A nationwide survey of non-IgE-mediated gastrointestinal food allergies in neonates and infants.

BACKGROUND: Non-IgE-mediated gastrointestinal food allergies (non-IgE-GIFAs) seem to be increasing rapidly worldwide. However, nationwide studies have been limited to food-protein-induced enterocolitis (FPIES) and food-protein-induced allergic proctocolitis (FPIAP), with little attention to other non-IgE-GIFA subgroups. The aim of this study was to elucidate the clinical features of all patients with non-IgE-GIFAs, not just certain subgroups. METHODS: We conducted a nationwide cross-sectional survey of non-IgE-GIFAs in Japan from April 2015 through March 2016. A questionnaire was sent to hospitals and clinics throughout Japan. The questionnaire asked about the number of physician-diagnosed non-IgE-GIFA patients, the status of fulfillment of the diagnostic criteria, tentative classification into 4 clusters based on the initial symptoms, the day of onset after birth, complications, and the suspected offending food(s). RESULTS: The response rate to that questionnaire was 67.6% from hospitals and 47.4% from clinics. Analyses were conducted about "diagnosis-probable" patient cohort (n = 402) and the "diagnosis-confirmed" patients (n = 80). In half of the reported non-IgE-GIFA patients, onset occurred in the neonatal period. The patients were evenly distributed among 4 non-IgE-GIFA clusters. In Cluster 1, with symptoms of vomiting and bloody stool, the onset showed a median of 7 days after birth, which was the earliest among the clusters. Cow's milk was the most common causative food. CONCLUSIONS: In half of the patients, the onset of non-IgE-GIFAs was in the neonatal period. This highlights the importance of studying the pathogenesis in the fetal and neonatal periods.

Portal vein thrombosis and food protein-induced allergic proctocolitis in a premature newborn with hypereosinophilia: a case report.

BACKGROUND: Peripheral blood eosinophilia is identified in numerous medical conditions associated with allergic, infectious, and inflammatory processes mostly as reactive eosinophilia with or without tissue eosinophilia. In hospitalized neonates, eosinophilia is common with an inverse relationship with gestational age and occurs solely as mild eosinophilia in the majority of cases. In the literature, eosinophilia has been proposed as a possible risk factor for venous thromboembolism. However, few reports are found on thromboembolic events including portal vein thrombosis (PVT) associated with eosinophilia in the newborn period. Neonates, particularly preterm infants, are vulnerable to thrombosis due to the immature and developing hemostatic system with little reserve capacity, which occurs as catheter-related thrombosis in most cases. CASE PRESENTATION: A male newborn at 34+ 5 weeks' gestation presented with a left portal venous thrombus and hematochezia after initial cow's milk feeding in the setting of blood hypereosinophilia for a prolonged period of time without central venous catheterization. The infant was diagnosed with PVT and food protein-induced allergic proctocolitis (FPIAP) and showed complete resolution of the conditions with expectant management with food avoidance, including the normalized eosinophil count. CONCLUSIONS: Our experience suggests that in the setting of hypereosinophilia with a prolonged duration in premature neonates, FPIAP should be suspected in case of hematochezia in otherwise healthy infants, and considering the increased thrombotic risk by the hypereosinophilia and premature newborn status, evaluation for neonatal thrombosis may be needed, including PVT with the potential risk for the more serious, but uncommon, late complications encompassing portal hypertension.

Pyoderma gangrenosum successfully treated with golimumab: Case report and review of the literature.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis frequently related to chronic inflammatory bowel disease (IBD) often associated with exacerbation of intestinal disease and/or loss of treatment efficacy. However, in patients with comorbidities, such as diabetes, the diagnosis may be a challenge. Here, we report the case of a 68-year-old man with a history of ulcerative rectocolitis (URC), type II diabetes and arterial hypertension, who had been treated with infliximab and adalimumab in the past. In September 2017, patient developed an erythematous, infiltrated and painful lesion of the third distal part of his left leg, with ulcerative evolution, rapidly worsened despite a broad-spectrum antibiotic treatment had been introducted. A worsening of rectocolitis occurred simultaneously. In agreement with the gastroenterologists, patient started a new biological therapy with golimumab, and oral prednisone with slow tapering of steroid dosage following the improvement of both cutaneous and intestinal symptoms. Dermatologists should be aware about the risk of PG in patient suffering from IBDs, and consider this diagnosis in all patients affected by URC developing rapidly extending ulcerative skin lesion. Moreover, therapeutic choice should take into consideration the effectiveness of golimumab on the inflammatory background, which sustains both intestinal and skin disease in this type of patients.

