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Objective: To report a common site of external ear canal erosion in multiple pathologies, located inferiorly at 6 o'clock., Patients: Otology patients who came in 2023 for treatment of external auditory canal erosions., Intervention: This clinical capsule is an observational report of the external canal's propensity to erosion at the 6 o'clock location. Patient treatments were canalplasty, mastoidectomy, and medical management., Main Outcome Measure: Documentation of the propensity to erosion at the 6 o'clock location in the external auditory canal. Locations of the niduses of prior series of external auditory canal pathologies are documented., Results: Eight patients are presented with external auditory canal erosion in 10 ears originating at the 6 o'clock position medial to the bony-cartilaginous junction. No other patient with spontaneous canal erosion presented with their nidus of pathology in another canal location. (A review of 42 case series of 291 patients found that keratosis obturans and bisphosphonate-induced osteonecrosis tended to arise from the same 6 o'clock lateral bony canal location, while 26% of necrotizing otitis externa cases arose there.)., Conclusions: The "6 o'clock spot" in the external canal is a common location of canal erosion for spontaneous wax and keratin collections and may be the precursor to keratosis obturans, bisphosphonate-induced osteonecrosis of the ear canal, and necrotizing otitis externa., Competing Interests: The authors have no conflicts of interest to report, and this study had no funding., (Copyright © 2024, Otology & Neurotology, Inc.)

An obliterated Eustachian tube (ET) is a rare occurrence that can lead to chronic otitis media (OM) and aural fullness even with treatment. Our study presents a review of the literature on methods of stenting the ET. We additionally present a case of a man with mucoepidermoid carcinoma of the ET who underwent a radical nasal pharyngectomy with reconstruction and adjuvant radiation, and who had symptoms of intolerable otorrhea after tympanostomy tube placement to treat aural fullness and mucoid OM. We used a novel method of stenting the ET using a transnasal lighted guidewire catheter and steroid eluting stents placed along the entire medial ET. Previously described methods in the literature were unable to be used due to the complex middle ear anatomy filled with granulation tissue and the lack of a visible nasopharyngeal ET ostium available for straightforward placement of the stent. The procedure was successful, and postoperatively, the patient experienced decreased otorrhea., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Imaging of the temporal bone and middle ear is challenging for radiologists due to the abundance of distinct anatomical structures and the plethora of possible pathologies. The basis for a precise diagnosis is knowledge of the underlying anatomy as well as the clinical presentation and the individual patient's otological status. In this article, we aimed to summarize the most common inflammatory lesions of the temporal bone and middle ear, describe their specific imaging characteristics, and highlight their differential diagnoses. First, we introduce anatomical and imaging fundamentals. Additionally, a point-to-point comparison of the radiological and histological features of the wide spectrum of inflammatory diseases of the temporal bone and middle ear in context with a review of the current literature and current trends is given.

Auriculocondylar syndrome (ARCND) is a rare craniofacial birth defect characterized by malformations in the mandible and external ear (Question Mark Ear). Genetically, three distinct subtypes of ARCND (ARCND1, ARCND2, and ARCND3) have been identified. ARCND2 is linked to pathogenic variants in the PLCB4 gene (phospholipase C β4). PLCB4 is a key effector of the EDN1-EDNRA pathway involved in craniofacial development via the induction, migration, and maintenance of neural crest cells. ARCND2 is typically inherited in an autosomal dominant pattern, with recessive inheritance pattern being rare. In this study, we report the first homozygous missense variant (NM_000933.4: c.2050G>A: p.(Gly684Arg)) in the PLCB4 gene causing ARCND in a 3-year-old patient with a severe clinical phenotype of the syndrome. The patient presented with typical craniofacial ARCND features, in addition to intestinal transit defect, macropenis, and hearing loss. These findings further delineate the phenotypic spectrum of ARCND associated with autosomal recessive PLCB4 loss of function variants. Notably, our results provide further evidence that these variants can result in a more severe and diverse manifestations of the syndrome. Clinicians should consider the rare features of this condition for better management of patients., (© 2023 Wiley Periodicals LLC.)

