III. case report

advertisement
Thermography in Surveillance of Ulcerative
Colitis – a Case Report
Tonći Božin 1, Svetlana Antonini 2, Darko Kolarić 3, Željko Ferenčić 4, Tomislav Kuliš 5, Marko Banić 1
1
2
University Hospital Dubrava, Zagreb, Croatia
Primary Health Care Zagreb - Center, Zagreb, Croatia
3
Ruđer Bošković Institute, Zagreb, Croatia
4
Children's Hospital Srebrnjak, Zagreb, Croatia
5
University Hospital Center Zagreb, Zagreb, Croatia
tbozin@gmail.com
Abstract - Ulcerative colitis represents a chronic condition
occurring in relapsing and remitting fashion with uncertain
outcome and requires lifelong treatment with considerable
sideffects. Diagnostic methods currently in use give an insight
into disease activity, but are possibly associated with significant
discomfort for the patient. For that reason there is a need for a
noninvasive, biologically inert method for evaluation of disease
activity in inflammatory bowel disease. The aim of this paper is
to present the potential of thermography in surveillance of
ulcerative colitis. The authors present two cases of patients with
ulcerative pancolitis. The thermographic patterns, taken before
starting the anti-inflammatory treatment, and upon reaching the
remission of the disease correlated with clinical and laboratory,
and endoscopic findings, as well. This case report points out to
diagnostic potential of infrared thermography as a feasible and
noninvasive method in evaluation of disease activity, such as
acute pancolitis.
Keywords – Ulcerative colitis; Colonoscopy; Thermography
I.
INTRODUCTION
Inflammatory bowel diseases (IBD), Crohn's disease and
ulcerative colitis delineate idiopathic chronic inflammation of
the small and large intestines. IBD represent relapsing and
remitting condition characterized by chronic inflammation at
various sites in gastrointestinal tract that result in diarrhea and
abdominal pain [1]. Crohn´s disease shows segmental
inflammation that can affect any segment of the gastrointestinal
tract from mouth to rectum and affects all wall layers. The
most common localization is the terminal ileum, in 87% of
cases. Small intestine and colon are affected in 41-55%.
Gastrointestinal tract above ligament of Treitz is affected in
less than 5% of cases. Ulcerative colitis starts in the rectum but
can spread to all segments of the colon and is characterized by
circular inflammation affecting only the mucosal membrane.
Rectosigmoid only, is affected in 57% of cases. It is not always
possible to distinguish between Crohn´s disease and ulcerative
colitis. The definitive differentiation between Crohn´s disease
and ulcerative colitis often evolves during the course of the
disease. The causes of IBD remain unknown. Inflammation
results as a loss of tolerance to normal intestinal flora,
provoking the immune response that includes the release of
inflammatory mediators, such as cytokines, interleukins and
tumor necrosis factor, as well [2-3]. Unlike in healthy
individuals, in patients with IBD the equilibrium between proand anti-inflammatory cytokines is significantly deranged.
Dysregulation of the immune reaction leads to excessive
activation of pro-inflammatory cytokines. Ethiopathogenetic
factors for loss of tolerance to normal host microbiota and
subsequent chronic inflammatory cascade include multifactor
genetic predisposition that can lead to abnormal epithelial
barrier and altered mucosal immune defenses [4-6]. Genetic
factors play an important role, as shown by epidemiological
studies on monozygotic twins. Nearly 200 different genes and
gene loci have been identified that are associated with IBD. Of
these, the best understood is the NOD2/CARD 15 gene [7]. In
more recent years, it was postulated that the physiological
flora, which lives in symbiosis within the gastrointestinal tract,
may play an important role in the development and
perpetuation of inflammatory bowel disease [8]. In addition,
the total bacterial count appears to be important [9]. Indicating
signs at first manifestation for Crohn`s disease include
abdominal pain, diarrhea, rectal bleeding, anal fistulae, weight
loss, fever, anemia, arthralgia, eye involvement and erythema
nodosum. Diagnostic evaluation of inflammatory bowel
diseases includes clinical examination, laboratory tests, activity
indices and imaging methods, such as endoscopy and methods
of radiology. It is important to stress out that in Crohn´s disease
clinical symptoms do not necessarily correspond with patient’s
endoscopic or histological findings or with individual
laboratory parameters. For this reason indices have been
developed to assess disease activity and guide treatment. The
most widely used is the Crohn´s Disease Activity Index
(CDAI) [10]. Typical signs and symptoms at initial diagnosis
of ulcerative colitis on the other hand, are intestinal bleeding,
diarrhea, abdominal pain, rarely anal fissures and fistulae.
