ODMIENNOŚCI CHOROBY CROHNA U DZIECI – DROGA OD WERYFIKACJI DIAGNOZY DO ROZWOJU
POWIKŁAŃ (OPIS PRZYPADKU KLINICZNEGO)
Tetyana O. Kryuchko, Olha A. Poda, Inna M. Nesina, Vira P. Harshman
Department of Pediatrics No. 2, Higher State Educational Establishment of Ukraine “Ukrainian Medical Stomatological Academy”, Poltava, Ukraine
Introduction: Despite increasing frequency of inflammatory diseases of the intestine in the children worldwide, verification of Crohn’s disease (CD) diagnosis in pediatric practice has not studied yet and it is difficult for clinician to determine the stage of the disease.
The aim of our study was to analyze clinical case of Crohn’s disease (CD) in a child based on literature data and own monitoring.
Materials and methods: 13 year old patient was involved in our examination who took complex lab and instrumental investigation, which allows verifying inflammatory intestinal pathology such as Crohn’s disease.
Clinical case of the disease demonstrates that clinical symptomatic picture, difficulties of differential diagnostics and the absence of effective interaction between relatives of the patient and doctor can’t give the possibility to make correct diagnosis in pediatric practice and it can lead to complications of the development of disablement.
Conclusions: Crohn’s disease is a serious inflammatory intestinal disease that requires an interdisciplinary diagnostic approach for the successful verification of the diagnosis.
Wiad Lek 2018, 71, 3 cz. I
Inflammatory disorders of the intestine present chronic pathology of digestive organs in children. The frequency of such disorders significantly increases worldwide. Crohn’s disease (CD) is the chronic, immune-mediated, granulomatous inflammatory disease of the digestive tract which can cover all regions but it is characterized by the damage of the subileum with the development of ileocolitis. Based on literature the spread of CD in children and teenagers varies in different European countries and contains from 50 to 70 cases per 100 000 population [1;2]. The increase of the frequency of the CD development is an important fact in comparison with ulcerative colitis in early childhood. But at the same time based on statistical data in 2014 in Ukraine 100 cases of CD in children were registered , and it can indicate the insufficient level of the diagnostics of early disease in pediatric practice.
Below clinical picture of Crohn’s disease in 13-year old boy was presented. This clinical case will be interested and important for pediatricians and general practitioners (GP) and also for specialized physicians (gastroenterologists, hematologists, immunologists, infectilogists, child’s surgeons) because there are definite difficulties of diagnostics of early disease.
The aim of our study was to analyze clinical case of Crohn’s disease (CD) in a child based on literature data and own monitoring.
Materials and methods
13 year old patient was involved in our examination who took complex lab and instrumental investigation, which allows verifying inflammatory intestinal pathology such as Crohn’s disease.
13 year old patient admitted to the gastroenterological department of the Regional Children’s Hospital in March, 2014 with complains of periodic spastic pains in the abdominal region of diffuse character, but they appear in the right ileac region which do not depend on the food intake, emotional stresses, and physical activity, periodic nausea, liquid stool with admixtures of mucus to 3-4 times per day (during last two weeks with periodic blood), often bloating, bad appetite, temperature rise to 37,5˚С, general weakness, growth and weight retardation, which were manifested from early childhood. It is known that a child suffers from this disease from May 2012 (11-year old boy), when periods of temperature rise, weakness were appeared. A boy also periodically noticed liquid stool twice per day, the presence of which he and his relatives explained as emotional stresses and food intake. Inflammatory changes in blood like leucocytosis with neutrophil formula’s change to left, increase of blood sedimentation rate to 35-40 mm/h, anemia based on temperature rise and he got antibacterial therapy. In August 2012 a child was hospitalized in the surgical department where he underwent surgical intervention of acute purulent paraproctitis. In two weeks after operation he was recurrently hospitalized with the diagnosis perianal fistula. Inflammatory changes of blood and the presence of sudfebrile temperature curve were evaluated as the pathology of rectum. In September 2012 a child took a course of examination in children’s gastroenterological department because he suffers from periodic diarrhea based on emotional stresses. A boy was examined by instrumental and lab methods of diagnostics but his parents refused from endoscopic examination. A child was discharged and he was under the care of pediatrician with such diagnosis as: irritable bowel syndrome with diarrhea, chronic superficial gastritis with remained acid-producing stomach function, exacerbation period, duodenal and gastric reflux, functional disorders of gallbladder, pituitary dwarfism. In 2013 periods of subfebrile temperature with the presence of inflammatory changes in blood were appeared. Out-patiently, he was examined on the markers of vital hepatitis and HIV-infection, systemic inflammatory diseases of connective tissue and TORHC infection, inoculation of biological liquids were done, X-ray of chest, CT of brain were also done. Periods of subfebrility stopped and changed into normal body’s temperature. In November, 2013 a patient was hospitalized in Children’s oncohematological department because he suffered from subfebrile temperature, poor medicamentous correction and anemia. He was received rectosigmoidoscopy in hospital, pathological changes on the visible region of colon were not noticed. After examination, which excluded the presence of oncohematological pathology a child was discharged under pediatrician’s care. In March 2014 child’s condition deteriorated and significant pains in the abdomen, episodes of liquid stool were appeared and the child saw the blood admixtures. He was hospitalized in Children’s gastroenterological department with such complaints.