The incidence of sebaceous carcinoma (SC) in the outer one-third of the external auditory canal is considered extremely rare, and only eight case reports have been published. We present a case of a male patient in his late 70s known case of hypertension on indapamide. His medical history included a postspinal tumour that had been treated with surgery and radiation more than 40 years ago and current complaints of right ear pain and purulent discharge. A right ear soft granular tissue mass was found. Complete debulking of the right ear mass was done in conjunction with middle ear exploration, moderately differentiated SC diagnosis was made based on the histopathological analysis. The patient was free of recurrence but then died of an unrelated pulmonary infection. SC should be suspected in elderly patients who present with long-term complaints of a mass with or without otalgia, and these patients should be examined for the presence of such tumours especially if they report a history of radiation. Additionally, more research is warranted to investigate the association of diuretics with SC., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the rate of dilatory (chronic obstructive) eustachian tube dysfunction (ETD) in adult patients scheduled for surgery for chronic inflammatory middle ear disease., Patients: We included adult patients with chronic inflammatory middle ear disease (chronic suppurative otitis media, adhesive otitis media [middle ear atelectasis], cholesteatoma). We excluded patients with pathologies that do not stem from ETD (e.g., noninflammatory chronic middle ear disease [e.g., otosclerosis], tumors, solely external auditory canal conditions), patients scheduled for implantable electronic hearing devices independent of disease, patients with otitis media with effusion and scheduled paracentesis or ventilation tubes only, patients with previous radiotherapy or previous balloon eustachian tuboplasty, and children and patients unable to complete questionnaires., Interventions: We evaluated ETD with Valsalva maneuver and in case of negative or unclear Valsalva with the eustachian tube score (ETS). A negative Valsalva maneuver and an ETS score of 5 or lower were used to define dilatory (chronic obstructive) ETD., Main Outcome Measures: Rate of ETD in the included patients., Results: From a total of 482 consecutive patients, 350 patients had positive Valsalva maneuver or ETS score higher than 5. From the 193 patients with negative or unclear Valsalva maneuver, 77 patients had an ETS score of 5 or lower, and 55 rejected further diagnostics with ETS., Conclusions: Based on a large cohort of adult patients with chronic inflammatory middle ear disease scheduled for middle ear surgery, the majority (82%) seems to have no dilatory (chronic obstructive) ETD that can be detected with current routine clinical methods and tubomanometry. Common pathophysiological explanations should be questioned critically, especially in the context of communication with patients., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

Introduction: External auditory canal cholesteatoma (EACC) is a rare disease, with an estimated incidence of approximately 1:1,000 adult and 1.6:1,000 pediatric otologic patients. Systematic studies of chronic ear disease and taste alteration prior to surgery are rare; in fact, there are no such studies for EACCs. Therefore, we describe chorda tympani nerve (CTN) dysfunction and the related clinical consequences in EACC patients., Methods/study Design: Between 1992 and 2021, we retrospectively analyzed the symptoms, signs, and radiological and intraoperative descriptions of CTN involvement in 73 patients. Liquid taste tests and, since 2009, Taste StripsTM as well as an olfactory screening test (Smell DiskettesTM) have been performed for all symptomatic patients and, when feasible, all other EACC patients., Results: Ten of 73 patients complained subjectively of dysfunction, and 8 showed abnormal taste test results. Four patients complained of olfactory dysfunction (3 cases with pathological taste tests). Gustatory dysfunction was most frequent in radiogenic EACC cases (n = 4), followed by postoperative EACC (n = 3). Two postoperative patients were asymptomatic despite abnormal test results. Rarely, patients with idiopathic (n = 2) and posttraumatic (n = 1) EACC showed acute taste dysfunction that was confirmed in each with abnormal test results., Discussion/conclusion: CTN dysfunction often developed asymptomatically in chronic ears, except for idiopathic and posttraumatic EACCs under previous healthy middle ear conditions. Taste disturbance is not a cardinal symptom of EACC, but objective testing suggests that up to one out of 10 EACC patients with advanced disease may experience regional gustatory dysfunction prior to surgery. Especially in context of a new and acute presentation, regional taste dysfunction may alert the clinician of potential progressive EACC invasion and danger to the facial nerve., (© 2023 S. Karger AG, Basel.)

Background: Auriculocondylar syndrome (ARCND) is a rare genetic disease that affects structures derived from the first and second pharyngeal arches, mainly resulting in micrognathia and auricular malformations. To date, pathogenic variants have been identified in three genes involved in the EDN1-DLX5/6 pathway ( PLCB4 , GNAI3 and EDN1 ) and some cases remain unsolved. Here we studied a large unsolved four-generation family., Methods: We performed linkage analysis, resequencing and Capture-C to investigate the causative variant of this family. To test the pathogenicity of the CNV found, we modelled the disease in patient craniofacial progenitor cells, including induced pluripotent cell (iPSC)-derived neural crest and mesenchymal cells., Results: This study highlights a fourth locus causative of ARCND, represented by a tandem duplication of 430 kb in a candidate region on chromosome 7 defined by linkage analysis. This duplication segregates with the disease in the family (LOD score=2.88) and includes HDAC9 , which is located over 200 kb telomeric to the top candidate gene TWIST1 . Notably, Capture-C analysis revealed multiple cis interactions between the TWIST1 promoter and possible regulatory elements within the duplicated region. Modelling of the disease revealed an increased expression of HDAC9 and its neighbouring gene, TWIST1 , in neural crest cells. We also identified decreased migration of iPSC-derived neural crest cells together with dysregulation of osteogenic differentiation in iPSC-affected mesenchymal stem cells., Conclusion: Our findings support the hypothesis that the 430 kb duplication is causative of the ARCND phenotype in this family and that deregulation of TWIST1 expression during craniofacial development can contribute to the phenotype., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To describe cases of patulous Eustachian tube (PET) or patent ET conditions in oculopharyngeal muscular dystrophy (OPMD)., Patients: Four cases of PET or patent ET conditions with OPMD., Main Outcome Measures: Clinical case records, objective ET function tests (tubo-tympano-aerodynamic graphy and sonotubometry), and swallowing function (videoendoscopic examination and Food Intake Level Scale) were analyzed., Results: Two cases of definite PET, one case of possible PET, and one case lacking aural symptoms with findings of patent ET. All patients have ptosis, and three cases have dysphagia. Body mass index indicated that three cases were underweight. Magnetic resonance imaging in case 4 showed atrophy and fat replacement of palatine and masticatory muscles., Conclusions: It is important to consider PET or patent ET conditions when OPMD patients describe aural symptoms., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

