Psychiatric manifestations of multiple sclerosis and acute disseminated encephalomyelitis

It is unusual for acute disseminated encephalomyelitis and multiple sclerosis to present as purely psychiatric disorders. We report five patients with such demyelinating diseases and symptoms of psychosis, depression or anxiety. The importance of excluding demyelination as the basis for these psychiatric disturbances is emphasized, especially in the presence of unexplained neurologic findings. The possible relationship between psychiatric symptoms and demyelinating disorders is explored

Case report: Sevelamer-associated colitis—a cause of pseudotumor formation with colon perforation and life-threatening bleeding

Chronic kidney disease (CKD) is a very common chronic non-communicable disease. Phosphate and calcium metabolism disorders are one of the most common features of CKD. Sevelamer carbonate is the most widely used non-calcium phosphate binder. Gastrointestinal (GI) injury associated with sevelamer use is a documented adverse effect but is underrecognized as a cause of gastrointestinal symptoms in patients with CKD. We report a case of a 74-year-old woman taking low-dose sevelamer with serious gastrointestinal adverse effects causing colon rupture and severe gastrointestinal bleeding

Epidemiološka studija varijanti tiopurin-metiltransferaze u skupini hrvatskih bolensika s upalnim bolestima crijeva

Thiopurine S-methyltransferase (TPMT) is an enzyme that converts thiopurine drugs into inactive metabolites. Over 20 variant TPMT-encoding alleles, which cause reduced enzymatic activity, have been discovered so far. Our aim was to investigate the frequencies of variant alleles, i.e. genotypes in inflammatory bowel disease (IBD) patients and healthy individuals and to compare these frequencies with selected world populations. The most common variant alleles TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C were analyzed with polymerase chain reactionbased assays and allele-specific polymerase chain reaction-based assays in 685 participants including 459 IBD patients and 226 healthy volunteers. Study results revealed 434/459 (94.55%) IBD patients and 213/226 (94.25%) healthy subjects to be homozygous for the wild-type allele (TPMT*1/*1). TPMT*1/*2 and TPMT *1/*3C genotypes were found in 4/459 (0.87%) and 7/459 (1.53%) IBD patients, respectively; in healthy volunteers they were not found. TPMT*1/*3A genotype was found in 14/459 (3.05%) IBD patients and 13/226 (5.75%) healthy subjects. Variant genotypes were statistically significantly more common in Crohn’s disease subgroup than in ulcerative colitis subgroup. The prevalence of variant genotypes was 23/338 (6.80%) in Crohn’s disease subgroup as compared with 2/121 (1.65%) in ulcerative colitis subgroup (χ2=4.59; p=0.032). In conclusion, the most frequently occurring nonfunctional TPMT allele in Croatian population is TPMT*3A. The overall frequency of mutant alleles in our population is statistically nonsignificantly lower when compared with other populations of Caucasian origin. The Crohn’s disease group had more mutant alleles than the ulcerative colitis group.Tiopurin S-metiltransferaza (TPMT) je enzim koji sudjeluje u konverziji tiopurinskih lijekova u inaktivne metabolite. Dosad je otkriveno više od 20 varijanti TPMT-kodirajućih alela. Ovi aleli uzrokoju smanjenu enzimatsku aktivnost. Naš cilj je bio istražiti frekvenciju varijantnih alela odnosno genotipova u bolesnika oboljelih od upalnih bolesti crijeva i u zdravih osoba te usporediti dobivene frekvencije s frekvencijama odabranih svjetskih populacija. Najčešći varijantni aleli TPMT*2, TPMT*3A, TPMT*3B i TPMT*3C analizirani su metodama lančane reakcije polimeraze, odnosno alelspecifičnim metodama lančane reakcije polimeraze. U istraživanje je bilo uključeno 685 ispitanika; 459 ispitanika bili su bolesnici s upalnom bolesti crijeva, a 226 bili su zdravi dobrovoljci. Rezultati su pokazali da su 434/459 (94,55%) pacijenata s upalnom bolesti crijeva i 213/226 (94,25%) zdravih osoba homozigoti za divlji tip alela (TPMT*1/*1). Genotipovi TPMT*1/*2 i TPMT*1/*3C nađeni su u 4/459 (0,87%) odnosno 7/459 (1,53%) bolesnika; u zdravih dobrovoljaca nisu nađeni. Genotip TPMT*1/*3A nađen je u 14/459 (3,05%) bolesnika i 13/226 (5,75%) zdravih dobrovoljaca. Varijantni genotipovi bili su statistički značajno češći u podskupini bolesnika s Crohnovom bolešću, s učestalošću od 23/338 (6,80%) u odnosu na podskupinu bolesnika s ulceroznim kolitisom, gdje je učestalost varijantnih genotipova bila 2/121 (1,65%) (χ2=4,46; p=0,035). U zaključku, najčešći nefunkcionalni TPMT alel u Hrvatskoj populaciji je TPMT*3A. Ukupna frekvencija varijantnih alela u našoj je populaciji statistički neznačajno niža u odnosu na druge populacije bjelačkog podrijetla. Bolesnici s Crohnovom bolešću imaju više varijantnih alela u odnosu na podskupinu bolesnika s ulceroznim kolitisom

