Extraintestinal Manifestations Of Celiac Disease Research Articles

The problem of excessive hair loss as a signal for the diagnosis of coeliac disease – A family case

Celiac disease is an autoimmune disorder in which the small intestine is damaged after ingesting gluten. Baldness often co-occurs with various systemic diseases including autoimmune diseases. In addition, alopecia can result from nutritional deficiencies. In the case of celiac disease, we are mainly talking about deficiencies of iron, fat-soluble vitamins (A,D,E,K), vitamin B12 and folic acid. Telogenetic alopecia (TE) is diffuse and reversible alopecia, and the causes of this condition can be nutritional deficiencies and impaired absorption. Celiac disease has been linked to alopecia areata (AA). We describe the case of a mother and daughter with a history of hair loss, which represented the only incipient (mother’s case) and subsequent (daughter’s case) extraintestinal manifestation of celiac disease.

Extra-intestinal manifestations of celiac disease in children

Celiac disease, also known as gluten-sensitive enteropathy, is a chronic disorder of digestive tract mediated by immune mechanisms, resulting in an inability to tolerate gluten and its related proteins in genetically predisposed individuals. Gluten is one protein commonly found in wheat, rye and barley. This disease has a wide spectrum clinical presentations and affects a wide age range on which it has a significant impact in terms of development and morbidity. Therefore, we found it important to study investigation of the variety of extraintestinal manifestations in pediatric celiac patients and identification of possible strategies that can be adapted to diagnose and treat them as soon as possible.

Differences in the detection of circulating Hsp90 alpha between patients with atopic dermatitis and dermatitis herpetiformis.

Heat shock protein 90 alpha (Hsp90α) is one of the key intra- and extracellular chaperones responsible for the biological activity of various signaling molecules that are involved in (auto)immune-mediated inflammatory diseases. Recent epidemiologic data suggest that patients with atopic dermatitis (AD) are at risk for several autoimmune diseases, including dermatitis herpetiformis (DH), an extraintestinal manifestation of celiac disease (CD). In addition, pruritic diseases such as AD may be confused clinically with DH. In this study, we aimed to determine the role of circulating Hsp90α in patients with AD in relation to patients with DH, CD, and healthy controls. Using an enzyme-linked immunosorbent assay, levels of circulating Hsp90α were determined in serum samples derived from patients with AD (n = 31), DH (n = 26), CD (n = 15), and healthy controls (n = 55). Although serum concentrations of Hsp90α were similar between patients with DH, CD, and healthy controls, we found that serum levels of Hsp90α were significantly higher (mean value of 5.08-fold; p < 0.0001) in patients with AD when compared to patients with DH. A cutoff value calculated as 2 × standard deviation above the mean concentration of Hsp90α in DH patients revealed that 83.9% (26/31) of AD patients were Hsp90α positive, whereas none of the DH patients (0/26) displayed such a positivity. This preliminary study suggests a distinct role for extracellular Hsp90α in the pathogenesis of AD compared to DH and its potential use in distinguishing AD from DH. Nevertheless, the potential role of the evaluation of extracellular Hsp90α for distinguishing between AD and DH is at present speculative and requires further and careful observations.

Pathological Manifestations of Gluten-Related Neuro-Psychiatric Disorders and the Impact of Gluten-Free Diet in a Pediatric Age Group: A Systematic Review.