Anemia is common, weight loss, fever and arthralgia. Different
indices have been developed to assess disease activity and to
take into account clinical and laboratory parameters and/or
endoscopic findings. In this paper the authors used Mayo
endoscopic subscore to evaluate disease activity [11].
Extraintestinal symptoms of IBD occur in about 60% of
patients. They may be prominent and must often affect joints,
skin, eyes, liver and the bile ducts. Other organs (lung, heart,
kidneys) are less frequently affected. The symptoms can occur
as initial symptoms, especially joint pain and erythema
nodosum. Occasionally, diagnosis of primary sclerosing
cholangitis (PSC) leads to the diagnosis of ulcerative colitis. As
1
epidemiology goes incidence of Crohn´s disease is increasing
with a peak occurrence in the third decade. Peak occurrence of
ulcerative colitis is at about age 20 [12]. However, there is a
need for simple, noninvasive and reproducible test that could
accurately reflect the disease activity, and that could be used
safely and repeatedly, during biological course of inflammatory
bowel disease. The aim of this paper is to present the
possibility of thermal imaging in surveillance of ulcerative
colitis on two patients with this condition. Therapy of IBD is
aimed to reduce or eliminate symptoms during the acute flare
or exacerbation as well as to maintain remission. Surgery is
employed in life-threatening situations and fistulas or
abscesses.
II.
METHODS
In this case report, in purpose of evaluating the extent of
intestinal inflammation, two patients underwent standard
diagnostic workup for ulcerative colitis that included physical
exam, laboratory tests including C – reactive protein,
esophagogastroduodenoscopy and total colonoscopy with
terminal iloescopy, as well. The microbiology stool sampling,
including A / B Cl. difficile toxin was performed in order to
exclude any infective pathogens. The patients also underwent
thermal imaging, provided in real time using infrared camera
FLIR T335, during all the measurements. The measurements
were done before the preparations for endoscopy, to exclude
any potential influence of bowel cleansing and endoscopic
procedure itself, as well. The thermographic measurements
were done in two interval times: before initiating the therapy
and after the patient had reached the remission of colitis,
according to clinical, laboratory and endoscopic evaluation
[13]. The imaging itself was preformed accordingly; patients
were positioned in front of the camera, approximately at 1m so
that the whole abdomen was captured by the camera lens. They
were undressed and asked to stand in front of the camera not
touching there abdomen in order to achieve thermal
equilibrium. This process took about 5 to 10 minutes and was
documented as a thermogram. Upon achieving equilibrium the
patient´s abdomen was cooled with alcohol and then interval
thermograms were taken until equilibrium was achieved again.
Differences in thermal patterns and peak temperatures were
documented. For easier examination taken thermograms were
divided in quadrants representing colonic segments, the
rectosigmoid, descending colon, transverse colon and the
descending colon. The same process of thermal imaging was
performed before starting therapy and upon achieving clinical
remission of the disease. Differences in observed
thermographic patterns and peak temperatures were compared.
III.
mixed with mucus and blood). The laboratory tests revealed
elevated leucocyte levels. Total colonoscopy revealed severe
left-sided colitis with Mayo endoscopic sub score of 2 (ranging
0-3). Severe inflammatory activity of the disease correlated
nicely with the pattern of thermographic infrared pictures,
taken before treatment, as shown on Figure 1. Observed
temperatures in quadrants representing the left colon (the
rectosigmoid and the descending colon) were 2 centigrade
higher than in the unaffected part of the abdomen. After 12
days of hospitalization the patient was discharged clinically in
better shape. The plan was to take another thermogram of the
patient’s abdomen, upon achieving whole remission. Seven
months later there were no obvious signs of disease activity.
Stool frequency and consistency was normal, but the patient
did complain of some discomfort in the lower left quadrant of
the abdomen.
Figure 1. Marked areas of severe inflammatory activity.
We took a control thermogram only to be surprised to detect
disease activity. Observed temperatures in quadrant
representing the left colon were almost the same as 7 months
earlier, as shown in Figure 2.