Celiac Disease in Adults

Celijakija je česta kronična autoimunosna bolest koja se javlja u 1% zapadne populacije, a karakterizira je doživotna nepodnošljivost glutena u genski predisponiranih osoba. Bolest ima vrlo šarenu kliničku sliku, može se očitovati u bilo kojoj životnoj dobi, a mogu nastupiti teške komplikacije ako se ne liječi. Zlatni standard u postavljanju dijagnoze celijakije u odrasloj populaciji je patohistološka verifikacija atrofije tankog crijeva iako su serološki testovi (protutijelo na tkivnu transglutaminazu, antiendomizijsko protutijelo) prvi korak u identifikaciji potencijalnih bolesnika. Dijagnostičku obradu (serološki testovi i biopsija sluznice) potrebno je zaključiti prije isključivanja glutena iz dijete. Bolest se liječi isključivo doživotnom bezglutenskom prehranom. Edukacija bolesnika ključna je za uspješno liječenje. Neliječeni bolesnici imaju veće zdravstvene rizike od bolesnika koji se pravilno pridržavaju bezglutenske prehrane. Osim celijakije gluten u ljudi može izazvati još dva poremećaja: alergiju i osjetljivost na gluten. U podlozi ovih poremećaja različiti su patomehanizmi i vrlo je važno razlikovati ih i pravilno dijagnosticirati.Celiac disease is a frequent chronic autoimmune disease affecting approximately 1 % of the population in the Western hemisphere. It is characterized by an abnormal response to gluten in genetically predisposed individuals. The disease has various clinical manifestations and serious complications can occur if left untreated. It can develop at any point in time during life. Intestinal biopsy with confirmation of mucosal atrophy is the gold standard in diagnosing adult celiac disease, but serologic tests (anti-endomysial antibody, anti-tissue transglutaminase antibody) provide an effective first step in identifying biopsy candidates. Serologic testing and biopsy should be done before initiating a gluten-free diet. A lifelong adherence to a gluten-free diet is the only available treatment. Patient education is crucial to successful treatment. Patients with untreated celiac disease have greater health risks than those who adhere to this treatment. Besides celiac disease, there are two forms of gluten-related diseases: wheat allergy and gluten sensitivity. Due to pathogenic differences, it is very important to properly diagnose various forms of gluten-related disorders

Visoka učestalost neliječene i nedovoljno liječene deficijencije i insuficijencije vitamina D u bolesnika s upalnim bolestima crijeva