Allergic Proctocolitis Is a Risk Factor for Functional Gastrointestinal Disorders in Children.

OBJECTIVE: To test the hypothesis that allergic proctocolitis, a cause of self-limiting rectal bleeding in infants, can predispose to the development of functional gastrointestinal disorders (FGIDs) later in childhood. STUDY DESIGN: We studied a cohort of 80 consecutive patients diagnosed with allergic proctocolitis. Their sibling or matched children presenting to the same hospital for minor trauma served as controls. Parents of the patients with allergic proctocolitis and controls participated in a telephone interview every 12 months until the child was at least 4 years old. At that time, they were asked to complete the parental Questionnaire on Pediatric Gastrointestinal Symptoms, Rome III version. RESULTS: Sixteen of the 160 subjects (10.0%) included in the study met the Rome III criteria for FGIDs. Among the 80 patients with allergic proctocolitis, 12 (15.0%) reported FGIDs, compared with 4 of 80 (5.0%) controls (P = .035). After adjustment for age and sex, the OR for FGIDs in allergic proctocolitis group was 4.39 (95% CI, 1.03-18.68). FGIDs were significantly associated with iron deficiency anemia, duration of hematochezia, and younger age at presentation. In a multivariate analysis, only the duration of hematochezia was significantly associated with the development of FGIDs (OR, 3.14; 95% CI,1.72-5.74). CONCLUSIONS: We have identified allergic proctocolitis as a new risk factor for the development of FGIDs in children. Our data suggest that not only infection, but also a transient early-life allergic inflammatory trigger may induce persistent digestive symptoms, supporting the existence of "postinflammatory" FGIDs.

Severe ischemic cytomegalovirus proctocolitis with multiple perforation.

Cytomegalovirus (CMV) typically causes gastrointestinal infections in immunocompetent patients. Colonic perforations secondary to CMV are exceeding rare. We describe a 88-year-old male presenting with a week-long history of intractable abdominal discomfort, bloating, nausea and diarrhea. Flexible sigmoidoscopy revealed significant ulceration with yellowish slough. Emergency surgery was performed subsequently in view of multiple perforations in the rectosigmoid junction. CMV gastrointestinal infections demonstrated an ischemic process secondary to vasculitis, which accelerated the pathway to colonic perforation. CMV gastrointestinal infection should be considered as a differential diagnosis in patients with colonoscopy findings similar to ischemic colitis and Clostridium difficile infections.

Efficacy of topical 5-aminosalicylate monotherapy in patients with ulcerative proctitis with skip inflammation.

BACKGROUND AND AIM: In some patients with ulcerative proctitis (UP), skip inflammation is noted in the right side of the colon, but little is known about its clinical course. The aim of this study was to evaluate the clinical course of UP with skip inflammation and the efficacy of topical 5-aminosalicylate (5-ASA) monotherapy. METHODS: This study reviewed the data of 388 patients with an initial diagnosis of UP from January 2005 to October 2015. This study matched each UP patient with skip inflammation 1:2 with controls who had UP without skip inflammation; to reduce bias, this study matched the controls with the cases by age, gender, and initial disease activity. RESULTS: During the follow-up period (median: 69.5 months), the overall progression rates for the control group (n = 192) and the skip inflammation group (n = 96) were 24.0% and 32.9% at 10 years, respectively (log-rank P = 0.71). In the skip inflammation group, the progression rates were not significantly different between the 5-ASA combination group and the topical group, 33.4% and 26.6% at 10 years, respectively (log-rank P = 0.96). The overall acute exacerbation rates for the control and skip inflammation groups were 17.2% and 26.8% at 10 years, respectively (log-rank P = 0.68). In the skip inflammation group, the exacerbation rates were also not significantly different between the combination and topical treatment groups, 26.6% and 23.6% at 10 years, respectively (log-rank P = 0.88). CONCLUSION: The clinical course of UP with skip inflammation was not different from that of typical UP, and topical 5-ASA monotherapy for maintaining remission was as effective as 5-ASA combination therapy irrespective of the presence of skip lesions.

