Katalin Lorinczy

Anti-TNF trough levels and detection of antibodies to anti-TNF in inflammatory bowel disease: are they ready for everyday clinical use?

Introduction: In the last two decades, with the development of biological (anti-TNFα) therapy, the treatment paradigms for Crohns disease and ulcerative colitis have evolved, with a continuously increasing role of biologicals. Some patients, however, experience lack- or loss of response (LOR) to treatment, and management of such patients is often empirical. Areas covered: The available data regarding the relationship between serum anti-TNF concentrations, antibodies against anti-TNF agents, and clinical efficacy, as well as the development of adverse events and management of LOR. Expert opinion: Monitoring drug levels and antibodies is expected to play an emerging role in the management of LOR (i.e., to confirm adherence, allow for dose adjustment, or provide a rationale for switching to another anti-TNF agent or to a different class of biological agent) in the coming years. The optimal method of detection is however not clear. In clinical practice, meticulous complex assessment of clinical symptoms, confirmation of active disease by endoscopic or radiological imaging, and exclusion of complications remains necessary.

Does dermatitis herpetiformis result in bone loss as coeliac disease does?: a cross sectional study

INTRODUCTION AND OBJECTIVES coeliac disease (CD) and its cutaneous manifestation, dermatitis herpetiformis are both (DH) gluten-sensitive diseases. Metabolic bone disease is common among patients with CD, even in asymptomatic forms. Data are scarce about bone density in patients with dermatitis herpetiformis. The aim of our study was to compare bone mineral density (BMD) of celiac and dermatitis herpetiformis patients. METHODS 34 coeliac patients, 53 with dermatitis herpetiformis and 42 healthy controls were studied. The mean age was 38.0 +/- 12.1, 32.18 +/- 14.95, 35.33 +/- 10.41 years in CD, dermatitis herpetiformis, and healthy controls, respectively. Bone mineral density of the lumbar spine, the left femoral neck and radius were measured by dual-energy X-ray absorptiometry. Low bone density, osteopenia and osteoporosis were defined as a body mass density (BMD) T-score between 0 and -1, between -1 and -2.5, and under -2.5, respectively. RESULTS at lumbar region, consisting of dominantly trabecular compartment, a decreased BMD was detected in 49 % (n = 26) patients with dermatitis herpetiformis, 62 % (n = 21) of CD patients, and 29 % (n = 12) of healthy controls, respectively. Lower BMD were measured at the lumbar region in dermatitis herpetiformis and CD compared to healthy subjects (0.993 +/- 0.136 g/cm2 and 0.880 +/- 0.155 g/cm2 vs. 1.056 +/- 0.126 g/cm2; p < 0.01). Density of bones consisting of dominantly cortical compartment (femoral neck) did not differ in dermatitis herpetiformis and healthy subjects. CONCLUSIONS our results show that a low bone mass is also frequent among patients with dermatitis herpetiformis. Bone mineral content in these patients is significantly lower in those parts of the skeleton which contain more trabecular than cortical bone.

Antibody and cell-mediated immune response to whole virion and split virion influenza vaccine in patients with inflammatory bowel disease on maintenance immunosuppressive and biological therapy