Purpose: Auricular pseudocyst (AP) is a benign, noninflammatory swelling to the ear, located on either the front or side surface. Deroofing surgery with variable compression methods is considered the most effective method. However, post-operative wound pain is the main drawback following compression. We are introducing a novel painless surgical procedure which involves deroofing technique followed by Merocel® compression dressing., Methods: From 2015 to 2020, thirty-one patients with AP received this new surgical compression method in our university-affiliated tertiary hospital. Retrospective chart review and the analysis of the results were conducted., Results: All patients had unilateral lesions, with left side lesions (58.1%) predominant. The concha cymba (38.7%) and concha cavum (35.8%) were the most common sites. Previous aspiration or drainage had been performed for the cysts in eight patients (25.8%). Only one patient had the recurrence after post-operative 3 months and received the revised surgery without following recurrence and discomfort. Among all patients, 29 (93.5%) patients claimed minimal pain around 0 or 1 in numeric rating scale of pain score. Three patients had mild ecchymosis but recovered after conservative treatment. One patient had mild auricular deformity after surgery due to pre-treatment partial cartilage necrosis. All patients had follow-up for at least 6 months., Conclusion: This novel Merocel® compression dressing technique to treat AP after deroofing is an effective procedure. Minimal pain, simple to do and easily acquired materials were the advantages of this novel procedure., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: Chondrodermatitis nodularis helicis is an inflammatory condition affecting the helix or antihelix of the ear. It is commonly described as a solitary, painful, ulcerated nodule affecting the cartilage or skin because of continuous pressure, trauma, sun exposure, or ischemic changes. In this case report, we present a rare variant of chondrodermatitis, named chondrodermatitis nodularis nasi, which affects the skin and cartilage of the nose. Clinical resemblance to neoplasms of the skin such as squamous cell carcinoma and basal cell carcinoma requires that a biopsy be performed for definitive diagnosis. On histopathological examination, chondrodermatitis presents as a central ulcer bordered by epidermal hyperplasia, hypergranulosis, hyperkeratosis, and parakeratosis with fibrin deposits in the papillary dermis admixed with sparse inflammatory cells. Included in this case report is a discussion of the clinical and histopathology of chondrodermatitis nodularis nasi. With increased frequency of diagnosing this rare variant, better management and treatments can be explored., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Here, we report a unique case in which a fibroepithelial polyp was found in the cartilaginous part of the external auditory canal of a 2-year-old child. The polyp was successfully treated by excision using an endaural approach and healed without complications. This is the very first report of a fibroepithelial polyp in the external auditory canal in the pediatric population. Although fibroepithelial polyp is an extremely rare diagnosis, it should be considered in the differential diagnosis of a child's external auditory canal polyp.

Objective: To present a rare case of a middle ear capillary hemangioma in an adult., Patient: A 31-year-old woman with a 6-month history of left ear fullness, pressure, tinnitus, and progressive hearing loss., Intervention: Endoscopic laser-assisted resection., Main Outcome Measures: Clinical, radiographic, and histopathological findings of a capillary hemangioma., Results: Otoscopy revealed an erythematous and slightly pulsating multilobulated middle ear retrotympanic mass. Her audiogram demonstrated a left-sided mixed hearing loss with air-conduction thresholds in the severe-to-profound range. Computed tomography (CT) imaging was significant for total opacification of the left middle ear and mastoid air cells. She underwent a combined endoscopic transcanal and transmastoid excision of the mass with ossicular chain reconstruction. A KTP laser was used to ablate and shrink down the periphery of the lesion. Pathology of the specimen was consistent with a capillary hemangioma. The patient's pulsatile tinnitus and spontaneous vertigo resolved postoperatively., Conclusions: Capillary hemangiomas are an uncommon cause of vascular middle ear lesions in adults and typically present with symptoms of aural fullness, pulsatile tinnitus, conductive hearing loss, otalgia, and vertigo. Surgery resection provides definitive treatment and the use of laser ablation techniques can allow for hemostasis and excellent visualization., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021, Otology & Neurotology, Inc.)

Auriculocondylar syndrome (ARCND) is an autosomal monogenic disorder characterised by external ear abnormalities and micrognathia due to hypoplasia of the mandibular rami, condyle and coronoid process. Genetically, three subtypes of ARCND (ARCND1, ARCND2 and ARCND3) have been reported. To date, five pathogenic variants of GNAI3 have been reported in ARCND1 patients. Here, we report a novel variant of GNAI3 (NM_006496:c.807C>A:p.(Asn269Lys)) in a Japanese girl with micrognathia using trio-based whole exome sequencing analysis. The GNAI3 gene encodes a heterotrimeric guanine nucleotide-binding protein. The novel variant locates the guanine nucleotide-binding site, and the substitution was predicted to interfere with guanine nucleotide-binding by in silico structural analysis. Three-dimensional computer tomography scan, or cephalogram, displayed severely hypoplastic mandibular rami and fusion to the medial and lateral pterygoid plates, which have been recognised in other ARCND1 patients, but have not been described in ARCND2 and ARCND3, suggesting that these may be distinguishable features in ARCND1., (© 2021. The Author(s).)