CASE REPORT
We present two patients with severe ulcerative colitis. The
first patient is a 47-year old male diagnosed with left-sided
ulcerative colitis (UC) in 2013. In September 2014 he was
admitted in Clinical Hospital Dubrava due an exacerbation of
the disease. The patient presented with fever, fatigue, loss of
appetite and loss of body weight, in duration of 2 weeks before
admittance to University Hospital Dubrava. The disease was
characterized with abdominal cramps located in the lover left
quadrant of the abdomen, and diarrhea (7 – 10 stools / day,
Figure 2. Control thermogram showing disease activity
Two days later the patient was readmitted to Clinical Hospital
Dubrava with full blown exacerbation. Colonoscopy was
2
preformed showing active disease along the left part of the
colon, Mayo endoscopic sub score 2.
Temperatures in the affected quadrant were significantly lower
(Chart 1).
The second patient is a 42-year female, diagnosed with UC in
2005. In February 2015 she consulted her gastroenterologist
because of frequent bloody stools (7-8/day) and abdominal
pain. Colonoscopy revealed active disease extending to the
hepatic flexure. Laboratory tests revealed elevated
inflammatory markers (high leukocytosis and elevated C –
reactive protein). Microbiological stool analysis excluded any
infective causes. We made a thermogram of the patient’s
abdomen and observed a distinctive infrared pattern
corresponding with colonoscopy findings, as shown in Figure
3. Peak temperatures were highest in quadrants representing
the left and the transverse colon. After four weeks of intensive
treatment with anti-inflammatory drugs (methylprednisolone
and azathioprine, in combination with mesalamine), the patient
entered the remission of the disease, documented with
significant clinical, laboratory and imaging improvement in
disease activity [14-15].
Chart 1. Temperatures before (blue) and after treatment (red)
Figure 3. Thermogram of the patients abdomen documenting
disease activity
This finding, indicating the remission of active colitis
correlated with taken thermographic pictures showing only
mild abnormalities with the significant normalization in
abdominal surface temperature pattern, compared to initial
thermographic examination (Figure 4).
IV.
DISCUSSION
Ulcerative colitis is a recurrent inflammatory disease of the
colon and rectum characterized by ulcerations. Disease starts in
the rectum and spreads to a varying extend in a proximal
direction. Clinically, ulcerative colitis is characterized by
bloody diarrhea, cramping pain, anorexia and weight loss. The
diagnosis most often relies on colonoscopy and
macroscopically scoring of visualized inflammatory and
ulcerative mucosal pattern [16-18]. Taking into account the
standard imaging procedures for evaluating the activity and
extent of inflammatory disease, the thermal imaging, also
known as clinical thermography, is capable of providing noncontact, in vivo diagnostic information in regard to body
temperature. Infrared imaging also has the possibility to map
small variations of the body surface temperature and identify
thermal abnormalities that accompany various physiological
conditions. Being a passive technique, (i.e. without external
sources of radiation) thermography is non-invasive and
therefore intrinsically harmless. The findings in this case report
indicate the correlation of standard laboratory and imaging
tests and infrared imaging in evaluating the initial activity of
active ulcerative colitis as well as during remission. In addition,
in our case report, thermography was able to detect disease
activity prior to clinical presentation. We believe that blood
vessel activity during the process of active inflammation
induces the increase in body surface temperature that would be
higher than in normal tissue [13]. Our findings point out to
diagnostic potential of infrared thermography as a feasible and
noninvasive method in evaluation of disease activity, in the
patient with severe inflammatory bowel disease, such as acute
colitis [19-20]. It is our opinion that thermography has the
potential to be a good complementary method to standard
methods in evaluating disease activity. However, there is a
need for further clinical trials in order to evaluate and validate
infrared thermography in assessing the activity and extent of
intestinal inflammation. Further studies in data standardization
concerning abdominal thermography are also essential in the
process of implementing thermography in algorithms of
gastrointestinal and hepatic diseases diagnosis and
management.
Figure 4. Thermogram of the same patient, after 4 weeks
of treatment
3
REFERENCES
[1]
G Katsanos KH, Tsianos VE, Zois CD et al. Northwest Greece IBD
Study Group. “Inflammatory bowel disease and hepatitis B and C in
Western Balkans: a referral centre study and review of the literature”. J
Crohns Colitis. 2010; 4(4):450-465.
[2] Silva LC, Ortigosa LC, Benard G., “Anti-TNF-α agents in the treatment
of immune-mediated inflammatory diseases: mechanisms of action and
pitfalls”. Immunotherapy. 2010;2(6):817-833.