Abstract Objective. Influenza vaccination is recommended for inflammatory bowel disease (IBD) patients on immunosuppressive therapy. The objective was to evaluate the antibody and cell-mediated immune response to the split and whole virion influenza vaccine in patients with IBD treated with anti-TNF-α and immunosuppressive therapy. Patients and methods.One hundred and fifty-six immunocompromised IBD patients were vaccinated. Fifty-three patients (control group) refused vaccination. Split virion vaccine and whole virion vaccine were used. Serum samples were obtained for pre- and postimmunization antibody titers to influenza vaccine (A/California/7/2009 [H1N1], A/Victoria/361/2011 [H3N2], B/Wisconsin/1/2010–like B/Hubei-Wujiagang/158/2009). Cell-mediated response was evaluated using an interferon (INF)-γ, interleukine (IL)-2 and tumor necrosis factor (TNF)-α ELISA. Results. Postimmunization titers of both influenza subtypes increased significantly after the administration of split virion vaccines compared to the controls and to those who received whole virion vaccine. The antibody titers of Influenza B also increased significantly in patients immunized with split vaccine and treated with anti-TNF-α therapy. After influenza vaccination, the level of serum IL-2 significantly decreased. No serious side effects developed occurred after influenza vaccination, and the influenza-like symptoms did not differ significantly between vaccinated versus control patients. The relapse of the disease was observed in only 10% of the patients and was more common in vaccinated than in control subjects. Conclusion. Split virion vaccines seem to be more effective than whole virion vaccines. Measuring the antibody responses is worthwhile in patients treated with immunosuppressants to determine the efficacy of influenza vaccination.

[Epidemiology, predictors and clinical aspects of loss of response to biological therapy].

In the last two decades, the treatment paradigms for Crohns disease and ulcerative colitis have significantly changed inclusive of a continuously increasing role of biological therapy (anti TNFs). Some patients, however, experience lack or loss of response to biological treatment, and in such cases the management of patients is often empirical. In this review, the authors aim to summarize the available data regarding epidemiology and predictors of loss of response to biological therapy considering the clinical factors and the relationship between serum concentrations, antibodies against biological agents, respectively. Monitoring drug levels and antibodies is expected to play an important role in the management of loss of response (i.e. to confirm adherence, allow dose adjustment, or provide rationale for switching to another biological agent or to a different class of biological agent) in the coming years. The optimal method of detection and cut-off values are, however, not clear. In clinical practice, meticulous complex assessment of clinical symptoms, confirmation of active disease by endoscopic or radiological imaging, and excluding complications remain necessary.

A gyomor polypoid képleteinek gyakorisága egy endoszkópos centrumban

Bevezetes: A gyomor polypoid elvaltozasainak hazai előfordulasi gyakorisaga nem ismert. Cel: A szerzők celul tűztek ki a Semmelweis Egyetem, II. Belgyogyaszati Klinika endoszkopos centrumaban a gyomorpolip gyakorisaganak es az azt befolyasolo koroki tenyezőknek a vizsgalatat. Modszerek: 16 honap alatt vegzett felső panendoszkopiak egyseges szovettani es klinikai adatait ertekeltek. Eredmenyek: 4174 gasztroszkopia soran 193 (4,62%) polipot eszleltek. A betegek atlageletkora a diagnoziskor 65,9±12,7 ev volt. A polipok 33,67%-a hyperplasticus, 31,09%-a fundusmirigypolip, 2,07%-a malignus volt. A fundusmirigypolipos betegek koreben gyakoribb volt a protonpumpagatlo-hasznalat (p = 0,007), mig a hyperplasticus polipos csoportban gyakrabban talaltunk idult gastritist (p = 0,032). A Helicobacter pylori-fertőzottseg egyik szovettanu polip jelenletevel sem fuggott ossze. Kovetkeztetes: Hazai betegek koreben gyakoribb a gyomorpolip, mint az az irodalmi adatok alapjan varhato lenne. A fundusmirigypolipok gyakoribbak tartos protonpumpagatlo-hasznalo betegekben, a hyperplasticus polipok előfordulasa pedig az idult gastritisek gyakorisagaval mutat osszefuggest. Orv. Hetil., 2013, 154, 770–774. | Background: The prevalence of gastric polyps is unknown in Hungary. Aim: The aim of the authors was to assess the prevalence of polypoid lesions of the stomach in the endoscopic centre of the 2nd Department of Medicine, Semmelweis University. Methods: Results of upper gastrointestinal endoscopies carried out between March 2010 and June 2011 were analysed. Results: 193 cases with polyps were diagnosed in 4174 endoscopies (4.62%). Hyperplastic polyps, fundic gland polyps and malignant lesion were detected in 33.67%, 31.09% and 2.07% of the cases, respectively. Proton pump inhibitor use was more frequent among patients diagnosed with fundus gland polyps (p = 0.007), while hyperplastic polyps were diagnosed more frequently in patients with chronic gastritis (p = 0.032). Conclusions: The frequency of gastric polyps was higher than expected from data published in the literature. Long-term proton pump-inhibitor use and chronic gastritis were associated with fundus gland and hyperplastic polyps, respectively. Orv. Hetil., 2013, 154, 770–774.BACKGROUND The prevalence of gastric polyps is unknown in Hungary. AIM The aim of the authors was to assess the prevalence of polypoid lesions of the stomach in the endoscopic centre of the 2nd Department of Medicine, Semmelweis University. METHODS Results of upper gastrointestinal endoscopies carried out between March 2010 and June 2011 were analysed. RESULTS 193 cases with polyps were diagnosed in 4174 endoscopies (4.62%). Hyperplastic polyps, fundic gland polyps and malignant lesion were detected in 33.67%, 31.09% and 2.07% of the cases, respectively. Proton pump inhibitor use was more frequent among patients diagnosed with fundus gland polyps (p = 0.007), while hyperplastic polyps were diagnosed more frequently in patients with chronic gastritis (p = 0.032). CONCLUSIONS The frequency of gastric polyps was higher than expected from data published in the literature. Long-term proton pump-inhibitor use and chronic gastritis were associated with fundus gland and hyperplastic polyps, respectively.