Gluten, as a term, causes unease amonga vast majority of the population. The reason is the body's inability to process gluten, causing various pathological manifestations. While celiac disease is predominantly a gastrointestinal disease, it also has various extra-intestinal manifestations. Many children receive diagnoses of idiopathic neuropsychiatric symptoms such as epilepsy, attention-deficit hyperactivity disorder (ADHD), restless leg syndrome (RLS), and peripheral neuropathy without ever finding the root cause. A majority of these cases may be associated with celiac disease if only their antibody titers and other appropriate investigations were conducted. The treatment of these manifestations may be eliminated or at least controllable with dietary modification to a gluten-free diet (GFD). In this paper, we will discuss the pathology of celiac disease and the impact of GFD on the neuropsychiatric aspects of this disease, which is of higher prevalence in the pediatric population. A comprehensive literature search was conducted in prominent databases, namely PubMed and Google Scholar, to include studies that provided individual-level data on the neuropathological manifestations and the impact of a GFD on extra-intestinal manifestations of celiac disease. The research protocol was registered in the PROSPERO database (International Prospective Register of Systematic Reviews) with the registration ID: CRD42023415100. Based on the inclusion and exclusion criteria, we included prospective studies, observational studies, and case reports on pediatric patients with biopsy-proven celiac disease, serologically positive celiac disease, celiac disease with neuropsychiatric manifestations, and studies reporting the impact of GFD. After a rigorous quality assessment to remove the risk of bias, we finally included 20 studies to be discussed. In 6 (30%) studies, patients with neuropsychiatric manifestations had positive serology findings and a relatively higher grade of biopsy results. Seven studies discussed the positive impact of GFD. Five of these seven studies reported statistically significant results (p ≤ 0.001).Our study suggests that gluten plays a role in the severity of neuropsychiatric manifestations of celiac disease. Considering the results of our study, we can see that GFD does impact the prognosis of the disease. Neuropsychiatric findings without gastrointestinal manifestations are more common in the pediatric age group. We have clear evidence that several neurological conditions (neuropathy, ADHD, epilepsy, and RLS) have not only a significant association with gluten but can also potentially benefit from GFD. Thus, screening, with a combination of serological, biopsy, and imaging techniques, must be adapted into the guidelines for early detection and induction of GFD. Furthermore, studies should aim at introducing GFD in the pediatric population as a mode of primary prevention. In conclusion, our review underscores the importance of gluten while dealing with idiopathic neurological conditions in children and hopes to shed light on this commonly misdiagnosed and easily manageable disease.

Uveitis as a Manifestation of Celiac Disease: A Population-Based Study

Introduction: The prevalence of celiac disease (CD) in the United States population has been estimated to be 0.71%, or 1 in 141, with the prevalence in first- and second-degree relatives of those affected being 4.55% and 2.59% respectively. Due to the multitude of ways in which this disease may initially present, it is important to screen for CD to avoid the potential consequences of inadequately managed disease. Many ophthalmic conditions have also been implicated as extraintestinal manifestations of CD, including uveitis. Despite several studies and case reports suggesting a positive correlation between CD and uveitis, there has yet to be a nationwide study in the United States quantifying this relationship. Therefore, the aim of this study is to conduct a large-scale multi-center population-based study to assess whether there is a statistically significant increased risk of uveitis in individuals with celiac disease. Methods: A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States consisting of data accumulated from 1999 to September 2022 was utilized to construct this study. We excluded patients with a history of autoimmune diseases, cataract surgery, or any type of eye infection. We included a subgroup of patients with a diagnosis of “uveitis” for further analysis. The risk of developing uveitis was calculated using a univariate logistic regression. A multivariate analysis was also done to account for confounding variables including African American ethnicity, male gender, sexually transmitted diseases, and celiac disease. Results: 70,632,440 patients were screened and a cohort of 46,895,750 individuals was selected for the final analysis after accounting for inclusion and exclusion criteria were met. The incidence of uveitis in patients with celiac disease in the past 3 years was 280 per 100,000 people. The prevalence of uveitis in the US population from 1999 to September 2022 was 150 per 100,000 people (0.15%). In order to adjust for confounding variables, a multivariate regression analysis was performed and showed an increased risk of being African-American (OR: 3.20%; 95% CI: 3.14-3.26) and male (OR: 1.13%; 95% CI: 1.12-1.16); and having a diagnosis of celiac disease (OR: 3.80%; 95% CI: 3.35-4.28) and sexually transmitted diseases (OR: 4.12%; 95% CI: 3.96-4.29) in patients with uveitis. Discussion: Recent population-based studies demonstrated that the prevalence of CD in the United States is much greater than previously thought, such that a trend of underdiagnoses is suspected to have occurred for several years. Many newly diagnosed uveitis cases, 48%, have been classified as idiopathic uveitis even after a complete workup was done. Several studies have been published in which a correlation between uveitis and CD is reported. The findings of this study further emphasize the importance of a thorough workup to evaluate for an underlying inflammatory process prior to diagnosing uveitis as idiopathic. Conclusion: In conclusion, we established that patients with celiac disease are at increased risk of developing uveitis after excluding and controlling for any confounding variables. In further studies, it could be interesting to investigate the impact of gluten-free diet in patients with celiac disease on the risk of developing uveitis.