When a child was hospitalized, physical retardation was obvious. 13 year old boy had height 130 sm and body weight – 30 kg. Physical examination of cardiovascular, respiratory and urinary systems did not detect any significant changes. The abdomen is soft, free for palpation and it is moderately painful in gastroduodenal region and mostly in the right side of ileum. Based on results of complex lab investigation inflammatory changes in blood were detected – stab neutrophils – 23%, thrombocytes – 638 * 109/l, ESR – 40 mm/h, C-reactive protein (CRP) – 48 mg/l and anemia – Hb – 92 g/l, Ер – 3,96 * 1012 /l, col. ind. – 0,91. General urine analysis, parameters of biochemical blood test, glycemia level were within normal limits. FOB (feces occult blood) is negative, parasite eggs were not found out, bacteriological feces examination is without pathology. During coprological examination, poor signs of distal colitic syndrome were seen (small number of mucus, leukocytes 15-20, erythrocytes – single in the preparation). Signs of superficial gastropathy were determined during fibrogastroduodenoscopy, transabdominal ultrasound investigation determined only the presence of gallbladder deformation. The deformity in the region of cecum was detected during X-ray investigation with contrast study, other parts of colon are without pathological changes. A patient was directed to investigate the fecal calprotectin because suspected inflammatory process of the intestine and relative’s refusal from endoscopic examination. Indices of calprotectin practically exceed tenfold based on received results (480 mkg/gr). A child was made the main clinical diagnosis: ulcerative colitis, mild form, recurrent stage, active phase, without complications. Pathogenetic therapies (Mesalazine) in 50 mg/kg/day, enterosorbents, enzymes, sedative agents, probiotics were prescribed.
On the 12th day of hospital stay patient’s condition deteriorated. Based on temperature rise to 38,5˚С intense pain in hypogastrium was appeared (pains were significantly expressed in the right iliac region), and nausea, weakness were presented. Antiperistaltic formation of round shape with size 20*14 mm was detected and localized in right iliac region with single hyperechoic elements and increase of blood flow and increase of lymph nodes to 8 mm during ultrasound investigation. A child was directed for further examination in the surgical department because there was suspected appendix infiltrate. On the next day a child was operated: right hemicolectomy (removal of ileocecal edge of the intestine), ileocolic anastomosis was formed. Removed the part of small and large intestine (24 sm) was sent for histological investigation. Morphological conclusion: in the wall of the intestine there is infiltration of lymphocytes, histiocytes, plasmatic cells and field of granulation tissue with single gigantic Langerhans cells. Tumor growth was not detected. After rehabilitation period a child was discharged and sent for further hospitalization in gastroenterological department to determine treatment management with the diagnosis: Crohn’s disease, ileocolitis, infiltration period, exacerbation phase, moderate stage, chronic level, complicated by intestinal stenosis, anemia Ist stage. During hospitalization a child was prescribed: partial bed rest and therapeutic nutrition and also it is recommended partial enteral nutrition (mixture Modulen IBD). Considering moderate stage of the disease, the presence of perianal damages, the development of complications such as stenosis of ileocecal region of the intestine, basic therapy including Mesalazine in the dosage 50mg/kg was added by intake of Azathioprine (Imuran) in the dosage 1 mg/kg during 4-6 weeks with subsequent gradual decrease and therapy continuation. Based on therapy general condition of the patient increases, painful syndrome reduces, stool normalizes, inflammatory changes of peripheral blood disappeared.
