Sclerosteosis is a progressive sclerosing bone dysplasia with an autosomal recessive mode of inheritance. Radiologically, it is characterized by a generalized hyperostosis and sclerosis leading to a markedly thickened and sclerotic skull, with mandible, ribs, clavicles and all long bones also being affected. Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur. Sclerosteosis is clinically and radiologically very similar to van Buchem disease, mainly differentiated by hand malformations and a large stature in sclerosteosis patients. By linkage analysis in one extended van Buchem family and two consanguineous sclerosteosis families we previously mapped both disease genes to the same chromosomal 17q12-q21 region, supporting the hypothesis that both conditions are caused by mutations in the same gene. After reducing the disease critical region to approximately 1 Mb, we used the positional cloning strategy to identify the SOST gene, which is mutated in sclerosteosis patients. This new gene encodes a protein with a signal peptide for secretion and a cysteine-knot motif. Two nonsense mutations and one splice site mutation were identified in sclerosteosis patients, but no mutations were found in a fourth sclerosteosis patient nor in the patients from the van Buchem family. As the three disease-causing mutations lead to loss of function of the SOST protein resulting in the formation of massive amounts of normal bone throughout life, the physiological role of SOST is most likely the suppression of bone formation. Therefore, this gene might become an important tool in the development of therapeutic strategies for osteoporosis.

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Introduction The novel Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, may need intensive care unit (ICU) admission in up to 12% of all positive cases for massive interstitial pneumonia, with possible long-term endotracheal intubation for mechanical ventilation and subsequent tracheostomy. The most common airway-related complications of such ICU maneuvers are laryngotracheal granulomas, webs, stenosis, malacia and, less commonly, tracheal necrosis with tracheo-esophageal or tracheo-arterial fistulae. Materials and methods This paper gathers the opinions of experts of the Laryngotracheal Stenosis Committee of the European Laryngological Society, with the aim of alerting the medical community about the possible rise in number of COVID-19-related laryngotracheal stenosis (LTS), and the aspiration of paving the way to a more rationale concentration of these cases within referral specialist airway centers. Results A range of prevention strategies, diagnostic work-up, and therapeutic approaches are reported and framed within the COVID-19 pandemic context. Conclusions One of the most important roles of otolaryngologists when encountering airway-related signs and symptoms in patients with previous ICU hospitalization for COVID-19 is to maintain a high level of suspicion for LTS development, and share it with colleagues and other health care professionals. Such a condition requires specific expertise and should be comprehensively managed in tertiary referral centers.

Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we review the currently known associations of HPV infections in diseases of the larynx and their potential for oncogenicity. Using several methods of detection, HPV DNA has been detected in benign (papillomatosis), indolent (verrucous carcinoma), and malignant (squamous cell carcinoma) lesions of the larynx. Consistent with the known oncogenic risk of HPV infections, common HPV types associated with laryngeal papillomatosis include low-risk HPV types 6 and 11, with high-risk HPV types 16 and 18 more commonly present in neoplastic lesions (verrucous carcinoma and squamous cell carcinoma). Although a broad range of prevalence has been noted in individual studies, approximately 25% of laryngeal squamous cell carcinomas harbor HPV infections on meta-analysis, with common involvement of high-risk HPV types 16 (highest frequency) and 18. Preliminary results suggest that these high-risk HPV infections seem to be biologically relevant in laryngeal carcinogenesis, manifested as having viral DNA integration in the cancer cell genome and increased expression of the p16 protein. Despite this knowledge, the clinical significance of these infections and the implications on disease prevention and treatment are unclear and require further investigation.

This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus‐based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue‐bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10–25% of patients laminin 332 is recognized. In 25–30% of MMP patients with anti‐laminin 332 reactivity, malignancies have been associated. As first‐line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first‐line regimens. Additional recommendations are given, tailored to treatment of single‐site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high‐quality randomized controlled trials.

Sclerostin is an inhibitor of bone formation expressed by osteocytes. We hypothesized that sclerostin is expressed by cells of the same origin and also embedded within mineralized matrices. In this study, we analyzed (a) sclerostin expression using immunohistochemistry, (b) whether the genomic defect in individuals with van Buchem disease (VBD) was associated with the absence of sclerostin expression, and (c) whether this was associated with hypercementosis. Sclerostin was expressed by cementocytes in mouse and human teeth and by mineralized hypertrophic chondrocytes in the human growth plate. In individuals with VBD, sclerostin expression was absent or strongly decreased in osteocytes and cementocytes. This was associated with increased bone formation, but no overt changes in cementum thickness. In conclusion, sclerostin is expressed by all 3 terminally differentiated cell types embedded within mineralized matrices: osteocytes, cementocytes, and hypertrophic chondrocytes.

In the last decades new endoscopic tools have been developed to improve the diagnostic work-up of vocal fold lesions in addition to normal laryngoscopy, i.e., contact endoscopy, autofluorescence, narrow band imaging and others. Better contrasted and high definition images offer more details of the epithelial and superficial vascular structure of the vocal folds. Following these developments, particular vascular patterns come into focus during laryngoscopy. The present work aims at a systematic pathogenic description of superficial vascular changes of the vocal folds. Additionally, new nomenclature on vascular lesions of the vocal folds will be presented to harmonize the different terms in the literature. Superficial vascular changes can be divided into longitudinal and perpendicular. Unlike longitudinal vascular lesions, e.g., ectasia, meander and change of direction, perpendicular vascular lesions are characterized by different types of vascular loops. They are primarily observed in recurrent respiratory papillomatosis, and in pre-cancerous and cancerous lesions of the vocal folds. These vascular characteristics play a significant role in the differential diagnosis. Among different parameters, e.g., epithelial changes, increase of volume, stiffness of the vocal fold, vascular lesions play an increasing role in the diagnosis of pre- and cancerous lesions.

Scarring of the vocal folds leads to a deterioration of the highly complex micro-structure with consecutively impaired vibratory pattern and glottic insufficiency. The resulting dysphonia is predominantly characterized by a reduced vocal capacity. Despite the considerable progress in understanding of the underlying pathophysiology, the treatment of scarred vocal folds is still an unresolved chapter in laryngology and phonosurgery. Essential for a successful treatment is an individual, multi-dimensional concept that comprises the whole armamentarium of surgical and non-surgical (i.p. voice therapy) modalities. An ideal approach would be to soften the scar, because the reduced pliability and consequently the increased vibratory rigidity impede the easiness of vibration. The chosen phonosurgical method is determined by the main clinical feature: Medialization techniques for the treatment of glottic gap, or epithelium freeing techniques for improvement of vibration characteristics often combined with injection augmentation or implantation. In severe cases, buccal mucosa grafting can be an option. New developments, include treatment with anxiolytic lasers, laser technology with ultrafine excision/ablation properties avoiding coagulation (Picosecond infrared laser, PIRL), or techniques of tissue engineering. However, despite the promising results by in vitro experiments, animal studies and first clinical trials, the step into clinical routine application has yet to be taken.