Clinical features, treatment, and outcomes of celiac-associated arthritis: a retrospective cohort study

BackgroundAlthough arthritis is recognized as an extra-intestinal manifestation of celiac disease, little is known about the clinical course and outcomes of pediatric celiac-associated arthritis. This study describes clinical characteristics, treatments, and outcomes of children with celiac-associated arthritis.MethodsThis was a retrospective cohort study of children with celiac disease seen in pediatric rheumatology clinic between 2004 and 2021 for joint complaints. Data was abstracted from electronic health records. Patient demographics and clinical manifestations were evaluated using standard descriptive statistics. Physician- and patient-reported outcomes were evaluated at the index visit, 6-month follow-up, and last recorded visit, and were compared using Wilcoxon signed-rank tests.ResultsTwenty-nine patients with celiac disease were evaluated for joint complaints, and 13 were diagnosed with arthritis. Their mean age was 8.9 years (SD 5.9), and 61.5% were female. Celiac disease diagnosis was made before arthritis diagnosis in only 2 cases (15.4%). Initial testing that led to the celiac disease diagnosis was obtained by the rheumatologist in 6 cases (46.2%). Only 8 patients (61.5%) had concomitant GI symptoms, and of these, 3 patients had BMI z-scores <-1.64 and 1 had impaired linear growth. Arthritis presentation was most often oligoarticular (76.9%) and asymmetric (84.6%). Most cases required systemic therapy (n = 11, 84.6%) with DMARDs, biologics, or both. Of the 10 patients who required systemic therapy and reported compliance with the gluten-free diet, 3 (30%) were able to stop systemic medications. Two of 3 patients who cleared celiac serologies came off systemic medications. Statistically significant improvement was noted in the number of joints involved (p = 0.02) and physician global assessment of disease activity (p = 0.03) between the index and final visit.ConclusionsRheumatologists play an important role in the identification of celiac disease, as arthritis was the presenting symptom in most cases and was not always associated with GI symptoms or poor growth. The arthritis was most often oligoarticular and asymmetric. Most children required systemic therapy. The gluten-free diet may not be sufficient to manage arthritis, but antibody clearance may be an indicator of higher likelihood of disease control off medications. Outcomes are promising with a combination of diet and medical therapy.

Liver damage in children and adolescents with newly diagnosed celiac disease: clinical and anamnestic, serological and morphological patterns

To analyze the frequency of hypertransaminasemia, clinical and anamnestic, serological and morphological picture in children in the active period of celiac disease. The study included 272 children with celiac disease aged from 8 months to 17 years. The patients were divided into two groups: the first - children with hypertransaminasemia, the second - without hypertransaminasemia. Hypertransaminasemia was detected in 55.9% of children with celiac disease. The age of manifestation of the disease in the first group was 1.0 [0.5; 2.0] years, in the second group - 1.9 [0.5; 4.0] years (p=0.0004). Children of the first group were diagnosed at 2.5 [1.7; 4.9] years, the second group - at 4.9 [3.0; 10.8] years (p<0.001). The duration of the latency period in children of the first and second groups was 1.4 [0.6; 3.1] years and 2.4 [0.9; 4.3] years, respectively (p=0.002). The average values of IgA anti-tTG antibodies in children of the analyzed groups did not differ, and the indicators of IgG anti-tTG antibodies in the first group were 1.6 (p=0.04) times higher. The level of EMA in children with hypertransaminasemia was 2 times higher than in children without hypertransaminasemia. Hypertransaminasemia is more often detected in young children with early manifestation of the disease, increases with the deepening of atrophy in the mucous membrane of the small intestine. Higher titers of celiac-specific antibodies were detected in children with hypertransaminasemia.

