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.

A different starting line for allergic march: food protein-induced allergic proctocolitis.

OBJECTIVE: The aim of this study is to investigate the long-term prognosis of food protein--induced allergic proctocolitis (FPIAP) patients, the risk of developing both allergic and gastrointestinal diseases, and to evaluate whether it leads to allergic march. METHODS: A total of 149 children who were diagnosed with FPIAP and developed tolerance at least 5 years prior to the study and 41 children (with no history of food allergy) as a control group were enrolled. Both groups were re-evaluated for allergic diseases as well as gastrointestinal disorders. RESULTS: The mean age of diagnosis for the FPIAP group was 4.2 ± 3.0 months, while the mean age of tolerance was 13.9 ± 7.7 months. The mean age of both FPIAP and control groups at the last visit was 101.6 ± 24.4 and 96.3 ± 24.1 months, respectively (P = 0.213). At the final evaluation of both groups, the comorbid allergic disease was significantly higher in the FPIAP group (P < 0.001). There was no significant difference between the two groups in terms of functional gastrointestinal disorders (FGIDs), eosinophilic gastrointestinal diseases, and inflammatory bowel disease (P = 0.198, 0.579, and 0.579, respectively).In the FPIAP group, the allergic disease was significantly higher at the final visit in patients with comorbid allergic disease at diagnosis (P < 0.001). In the FPIAP group, FGID was significantly higher in the group that developed allergic diseases in the future, compared to the group that did not develop allergic diseases in the future (P = 0.034). The proportion of both FGID and allergic diseases was significantly higher in subjects that developed tolerance at >18 months, compared to subjects that developed tolerance at >18 months (P < 0.001 and <0.001, respectively). CONCLUSIONS: Patients with FPIAP may develop allergic diseases as well as FGID in the long term.

First reported lymphogranuloma venereum cases in Russia discovered in men who have sex with men attending proctologists.

BACKGROUND: Several lymphogranuloma venereum (LGV) outbreaks among men who have sex with men (MSM) have been reported throughout the world since 2003. Nevertheless, no LGV cases have been internationally reported from Russia. We evaluated the prevalence of LGV among MSM attending proctologists in Moscow, Russia, and compared the LGV and non-LGV rectal Chlamydia trachomatis (CT) infections. METHODS: MSM (n = 534) attending for proctologic care were included. Rectal specimens were sampled for CT and Neisseria gonorrhoeae (NG) by nucleic acid amplification tests (NAATs). All CT-positive patients were tested with an LGV-specific NAAT. RESULTS: In total, 37.3% (95% CI 33.3-41.5; 199/534) of MSM were CT positive. Of these, 68.8% (95% CI 62.1-74.9; 137/199) had LGV and 31.2% (95% CI 25.1-37.9; 62/199) a non-LGV rectal CT infection. Older age (34 years vs. 31 years, p = 0.035) and group-sex practices (67.2% (92/137) vs. 33.9% (21/62), p < 0.0001) were associated with LGV. The LGV-positive MSM were also more likely to be HIV-positive (67.2% (92/137) vs. 41.9% (26/62), p = 0.001). Proctoscopy revealed ulcerative proctitis/proctocolitis in 99.3% (136/137) of LGV-positive MSM. No ulcerative or erosive proctitis was found in the MSM with non-LGV CT infection, but 58.1% (36/62) of them had anorectal disorders. Finally, mild catarrhal or hemorrhagic proctitis was diagnosed in only 21.6% (8/37) of MSM with non-LGV CT infection lacking concomitant NG or syphilis (p < 0.0001). CONCLUSIONS: LGV is widely spread among MSM attending proctologists in Moscow. Clinically, acute LGV proctitis/proctocolitis can be difficult to distinguish from inflammatory bowel disease that leads to mismanaged LGV infections. LGV diagnostic laboratory testing is essential, however, currently mainly lacking for MSM in Russia. All MSM with CT-positive rectal specimens should be subsequently tested for LGV.

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.

The Low Maternal Consumption of Homemade Fermented Foods in Pregnancy Is an Additional Risk Factor for Food Protein-Induced Allergic Proctocolitis: A Case-Control Study.