Nowadays the clear cause of Crohn’s disease has not studied yet. According to modern presentations, disease is genetically determined with polygenic character and the development is induced by such factors as viral and bacterial agents, intestinal disorders, stress and others [4;5;6]. Among main risk factors which were defined by leading specialists of European organization (European Crohn’s and Colitis Organisation, ECCO): relevant family history, infectious gastroenteritis, often intake of NSAID and smoking [7;8;9]. Clinical manifestations of Crohn’s disease differ from variety and depend on localization of pathological process, disease stage and presence or absence of complications. The most common symptoms of the disease: colicky pain, chronic diarrhea, the presence blood in feces, which is present and visible only on the late stages of the disease, fever, often subfebrile character, anemia, poor appetite, weakness [10;11;12]. Presented by us clinical case is manifested by long-lasting diarrheal syndrome without visual presence admixture in feces, unstable periods of subfebrility and anemia, and it is characterized by the presence of Crohn’s disease. According to literature, stomach lesion and duodenum lesion in Crohn’s disease have similar signs with gastroduodenitis and the localization of inflammatory process in terminal regions of small intestine looks like acute appendicitis (by palpation in right ileac region soft formation can be present), and it was described in the clinical case. Many authors consider that in some cases (especially during involving the rectum in pathological process) Crohn’s disease can be manifested as acute paraproctitis with different perianal manifestations – macerations, cracks, and fistula, and it leads to the therapy in the surgical department without timely verification of the correct diagnosis. An extremely important sign in the clinical picture of Crohn’s disease in children is also a retardation in the body’s growth / mass and sexual development, which, in the opinion of some researchers, in rare cases may be the only sign of the disease in childhood, long preceding the picture of diarrheal syndrome [11;13].
“Gold” standard of CD diagnostics has not found yet. The diagnosis can be confirmed by clinical manifestations and signs of endoscopic, histological, radiological and biochemical criteria of the disease. The main diagnostic methods of the investigation include clinical urine and blood analysis, biochemical blood test, microbiological stool test, occult blood feces analysis, ultrasound investigation of the intestine and abdominal organs, esophagogastroduodenoscopy, irrigoscopy, ileocolonoscopy with obligatory biopsy from terminal region of ileum and all regions of large intestine. It should be noted the importance of ileocolonscopy because terminal regions of small intestine (ileocecal edge of intestine) and initial regions of large intestine indicate the pathological process. In presented case refusal from endoscopic investigation and previous endoscopy in incomplete stage (proctosigmoidoscopy) exclude the possibility to determine pathological process. As a result there is long-lasting chronic inflammation of intestinal wall and leads to the formation of connective tissue and stenosis of the damaged part of the intestine. For the early diagnosis of inflammatory intestinal diseases, fecal biomarkers of inflammation, such as calprotectin, are also widely used at the present stage. These markers of neutrophil inflammation allow us to assess the intensity and prevalence of the inflammatory process in the intestine and are used for the purpose of differential diagnosis of organic and functional diseases [14;15]. These studies remain particularly relevant in pediatric practice, as they are non-invasive and allow for timely screening by identifying a group of patients who need an endoscopic examination as soon as possible. According to literature at increasing number of fecal calprotectin more than 50 mkg/gr in children, who are older 4 years old, colonoscopy with biopsy should be done to prove or disprove the diagnosis . In the described clinical case, the child had a nearly tenfold increase in fecal calprotectin, which was a precursor for carrying out an endoscopic examination of the intestine. ECCO experts also recommend additional visualization studies (computer tomography enterography, enterotransmission, transabdominal ultrasound) that can detect disease in the intestinal wall and beyond and assess the state of mesenterium.
Presented clinical case clearly demonstrates the difficulties of early diagnosis of Crohn’s disease in children. Such clinical manifestations as unexplained, poorly amenable to medical correction anemia, long periods of subfebrility, unstable diarrheal syndrome with prolonged absence of visible blood in the stool, as well as height and weight retardation and it doesn’t not always give a cause for suspected Crohn’s disease in the early stages and often “lead” the clinician from the timely diagnosis and the beginning of pathogenetic therapy.