Extraintestinal manifestation of Celiac disease: A case series

Celiac disease (CD) is a multisystem chronic inflammatory disorder with an autoimmune component in genetically susceptible individuals elicited by gluten and related prolamines. CD is becoming a common disorder arising at any age with a broad spectrum of symptoms ranging from intestinal to extraintestinal manifestations. Extraintestinal symptoms being more common after 2 years of life, can affect various systems and organs of the body. Knowledge of the extraintestinal manifestations of celiac disease is of utmost importance for the diagnosis of CD. Owing to the high risk of complications among the undiagnosed cases of CD, patients with extraintestinal manifestations should undergo appropriate diagnosis and treatment for CD.

Extra-intestinal manifestations of Celiac disease in children: their prevalence and association with human leukocyte antigens and pathological and laboratory evaluations

BackgroundCeliac disease (CD) is an autoimmune disease caused by gluten intake. Traditionally CD was believed to be a disease of the gut, although a wide range of extra-intestinal manifestations (EIM) was recognized. The exact prevalence of EIM and the associated risk factors have not been well studied.AimWe aimed to assess the prevalence of EIM in children with CD and their association with human leukocyte antigen (HLA) typing, and pathological and laboratory indices.MethodWe conducted a cross-sectional study on children and adolescents with a definite diagnosis of CD. They were followed in the main Celiac Clinic of Southern Iran.ResultsWe included 204 children who were visited between 2012 and 2017. Nearly 85% of them were positive for HLA-DQ2 and 40.6% for HLA-DQ8. The most prevalent intestinal complaints reported were abdominal pain (42.6%) and chronic constipation (19.1%). Failure-to-thrive (32.7%), iron deficiency anemia (25%), short stature (20.5%), and eczema (18.6%) were the most common EIMs. However, failure-to-thrive and short stature were presented at significantly younger ages, whereas those patients with concomitant type 1 diabetes mellitus (DM) were significantly older. We also found significant relationships between autoimmune thyroid disease and HLA-DQ5, and the presence of headaches with HLA-DQ7. The prevalence of HLA types of DQ2, DQ8, DQ6, and DQ7 significantly varied among different Marsh groups. Patients who were positive for HLA-DQ8, were significantly older, taller, and weightier. No significant association was found between HLA types and any of the gastrointestinal symptoms, anti-tTG and compliance to gluten free diet. Moreover, there were no statistically significant differences detected between the presence of each individual EIM, the level of IgA anti-tTG, sex, and Marsh typing.ConclusionThis study highlights the presence of EIM in CD and their associated factors. We show the potential role of HLA typing in some EIMs, which may shed light for future studies.

Bone mineral density in Iranian children with celiac disease.

The current study aims to evaluate bone mineral density (BMD) in patients with celiac disease who were referred to the celiac clinic of Shahid Rahimi Hospital in Khorramabad, Iran, in 2020. Extraintestinal presentations of celiac disease are widespread and, if neglected, can be devastating. Osteoporosis, one of the extraintestinal manifestations of celiac disease, often remains undiagnosed until advanced stages and can impose a significant burden on patients with celiac and health systems. Nonetheless, the prevalence and characteristics of osteoporosis in celiac disease are unknown in Iran. This was a cross-sectional study at the celiac clinic of Shahid Rahimi Hospital in Khorramabad, Iran. Participants were 48 patients under 18 years diagnosed with Marsh II and Marsh III stages of celiac disease (who need to be on a gluten-free diet) at the pediatrics celiac clinic in 2020. All patients were recruited, completed a questionnaire, and had their blood biochemical parameters analyzed. Then their bone mineral density (BMD) was measured through dual-energy x-ray absorptiometry at the Asia Imaging Center in Khorramabad under the supervision of a radiologist and pediatric rheumatologist. The mean age of the children was 9.96±3.17 years. The minimum and maximum ages of the participants were 4 and 17 years, respectively. Of all 48 children who were included (48), 34 (70.8%) were female, and 14 (29.2%) were male. In the femoral region bone densitometry, 35.4% were normal, 41.7% had lower limit normal, and 22.9% had low bone density. In the lumbar region, 39.6% were normal, 25% were Lower limit normal, and 35.4% had low bone density. No significant correlation was found between age, sex, place of residence, Marsh stage, gluten-free diet, and bone densitometry in both lumbar and femoral regions. Nonetheless, we detected a statistically significant relationship between bone density in the lumbar region and two HLA types, namely HLA DQ8 and HLA DQ2/8 (P=0.016). The results of the current study provided further evidence that all children with advanced celiac disease should be screened for metabolic bone diseases. Besides those in Marsh II and Marsh III, patients in Marsh I stage should also be investigated for low bone mineral density.

