Extra-intestinal manifestations of non-celiac gluten sensitivity: an expanding paradigm

Non celiac gluten sensitivity(NCGS) is a syndrome characterized by a cohort of symptoms related to the ingestion of gluten-containing food in subjects who are not affected by celiac disease(CD) or wheat allergy. The possibility of systemic manifestations in this condition has been suggested by some reports. In most cases they are characterized by vague symptoms such as ‘foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness even if more specific complaints have been described. NCGS has an immune-related background. Indeed there is a strong evidence that a selective activation of innate immunity may be the trigger for NCGS inflammatory response. The most commonly autoimmune disorders associated to NCGS are Hashimoto thyroiditis, dermatitis herpetiformis, psoriasis and rheumatologic diseases. The predominance of Hashimoto thyroiditis represents an interesting finding, since it has been indirectly confirmed by an Italian study, showing that autoimmune thyroid disease is a risk factor for the evolution towards NCGS in a group of patients with minimal duodenal inflammation. On these bases, an autoimmune stigma in NCGS is strongly supported; it could be a characteristic feature that could help the diagnosis and be simultaneously managed. A possible neurological involvement has been underlined by NCGS association with gluten ataxia, gluten neuropathy and gluten encephalopathy. NCGS patients may show even psychiatric diseases such as depression, anxiety and psychosis. Finally, a link with functional disorders(irritable bowel syndrome and fibromyalgia) is a topic under discussion. In conclusion, the novelty of this matter has generated an expansion of literature data with the unavoidable consequence that some reports are often based on low levels of evidence. Therefore, only studies performed on large samples with the inclusion of control groups will be able to clearly establish whether the large information from the literature regarding extra-intestinal NCGS manifestations could be supported by evidence-based agreements.

Risk of cancer,with special reference to extra-intestinal malignancies,in patients with inflammatory bowel disease

AIM:To determine the incidence and characteristics of intestinal and extra-intestinal cancers among patients with inflammatory bowel disease in a Spanish hospital and to compare them with those of the local population.METHODS:This was a prospective,observational,7-year follow-up,cohort study.Cumulative incidence,incidence rates based on person-years of follow-up and relative risk were calculated for patients with inflammatory bowel disease and compared with the background population.The incidence of cancer was determined using a hospital-based data registry from Hospital Universitario de Fuenlabrada.Demographic data and details about time from diagnosis of inflammatory bowel disease to occurrence of cancer,disease extent,inflammatory bowel disease treatment,cancer therapy and cancer evolution were also collected in the inflammatory bowel disease cohort.RESULTS:Eighteen of 590 patients with inflammatory bowel disease developed cancer[cumulative incidence=3%(95%CI:1.58-4.52)vs 2%(95%CI:1.99-2.11)in the background population;RR=1.5;95%CI:0.97-2.29].The cancer incidence among inflammatory bowel disease patients was 0.53%(95%CI:0.32-0.84)per patient-year of follow-up.Patients with inflammatory bowel disease had a significantly increased relative risk of urothelial carcinoma(RR=5.23,95%CI:1.95-13.87),appendiceal mucinous cystadenoma(RR=36.6,95%CI:7.92-138.4),neuroendocrine carcinoma(RR=13.1,95%CI:1.82-29.7)and rectal carcinoid(RR=8.94,95%CI:1.18-59.7).Colorectal cancer cases were not found.CONCLUSION:The overall risk of cancer did not significantly increase in our inflammatory bowel disease patients.However,there was an increased risk of urinary bladder cancer and,with less statistical power,an increased risk of appendiceal mucinous cystadenoma and of neuroendocrine tumors.Colorectal cancer risk was low in our series.

Oral manifestation in inflammatory bowel disease:A review

Inflammatory bowel diseases(IBDs),including Crohn’s disease(CD)and ulcerative colitis,not only affect the intestinal tract but also have an extraintestinal involvement within the oral cavity.These oral manifestations may assist in the diagnosis and the monitoring of disease activity,whilst ignoring them may lead to an inaccurate diagnosis and useless and expensive workups.Indurated tag-like lesions,cobblestoning,and mucogingivitis are the most common specific oral findings encountered in CD cases.Aphthous stomatitis and pyostomatitis vegetans are among non-specific oral manifestations of IBD.In differential diagnosis,side effects of drugs,infections,nutritional deficiencies,and other inflammatory conditions should also be considered.Treatment usually involves managing the underlying intestinal disease.In severe cases with local symptoms,topical and/or systemic steroids and immunosuppressive drugs might be used.

Acute respiratory distress syndrome associated with severe ulcerative colitis

Various extraintestinal manifestations including pulmonary abnormalities have been reported in patients with ulcerative colitis. Acute respiratory distress syndrome (ARDS) is a serious and fatal pulmonary manifestation. We have experienced a 67-year-old male patient with ARDS associated with a severe type of ulcerative colitis (UC). Severe dyspnea symptoms occurred during the treatment of UC in a previous hospital and the patient was transferred to our hospital on June 27, 2007. Both blood and sputa cultures for bacteria and fungi were negative. Cytomega-lovirus antigenemia was also not detected. From the clinical and radiological [Chest X-ray, computed tomography (CT)] findings, the patient was diagnosed with ARDS on the basis of the def inition of ARDS developed by the European-American Consensus Conference on ARDS. Both colonic inflammations and ARDS symptoms of the patient were resistant to any medical treatment includingcorticosteroids and antibiotics. However, ARDS symptoms were dramatically improved after surgical colectomy. We believe that severe colonic inflammation from UC was closely associated with the onset of ARDS of the patient. Our case report suggests that a severe type of ulcerative colitis might be taken into consideration as one of the predisposing factors of ARDS.