INTRODUCTION: Food protein-induced allergic proctocolitis (FPIAP) is the most common non-IgE-mediated food allergy and it varies between 4% and 8% in infants. The aim of the study was to evaluate the potential association between FPIAP in infants and maternal daily consumption of homemade fermented foods (FFs) during pregnancy. METHODS: Two hundred and seven infants were included in this case-control study, 106 with physician-diagnosed FPIAP (FPIAP group) and 101 age- and gender-matched healthy infants (control group), together with their mothers. The frequency and diversity of the 8 most consumed homemade FFs in traditional Turkish cuisine and daily maternal consumption of these during pregnancy were evaluated retrospectively using a structured questionnaire. RESULTS: Rates of vaginal delivery, maternal smoking during pregnancy, educational status, and monthly household income were higher in the FPIAP group than the control group (p = 0.046, p = 0.014, p < 0.001, and p = 0.009, respectively). The 3 most common daily-consumed FFs during pregnancy were, in order, yogurt, cheese, and tarhana. The diversity of daily-consumed FFs during pregnancy (p = 0.004) and the consumption of the 3 most common FFs (p = 0.011) were lower in the FPIAP group than in the control group. Maternal smoking during pregnancy (odds ratio [OR]: 2.97, 95% confidence interval [CI]: 1.19-7.41, p = 0.019) and a higher maternal educational status (OR: 3.34, 95% CI: 1.63-6.84, p = 0.001) increased the risk of FPIAP at multivariate logistic regression, while the diversity of maternal FF consumption was protective against FPIAP (OR: 0.75, 95% CI: 0.58-0.96, p = 0.025). CONCLUSION: Daily maternal consumption of yogurt, cheese, and tarhana during pregnancy was less common in FPIAP. The diversity of traditional Turkish homemade FFs may reduce the risk of FPIAP, whereas maternal smoking and a higher maternal educational status were associated with an increased risk of FPIAP.

Low Incidence of Inflammatory Bowel Disease Adverse Events in Adalimumab Clinical Trials Across Nine Different Diseases.

OBJECTIVE: Adalimumab is approved for treatment of Crohn's disease and ulcerative colitis. Thus, we postulated that exacerbation or new-onset of inflammatory bowel disease (IBD) would be rare events in patients treated with adalimumab for non-IBD indications. The objective was to evaluate the incidence of IBD adverse events (AEs) across adalimumab trials. METHODS: IBD AE rates in 75 adalimumab clinical trials in rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, pediatric enthesitis-related arthritis, uveitis, hidradenitis suppurativa, adult and pediatric psoriasis, psoriatic arthritis, nonpsoriatic arthritis peripheral spondyloarthritis (SpA), axial SpA, including nonradiographic axial SpA, and ankylosing spondylitis, were analyzed. Search terms for IBD AEs (new onset or worsening/flare) included IBD, ulcerative colitis, Crohn's disease, and ulcerative proctitis. RESULTS: This analysis included 24,114 patients, representing 36,508 patient-years of adalimumab exposure. The overall rate of IBD AEs in adalimumab-treated patients was 0.1 (95% confidence interval [95% CI] 0.1-0.2)/100 patient-years (41 events), ranging from no events (psoriatic arthritis, uveitis, and pediatric trials) to 0.8 (95% CI 0.2-2.2)/100 patient-years in peripheral SpA. The rate of IBD in axial SpA was 0.6 (95% CI 0.4-1.0)/100 patient-years. During placebo-controlled trials, the overall IBD rate was 0.1 (95% CI 0.0-0.3)/100 patient-years for adalimumab groups (3 events in 6,781 patients; 2,752 patient-years of exposure) and 0.1 (95% CI 0.0-0.4)/100 patient-years for placebo groups (1 event in 3,493 patients; 1,246 patient-years of exposure). IBD rates in axial SpA were 0.5 (95% CI 0.1-1.4)/100 patient-years for adalimumab and 0.6 (95% CI 0.0-3.1)/100 patient-years for placebo. CONCLUSION: The rates of IBD AEs in adalimumab clinical trials were generally low across the evaluated diseases, including axial SpA; all events occurred in adult patients.

Microbiota in non-IgE-mediated food allergy.

PURPOSE OF REVIEW: To perform a nonsystematic review of the literature on the microbiota in the different types of non-IgE-mediated food allergy. RECENT FINDINGS: The commonest non-IgE-mediated disorders managed by allergists include: eosinophilic esophagitis, food protein-induced enteropathy, food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis. The review of the literature describes how at phylum level we observe an increase of Proteobacteria in eosinophilic esophagitis esophageal microbiota and in food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis gut microbiota, while we observe an increase of Bacteroidetes in healthy controls. Several studies endorse the concept that a bloom of Proteobacteria in the gut reflects dysbiosis or an unstable gut microbial community structure. In several studies, the type of diet, the use of probiotics and in a single experience the use of fecal microbiota transplantation has produced significant variations of the microbiota. SUMMARY: Genetic factors alone cannot account for the rapid rise in food allergy prevalence and the microbiome might be contributing to allergy risk. Our review showed that common features of the pathological microbiota among different types of non-IgE-mediated food allergy can be identified. These evidences suggest a possible role of the microbiota in the pathogenesis and non-IgE-mediated food allergies and the need to understand the effects of its modulation on the disorders themselves.