Development of Celiac Disease Therapeutics: The Sixth Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics Workshop

Development of Celiac Disease Therapeutics: The Sixth Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics Workshop

S1705 Celiac Disease and Chronic Pancreatitis

Introduction: Celiac disease involves a T-cell-mediated immune response to dietary gluten. Celiac disease has 3-fold increased risk for developing chronic pancreatitis but only has a reported incidence of 0.52%. We present a case of a 61-year-old male with newly diagnosed celiac disease who was incidentally found to have associated chronic pancreatitis. Case Description/Methods: A 61-year-old male with a past medical history of diabetes, hypertension, coronary artery disease, and a remote history of hepatitis presented to our clinic for his first screening colonoscopy and recent anemia. Prior to colonoscopy, the patient noted a 45-pound unintentional weight loss over the past few years, and with recent lab studies revealing a hemoglobin level of 11.7 g/dL. The patient then underwent colonoscopy, esophagogastroduodenoscopy (EGD), and an extensive laboratory work-up that was significant for iron deficiency anemia, anti-gliadin (AGA) IgA >150 U/mL, AGA-IgG 134 U/mL, endomysial (EMA)-IgA positive, tissue transglutaminase (tTG)-IgA >100 U/mL, total IgA 280 mg/dL, fecal elastase 31 mcg/g and was positive for anti-smooth muscle antibodies (1:160). Subsequent results were negative for viral hepatitis panel, antinuclear antibodies, anti-mitochondrial antibodies, alpha-1 antitrypsin levels, and normal ceruloplasmin levels. Colonoscopy was unrevealing except for a diminutive tubular adenoma. EGD later revealed blunted villi with flat mucosa in the first and second portion of the duodenum. Biopsy results later confirmed pathology results compatible with celiac disease. During this course of workup, the patient developed nephrolithiasis and with incidental findings of pancreatic atrophy and pancreatic head calcifications detected on CT urogram. Chronic pancreatitis was later confirmed on endoscopic ultrasound with evidence of multiple intraductal stones. Patient did not have a history of alcohol use or pancreatic problems in the family. After being diagnosed with Celiac disease and secondary chronic pancreatitis with exocrine pancreatic insufficiency, he was started on a gluten-free diet and pancrelipase. Patient was noted to have 9-pound weight gain during a 4 month follow-up appointment. Discussion: Chronic pancreatitis is a rare extraintestinal manifestation of celiac disease, reported to have a threefold increased risk but only with a reported incidence of 0.52% at least 30 days after diagnosis of celiac disease compared to 0.13% in non-celiac disease patients.

S1562 Subclinical Celiac Disease in the U.S. Hispanic Population: Results From the Los Angeles County Department of Health Services