Objectives: Sarcoidosis is a multisystemic inflammatory disease with extrathoracic manifestations, most commonly affecting the young and middle-aged, female and Black populations. Diagnosis usually requires evidence of non-caseating granulomata and, when treated, prognosis is usually favourable. We aim to establish the incidence, clinical features and optimal treatment of ENT manifestations of this disease., Design: We performed a PubMed literature review to determine the evidence base supporting this., Results: ENT manifestations are present in 5%-15% of patients with sarcoidosis, often as a presenting feature, and require vigilance for swift recognition and coordinated additional treatment specific to the organ. Laryngeal sarcoidosis presents with difficulty in breathing, dysphonia and cough, and may be treated by speech and language therapy (SLT) or intralesional injection, dilatation or tissue reduction. Nasal disease presents with crusting, rhinitis, nasal obstruction and anosmia, usually without sinus involvement. It is treated by topical nasal or intralesional treatments but may also require endoscopic sinus surgery, laser treatment or even nasal reconstruction. Otological disease is uncommon but includes audiovestibular symptoms, both sensorineural and conductive hearing loss, and skin lesions., Conclusions: The consequences of ENT manifestations of sarcoidosis can be uncomfortable, disabling and even life-threatening. Effective management strategies require good diagnostic skills and use of specific therapies combined with established treatments such as corticosteroids. Comparisons of treatment outcomes are needed to establish best practice in this area., (© 2021 John Wiley & Sons Ltd.)

There are a large number of remedies in traditional medicine focused on relieving pain and inflammation. Flavanones have been a potential source in the search for leading compounds and biologically active components, and they have been the focus of much research and development in recent years. Eysenhardtia platycarpa is used in traditional medicine for the treatment of kidney diseases, bladder infections, and diabetes mellitus. Many compounds have been isolated from this plant, such as flavones, flavanones, phenolic compounds, triterpenoid acids, chalcones, sugars, and fatty acids, among others. In this paper, natural flavanone 1 (extracted from Eysenhardtia platycarpa ) as lead compound and flavanones 1a - 1d as its structural analogues were screened for anti-inflammatory activity using Molinspiration ® and PASS Online in a computational study. The hydro alcoholic solutions (FS) of flavanones 1 , 1a - 1d (FS 1 , FS 1a -FS 1d ) were also assayed to investigate their in vivo anti-inflammatory cutaneous effect using two experimental models, a rat ear edema induced by arachidonic acid (AA) and a mouse ear edema induced by 12- O -tetradecanoylphorbol acetate (TPA). Histological studies and analysis of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were also assessed in AA-inflamed rat ear tissue. The results showed that the flavanone hydro alcoholic solutions (FS) caused edema inhibition in both evaluated models. This study suggests that the evaluated flavanones will be effective when used in the future in skin pathologies with inflammation, with the results showing 1b and 1d to be the best.

Branchial cleft anomalies (BCA) are among the most common congenital anomalies found in the pediatric head and neck. The embryology of these congenital anomalies is well understood, which allows clinicians to anticipate their diagnosis when a pediatric patient presents with a head or neck mass. The predictable anatomy of the various types of BCA allows for improved surgical planning to prevent recurrence and ensure complete resection. This report details an unusual location of a first BCA located in the ear lobule of a 10-month old male. There has been no documented first BCA at the ear lobule in the literature., (Copyright © 2021. Published by Elsevier Inc.)

Early detection and appropriate medical treatment are of great use for ear disease. However, a new diagnostic strategy is necessary for the absence of experts and relatively low diagnostic accuracy, in which deep learning plays an important role. This paper puts forward a mechanic learning model which uses abundant otoscope image data gained in clinical cases to achieve an automatic diagnosis of ear diseases in real time. A total of 20,542 endoscopic images were employed to train nine common deep convolution neural networks. According to the characteristics of the eardrum and external auditory canal, eight kinds of ear diseases were classified, involving the majority of ear diseases, such as normal, Cholestestoma of the middle ear, Chronic suppurative otitis media, External auditory cana bleeding, Impacted cerumen, Otomycosis external, Secretory otitis media, Tympanic membrane calcification. After we evaluate these optimization schemes, two best performance models are selected to combine the ensemble classifiers with real-time automatic classification. Based on accuracy and training time, we choose a transferring learning model based on DensNet-BC169 and DensNet-BC1615, getting a result that each model has obvious improvement by using these two ensemble classifiers, and has an average accuracy of 95.59%. Considering the dependence of classifier performance on data size in transfer learning, we evaluate the high accuracy of the current model that can be attributed to large databases. Current studies are unparalleled regarding disease diversity and diagnostic precision. The real-time classifier trains the data under different acquisition conditions, which is suitable for real cases. According to this study, in the clinical case, the deep learning model is of great use in the early detection and remedy of ear diseases.

