RNF213-associated urticarial lesions with hypercytokinemia.

BACKGROUND: Urticarial lesions are observed in both cutaneous and systemic disorders. Familial forms of urticarial syndromes are rare and can be encountered in systemic autoinflammatory diseases. OBJECTIVE: We sought to investigate a large family with dominantly inherited chronic urticarial lesions associated with hypercytokinemia. METHODS: We performed a genetic linkage analysis in 14 patients from a 5-generation family, as well as whole-exome sequencing, cytokine profiling, and transcriptomic analyses on samples from 2 patients. The identified candidate protein was studied after in vitro expression of the corresponding normal and mutated recombinant proteins. An unsupervised proteomic approach was used to unveil the associated protein network. RESULTS: The disease phenotype of the most affected family members is characterized by chronic urticarial flares associated with extremely high plasma levels of proinflammatory (IL-1ß, IL-6, and TNF-α) and anti-inflammatory (IL-10 and IL-1 receptor antagonist [IL-1RA]) cytokines, with no secondary organ dysfunction, no susceptibility to infections, no fever, and normal C-reactive protein levels. Monocyte transcriptomic analyses identified an immunotolerant profile in the most affected patient. The affected family members carried a loss-of-function mutation in RNF213 that encodes mysterin, a protein with a poorly known physiologic role. We identified the deubiquitinase CYLD, a major regulator of inflammation, as an RNF213 partner and showed that CYLD expression is inhibited by wild-type but not mutant RNF213. CONCLUSION: We identified a new entity characterized by chronic urticarial lesions associated with a clinically blunted hypercytokinemia. This disease, which is due to loss of function of RNF213, reveals mysterin's key role in the complex molecular network of innate immunity.

The economics of cochlear implant management in France: a multicentre analysis.

This study assessed the direct medical cost of cochlear implantation in children and adults in France. A prospective multicentre study involving 19 French University Hospitals included 268 children and 201 adults who were severely to profoundly hearing-impaired. Medical resources utilisation included diagnostic tests, in-patient care, device implants, adverse events and follow-up visits for rehabilitation in the 1st year. The mean costs were 34,686 per child and 31,946 per adult. The cost of device implant represents 64.4% and 68.8% of the total cost for children and adults, respectively. The current reform of financing of the healthcare system requires detailed knowledge of the costs of interventions, hence the costs of cochlear implantation should be factored into resource allocation decisions. Differences in our results compared to other studies can be explained mostly by methodological differences in cost analyses.

Severe sialadenitis: a new complication of drug reaction with eosinophilia and systemic symptoms.

BACKGROUND: Drug cutaneous reaction and isolated cases of parotitis induced by terbinafine have been reported. OBSERVATION: We report a case of drug reaction with eosinophilia and systemic symptoms induced by terbinafine associated with a severe sialadenitis and a complete sicca syndrome. Evolution was protracted with a slow recovery of the rash but sicca syndrome persisted with only a very mild improvement at 6 months. CONCLUSION: Liver, kidneys, lungs, and heart are the organs the most frequently involved in drug reaction with eosinophilia and systemic symptoms. Salivary and lacrimal glands can also be severely involved in the course of drug reaction with eosinophilia and systemic symptoms.

Colonization of the oral cavity by Candida species: risk factors in long-term geriatric care.

The population of elderly people in hospitals for long-term geriatric care presents many risk factors for nosocomial infection by Candida species. The aim of this work was to reduce the risk of C. albicans nosocomial infections starting from colonization of the oral cavity. The population of concern was the patients in long-stay geriatrics units; a sample of 110 people was selected by drawing lots. The clinical and biological parameters of each patient included in the study were recorded. The oral cavity was colonized by Candida spp in 67% of cases. The distribution of the strains showed that C. albicans was the most frequently identified strain, followed by C. glabrata; of the 73 patients with at least one strain of Candida spp., 47 had a clinically diagnosed candidiasis (64.4%). The wearing of dentures was not statistically linked with the development of oral candidiasis. Detecting which patients have been colonized, identifying the risk factors and applying preventive measures should reduce the probability of elderly people falling into the vicious circle of infection-malnutrition-immune-depression.