Introduction: Anemia is a common extraintestinal manifestation of celiac disease (CeD). Although perceived as a predominantly White disease with a 1% prevalence, CeD also affects other underreported populations, such as the Hispanic population. We aimed to estimate the prevalence of CeD in Hispanic patients presenting with unexplained anemia. Methods: A cross-sectional study was completed through a clinical management database and electronic medical record after receiving Institution Review Board approval. Adult Hispanic patients with unexplained anemia who underwent upper endoscopy with duodenal biopsies between 2013 and 2020, were included. This study was conducted at the Los Angeles County Department of Health Services, a safety-net public health care system with a predominantly Hispanic (65%) population. Electronic medical records were queried for the diagnosis of biopsy-proven CeD. Results: Two hundred six subjects underwent upper endoscopy for unexplained anemia, of which 61 were excluded (18 underwent an upper endoscopy without biopsy, 7 were non-Hispanic, and 36 patients had normal hemoglobin levels; Table). Among all Hispanic patients referred for endoscopic evaluation of unexplained anemia (N = 145), the mean age was 53.9 years, and 66% were female. The overall prevalence of biopsy-proven CeD was 4.8% (N = 7/145). In patients with iron-deficiency anemia (IDA) specifically, the prevalence of CeD was 4.5% (N = 3/67). Of the 7 patients with confirmed CeD, only one in retrospect had associated diarrhea. None of the patients had a family history of CeD. Interestingly, only one of 5 tested patients had positive IgA tissue transglutaminase antibody, and the remainder were seronegative. Other CeD-related laboratory testing including vitamin B12 and liver function tests were unremarkable; thyroid stimulating hormone (TSH) levels were within normal range except for one patient with elevated levels due to poorly controlled hypothyroidism. Conclusion: The prevalence of CeD in adult Hispanic patients with unexplained anemia (unspecified or IDA) is similar to the prevalence in White patients, a finding not previously reported in the literature. Screening for CeD in patients with unexplained anemia in general, and IDA specifically, is of value in Hispanic patients as well as White ones. Seronegative CeD requires endoscopic evaluation with duodenal biopsies for diagnosis. Table 1. - Clinical and Lab Characteristics of Patients with Biopsy-Confirmed Celiac Disease tTG: IgA tissue transglutaminase within <4 months from index endoscopy; TSH: thyroid stimulating hormone; M: male; F: female; AST: aspartate aminotransferase; ALT: alanine transaminase ID Hemoglobin (Ferritin) AST/ALT Total Bilirubin IgA tTG Vitamin B12 TSH Other Comorbidities 49 F 8.5 33/17 0.5 None 652 12.8 Hypothyroidism, Rheumatoid arthritis on sulfasalazine and methotrexate 42 F 11.6 (70.7) None None < 1 596 None Refractory GERD s/P fundoplication 57 F 8.4 (7.6) 42/51 0.6 >100 NA None Hypothyroidism, Chronic hepatitis C 34 F 11.7 16/12 0.6 < 1 325 None None 40 M 10.7 29/40 0.6 None 481 0.83 Substance abuse, Coronary artery disease with NSTEMI, Osteoporosis 50 F 9.9 (5.4) 22/23 0.5 < 1 291 2.1 Stage II breast cancer 44 F 9.5 (3.1) 29/33 0.6 < 1 NA 1 Type II diabetes

Anemia in Celiac Disease: Prevalence, Associated Clinical and Laboratory Features, and Persistence after Gluten-Free Diet.

Anemia is considered to be the most frequent extra-intestinal manifestation of Celiac Disease (CD). We assessed frequency, severity, morphologic features, and pathogenic factors of anemia in patients of the Sicilian Regional Network of Celiac Disease and attempted to identify putative pre-diet factors influencing anemia persistence. We retrospectively analyzed CD patients admitted to three centers between 2016–2020. 159 patients entered the study (129 females). More than half (54.7%) had mild-moderate, hypochromic and microcytic anemia, associated with below normal total serum iron and ferritin, indicative of iron deficiency anemia (IDA). One year after diagnosis, 134 patients were following ‘strict’ GFD. Hypochromic and microcytic anemia persisted in 46% of subjects who were anemic at diagnosis. Patients with persistent anemia had at diagnosis a higher prevalence of female gender (p = 0.02), lower body mass index (BMI, p = 0.01), higher prevalence of poly/hypermenorrhea (p = 0.02) and atopy (p = 0.04), and lower ferritin levels (p = 0.05) than the whole group of non-anemic ones. IDA is found in more than 50% of CD patients at diagnosis; nevertheless, in a lot of women IDA is not corrected by ‘strict’ GFD. Low BMI and poly/hypermenorrhea at diagnosis characterize this subgroup, suggesting that IDA might be due to iron loss rather than malabsorption, or to their coexistence/overlap.