Objectives: The post-traumatic ear deformity, known today as cauliflower ear, has been described since antiquity. It has long been associated with pugilistic sports (wrestling, boxing) as well as among the mentally ill. The aim of this study is to present the various terms used since antiquity to describe these traumatic deformations of the auricle and to trace the origin of the modern moniker "cauliflower ear.", Methods: Historical study, only based on original documentation accessed through personal libraries and universities repositories, completed with online sources and etymological dictionaries., Results: We were able to identify no fewer than 39 names for the deformity. The term cauliflower ear is of relatively recent origin. It was coined in the first decade of the 20th century, initially in the popular press and subsequently adopted by the medical profession., Conclusion: Ironically, the deformity has only superficial resemblance to a cauliflower. The vegetable, which is part of the cabbage family, has a symmetrical and highly ordered fractal geometry with well-circumscribed excrescences. Cauliflower ear, by contrast, notably lacks symmetry and its rounded protuberances flow into one another. Although somewhat a misnomer, the term is deeply rooted in both popular and medical culture., Level of Evidence: N/A Laryngoscope, 131:E1315-E1321, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Chronic obstructive Eustachian tube dysfunction (ETD) is a common disorder of the middle ear. In recent years, two main diagnostic tools have become available: Eustachian tube score (ETS-7) and computed tomography (CT) combined with Valsalva maneuver. The aim of this study is to evaluate the outcomes of ETS-7 and CT in a group of patients affected by middle ear atelectasis with a strong suspicion of ETD. Three males and nine females, affected by middle ear atelectasis with retraction of the TM were enrolled. Each patient underwent to Eustachian tube dysfunction evaluation adopting the ETS-7 score and a temporal bone CT with Valsalva maneuver. The ears analyzed at steady state were divided into 2 groups: ETS<7 group and ETS≥ 7 group. The same division was applied for the ears analyzed after the Valsalva maneuver: ETS<7 group and ETS≥ 7 group. ETs were categorized as "well defined" (WD) and "not defined" (ND). The results of the analysis of the ETS-7 score in all 24 ears showed that 42% presented ETS ≥7, while 58% had ETS <7, indicating a diagnosis of ETD. In the ETS<7 group after Valsalva, ET was visualized in 33% of patients. In the ETS≥7 group it was WD in 29% after the Valsalva manoeuver. In both groups the comparison between the visualization of the ET before and after the Valsalva manoeuver did not present a statistical difference. No correlation emerged between ET evaluation with CT scan during Valsalva maneuver and ETS-7 score. It confirms that there is not a gold standard for the study of ET dysfunction., Competing Interests: The authors have declared that no competing interests exist.

Atopic dermatitis (AD) is a complex, often lifelong allergic disease with severe pruritus affecting around 10% of both humans and dogs. To investigate the role of mast cells (MCs) and MC-specific proteases on the immunopathogenesis of AD, a vitamin D 3 -analog (MC903) was used to induce clinical AD-like symptoms in c-kit-dependent MC-deficient Wsh -/- and the MC protease-deficient mMCP-4 -/- , mMCP-6 -/- , and CPA3 -/- mouse strains. MC903-treatment on the ear lobe increased clinical scores and ear-thickening, along with increased MC and granulocyte infiltration and activity, as well as increased levels of interleukin 33 (IL-33) locally and thymic stromal lymphopoietin (TSLP) both locally and systemically. The MC-deficient Wsh -/- mice showed significantly increased clinical score and ear thickening albeit having lower ear tissue levels of IL-33 and TSLP as well as lower serum levels of TSLP as compared to the WT mice. In contrast, although having significantly increased IL-33 ear tissue levels the chymase-deficient mMCP-4 -/- mice showed similar clinical score, ear thickening, and TSLP levels in ear tissue and serum as the WT mice, whereas mMCP-6 and CPA3 -deficient mice showed a slightly reduced ear thickening and granulocyte infiltration. Our results suggest that MCs promote and control the level of MC903-induced AD-like inflammation.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare, benign vascular tumor. Although its etiology is not clearly known, infection, hormonal factors, and trauma are the suspected reasons. There are few cases considered to be related to pregnancy described in the literature. Granulomas are rarely seen in the histopathology and only four patients with granulomas have been described. Herein, we will present a 28-year-old woman who has been pregnant three times; in every pregnancy, she developed pink nodular lesions on the back of her ear. In the first two pregnancies, the lesions had appeared during the pregnancy and regressed completely in the postpartum period. In her third pregnancy, the condition emerged again and lasted 1.5 years after birth of her child. Histopathology exhibited ALHE with granulomas. Although the relationship between ALHE and pregnancy is already known, there are few cutaneous ALHE cases associated with pregnancy reported in the literature. This association is further supported by this case having recurrent ALHE during each pregnancy period. Also, the presence of naked granuloma in histopathology, unlike most of the cases, contributes to the current histopathological data.