What is the predictor of surgical mortality in adult colorectal perforation? The clinical characteristics and results of a multivariate logistic regression analysis.

PURPOSE: Colorectal perforations are a serious condition associated with a high mortality. The aim of this study was to describe the clinical characteristics and identify predictors for the surgical mortality in adult patients with colorectal perforation, thereby achieving better outcomes. METHODS: A retrospective study of adult patients diagnosed with colorectal perforation operated was performed. The clinical variables that might influence the surgical mortality were first analyzed, and the significant variables were then analyzed using a logistic regression model. RESULTS: A total of 423 patients were identified, and the surgical mortality rate was 36.9 %. The most common etiology was diverticulitis (38.2 %). The highest etiology-specific mortality was for colorectal cancer (61.5 %) and ischemic proctocolitis (59.8 %). In a logistic analysis, the significant predictors for the surgical mortality were ≥3 comorbidities (p = 0.034), preoperation American Society of Anesthesiologists score ≥4 (p = 0.025), preoperative sepsis or septic shock (p < 0.001), colorectal cancer or ischemic proctocolitis (p = 0.035), reoperation (p = 0.041), and Hinchey classification grade IV (p = 0.024). CONCLUSION: We demonstrated that ≥3 comorbidities, a preoperation American Society of Anesthesiologists score ≥4, preoperative sepsis or septic shock, colorectal cancer or ischemic proctocolitis, reoperation, and Hinchey classification grade IV are predictors for the surgical mortality in the adult cases of colorectal perforation. These predictors should be taken into consideration to prevent surgical mortality and to reduce potentially unnecessary medical expenses.

Clinical pattern and progression of ulcerative proctitis in the Japanese population: a retrospective study of incidence and risk factors influencing progression.

AIM: The rate of extension of proctitis in Western countries has been reported, but no data regarding long-term follow-up have been described for the Japanese population. Additionally, patients with long-standing or extensive ulcerative colitis have an increased risk for developing colorectal cancer. This study evaluated both the rate of extension of the disease and the development of neoplasia among patients with an initial diagnosis of ulcerative proctitis. METHOD: We retrospectively investigated the medical charts of patients with proctitis from 1979 to 2014. The primary focus of this research was the extension of the inflammatory area. The secondary focus included risk factors for disease extension and the development of neoplasia. RESULTS: Sixty-six patients satisfied the inclusion criteria. Proximal extension of the disease occurred in 34 patients: 19 patients had left-sided colitis and 15 had pancolitis. According to a multivariate analysis, disease extension was significantly higher in patients with disease onset before 25 years of age (P-value = 0.043). The cumulative rates of disease extension at 10 and 20 years were 33.8% and 52.2%, respectively. Three patients were diagnosed with dysplasia during follow-up, all of whom experienced disease extension before the development of dysplasia. CONCLUSION: The rate of extension of ulcerative colitis in the Japanese population was comparable to that in Western countries. A younger age of disease onset was associated with disease extension. Extension of proctitis may be associated with an increased risk of colorectal cancer.

Improvement of Refractory Ulcerative Proctitis With Sacral Nerve Stimulation.