To conclude it should be noted that Crohn’s disease is a serious inflammatory intestinal disease that requires an interdisciplinary diagnostic approach for the successful verification of the diagnosis. Modern methods of diagnostics and therapy, provided in time for a suspected diagnosis, allow patients to avoid the development of complications, maintain stable periods of remission and improve the quality of life of children with this pathology.
1. Benchimol EI, Fortinsky KJ, Gozdyra P et al. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends. Inflamm Bowel Dis. 2011; 17(1):423–439.
2. Ruemmele FM, Veres G, Kolho KL et al. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn’s disease. J Crohns Colitis. 2014 Oct; 8(10):1179–1207. http://dx.doi.org/10.1016/j.crohns.2014.04.005
3. Shadrin O.G. Bolezn Krona u detey: sostoyanie problemyi i perspektivyi ee resheniya v Ukraine [Crohn’s disease in children: the state of the problem and the prospects for its solution in Ukraine]. Health of Ukraine. Medical Newspaper. 2015; 1: 3-5.
4. Denson LA. The role of the innate and adaptive immune system in pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2013; 19:2011–2020.
5. Ruel J, Ruane D, Mehandru S, et al. IBD across the age spectrum: Is it the same disease? Nat Rev Gastroenterol Hepatol. 2014;11:88-98.
6. Beketova G.V., Soldatova O.V. Bolezn Krona u detey i podrostkov (klinicheskaya lektsiya) [Crohn’s disease in children and adolescents (clinical lecture)] «Pediatrics. Eastern Europe». 2017; 5(4):472-490.
7. Ananthakrishnan AN, Higuchi LM, Huang ES et al. Aspirin, nonsteroidal anti-inflammatory drug use, and risk for Crohn disease and ulcerative colitis: a cohort study. Ann Intern Med. 2012;156:350-359.
8. Higuchi LM, Khalili H, Chan AT et al. A prospective study of cigarette smoking and the risk of inflammatory bowel disease in women. Am J Gastroenterol. 2012;107:1399-1406.
9. Gomollón F, Dignass A, Annese V. 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease 2016: Part 1: Diagnosis and Medical Management. J Crohns Colitis. 2017 Jan; 11(1):3-25. doi: 10.1093/ecco-jcc/jjw168
10. Ford AC, Moayyedi P, Bercik P et al. Lack of utility of symptoms and signs at first presentation as predictors of inflammatory bowel disease in secondary care. Am J Gastroenterol. 2015;110:716-724.
11. Denisova M.F., Chernega N.V., Muzyika N.N. i dr. Sravnitelnaya kliniko-paraktinicheskaya harakteristika yazvennogo kolita i bolezni Krona u detey [Comparative clinical and paraclinical characteristics of ulcerative colitis and Crohn’s disease in children]. Zdorove rebenka. 2015; 2(70):10-15.
12. Harbord M, Annese V, Vavricka SR et al. The First European Evidence-based Consensus on Extra-intestinal Manifestations in Inflammatory Bowel Disease. J Crohns Colitis. 2016;10:239-254.
13. Grona V.N., Litovka V.K., Gunkin A.Yu. Ob osobennostyah kliniki i diagnostiki bolezni krona u detey [About the features of clinic and diagnostics of Crohn’s disease in children]. Zdorove rebenka. 2009; 2(17):12-18.
14. Kryuchko T.O., Nesina I.M., Poda O.A., Kolenko I.O. Algoritm diferentsIynoYi dIagnostiki zahvoryuvan kishechnika u ditey [The algorithm of differential diagnosis of intestinal diseases in children]. Dityachiy likar. 2016; 3(48):21-24.
15. Pavlenko N.V., Voloshin K.V, Ganziy O.B. Viznachennya markeriv kishechnogo zapalennya u diagnostichnomu poshuku u ditey iz patologieyu kishechnika [Determination of markers of intestinal inflammation in diagnostic search in children with intestinal pathology]. Zdorove rebenka. 2016;5.1 (73.1):47-50.
Given article was done within Initiative scientific and research work of HSEE of Ukraine “Ukrainian Medical Stomatological Academy”. «Study of pathogenetic mechanisms of realization of the most widespread diseases of childhood, optimization of diagnostics and treatment». Deadline for completion 2017-2021 (Number state registration – 0117.U004683).
ADDRESS FOR CORRESPONDENCE
Olha A. Poda
23 Shevchenka Str., 36011, Poltava, Ukraine
tel.: +380532-606-491; mob. tel.: +38066-788-47-98