H influenzae LPS colocalization with Toll-like receptor 4 in eosinophilic esophagitis.

Background: Patients with eosinophilic esophagitis (EoE) have a unique esophageal microbiome with increased presence of Haemophilus influenzae, but its role in the disease is unclear. Objective: Microbiome-derived bacterial LPS activation of Toll-like receptors (TLR) is a potential mechanism for inducing inflammation in other chronic inflammatory diseases, but it has not been studied in EoE. Our aim was therefore to study microbiome-derived bacterial LPS activation of TLRs in EoE. Methods: We studied 10 patients with active EoE, 9 patients with inactive EoE, and 10 control patients. Esophageal biopsy samples from the controls, patients with active EoE (>15 eosinophils/hpf), and patients with inactive EoE were immunostained for the presence of H influenzae LPS, presence of TLR4, and colocalization of LPS and TLR4. Staining intensity was measured by using confocal laser microscopy and scored on a scale from 0 to 3 as the average score assigned by 2 blinded observers. Results: H influenzae LPS was detected by positive staining in 20 of the 29 patients (69.0%), including 9 of the 10 patients with active EoE (90.0%), 8 of the 9 patients with inactive EoE (89.9%), and 3 of the 10 controls (30%); its level was greater in the patients with active EoE than in the controls (P = .063). TLR4 was detected by positive staining in 19 of the 29 patients (65.5%), including 9 of the 10 patients with active EoE (90.0%), 4 of the 9 patients with inactive EoE (44.4%), and 6 of the 10 controls (60.0%); its level was higher in the patients with active EoE than in those with inactive EoE (P = .096). The result of testing for colocalization of LPS and TLR4 was positive in 8 of 10 patients with active EoE (80.0%), 1 of 9 patients with inactive EoE (11.1%), and 1 of 10 control patients (10.0%), with greater colocalization of H influenzae LPS and TLR4 staining density in the samples from patients with active EoE than in the controls or the patients with inactive EoE (P = .009 and P = .018, respectively). Conclusion: Esophageal microbiome-rich H influenzae LPS colocalizes to TLR4 in active EoE. These data lend further support to a role for the esophageal microbiome in modulating the activity of EoE.

AAAAI Mast Cell Disorders Committee Work Group Report: Mast cell activation syndrome (MCAS) diagnosis and management.

Our current recommendations for diagnosing and treating primary mast cell (MC) activation syndrome make use of the latest studies and consensus guidelines for clinically recognizing systemic anaphylaxis in real time, regardless of whether allergen-triggered or other pathways are involved; our current understanding of the biomarkers secreted by activated MCs that best discriminate this disorder from other conditions; and the therapeutic drugs that might selectively affect those mediators or MCs themselves. Finding familial or somatic mutations of genes that cause MCs to be hyperactivatable would extend our diagnostic tools and potentially indicate new therapeutic interventions, targeting either the mutated gene product or the associated molecular pathway. In conclusion, we trust that the clinical, laboratory, and therapeutic criteria for primary MC activation syndromes described herein will provide clinicians with practical criteria of sufficient sensitivity and specificity to diagnose most cases without overdiagnosing the disorder in patients who likely have other conditions.

Mast Cell Mediators of Significance in Clinical Practice in Mastocytosis.

Mast cells leave evidence, a "fingerprint," of their participation in acute and chronic clinical events. That fingerprint is an elevation, either chronic or acute, in levels of their secreted mediators or their metabolites. Of these, only serum tryptase is currently one of the diagnostic criteria for systemic mastocytosis or mast cell activation. Combinations of easily obtained and quantified urinary mast cell mediator metabolite levels correlate well with bone marrow findings of systemic mastocytosis. By inhibiting synthesis of or blockading receptors to the elevated mast cell mediator, relief of clinical symptoms can often be achieved.

Colectomy in refractory Crohn's colitis improves nutrition and reduces steroid use.