BACKGROUND AND AIMS: Sacral nerve stimulation (SNS) is recognized for its efficiency and safety for anal incontinence, preventing high morbidity. Evidence from the literature suggests extending SNS to diseases associated with problems of intestinal barrier permeability. The aim of this study was to highlight clinical evidence of the beneficial impact of SNS in a refractory proctitis case report. MATERIALS AND METHODS: A permanent SNS was performed successfully in a patient with proctitis after implantation of the neuromodulator. Despite immunosuppressive drugs, the patient was experiencing mucus and blood discharge, pain, and fecal incontinence. To relieve fecal incontinence, SNS was tested without modification of medications. Disease activity, endoscopic and histologic score, ex vivo barrier permeability, expression of inflammatory cytokines (transforming growth factor-ß, tumor necrosis factor α, Interleukin-6, Interleukin-8), and junctional proteins (ZO-1, claudin-1, occludin) were assessed before and after SNS to observe the impact of SNS other than for incontinence. RESULTS: After a 3-week period of temporary stimulation, the patient experienced significant improvement with a decrease in fecal incontinence and disease activity scores. Both endoscopic and histologic scores showed improvement. The rectal barrier permeability decreased with SNS, whereas junctional protein mRNA expression transiently increased. Clinical and histologic improvement was sustained over time. After 18 months of permanent stimulation, the patient remained improved by SNS. CONCLUSION: This work demonstrates the relevance to explore further indications of SNS beyond fecal incontinence.

Outcome of infants presenting rectal bleeding: a retrospective study in a single institution.

BACKGROUND: Although rectal bleeding in infancy (RBI) is not a rare phenomenon, the clinical course of RBI is not fully understood. METHODS: To investigate the outcome and pathogenesis of RBI, especially when concomitant with food-protein-induced proctocolitis (FPIP) and neonatal transient eosinophilic colitis (NTEC), 22 neonates with rectal bleeding with FPIP and NTEC from January 2008 to June 2012 were enrolled and their clinical course and mechanisms of inflammation were examined. RESULTS: Thirteen infants showed rectal bleeding after feeding and were diagnosed with FPIP, and nine infants showed rectal bleeding before feeding and were diagnosed with NTEC. Elevated peripheral white blood cell (12,685 ± 3754/µl and 30,978 ± 16,166/µl) and eosinophil (1084 ± 816/µl and 4456 ± 3341/µl) were confirmed in FPIP and NTEC, respectively. Colonoscopy revealed nodular lymphoid hyperplasia, a pale mucosal surface and oozing with diffuse infiltration of neutrophils, lymphocytes, and eosinophils in both groups. Reverse transcription polymerase chain reaction analysis revealed enhanced expression of the interleukin-6, CCL11, and CXCL13 genes, where CXCL13 expression was more prominent in FPIP. Mucosal infiltration by CD3- and immunoglobulin-A- but not immunoglobulin-E-positive cells was confirmed. Among them, only one infant with FPIP developed milk allergy, whereas none with NTEC had developed milk allergy at the age of 1 year. CONCLUSIONS: FPIP in infancy and NTEC are similar diseases and interleukin-6, CCL11, and CXCL13 may play a major role in the pathogenesis of rectal bleeding. Although the involvement of allergic reaction is possible, milk allergy was not a common outcome after 1 year of follow up.

[Management of intestinal complications in inflammatory bowel diseases]. / Traitement des complications digestives des maladies inflammatoires chroniques de l'intestin.

The evolution of inflammatory bowel disease (IBD) is characterized by the occurrence of gastrointestinal complications. For Crohn's disease (CD), it is mainly strictures, fistulas and abdominal or pelvic abscess in luminal forms and perianal lesions (ulcers, fissures, fistula/abscess) in the perineal forms. For ulcerative colitis (UC), main complications are severe flare up and dysplasia/cancer. In Crohn's disease, stenosis can be treated medically in first line (steroid-immunosupppresseurs or antiTNF) especially when the inflammatory component is predominant or in extensive lesions. In case of limited lesions (< 4 cm) and low inflammatory component, endoscopic dilatation can be propose before surgery, especially in patients previously operated on. Abdomino-pelvic abscess should be drained if the size is greater than 4-5 cm and treated with antibiotics. If obstructive signs are present after the resolution of the abscess, surgery is usually required. In some cases, an antiTNF therapy can be discussed (ongoing trial with the GETAID). Surgery during the MC should be performed laparoscopically, particularly in uncomplicated forms (first ileocecal resection) but also whenever possible for complicated diseases. Anoperineal abscess must be drained by non-tight setons. Medical treatment also involves antibiotics and antiTNF, usually in combotherapy. Biological glue is especially interesting in simple fistulas. Collagen plugs have not demonstrated efficacy in simple or complex perianal Crohn's disease fistulas and may have a deleterious effect. They are therefore not recommended. Severe UC flare up are still conventionally treated with corticosteroids IV for 3-5 days, followed in case of failure of a 2nd line treatment with infliximab or ciclosporin. The place of emergency colectomy had regressed due to the effectiveness of medical treatments.