Primrose syndrome is characterized by variable intellectual deficiency, behavior disorders, facial features with macrocephaly, and a progressive phenotype with hearing loss and ectopic calcifications, distal muscle wasting, and contractures. In 2014, ZBTB20 variants were identified as responsible for this syndrome. Indeed, ZBTB20 plays an important role in cognition, memory, learning processes, and has a transcription repressive effect on numerous genes. A more severe phenotype was discussed in patients with missense single nucleotide variants than in those with large deletions. Here, we report on the clinical and molecular results of 14 patients: 6 carrying ZBTB20 missense SNVs, 1 carrying an early truncating indel, and 7 carrying 3q13.31 deletions, recruited through the AnDDI-Rares network. We compared their phenotypes and reviewed the data of the literature, in order to establish more powerful phenotype-genotype correlations. All 57 patients presented mild-to-severe ID and/or a psychomotor delay. Facial features were similar with macrocephaly, prominent forehead, downslanting palpebral fissures, ptosis, and large ears. Hearing loss was far more frequent in patients with missense SNVs (p = 0.002), ectopic calcification, progressive muscular wasting, and contractures were observed only in patients with missense SNVs (p nonsignificant). Corpus callosum dysgenesis (p = 0.00004), hypothyroidism (p = 0.047), and diabetes were also more frequent in this group. However, the median age was 9.4 years in patients with deletions and truncating variant compared with 15.1 years in those with missense SNVs. Longer follow-up will be necessary to determine whether the phenotype of patients with deletions is also progressive.

Primrose syndrome (OMIM 259050) is a rare disorder characterised by macrocephaly with developmental delay, a recognisable facial phenotype, altered glucose metabolism, and other features such as sensorineural hearing loss, short stature, and calcification of the ear cartilage. It is caused by heterozygous variants in ZBTB20, a member of the POK family of transcription repressors. Recently, this gene was shown to have a role in skeletal development through its action on chondrocyte differentiation by repression of SOX9. We describe five unrelated patients with Primrose syndrome and distinct skeletal features including multiple Wormian bones, platybasia, bitemporal bossing, bathrocephaly, slender bones, epiphyseal and spondylar dysplasia. The radiological abnormalities of the skull and the epiphyseal dysplasia were the most consistent findings. This novel constellation of skeletal features expands the phenotypic spectrum of the disorder., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Juvenile xanthogranulomas (JXG) are the most common type of self-limiting non-Langerhans cell histiocytosis (LCH) usually presenting in infancy and early childhood. Clinically, they present as solitary to multiple rounded cutaneous nodules which resolve over time. Adult type xanthogranulomas (AXG), though histologically similar to JXG, are usually single and do not regress spontaneously. AXG arising in the external auditory canal (EAC) is a rare occurrence with very few cases reported in literature. We present a case of AXG in a 48-year-old man, arising from the right EAC. This case is unique as it is the only case to be described with both cytology and histology correlation. On cytology, smears showed scattered foamy histiocytes, inflammatory cells and thick stromal fragments. Cytology differential diagnoses of xanthomatous lesion, benign fibrous histiocytoma (BFH) and ceruminous adenoma were given; final diagnosis was deferred to histopathology which confirmed it to be an AXG. Thus, it is important to keep the diagnosis of AXG in mind while dealing with solitary polypoidal lesions in EAC showing prominent foam cell component. Lipidised BFH forms a close differential diagnosis, however can be excluded by subtle points on cytology and on histopathology., (© 2020 Wiley Periodicals, Inc.)

Primrose syndrome (PS; MIM# 259050) is characterized by intellectual disability (ID), macrocephaly, unusual facial features (frontal bossing, deeply set eyes, down-slanting palpebral fissures), calcified external ears, sparse body hair and distal muscle wasting. The syndrome is caused by de novo heterozygous missense variants in ZBTB20. Most of the 29 published patients are adults as characteristics appear more recognizable with age. We present 13 hitherto unpublished individuals and summarize the clinical and molecular findings in all 42 patients. Several signs and symptoms of PS develop during childhood, but the cardinal features, such as calcification of the external ears, cystic bone lesions, muscle wasting, and contractures typically develop between 10 and 16 years of age. Biochemically, anemia and increased alpha-fetoprotein levels are often present. Two adult males with PS developed a testicular tumor. Although PS should be regarded as a progressive entity, there are no indications that cognition becomes more impaired with age. No obvious genotype-phenotype correlation is present. A subgroup of patients with ZBTB20 variants may be associated with mild, nonspecific ID. Metabolic investigations suggest a disturbed mitochondrial fatty acid oxidation. We suggest a regular surveillance in all adult males with PS until it is clear whether or not there is a truly elevated risk of testicular cancer., (© 2020 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Objectives/hypothesis: This study compares image quality and appropriateness for teleconsultations for three different otological conditions., Study Design: Web-based survey., Methods: We compared four digital otoscopes via a Web-based questionnaire distributed to all Finnish ear, nose, and throat (ENT) specialists and residents. The survey consisted of three fictional patient cases, each of which was presented with images taken using the otoscopes studied. Respondents assessed the image quality on a visual analog scale (VAS), assessing its appropriateness for teleconsultations and comparing images taken using different otoscopes to one another., Results: In total, 98 individuals responded, consisting of 81 ENT specialists and 17 ENT residents. The CellScope Oto and Digital MacroView received higher VAS scores for image quality and appropriateness for teleconsultations than the FireFly and Delfino otoscopes (P < .001 for all comparisons). Respondents considered the CellScope Oto more appropriate for teleconsultations for exostoses than the three other otoscopes. The CellScope Oto and Digital MacroView were equally appropriate in the two other cases (normal ear and perforated tympanic membrane)., Conclusions: Both digital otoscopes and the underlying otological conditions affect the appropriateness of teleconsultations. Moreover, both factors should be considered when evaluating the suitability of otologic teleconsultations. Among the otoscopes evaluated, images taken using the CellScope Oto received the best overall assessments., Level of Evidence: NA Laryngoscope, 130:1572-1576, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Auriculocondylar syndrome (ARCND, MIM #614669, #602483, and #615706); also known as ''question-mark ear syndrome'' or ''dysgnathia complex'', is a rare craniofacial malformation of first and second branchial arches with a prevalence of <1/1,000,000. It is characterized by a distinctive auricular malformation (question mark ear (QME)) and highly variable mandibular anomalies. Variants found in PLCB4, GNAI3, and in EDN1 genes are responsible for >90% of tested ARCND patients. Whole exome sequencing in a multigenerational Egyptian kindred with high intrafamilial variability revealed a known heterozygous missense variant in PLCB4 (NM&#95;000933.3:c.1862G>A:p.(Arg621His)). This report increases the number of molecularly characterized ARCND patients to 29 and emphasizes the highly variable clinical presentation within families., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