Celiac Disease and Thrombotic Events: Systematic Review of Published Cases.

Extraintestinal manifestations of celiac disease (CD) should be considered, even in patients without typical intestinal symptoms. The aim of our study is to examine the literature regarding the occurrence of thrombotic events in CD, and to synthesize the data from case reports and case series. A systematic review of the literature was conducted by searching the Pub-Med/MEDLINE database, from the date of database inception to January 2022, to identify published cases and case series on this topic, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 55 cases were included in the study. The majority of patients were previously healthy individuals, with no comorbidities. In less than one-third of the cases (30.91%), the diagnosis of CD was established before the onset of thrombosis, while in the remaining cases (34.54%), thrombosis preceded the diagnosis or was diagnosed concomitantly with CD. The most common sites for thrombosis occurrence were hepatic veins (30.91%), while thrombosis of cerebral blood vessels, deep venous thrombosis of lower extremities, and pulmonary thromboembolism were less frequent. Thrombosis was most commonly isolated to one site only (78.18%). In 69.09% of cases (n = 38), some form of anticoagulation, along with a gluten-free diet, was initiated.

Extra-Intestinal Manifestations of Celiac Disease: What Should We Know in 2022?

Celiac disease (CD) is a chronic, small-intestinal, immune-mediated enteropathy due to gluten exposition in genetically predisposed individuals. It occurs in about 1% of the population and often remains an underdiagnosed condition. This could be due to the fact that the adult population often lacks the classical signs and symptoms of CD, manifesting only atypical symptoms. In this review we analyzed the main extra-intestinal manifestations of CD which include cutaneous and endocrinological disorders, abnormal liver function tests, and neuropsychiatric features. When CD is not diagnosed and therefore is not treated with a gluten-free diet (GFD), it can predispose to severe complications, not only gastrointestinal. Thus, it is important for clinicians to quickly recognize the atypical manifestations of CD, considering that an early diagnosis can significantly impact on a patient’s prognosis.

Acrodystrophic axonal polyneuropathy with celiac disease: a case report

BackgroundPatients with celiac disease present with not only gastrointestinal symptoms but also extraintestinal manifestations such as anemia, osteopathy, dermatitis herpetiformis, and celiac neuropathy. Despite a fairly wide range of celiac neuropathies, we report a case of the acrodystrophic variant of celiac polyneuropathy, which has not been previously described.Case presentationA 41-year-old Ukrainian male suffered from symmetric, sensorimotor axonal polyneuropathy and encephalopathy associated with celiac disease, which is characterized by severe trophic disorders in the lower extremities (trophic ulcers, hyperkeratosis, and anhidrosis). Acrodystrophic changes in the lower extremities were due to both neurogenic and direct immunoinflammatory damaging effects. Clinical–electrophysiological dissociation was also noted, which was represented by a gross axonal lesion with the preservation of muscle strength. The absence of enteropathic manifestations was accompanied by the pronounced histological changes in the duodenal mucosa by IIIb stage of Marsh. A gluten-free diet in combination with membrane plasma exchange and intravenous pulse methylprednisolone was prescribed to reduce the severity of sensory disorders and regression of encephalopathy within 7 months.ConclusionCeliac disease may be a potential cause of neuropathy and encephalopathy in adult patients. Further immunosuppressive treatment protocols for both intestinal and extraintestinal manifestations of celiac disease are required.

Elevated liver enzymes of newly diagnosed pediatric celiac patients-a prospective-observational study.

