Age of onset of recurrent respiratory papillomatosis: a distribution analysis.

OBJECTIVE: Distribution of age of onset of recurrent respiratory papillomatosis (RRP) is generally described to be bimodal, with peaks at approximately 5 years and 30 years. This assumption has never been scientifically confirmed, and authors tend to refer to an article that does not describe distribution. Knowledge of the distribution of age of onset is important for virological and epidemiological comprehension. The objective of this study was to determine the distribution of age of onset of RRP in a large international sample. DESIGN: Cross-sectional distribution analysis. PARTICIPANTS: Laryngologists from 12 European hospitals provided information on date of birth and date of onset of all their RRP patients treated between 1998 and 2012. Centers that exclusively treated either patients with juvenile onset RRP or patients with adult onset RRP, or were less accessible for one of these groups, were excluded to prevent skewness. MAIN OUTCOME MEASURES: A mixture model was implemented to describe distribution of age of onset. The best fitting model was selected using the Bayesian information criterion. RESULTS: Six hundred and thirty-nine patients were included in the analysis. Age of onset was described by a three component mixture distribution with lognormally distributed components. Recurrent respiratory papillomatosis starts at three median ages 7, 35 and 64 years. CONCLUSIONS: Distribution of age of onset of RRP shows three peaks. In addition to the already adopted idea of age peaks at paediatric and adult age, there is an additional peak around the age of 64.

Safety of intralesional cidofovir in patients with recurrent respiratory papillomatosis: an international retrospective study on 635 RRP patients.

Intralesional use of cidofovir (Vistide(®)) has been one of the mainstays of adjuvant therapy in patients with recurrent respiratory papillomatosis (RRP) since 1998. In 2011, a communication provided by the producer of cidofovir addressed very serious side effects concerning its off-label use. As this was a general warning, it was inconclusive whether this would account for its use in RRP. The aim of this study is to determine whether nephrotoxic, neutropenic, or oncogenic side effects have occurred after intralesional use of cidofovir in patients with RRP. Update of recent developments in RRP, a multicentre questionnaire and a multicentre retrospective chart review. Sixteen hospitals from eleven countries worldwide submitted records of 635 RRP patients, of whom 275 were treated with cidofovir. RRP patients received a median of three intralesional injections (interquartile range 2-6). There were no statistical differences in occurrence of neutropenia or renal dysfunction before and after cidofovir. There was no statistical difference in occurrence of upper airway and tracheal malignancies between the cidofovir and the non-cidofovir group. In this retrospective patient chart review, no clinical evidence was found for more long-term nephrotoxicity, neutropenia or laryngeal malignancies after the administration of intralesional cidofovir in RRP patients.

Dermatological manifestations of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome.

BACKGROUND: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED; OMIM 240300) is a rare autosomal recessive disorder defined by a variable combination of endocrine failure, chronic mucocutaneous candidiasis (CMC), and dystrophy of the dental enamel and nails. APECED is caused by mutations in the autoimmune regulator gene (AIRE). Alopecia areata (AA) and vitiligo are diseases with autoimmune pathogeneses, and have been recognized as part of the APECED complex. There are rare reports of other cutaneous manifestations. OBJECTIVES: We sought to delineate the dermatological features of APECED in an Irish case series with emphasis on timing of their appearance and association with disease severity. Furthermore, we looked for evidence of genotype: phenotype correlation. Finally, we wanted to determine if the ectodermal changes described represent a primary ectodermal dysplasia or whether the ectodermal manifestations are secondary phenomena. METHODS: Irish patients with APECED were invited to attend a multidisciplinary clinic (Dermatology, Endocrinology, Dentistry and Ophthalmology) held in Our Lady's Hospital for Sick Children, Dublin. Clinical data were compiled from case notes and questionnaires. All patients had a detailed cutaneous examination. Blood samples were obtained for mutational analysis. RESULTS: Eighteen patients (seven males and 11 females) from 15 families were interviewed and examined. The mean age at diagnosis was 6 years (range 8 months-18 years). All patients had evidence of CMC, 13 (72%) had candidal onychomycosis or paronychia, six (33%) had AA and two had vitiligo. In the case of two patients the diagnosis was made on recognition of dermatological manifestations and confirmed by mutational analysis. Both patients developed Addison's disease on follow-up. CMC was an early feature, often predating diagnosis (10 of 18). AA and vitiligo presented later, and may reflect more severe disease in these cases. There was no correlation between the AIRE mutations identified on mutational analysis and the clinical presentation. We found no evidence of an isolated nail dystrophy or features consistent with a primary ectodermal dysplasia. CONCLUSIONS: APECED is a rare but complex and potentially life-threatening autoimmune disease. CMC is a common and early feature; diagnosis at this stage may pre-empt life-threatening endocrinological crises. It is important for dermatologists to be aware of this association as they are likely to be the earliest clinicians who encounter these children. AA and vitiligo in our series occurred in the setting of established disease. The term "ectodermal dystrophy" is misleading as the ectodermal features described in our series and in the literature are most likely to be secondary phenomena.