Inflammatory bowel disease (IBD) patients with vitamin D deficiency show an increased risk of hospital admission, surgery, and loss of response to biologic therapy while high vitamin D levels are identified as a protective factor. Our goal was to investigate the prevalence of untreated and undertreated vitamin D deficiency and factors associated with vitamin D deficiency. In this cross-sectional study, we measured serum vitamin D in a random sample of Caucasian IBD patients. Vitamin D deficiency was defined as <50 nmol/L and insufficiency as 50-75 nmol/L. Supplementation was defined as taking 800-2000 IU vitamin D daily. Untreated patients were defined as not taking supplementation and undertreated group as receiving supplementation but showing vitamin D deficiency or insufficiency despite treatment. Our study included 185 IBD patients, i.e. 126 (68.1%) with Crohn’s disease (CD) and 59 (31.9%) with ulcerative colitis (UC). Overall, 108 (58.4%) patients had vitamin D deficiency and 60 (32.4%) patients vitamin D insufficiency. There were 16 (14.8%) and 11 (18.3%) treated patients in vitamin D deficiency and vitamin D insufficiency group, respectively. The rate of untreated patients was 81.7% (n=49) in vitamin D deficiency group and 85.2% (n=92) in vitamin D insufficiency group. Tumor necrosis factor alpha inhibitors were associated with higher serum vitamin D levels in CD and UC, and ileal involvement, ileal and ileocolonic resection with lower levels. In conclusion, not only is vitamin D deficiency common in IBD patients but the proportion of untreated and undertreated patients is considerably high. We suggest regular monitoring of vitamin D levels in IBD patients regardless of receiving vitamin D supplementation therapy.Bolesnici s upalnim bolestima crijeva (inflammatory bowel disease, IBD) i manjkom vitamina D su pod povećanim rizikom hospitalizacije, operacije i gubitka odgovora na biološku terapiju, dok visoke serumske razine vitamina D predstavljaju zaštitni čimbenik. Cilj ove studije bio je istražiti učestalost neliječenih i nedovoljno liječenih bolesnika s IBD i manjkom vitamina D te čimbenike rizika. U ovoj presječnoj studiji mjerene su serumske razine vitamina D u slučajnom uzorku bolesnika s IBD bijele rase. Deficijencija je definirana kao razine <50 nmol/L, a insuficijencija kao 50-75 nmol/L. Nadoknada vitamina D je definirana kao uzimanje 800-2000 IJ vitamina D na dan. Neliječeni bolesnici su oni bez nadoknade, a nedovoljno liječeni oni s deficijencijom ili insuficijencijom usprkos nadoknadi. Uključeno je ukupno 185 bolesnika s IBD, tj. 126 (68,1%) s Crohnovom bolešću i 59 (31,9%) s ulceroznim kolitisom. Ukupno je 108 (58,4%) bolesnika imalo deficijenciju, a 60 (32,4%) insuficijenciju. Udio liječenih bolesnika s deficijencijom i insuficijencijom vitamina D iznosio je 14,8% (n=16) i 18,3% (n=11). Udio neliječenih s deficijencijom iznosio je 81,7% (n=49), a s insuficijencijom 85,2% (n=92). Terapija inhibitorima faktora tumorske nekroze alfa bila je povezana s višim razinama vitamina D. Niže razine vitamina D su zabilježene kod bolesnika s upalom u području ileuma i resekcijom ileuma ili ileokolona. U zaključku, niske serumske razine vitamina D su česta pojava kod bolesnika s IBD, a dodatno je udio neliječenih i nedovoljno liječenih također visok. Naša preporuka je kontinuirano praćenje razina vitamina D u serumu svih bolesnika s IBD uključujući i one na nadoknadi vitaminom D

Increased arterial stiffness – similar findings in patients with inflammatory bowel disease without prior hypertension or diabetes and in patients with well-controlled hypertension

PURPOSE: Chronic inflammatory diseases are related with earlier onset of atherosclerosis. We hypothesized that inflammatory bowel disease patients with chronic, systemic inflammation have an increased arterial stiffness associated with the disease duration. Also, we wanted to compare arterial stiffness markers between inflammatory bowel disease and well-controlled hypertension patients. ----- MATERIALS AND METHODS: A total of 89 inflammatory bowel disease patients (60 patients with Crohn's disease and 29 patients with ulcerative colitis, age range 20-64 years) without history of arterial hypertension or diabetes were enrolled and age matched with a control group of patients (73 patients, age range 25-69 years, 41 (56.1%) males) with known history of well-controlled arterial hypertension. We have used a noninvasive device that simultaneously measures brachial blood pressure and estimates PWV and AIx in inflammatory bowel disease and hypertension groups of patients. ----- RESULTS: Patients with pathological PWV values were significantly older, had significantly longer duration of inflammatory bowel disease, higher values of serum cholesterol and HDL-cholesterol, and higher AIx (17.4% vs. 9.8%) (all p < .05). Higher PWV was associated with age and duration of inflammatory bowel disease in the linear regression model. PWV values were higher in hypertensive patients in the first two age quartiles while interestingly, in the last two quartiles, PWV was lower than in inflammatory bowel disease group of patients. ----- CONCLUSIONS: Chronic subclinical inflammation is responsible for dyslipidemia and accelerated atherosclerosis which consequently alterates arterial elasticity. Inflammatory bowel disease and its duration should also be considered a risk factor for subclinical organ damage, as well as hypertension

Terminal ileum resection as a trigger for strongyloides stercoralis hyperinfection and ensuing serial sepsis in a 37-year-old patient with complicated Crohnʼs disease: a case report