In this study, we isolated from the aerial parts of Baccharis conferta Kunth (i) a new neoclerodane, denominated "bacchofertone"; (ii) four known terpenes: schensianol A, bacchofertin, kingidiol and oleanolic acid; and (iii) two flavonoids: cirsimaritin and hispidulin. All structures were identified by an exhaustive analysis of nuclear magnetic resonance (NMR) and mass spectroscopy (MS). Extracts from aerial parts were screened for anti-inflammatory activity in the mice ear edema model of 12- O -tetradecanoylforbol-13-acetate mice. Dichloromethane extract (BcD) exhibited 78.5 ± 0.72% inhibition of edema, followed by the BcD2 and BcD3 fractions of 71.4% and 82.9% respectively, at a dose of 1 mg/ear. Kingidiol and cirsimaritin were the most potent compounds identified, with a median effective dose of 0.12 and 0.16 mg/ear, respectively. A histological analysis showed that the topical application of TPA promoted intense cell infiltration, and this inflammatory parameter was reduced with the topical application of isolated compounds.

Objectives/hypothesis: To review an institutional experience with auricular hematoma across all clinical settings including the emergency department (ED) and outpatient clinics at an urban tertiary care academic hospital, characterize practice patterns across setting and specialty, and assess for factors predictive of treatment success., Methods: Patients presenting to the ED, admitted to an inpatient ward, or seen in the outpatient setting between 2000 and 2017 with a diagnosis of auricular hematoma were reviewed. A number of relevant patient features including demographic factors, medications, and social risk factors were analyzed, as were several factors related to the presentation and management of the hematoma to identify variables of clinical significance., Results: A total of 87 individual cases were identified. Auricular hematomas most commonly occurred in males after sports-related trauma (e.g., martial arts, wrestling, boxing). Factors associated with lower rates of recurrence included initial treatment by or in consultation with an otolaryngologist and application of a bolster dressing., Conclusions: In our cohort, initial management of auricular hematoma by an otolaryngologist or with an otolaryngology consultation and placement of a bolster dressing was associated with lower rates of hematoma recurrence., Level of Evidence: 2b Laryngoscope, 130:628-631, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Primrose syndrome is a congenital malformation syndrome characterized by intellectual disability, developmental delay, progressive muscle wasting, and ear lobe calcification. Mutations in the ZBTB20 gene have been established as being accountable for this syndrome. In this study, a novel de novo ZBTB20 mutation, NM&#95;001164342.2:c.1945C>T (p.Leu649Phe), has been identified through whole exome sequencing (WES) in a female patient presenting a typical Primrose phenotype. Because the present patient exhibited recurrent otitis media, detailed immunological examinations were performed in this study and subnormal immunoglobulin levels were firstly identified in a Primrose patient. Anatomical anomaly of the inner ear has never been reported in this patient and WES data did not include any relevant variants causally linked with the immunologic defect. Thus, there is a possibility of a relation between an unclassified immunodeficiency with selective IgG2 deficiency and Primrose syndrome and this may be the reason of recurrent otitis media frequently observed in Primrose patients. Because subnormal levels of IgG2 in this patient might be caused by an unrelated and still uncharacterized genetic cause, further studies are required to prove the causal link between aberrant ZBTB20 function and immunodeficiency., (© 2019 Wiley Periodicals, Inc.)