Celiac disease clinical presentation is constantly changing. We set to determine the prevalence of elevated transaminases in newly diagnosed celiac patients and to evaluate this sub-group of patients for associated clinical and laboratory findings and assess their natural course of disease following therapeutic diet initiation. We conducted a prospective-observational study of all newly diagnosed pediatric celiac patients, between August 2016 and April 2018, in a pediatric gastroenterology clinic. Clinical data, anthropometrics, and blood test results were recorded at diagnosis and at 3, 6, and 12months, respectively, of follow-up. We compared patients with normal and elevated transaminases at diagnosis. ALT threshold was set at 24 U/l. Of 125 newly diagnosed celiac patients, 31 (24.8%) had elevated ALT at diagnosis; two (1.6%) with over 3 × ULN. Patients with elevated ALT at diagnosis were significantly younger (mean age 5.5 (SD 3.4) vs. 7.3 (SD 3.7) years, p < 0.01) and more commonly presented with diarrhea (32.3% vs. 14.9%, p = 0.03). Eighty percent of patients with elevated ALT levels normalized their ALT within 3months and all within 1year. Following gluten-free diet initiation, patients with elevated ALT had similar clinical course, growth, serology normalization rate, and laboratory results, compared to patients with normal ALT over a 1-year follow-up. A single patient was simultaneously co-diagnosed with celiac disease and autoimmune hepatitis.Conclusion: Clinically significant ALT abnormalities are rare among newly diagnosed pediatric celiac patients. Significant elevations failing to normalize on a gluten-free diet should raise concern of a concomitant primary liver disease and warrant further investigations. What is Known: • Elevated liver enzymes may be an extra-intestinal manifestation of celiac disease. • Reported prevalences of ALT elevations among children with a new diagnosis of celiac disease ranges between 5 and 40%. What is New: • ALT elevations are present in 25% of children with a new diagnosis of celiac disease. • Significant elevations (>3 × ULN) are rare (1.6%). • Elevated liver enzymes are associated with earlier age at diagnosis. • The natural history of patients with elevated liver enzymes at diagnosis is comparable to those without.

Could it be gluten? Additional skin conditions associated with celiac disease.

Celiac disease is a multifactorial, inflammatory disorder initiated and sustained by the ingestion of gluten. Occurring across a broad population, the intestinal and extraintestinal manifestations of celiac disease are variable in severity and may be nonspecific in presentation. Given that environmental, genetic, and immune factors involved in the pathogenesis of celiac disease that the digestive tract and skin share many characteristics, and with a prevalence of 0.5-1% in most populations, it is reasonable to consider varying presentations of skin conditions that are linked with celiac disease. The association between celiac disease and skin conditions has been discussed earlier, but new studies have emerged suggesting cutaneous involvement in addition to dermatitis herpetiformis. We review the current literature identifying the relationship and potential mechanisms between celiac disease and various skin conditions.

Acne as a common extraintestinal manifestation of celiac disease. Treatment approaches

Introduction. At present, global prevalence of celiac disease attracts increasingly greater attention of researchers. The study of its extraintestinal manifestations is a crucial task for early and timely diagnosis of the disease, as well as the identification of new risk groups. To date, there are only isolated publications concerning the study of celiac disease incidence in patients with acne. This topic is of particular interest since systemic retinoids with a hepatotoxic effect and antibiotics significantly affecting the intestinal microflora are the first-line drugs in the treatment of moderate and severe acne. Undoubtedly, these side effects influence on the course of acne in celiac patients. So, to prevent the complications of the treatment, it is necessary to search, develop and introduce into practice safe combinations, including drugs having a protective effect both for the intestinal microflora and for the liver. It is known that psyllium (Plantago ovata seed shells/Ispaghula husks) have similar effects.Objective. To study the effect of psyllium on the tolerability and effectiveness of systemic therapy with isotretinoin and doxycycline in patients with moderate acne with celiac disease. Material and methods. We examined 65 patients with celiac disease suffering from moderate acne, who were randomized into two groups – group 1 (taking an antibiotic – doxycycline) and group 2 (taking a systemic retinoid – isotretinoin), then each group was divided into two subgroups A and B, depending on the prebiotic intake (powder of oval plantain seeds shells Plantago ovata Forssk (psyllium). The patients were followed up for 8 and 24 weeks, respectively. All patients received adjuvant topical therapy. In each group, a medical check-up was done before treatment, 2 months after the onset and then after the treatment completion.Conclusion. Patients in both subgroups who received psyllium in addition to antibiotics and systemic retinoids treatment showed better results after treatment in terms of skin condition, overall health and quality of life.