The nematode Strongyloides stercoralis, outside the tropics and subtropics present in small endemic foci, can cause an infection after direct skin contact with contaminated soil containing infective filariform larvae and, rarely, after intimate interhuman contact or after transplantation of an infected solid organ. Following skin penetration, migration, and maturation through several stages, a small number of invasive filariform larvae can develop anew in the gut lumen, perpetuating new cycles of penetration, tissue migration, and reproduction, without leaving the host. In a state of immunosuppression, autoinfection can progress to life-threatening hyperinfection and/or infection disseminated through virtually any organ. In developed countries, the most frequently recognized risk for severe hyperinfection is corticosteroid therapy, but this has been also described in malnourished, alcoholic, cancer, and transplant patients. Due to the frequent need for immunosuppressive therapy, patients suffering from inflammatory bowel disease (IBD) are susceptible to develop overwhelming strongyloidiasis. Strongyloidiasis can be easily overlooked in clinical settings, and in many European regions there is poor insight into the epidemiological burden of this disease. We present a case of S. stercoralis hyperinfection that triggered 3 successive episodes of sepsis caused by pathogens of the gut flora in a young patient suffering from stenotic form of Crohn's disease. S. stercoralis hyperinfection occurred in the corticosteroid-free period, shortly after resection of the terminal ileum, which was probably the trigger for the overwhelming course. The patient was successfully treated with 10-day albendazole therapy

Barriers in inflammatory bowel disease care in Central and Eastern Europe: a region-specific analysis

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are chronic immune-mediated diseases with a high incidence and prevalence in Europe. Since these are diseases with associated disability, they require complex management and the availability of high-quality healthcare resources. We focused on the analysis of IBD care in selected countries of Central and Eastern Europe (Croatia, the Czech Republic, Hungary, Moldova, Poland, Romania and Slovakia) targeting the availability and reimbursement of diagnostic and therapeutic modalities, the role of IBD centers and also education and research in IBD. As part of the analysis, we created a questionnaire of 73 statements organized in three topics: (1) diagnostics, follow-up and screening, (2) medications and (3) IBD centers. The questionnaire was filled out by co-authoring IBD experts from individual countries, and then the answers and comments on the questionnaire were analyzed. We identified that despite the financial burden, which still partially persists in the region, the availability of some of the cost-saving tools (calprotectin test, therapeutic drug monitoring) differs among countries, mainly due to variable reimbursement from country to country. In most participating countries, there also remains a lack of dedicated dietary and psychological counseling, which is often replaced by recommendations offered by gastroenterologists. However, there is adequate availability of most of the currently recommended diagnostic methods and therapies in each participating country, as well as the implementation of established IBD centers in the region. © The Author(s), 2023

Association of polymorphic variants in serotonin re-uptake transporter gene with Crohn’s disease: a retrospective casecontrol study

Aim To analyze the distribution of SLC6A4 gene polymorphisms in Crohn’s disease (CD) patients and their association with the disease. Methods We evaluated the presence/absence of promoter (5-HTTLPR, rs25531) and intron 2 (STin2 VNTR) polymorphic variants of SLC6A4 gene in a retrospective case-control study including 192 CD patients and 157 healthy controls (HC). Genotyping was performed by polymerase chain reaction. The association of polymorphisms with CD and its clinical subtypes was analyzed using χ2 and Fisher exact test, binary logistic regression, and haplotype analysis.Results CD patients and healthy controls had similar sex (88 [45.8%] vs 84 [53.5%] women, respectively; P = 0.154) and age (41.3 ± 12.8 years vs 41.7 ± 8.8 years, respectively, P = 0.091) distribution. Significant differences were observed in the STin2 genotype and allele distribution between CD patients and healthy controls (P = 0.003 and P = 0.002, respectively) and between the corresponding female subgroups (P = 0.004 and P = 0.007, respectively), with a significant negative association of biallelic ss (STin2.9 and Stin2.10) STin2 genotype with CD (P = 0.013, age- and sexadjusted odds ratio [OR] 0.5, 95% confidence interval [CI] 0.29-0.86; women: P = 0.006, age-adjusted OR 0.32, 95% CI 0.14-0.72) and a significantly higher S-STin2.12 (5-HTTLPR/ rs25531: S-STin2: STin2.12) haplotype distribution in CD patients (P = 0.004, OR 1.62, 95% CI 1.16-2.26). There was no significant association between 5-HTTLRP and rs25531 genotype or allele frequencies and CD and between any SLC6A4 polymorphic loci with clinical CD subtypes. Conclusion STin2 VNTR polymorphism of SLC6A4 gene may contribute to CD pathogenesis