Chronic Lymphogranuloma Venereum Proctocolitis Masquerading as Inflammatory Bowel Disease.

Rectal infection with the L1, L2, and L3 serovars of Chlamydia trachomatis can cause lymphogranuloma venereum (LGV) proctocolitis, particularly among men who have sex with men (MSM). Symptoms of this sexually transmitted infection include anal pain, rectal bleeding and discharge, tenesmus, constipation, and fever. Clinicians should consider LGV when there is a history of receptive anal intercourse and symptoms of proctocolitis. A positive nucleic acid amplification test (NAAT) on a rectal sample is diagnostic. This report describes a man with HIV and chronic proctocolitis in whom the diagnosis of LGV was delayed because the clinical picture mimicked inflammatory bowel disease.

INDUCED PROCTOCOLITIS - ORAL FOOD CHALLENGE SHOULD BE DONE TO CONFIRM THE DIAGNOSIS OF COW'S MILK ALLERGY IN NEONATES?

BACKGROUND: Suspicion of food protein-induced proctocolitis based on empirical understanding of rectal bleeding can lead to misdiagnosis. OBJECTIVE: to verify clinical and evaluative characteristics of patients who presented neonatal rectal bleeding and were on a restricted cow's milk diet. METHODS: A cross-sectional retrospective study included patients followed up in a tertiary care center, who presented rectal bleeding in the neonatal period. The analyzed data included gender, gestational age, type of delivery, use of antibiotics during the last trimester of pregnancy, use of parenteral nutrition before the first manifestation, use of mechanical ventilation, initial clinical manifestations associated with rectal bleeding, diet before the first manifestation, period of elimination diet, oral food challenge (OFC) results and symptoms presented in cases of positive OFC. Fisher's exact test and Mann-Whitney test were used to analyze the data. The level of significance was set to 5%. RESULTS: Forty-two patients were selected: 30 preterm infants, 34 cesarean deliveries, 10 exclusively breastfed patients before rectal bleeding. Median age at OFC was 6.3 months old. Median of length of the elimination period before OFC was 5.9 months. OFC was negative in 33/42 (79%) patients and positive in 9/42 (21%). There was no association between OFC results and the evaluated data. The main symptom observed in patients with positive OFC was blood in stools. CONCLUSION: OFC was negative in most cases of suspected cow's milk allergy due to rectal bleeding in neonates, most of them with a history of prematurity.

Clinical Features and Clinical Course of Food Protein-Induced Allergic Proctocolitis: 10-Year Experience of a Tertiary Medical Center.

BACKGROUND: Food protein-induced allergic proctocolitis (FPIAP) is a food allergy characterized by bloody stools in well-appearing breast-fed infants. OBJECTIVE: To determine the clinical course of FPIAP and the factors affecting the development of tolerance. METHODS: Over a 10-year period, patients with a diagnosis of FPIAP who were followed at the outpatient Allergy-Immunology clinic in a tertiary care children's hospital in Turkey were retrospectively analyzed. RESULTS: The frequency of FPIAP was 0.18% among 64,549 patients. The median age of symptom onset was 2 months (interquartile range, 1.0-3.5 months), and the median age of tolerance development was 12 months (interquartile range, 8.0-17.21 months). The occurrence of symptoms in the neonatal period was associated with a history of premature birth (odds ratio, 3.75; 95% CI, 1.33-10.59; P = .031) and neonatal intensive care unit hospitalization (odds ratio, 4.72; 95% CI, 1.78-12.53; P = .002). Use of a cow's milk-based formula was associated with a higher risk of the onset of symptoms after 1 month (odds ratio, 2.69; 95% CI, 1.19-6.07; P = .016). The use of an amino acid-based formula and the presence of diarrhea at admission were associated with later development of tolerance (P = .023 and P < .001, respectively). An IgE-mediated reaction was observed during oral food challenge testing in 6% of the patients. CONCLUSIONS: The manifestations of FPIAP appeared earlier in premature infants and later in infants using formula. The use of amino acid-based formula and having had diarrhea were associated with delayed tolerance.