Crohn's disease-related'gastrocnemius myalgia syndrome'successfully treated with infliximab:A case report

BACKGROUND Extra-intestinal manifestations in inflammatory bowel diseases(IBD)are frequent and involve virtually all organs.Conversely,the clinical characteristics and course of inflammatory myopathies in IBD remain poorly described and mostly related to orbital myositis.Moreover,alternative therapeutic strategies in non-responder patients to corticosteroid therapy must still be clarified.CASE SUMMARY A 33-year-old woman with a history of unclassified colitis presented with acute bilateral calf pain.On admission,her clinical and biological examinations were non-specific.However,magnetic resonance imaging showed bilateral inflammatory changes in gastrocnemius muscles suggestive of myositis.Muscle biopsy confirmed the diagnosis of myositis and demonstrated an inflammatory infiltrate mainly located in the perimysial compartment including lympho-plasmocytic cells with the formation of several granulomatous structures while the endomysium was relatively spared.The combined clinical,biological and histomyopathological findings were concordant with the diagnosis of‘gastrocnemius myalgia syndrome’(GMS),a rare disorder associated with Crohn’s disease(CD).Ileocolonoscopy confirmed CD diagnosis and systemic corticosteroids(CS)therapy was started,resulting in a rapid clinical improvement.During CS tapering,however,she experienced a relapse of GMS together with a severe active ileocolitis.Infliximab was started and allowed a sustained remission of both conditions at the latest follow-up(20 mo).CONCLUSION The GMS represent a rare CD-associated inflammatory myopathy for which anti-tumour necrosis factor-αtherapy might be considered as an effective therapeutic option.

Nasal mucosa pyoderma vegetans associated with ulcerative colitis:A case report

BACKGROUND Pyoderma vegetans(PV)is not a common extra-intestinal manifestation of ulcerative colitis(UC),while nasal mucosa PV associated with UC is particularly rare.CASE SUMMARY We report a 28-year-old female with a history of UC and pyoderma gangrenosum who presented with nasal pain.A nasal lesion could be observed in her nose,and histopathological examination was indicative of PV.The patient was treated with oral prednisone(40 mg per day)with good response and became symptomatically free.There was no recurrent attack after 1 year of follow-up.CONCLUSION Inflammatory bowel disease patients presenting with nasal pain should be further investigated to rule out the coexistence of nasal mucosa PV.

Classical and Non-Classical Celiac Disease Comparison: Ten Years of Study

Objective: Celiac disease (CD) is an immune-mediated systemic disorder triggered by gluten. It has a variable combination of clinical manifestations and changes that have been occurring in recent decades however they are not known in detail. The purpose of the article is to compare Classical and Non-Classical CD cases in terms of demographic characteristics, duodenal biopsy, extraintestinal manifestations, and associated comorbidities. Materials and Methods: A comparative retrospective cohort study from January 2008 to December 2018. Results: A total of 128 cases were included: 84 Classical (66%) and 44 Non-Classical CD (34%). The family history of CD was identified in 14% of cases without differences between groups. The age at diagnosis was distinct for Classical and Non-Classical CD (4.9 ± 4 and 8.3 ± 4 years old;p 0.001), respectively. Important changes were found within the classical presentation, including mono symptoms and a significantly higher rate of intestinal atrophy;p = 0.04. The main Non-Classical CD symptom was recurrent abdominal pain. The extraintestinal manifestations (EIM) were identified in 42% and occurred in both groups. The comparison between groups showed differences in rates of migraine and vitamin D deficiency and was higher for Non-Classical CD (p 0.05). Associated diseases occurred in 10.9%, and type 1 diabetes was significant for the Non-Classical CD group (p = 0.04). Conclusion: The classical CD was the most prevalent profile and presented a decrease in the severity of symptoms however remain a higher rate of intestinal atrophy. Recurrent abdominal pain was the main symptom of Non-Classical CD. Extraintestinal manifestations and associated diseases presented an increasing trend of occurrence among cases of Non-Classical CD.

Clinical and Laboratory Diagnosis of Intestinal Tuberculosis

Background： Tuberculosis （TB） remains a worldwide problem. Intestinal TB （ITB） constitutes a major public health problem in developing countries and has been associated with significant morbidity and mortality. The aim of this study was to characterize the clinical, radiological, endoscopic, and pathological features of ITB and to define the strategy for establishing the diagnosis. Methods： A retrospective study （from January 2000 to June 2015） was carried out in Peking Union Medical College Hospital and all hospitalized cases were diagnosed as ITB during the study period were included. The relevant clinical information, laboratory results, microbiological, and radiological investigations were recorded. Results： Of the 85 cases, 61 cases （71.8%） were ranged from 20 to 50 years. The ileocecal region was involved in about 83.5% （71/85） of patients. About 41.2% （35/85） of patients had co-existing extra ITB, especially active pulmonary TB. Abdominal pain （82.4%） was the most common presenting symptom followed by weight loss （72.9%） and fever （64.7%）. Both T-cell spot of TB test （T-SPOT.TB） and purified protein derivatives （PPD） tests were performed in 26 patients： 20 （76.9%） positive T-SPOT.TB and 13 （50.0%） positive PPD were detected, with a statistical significant difference （P- 0.046）. Twenty cases （23.5%） were histopathology and/or pathogen confirmed TB; 27 cases （31.8%） were diagnosed by clinical manifestation consistent with ITB and evidence of active extra ITB; 38 cases （44.7%） were diagnosed by good response to diagnostic anti-TB therapy. Conclusions： ITB is difficult to diagnose even with modem medical techniques due to its nonspecific clinical and laboratory features. At present, combination of clinical, endoscopic, radiological, and pathological features continues to be the key to the diagnosis of ITB.