[3] Fiorino G, Peyrin-Biroulet L, Repici A, Malesci A, Danese S.,
“Adalimumab in ulcerative colitis: hypes and hopes”. Expert Opin Biol
Ther. 2011; 11(1):109-116.
[4] De Nitto D, Sarra M, Cupi ML, Pallone F, Monteleone G., “Targeting
IL-23 and Th17-cytokines in inflammatory bowel diseases”. Curr Pharm
Des. 2010;16(33):3656-3660.
[5] Pleško S, Banić M, Plečko V, Anić B, Brkić T, Renata H et al., “Effect
of Azithromycin on Acute Inflammatory Lesions and Colonic Bacterial
Load in a Murine Model of Experimental Colitis”. Dig Dis Sci. 2010;
55(8):2211-2218.
[6] Banić M, Anić B, Brkić T, Ljubicić N, Plesko S, Dohoczky C et al.,
“Effect of cyclosporine in a murine model of experimental colitis”. Dig
Dis Sci 2002;47(6):1362-1368.
[7] Hampe J, Grebe J, Nikolaus S, Solberg C, Croucher PJ, Mascheretti S et
al., “Association of NOD2 (CARD 15) genotype with clinical course of
Crohn's disease: a cohort study”. The Lancet. 2002;359(9318):16611665.
[8] Wallace KL, Zheng LB, Kanazawa Y, Shih DQ, “Immunopathology of
inflammatory bowel disease”. World J Gastroenterol. 2014; 20(1):6-21.
[9] Kostic AD, Xavier RJ, Gevers D, “The microbiome in inflammatory
bowel disease: current status and the future ahead”. Gastroenterology.
2014;146(6): 1489-1499.
[10] Sipponen T, Savilahti E, Kolho KL, Nuutinen H, Turunen U, Farkkila
M, “Crohn's disease activity assessed by fecal calprotectin and
lactoferrin: correlation with Crohn's disease activity index and
endoscopic findings”. Inflamm Bowel Dis. 2008; 14(1): 40-46.
[11] Bewtra M, Brensinger CM, Tomov VT, Hoang TB, Sokach CE, Siegel
CA et al, “An optimized patient-reported ulcerative colitis disease
activity measure derived from the Mayo score and the simple clinical
colitis activity Index”. Inflamm Bowel Dis. 2014; 20(6): 1070.
[12] Feuerstein JD, Cheifetz AS, “Ulcerative colitis: epidemiology,
diagnosis, and management”. In: Mayo Clinic Proceedings. Elsevier,
2014. p. 1553-1563.
[13] Merla A, Romani GL., “Biomedical applications of functional infrared
imaging”. In: Diakides NA, Bronzino JD, eds. Medical infrared imaging.
Boca Raton: CRC Press Taylor and Francis Group; 2008, pp 15-1 – 1520.
[14] Preiss JC, Zeitz M., “Use of methotrexate in patients with inflammatory
bowel diseases”. Clin Exp Rheumatol. 2010; 28(5 Suppl 61):S151-5.
[15] Talley NJ, Abreu MT, Achkar JP, Bernstein CN, Dubinsky MC,
Hanauer SB et al, « An evidence-based systematic review on medical
therapies for inflammatory bowel disease”. Am J Gastroenterol. 2011; 6
(Suppl 1):S2-25.
[16] Valentini L, Schulzke JD, “Mundane, yet challenging: the assessment of
malnutrition in inflammatory bowel disease”. Eur J Intern Med. 2011;
22(1):13-5.
[17] Dinesen LC, Walsh AJ, Protic MN, Heap G, Cummings F, Warren BF et
al., “The pattern and outcome of acute severe colitis”. J Crohns Colitis.
2010;4(4):431-7.
[18] Brakenhoff LK, van der Heijde DM, Hommes DW, Huizinga TW,
Fidder HH., “The joint-gut axis in inflammatory bowel diseases“. J
Crohns Colitis. 2010; 4(3):257-68.
[19] Purohit RC, Turner TA, Pascoe DD., “Use of infrared imaging in
Veterinary Medicine”. In: Diakides NA, Bronzino JD, eds. Medical
infrared imaging. Boca Raton: CRC Press Taylor and Francis Group;
2008, pp 21-1 – 21-8.
[20] Giordano J., “Ethical obligations in infrared imaging research and
practice”. In: Diakides NA, Bronzino JD, eds. Medical infrared imaging.
Boca Raton: CRC Press Taylor and Francis Group; 2008, pp 21-1 – 218.
4
Download