Mo1379 Vitamin D Level Doesn't Correlate With Disease Extent and Severity in Hungarian Patients With Inflammatory Bowel Diseases

Background: Many patients with inflammatory bowel disease (IBD) face multiple problems, including medical, surgical, nutritional, social, psychiatric related to their disease and require a holistic approach to care. To address this need, a multidisciplinary, prompt access IBD clinic was established at McMaster University Medical Centre, Hamilton, Canada. The prevalence of anxiety and depression among the patients attending the clinic is not known. Methods: Interdisciplinary team members consisting of gastroenterologists, surgeon, psychiatrists, nurse practitioner and dietitian providing prompt access holistic care for patients with IBD. All patients with IBD were assessed for demographic characteristics, quality of life using the Short Form-12 (SF-12), and psychological morbidity using the Hospital Anxiety and Depression Scale (HADS). The SF-12 has two components; physical composite score (PCS) and mental composite score (MCS); if either score is ,50 it was considered abnormal. HADS score can range from 0-42 and a score of .11 was considered abnormal. Results: The mean (SD) age of the 67 patients (males, 36%) was 35 (13) yrs. The majority (63%) had received college education. Of them, 40% had full-time employment, 18% had parttime employment, 24% were unemployed and 18% were on disability/sick leave. Of the 67 patients, 45% were in a stable marital relationship, 43% were single and 10% were either divorced or separated. The mean (SD) PCS was 41 (11) and MCS was 43 (12). The PCS was abnormal in 73% and MCS in 65% of the patients. HADS scores indicated that 75% were anxious/ depressed, while 8% had borderline anxiety/depression and 17% had normal scores. HADS scores showed a high degree of correlation with MCS (r=-0.717; p ,0.001) but no relationship to PCS, ESR or CRP. HADS scores were lower in those with higher income (.60,000

Magyarországi adatok a gyulladásos bélbetegsé gro″l, analitikai adatok a colitis ulcerosáról

/yr) than those with lower income (15±8 vs 21±6; p=0.037); and in those who had full time employment compared to those without (13±7.6 vs 17±8; p=0.05). The PCS showed a negative correlation with ESR (rho=-0.25; p=0.048) and CRP (rho=-0.25; p= 0.05). Only 27% (13/49) of the patients with abnormal HADS score received professional psychiatric help. Conclusions: Patients with IBD have a high prevalence of anxiety and depression. Anxiety and depression was found more often in those with lower income and no full time employment.. HADS score did not show any relationship to disease activity or physical functional capability. Patients with IBD need active evaluation for presence of underlying anxiety or depression.