Unique features of non-IgE-mediated gastrointestinal food allergy during infancy in Japan.

PURPOSE OF REVIEW: An increase in incidence of unique phenotypic non-IgE-mediated gastrointestinal food allergies (non-IgE GIFAs) has occurred in Japan ahead of Western countries. There are differences in clinical features of non-IgE GIFAs in Western and Japanese patients. As this phenotype has now come to be recognized internationally, we describe it in this review. RECENT FINDINGS: A large number of Japanese patients with non-IgE GIFAs present with vomiting accompanied by bloody stool, putting them between food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis. Some neonates and early infants with non-IgE GIFAs who present with fever and elevated C-reactive protein have symptoms consistent with severe systemic bacterial infections (e.g., sepsis). Some of these cases have now been defined in international guidelines as chronic FPIES. Eosinophils might be involved in the inflammatory process observed. The incidence of FPIES and food protein-induced allergic proctocolitis is increasing in Western countries and likely worldwide, after it has increased in Japan. SUMMARY: The phenotype observed in Japan shows distinct clinical features compared with the classical phenotype, that is, increased levels of eosinophils, suggestive of 'eosinophilic shift' alongside symptomatic differences, making it difficult to categorize.

Prospective Assessment of Pediatrician-Diagnosed Food Protein-Induced Allergic Proctocolitis by Gross or Occult Blood.

BACKGROUND: Food protein-induced allergic proctocolitis (FPIAP) is an early and common manifestation of food allergy, yet its epidemiology and relationship to other allergic diseases remain unclear. OBJECTIVE: To prospectively define the incidence of FPIAP as it is being diagnosed clinically in the community and to identify factors associated with its development. METHODS: A total of 1003 of 1162 eligible serial healthy newborn infants recruited from a single suburban pediatrics practice were followed prospectively for the diagnosis of FPIAP. Investigators reviewed each case to confirm prespecified inclusion criteria, including documented gross or occult blood in the stool. RESULTS: A total of 903 infants were analyzed (46% females, 89% term, 32% caesarian-section, 9% neonatal antibiotics); 153 cases met inclusion criteria, a cumulative incidence of 17%, while 63 (7%) had gross blood. Infants initially fed both breast milk and formula were 61% less likely to develop FPIAP compared with those exclusively formula-fed (hazard ratio, 0.39; P = .005). Breast milk and formula at any point during the first 4 months were also associated with lower risk compared with exclusive formula or exclusive breast milk (hazard ratio, 0.44; P = .005; hazard ratio, 0.62; P = .0497). Eczema (odds ratio, 1.5; 95% confidence interval, 1.1- 2.2; P = .02) or a first-degree relative with food allergies (odds ratio, 1.9; 95% confidence interval, 1.2-2.8; P = .005) were among risk factors for FPIAP development. CONCLUSIONS: The prospectively defined incidence of FPIAP when diagnosed clinically by community pediatricians without challenge is markedly higher than published estimates. Combination feeding of formula and breast milk is associated with the lowest rate of FPIAP in this population.

Single and multiple food allergies in infants with proctocolitis.

BACKGROUND: Food protein-induced allergic proctocolitis is a frequent cause of rectal bleeding in infants. Characteristics of infants with multiple food allergies have not been defined. OBJECTIVE: This study aimed to identify characteristics of infants with proctocolitis and compare infants with single and multiple food allergies. METHODS: A total of 132 infants with proctocolitis were evaluated retrospectively. All of the infants were diagnosed by a paediatric allergist and/or a paediatric gastroenterologist according to guidelines. Clinical features of the infants, as well as results of a complete blood count, skin prick test, specific immunoglobulin E, and stool examinations or colonoscopy were recorded. RESULTS: Cow's milk (97.7%) was the most common allergen, followed by egg (22%). Forty-five (34.1%) infants had allergies to more than one food. Infants with multiple food allergies had a higher eosinophil count (613±631.2 vs. 375±291.9) and a higher frequency of positive specific IgE and/or positive skin prick test results than that of patients with a single food allergy. Most of the patients whose symptoms persisted after two years of age had multiple food allergies. CONCLUSIONS: There is no difference in clinical presentations between infants with single and multiple food allergies. However, infants with multiple food allergies have a high blood total eosinophil count and are more likely to have a positive skin prick test and/or positive specific IgE results.

