma histamine and serum tryptase concentrations
in patients with collagenous colitis were not significantly
different from healthy controls (Table 1). Although urine
histamine concentrations in patients with collagenous colitis
were slightly elevated, this did not achieve statistical
significance. However, n-methylhistamine in urine was
significantly elevated in patients with collagenous colitis
compared with that of healthy subjects (Table 1).
Aetiopathogenesis of collagenous colitis is unknown,
and the role of accumulated mast cells in the colonic lamina
propria is unclear. This investigation for the first time
demonstrates evidence of mast cell activation in patients
with collagenous colitis. The highly significantly elevated n-
methylhistamine levels in urine support the hypothesis that
mast cells are not only increased in the inflammatory
infiltrate of colonic mucosa in patients with collagenous
colitis [3] but are also in an activated state with enhanced
histamine release. Since in man the methylation pathway
exceeds oxidative histamine degradation, intestinally secreted
histamine may be found as methylhistamine in urine [5]. In
addition, the patients under investigation had no atopic
disease and it can be further hypothesised that mast cell
mediators may contribute to the clinical picture of this
disease, since histamine is well known to induce a secretory
diarrhoea or increased smooth muscle contraction [3, 6].
However, we were unable to demonstrate increased
plasma- or 12h-urine-histamine levels in patients with colla-
genous colitis, although normal plasma histamine levels do
not rule out a small but continuous or pulsatile release of
histamine. The demonstration of only slightly elevated levels
of urine-histamine might reflect rapid metabolism of hista-
mine by the hepatic and intestinal methyltransferase, which
clears the blood of the portal venous system from histamine
originated in the colonic mast cells.
In agreement with the findings for histamine in plasma
and urine, we did not observe a significant elevation of
serum-tryptase in patients with collagenous colitis compared
to controls. This suggests that a systemic activation of mast
Inflamm. res., Supplement 1 (1998) 65

Table 1.
Mediator Collagenous colitis Controls p-value
(mean6SD) (mean6SD)
n=8 n = 150

Histamine (plasma)
[ng/ml × BSA] 0.2 6 0.2 0.3 6 0.2 n.s
Tryptase (serum)
[ng/ml × BSA] 0.3 6 0.2 0.3 6 0.1 n.s.
Histamine (12h-urine)
[mg/mmol creatinine × BSA] 2.1 6 2.1 1.8 6 0.6 n.s.
N-methyl-histamine (12h-urine)
[mg/mmol creatinine × BSA] 8.9 6 5.1 3.7 6 1.8 p = 0.002

BSA = body surface area, n.s. = not significant.

cells is unlikely but could also be due to different secretion References

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mast cells.
The clinical picture of collagenous colitis is charac-
terised by local rather than systemic clinical and objective
signs. Therefore, further investigations on mast cell activa-
tion should aim at the detection of local, i.e. colonic-mucosal
mast cell mediators to further elucidate the pathogenic role
of mast cells in collagenous colitis. These findings provide a
rationale for the observed efficacy of treatment with
histamine-receptor-antagonists [3], especially in those
patients with collagenous colitis who exhibit elevated urine
levels of n-methylhistamine.
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