Objective: Patulous eustachian tube (PET) is currently treated using a variety of conservative or surgical approaches. To further elucidate the pathology of PET and to establish new therapies, the development of an animal model is necessary. The objective of this study was to develop a highly reproducible and sustainable rat model of PET by mandibular nerve resection., Methods: Sixteen rats underwent mandibular nerve resection. Following an external incision, the main trunk of the mandibular nerve at the foramen ovale was identified in the pterygoid fossa, and its branches were resected. This surgery was performed on the right side, with the unoperated left side used as the control. To determine eustachian tube (ET) function, passive opening pressure (POP) was measured using inflation method up to Week 16 post-surgery. Changes in POP were statistically compared to the preoperative level on the operated and control sides. In addition, specimens of the ET and its surrounding tissue at Week 16 post-surgery were prepared for morphological evaluation in eight rats., Results: On the control side, POP did not significantly decrease across the 16 weeks post-surgery compared to the preoperative level. In contrast, on the operated side, POP was significantly decreased at Week 2 and continued to be lower than the preoperative level until at least Week 16 post-surgery. POP dropped 10% or more on the operated side examined in thirteen rats. Histologically, the medial pterygoid muscle was atrophied on the operated side mainly., Conclusion: Mandibular nerve resection in rats may be an effective method for generating an animal model of PET. It was suggested that this rat model may be useful for verifying new treatments for PET., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chondrodermatitis nodularis helicis (CNH) is a solitary, chronic, painful, often ulcerated lesion on the upper portion of the ear, mostly in older men. We present an unusual case of CNH in a 17-year-old adolescent boy who was a lifeguard. Correlation between clinical and histopathologic characteristics of CNH is outlined in the context of the existing literature to increase awareness of this condition in younger patients as well as to guide appropriate management and surveillance.

Previous study reported that either selective GSK-3β inhibitor or up-regulating autophagy can alleviate cisplatin-induced ototoxicity. Other studies indicate that the activity of GSK-3β is closely associated with the autophagy level. The purpose of this study is to primarily explore the role of autophagy in the alleviation effect of GSK-3β inhibition on cisplatin-induced ototoxicity in vivo and in vitro. We observed the autophagy changes induced by GSK-3β inhibitor in outer hair cells (OHCs) in a cisplatin-induced ototoxicity rat model. In addition, autophagy inhibitor 3-MA was used in vitro experiments to observe the influence of autophagy inhibition on the cell protection effect due to GSK-3β inactivation. The relationship among autophagy, GSK-3β and cell damage were inferred. Negative regulation of GSK-3β significantly enhanced autophagy and alleviated cisplatin-induced hearing loss, OHC death in vivo and apoptosis in vitro. The autophagy inhibitor 3-MA inverted the protective effect of negative regulation of GSK-3β. These results indicated that enhancing autophagy may be a key downstream effect of GSK-3β inhibition in the alleviation of cisplatin-induced ototoxicity both in vivo and in vitro., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To present the first case of osteonecrosis of the external auditory canal associated with sorafenib treatment., Patient: 58-year-old patient with right-sided otorrhea and otalgia was treated for otitis externa for 1 month without improvement. Otoscopic examination revealed a large defect in the inferior wall of the tympanic bone filled with skin debris and bony fragments. Previous medical history included treatment with sorafenib for metastatic renal cell cancer; he had never been exposed to radiotherapy. Computed tomography of the temporal bone showed a large right external auditory canal bony erosion with involvement of the tympanic bone and bony sequestra extending to the mastoid cells and temporomandibular joint. Histologic examination revealed necrotic bone and inflammatory changes with no signs of malignancy. A diagnosis of osteonecrosis of external auditory canal was made., Intervention: Right subtotal petrosectomy with obliteration of surgical cavity with abdominal fat was performed., Results: Final histological report revealed avascular necrosis of the bone with perivascular lymphocitic infiltration of the soft tissues. Diagnosis of medication-related external auditory canal osteonecrosis was confirmed., Conclusion: Medication-related osteonecrosis of the temporal bone is not a well-known entity among otolaryngologists and could therefore be misclassified as another diagnosis. In patients with othorrea and earache following sorafenib treatment, temporal bone osteonecrosis should be suspected.

External auditory exostoses (EAE) have been noted among the Neandertals and a few other Pleistocene humans, but until recently they have been discussed primary as minor pathological lesions with possible auditory consequences. An assessment of available western Eurasian late Middle and Late Pleistocene human temporal bones with sufficiently preserved auditory canals (n = 77) provides modest levels of EAE among late Middle Pleistocene archaic humans (≈20%) and early modern humans (Middle Paleolithic: ≈25%; Early/Mid Upper Paleolithic: 20.8%; Late Upper Paleolithic: 9.5%). The Neandertals, however, exhibit an exceptionally high level of EAE (56.5%; 47.8% if two anomalous cases are considered normal). The levels of EAE for the early modern humans are well within recent human ranges of variation, frequencies which are low for equatorial inland and high latitude samples but occasionally higher elsewhere. The Early/Mid Upper Paleolithic frequency is nonetheless high for a high latitude sample under interpleniglacial conditions. Given the strong etiological and environmental associations of EAE development with exposure to cold water and/or damp wind chill, the high frequency of EAE among the Neandertals implies frequent aquatic resource exploitation, more frequent than the archeological and stable isotopic evidence for Middle Paleolithic/Neandertal littoral and freshwater resource foraging implies. As such, the Neandertal data parallel a similar pattern evident in eastern Eurasian archaic humans. Yet, factors in addition to cold water/wind exposure may well have contributed to their high EAE frequencies., Competing Interests: The authors have declared that no competing interests exist.