BACKGROUND: Pediatric patients with severe refractory Crohn's colitis (CC) may require total colectomy (TC) or diverting loop ileostomy (DLI). Our understanding of outcomes (postoperative complications, nutrition and restoration of intestinal continuity) is currently limited. METHODS: Pediatric patients with severe CC who underwent TC or DLI were identified. Demographics, pre and postoperative anthropometric and biochemical data, surgical complications and medication requirements were recorded. RESULTS: Twenty-seven patients (TC=22, DLI=5) with a median age of 15.0years (range 3-18) were identified, 64% male with a median follow-up of 45months (range 3-120). Mean weight and BMI improved for TC patients by 1year postoperatively - weight z-score from -1.08 to -0.54 (p=0.02), BMI z-score from -0.83 to -0.38 (p=0.04), with a non-significant height change from - 0.79 to -0.65 (p=0.07). Mean hemoglobin and albumin both also improved - 9.88g/dl to 11.76g/dl (p=0.003) and 3.44g/dl to 4.03g/dl (p=0.004) respectively. These measures did not significantly improve after DLI. Most TC patients (59%) had attempted restoration of intestinal continuity with 45% in continuity at end of follow-up. One DLI patient underwent ileostomy takedown but subsequently needed re-diversion. CONCLUSIONS: In severe CC, TC offers an opportunity to improve nutrition and growth, with a reasonable likelihood of restoring intestinal continuity. LEVEL OF EVIDENCE: Level IV - Case series.

Mast cell activation syndrome: improved identification by combined determinations of serum tryptase and 24-hour urine 11ß-prostaglandin2α.

BACKGROUND: Mast cell activation syndrome (MCAS) describes patients with episodes of mast cell mediator release, with negative bone marrow biopsy results, and the failure to meet the criteria for systemic mastocytosis. OBJECTIVE: Identify elevation of mast cell mediators of patients with MCAS. METHODS: We performed a retrospective study of 25 patients with MCAS who were evaluated at Mayo Clinic from 2006 to 2012. Patients were reviewed for MCAS symptoms and mast cell mediators, including serum tryptase and 24-hour urine N-methyl histamine (N-MH) and 11ß-prostaglandin-F2α (11ß-PGF2α). The study was approved by the institutional review board. RESULTS: Urinary 11ß-PGF2α was the most frequently elevated product in MCAS of our 25-patient cohort. Flushing and pruritus had the greatest correlation with elevation of 24-hour urine 11ß-PGF2α value at baseline. The serum tryptase level was elevated in 10 patients, whereas the N-MH level was elevated with 2 patients. Eight of 9 patients with MCAS and with elevated 24-hour urine 11ß-PGF2α who underwent aspirin therapy and follow-up urinary studies had normalization of this mediator (1 patient did not have a follow-up urine study). Six of these 9 patients with MCAS who underwent aspirin therapy had symptomatic improvement. CONCLUSION: We recommend measurement of 24-hour urine 11ß-PGF2α and serum tryptase levels of patients with symptoms suggestive of MCAS. Measurement of 24-hour urine 11ß-PGF2α and serum tryptase levels can help avoid misdiagnosis and overinterpretation of MCAS symptoms in clinical practice. Given that an elevation of 24-hour urine N-MH level was found only in 2 patients, measurement of this mediator may be less helpful in diagnosing MCAS. We recommend aspirin therapy for patients with MCAS and with elevated 24-hour urine 11ß-PGF2α levels.

Wells' syndrome associated with ulcerative colitis: a case report and literature review.

Wells' syndrome, also termed eosinophilic cellulitis, is a dermatologic condition of unknown etiology that occurs as recurrent patches or plaques mimicking infectious cellulitis. Histopathology reveals an eosinophilic infiltrate and characteristic flame figures. Previous reports have associated this syndrome with parasitic infections, arthropod bites, pharmacologic agents, surgery, and hematologic disorders. We present a case report of a patient with Wells' syndrome associated with newly diagnosed ulcerative colitis. The dermatosis erupted concurrently with flares of ulcerative colitis. Furthermore, treatment of the ulcerative colitis led to resolution of the skin lesions. To our knowledge this describes the first association between inflammatory bowel disease and Wells' syndrome and argues for a distinct relationship between the two.