[Blastocystis hominis infection in a baby with food allergy].

The paper describes a rare manifestation of Blastocystis hominis infection in a 3-month-old baby with food allergy that appeared as atopic dermatitis and coloproctitis induced by food proteins (cow's milk, hen's egg). The fact that food allergy may be one of the predisposing factors in the development of clinical manifestations of B. hominis infection is discussed. The assumption that the amoeboid form of blastocysts accompanies the clinical manifestation of the infection is confirmed.

Osseous metaplasia of the colon in a diversion proctocolitis.

Osseous metaplasia within the gastrointestinal tract is a rare phenomenon, seen most frequently in mucinproducing left-sided colonic adenocarcinomas. It has also been documented in a variety of benign conditions, occurring in polyps and lesions associated with inflammation and ulceration. This is the first case report, to the authors' knowledge, of osseous metaplasia associated with a diversion proctocolitis. The diversion was performed following stricture formation, secondary to complicated diverticular disease with diverticular phlegmon formation. In common with other cases, in which osseous metaplasia arises within a background of inflammation, the present case demonstrated stromal fibroblastic proliferation. The underlying pathogenesis of osseous metaplasia has not yet been elucidated, but secretion of various bone morphogenic proteins (belonging to the transforming growth factor-beta superfamily) and increased alkaline phosphatase activity by both epithelial and stromal cells have been documented.

[Case of scattered gastritis associated with ulcerative proctitis].

A 59-year-old man who had ulcerative proctitis for 18 years visited our hospital because of stomach pain. Proctitis had been in remission stage for five recent years by the mesalazine administration. Esophagogastroduodenoscopy (EGD) showed scattered patchy erosions at the corpus of the stomach. Anti-acid secretory agents was administrated, however, erosive change worsened in multiplicity and in area. Biopsied specimen of gastric mucosa showed specific findings resembling to cryptitis, crypt abcess and focally enhanced gastritis. H. pylori infection was negative by some examinations. Our patient had no history of taking non steroidal anti-inflammatory drugs (NSAIDs) so far. From the findings above, it was considered that gastric lesion was strongly related to the ulcerative proctitis. 5-aminosalicylic acid (750 mg, three times daily) ground to powder was administered with predonisolon (20 mg, once daily). Five month later, all the erosions disappeared completely on EGD and biopsied specimen revealed a reduction of inflammatory cells. The present case has a rare gastric lesion with patchy pattern (not diffuse pattern) which is strongly associated with ulcerative proctitis.

Hermansky Pudlak syndrome: an unusual form of procto-colitis.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder consisting of oculocutaneous albinism, platelet dysfunction and systemic complications associated with lipofuscin deposition in the reticuloendothelial system. HPS has been associated with a granulomatous enterocolitis with pathologic features suggestive of Crohn's disease. It remains uncertain if HPS represents a truly distinct form of granulomatous enterocolitis. We report a series of two patients with HPS treated in Puerto Rico, and the results from medical and surgical intervention for gastrointestinal disease. Our experience with HPS patients has shown the difficult management of perineal disease similar in the management of Crohn's. However, complications from the bleeding diathesis necessitate caution during surgery and potential anesthesia complications. Furthermore, avoidance of a perineal wound is preferred, and when possible, ileostomies have fewer complications than colostomies as they do not involve the small bowel.