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. 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