Clinical features and outcome of acute ischemic proctocolitis / Características clínicas y pronóstico de la proctocolitis isqémica aguda

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Serum C-reactive protein in food protein-induced enterocolitis syndrome versus food protein-induced proctocolitis in Japan.

BACKGROUND: Some infants with food protein-induced enterocolitis syndrome (FPIES) have increased serum C-reactive protein (CRP) and fever in Japan. The aim of this study was therefore to clarify and compare the incidence of this in patients with FPIES versus patients with food protein-induced proctocolitis (FPIP). METHODS: One hundred and sixteen infants with non-IgE-mediated gastrointestinal food allergies were enrolled in this study and classified into three phenotypes: FPIES presenting with vomiting and/or diarrhea (n = 47); FPIP with bloody stool alone (n =19); and the mixed phenotype (MP), bloody stool with vomiting and/or diarrhea (n = 50). RESULTS: Serum CRP was increased in 55.3% of the FPIES group, similar to that in the MP group (54.0%), and significantly higher than in the FPIP group (15.8%; P < 0.01). Fever was observed in 29.8% of the FPIES group, significantly higher than in the MP group (8.0%; P < 0.01) and in the FPIP group (0%; P < 0.05). Patients with fever had significantly higher serum CRP than patients without fever (median, 12.8 vs <0.2 mg/dL, P < 0.00001). CONCLUSIONS: Serum CRP was significantly higher in the FPIES group than in the FPIP group. This suggests that serum CRP is a useful marker for differentiating the pathogenesis of FPIES from FPIP. From the perspective of serum CRP, the pathology of the intestinal inflammation in MP subjects is suggested to be similar to that of FPIES.

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.

Food allergy in childhood (infancy to school age).

Food allergy is a potentially life-threatening condition affecting almost 10% of children, with an increasing incidence in the last few decades. It is defined as an immune reaction to food, and its pathogenesis may be IgE mediated, mixed IgE and non-IgE mediated, or non-IgE mediated. Potentially all foods can cause food allergy, but a minority of foods are responsible for the vast majority of reactions reported. A good clinical history is crucial for an accurate diagnosis. Allergy tests, including the skin prick test and measurement of specific IgE antibodies, are useful tools in the case of IgE-mediated or mixed allergy but have not been shown to be of any help in delayed allergic reactions to foods.

[Lymphogranuloma venereum proctocolitis in men with HIV-1 infection]. / Respuesta completa al tratamiento con doxiciclina en pacientes con infección por VIH-1 con proctitis por linfogranuloma venéreo.

INTRODUCTION: We present a series of 15 cases with lymphogranuloma venereum (LGV) with the aim of evaluating the response to a 21-day oral course of doxycycline (100mg twice daily). PATIENTS AND METHODS: It is an observational study where we describe a series of cases with LGV diagnosed in the Hospital Germans Trias i Pujol's HIV Unit between March 2008 and April 2009. RESULTS: All our patients were HIV infected men who had sex with men with proctitis in 80% of the cases. In all of them Chlamydia trachomatis was determined by PCR on rectal swab specimens, with a negative result after 21 days of treatment with doxycycline. Serovar L2 was confirmed in all the specimens with the reverse hybridization technique. DISCUSSION: A high index of clinical suspicion is the mainstay to the early diagnosis of LGV since the clinical presentation remains unspecific. The treatment with doxycycline eradicates C. trachomatis in HIV patients with LGV.

Lymphogranuloma venereum proctocolitis: a silent endemic disease in men who have sex with men in industrialised countries.

Lymphogranuloma venereum (LGV) is a sexually transmitted disease (STD) caused by serovars L1-L3 of Chlamydia trachomatis. Rare in the western world prior to 2003, different outbreaks or clusters of LGV have been reported in Europe, North America and Australia among men who have sex with men (MSM) over the past few years. The majority were HIV infected MSM with high-risk sexual behaviour and a high rate of concomitant STD, including hepatitis C. Most of them presented with a proctitis syndrome and only a few with the classical bubonic form. A previously non-described serovar, L2b, has been identified as the main causative agent of the epidemic. A delay in diagnosis has been the rule because of the misleading symptomatology of LGV proctitis, the unfamiliarity of the disease to physicians, and the lack of a routine diagnostic test for LGV serovars. It is crucial to increase the awareness of the disease among physicians for prompt diagnosis and treatment, to avoid complications, and to stop ongoing transmission. It has additional public health implications since LGV may facilitate the transmission and acquisition of HIV and other STD.

Proctocolitis alérgica, enterocolitis inducida por alimento: mecanismos inmunes, diagnóstico y tratamiento / No disponible

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