Tu1237 Free DNA Level in Patients With Inflammatory Bowel Diseases

UNLABELLED Prospective data collection seems to be essential in evidence-based medicine. Because of the new therapeutic options, the need for standard data collection and testing has significantly increased. In Hungary, a registry for patients with inflammatory bowel disease has already been set up, which makes it possible for clinicians to collect prospective data on their patients. AIM Basic characteristics of the database of patients with ulcerative colitis are presented in this paper. METHODS The inflammatory bowel disease registry uses the programme of Microsoft Access database management system. Data are stored in a central server. RESULTS The incidence of inflammatory bowel diseases has been permanently increasing in Hungary; however, its overall prevalence is still low among the European countries. The frequent administration of immunosuppressive medications (azathioprine and corticosteroids) and their increased doses worsen the estimation of the activity. CONCLUSIONS 1., It would be very useful to gain prospective data from all national centres. This kind of database would be able to give a complete picture regarding the Hungarian therapeutical practice. 2., Medications of patients may alter the clinical value of the laboratory findings in the process of determining the severity of the disease.1Semmelweis Egyetem, Általános Orvostudományi Kar, II. Belgyógyászati Klinika, Budapest 2Szegedi Tudományegyetem, Általános Orvostudományi Kar, I. Belgyógyászati Klinika, Szeged 3Debreceni Tudományegyetem, Általános Orvostudományi Kar, II. Belgyógyászati Klinika, Belgyógyászati Intézet, Gasztroenterológiai Tanszék, Debrecen 4Miskolci Semmelweis Ignác Egészségügyi Központ és Egyetemi Oktató Kórház, Miskolc 5Bács-Kiskun Megyei Önkormányzat Kórháza, Kecskemét 6Szegedi Tudományegyetem, Általános Orvostudományi Kar, Természettudományi és Informatikai Kar, Orvosi Fizikai és Orvosi Informatikai Intézet, Szeged

Clinical relevance of changes in bone metabolism in inflammatory bowel disease.

Background: Recent results show that plasma free DNA concentration (fDNA) is increased in autoimmune and malignant diseases. Anti-nuclear antibody related to circulating fDNA plays a role in the disease pathogenesis in systemic lupus erythematosus. There is no data in regarding fDNA concentrations in inflammatory bowel disease (IBD). Our aim was to determine plasma fDNA in patients with clinically active and inactive IBD. Methods: We included 28 people into the study. 7 patients with active (aCD), 7 with inactive Crohn’s disease (iCD) and 7 inactive or mild ulcerative colitis (UC) and results were compared with 7 healthy controls. The CD was defined to be inactive by the Crohn’s disease activity index (CDAI <150), while it was considered to be active in case of the CDAI was more than 250 and CRP is more than 5mg/l. UC was considered inactive if the partial Mayo score was less than 3. Samples collected from patients were cooled after centrifugation. The fDNA was isolated with Roche Magna Pure Compact and measured with Qubit fluorometer. Results: The mean plasma fDNA concentration was 0.309±0.250 in the healthy control subjects. Concentrations of fDNA did not differed significantly in aCD, iCD and UC patients compared to healthy controls (0.331±0.318, p = 0.458; 0.158±0.061, p = 0.068; and 0.208±0176, p = 0.147; respectively). However, a strong correlation had been observed between plasma fDNA levels and C-reactive protein (r = 0.95) concentrations, and partial Mayo score (r = 0.78) also. Conclusions: Initial results indicate that the plasma concentration of fDNA does not help to diagnose inflammatory bowel disease. Further investigations are needed to determine the use of fDNA concentration as a surrogate marker of severity in UC patients.