Identification of a novel phenotype of external ear deformity related to Coffin-Siris syndrome-9 and literature review.

De novo germline variants of the SRY-related HMG-box 11 gene (SOX11) have been reported to cause Coffin-Siris syndrome-9 (CSS-9), a rare congenital disorder associated with multiple organ malformations, including ear anomalies. Previous clinical and animal studies have found that intragenic pathogenic variant or haploinsufficiency in the SOX11 gene could cause inner ear malformation, but no studies to date have documented the external ear malformation caused by SOX11 deficiency. Here, we reported a Chinese male with unilateral microtia and bilateral sensorineural deafness who showed CSS-like manifestations, including dysmorphic facial features, impaired neurodevelopment, and fingers/toes malformations. Using trio-based whole-exome sequencing, a de novo missense variant in SOX11 (NM_003108.4: c.347A>G, p.Y116C) was identified and classified as pathogenic variant as per American College of Medical Genetics guidelines. Moreover, a systematic search of the literature yielded 12 publications that provided data of 55 SOX11 intragenic variants affecting various protein-coding regions of SOX11 protein. By quantitatively analyzing phenotypic spectrum information related to these 56 SOX11 variants (including our case), we found variants affecting different regions of SOX11 protein (high-mobility group [HMG] domain and non-HMG regions) appear to influence the phenotypic spectrum of organ malformations in CSS-9; variants altering the HMG domain were more likely to cause the widest range of organ anomalies. In summary, this is the first report of CSS with external ear malformation caused by pathogenic variant in SOX11, indicating that the SOX11 gene may be not only essential for the development of the inner ear but also critical for the morphogenesis of the external ear. In addition, thorough clinical examination is recommended for patients who carry pathogenic SOX11 variants that affect the HMG domain, as these variants may cause the widest range of organ anomalies underlying this condition.

Necrotizing external otitis: diagnostic clues in the emergency department.

PURPOSE: The assessment of necrotizing external otitis requires a high index of suspicion by the attending physician. The purpose of the study is to determine the accuracy of parameters available at the Emergency Department for the diagnosis of this pathology. METHODS: Retrospective diagnostic accuracy study. Patients consulting at the Emergency Department for longstanding ear swelling, severe otalgia, and failure to respond to topical treatment were included. Otoscopy, physical examination, CT appearance, and analytical results were tested for the diagnosis of necrotizing external otitis, using nuclear imaging as gold standard. Sensitivity, specificity, likelihood ratios and ROC curves were calculated. RESULTS: 24 patients were included; 13 cases were necrotizing external otitis, and 11 cases were other external ear pathologies. Erythrocyte sedimentation rate and C-reactive protein levels were significantly associated with necrotizing external otitis (AUC 0.92 p < 0.001, and 0.8 p < 0.001). Positive likelihood ratios were 10.15 for values of erythrocyte sedimentation rate over 26 mm/h, and 8.25 for C-reactive protein levels over 10 mg/L. Negative likelihood ratios were 0.08 and 0.28, respectively. These results were significant. The rest of clinical and radiological parameters were less accurate. CONCLUSIONS: Erythrocyte sedimentation rate and C-reactive protein are useful parameters in the evaluation of a case of longstanding otitis with clinical suspicion of necrotizing external otitis. If any of them is elevated, the probability of suffering this condition is significantly increased. If they are within normal ranges, an alternative diagnosis should be sought.

Partial Central Anterior Reconstruction of the Auricle with One-Stage Combined Retroauricular Flaps.

SUMMARY: Basal cell carcinomas of the central anterior area of the auricle limited to the antihelix and scapha without peripheral infiltration of the helix are not uncommon. Resection is rarely transfixing, but resection of the underlying cartilage is often required. The complex anatomy of the ear and the lack of local tissue available makes its reparation challenging. Defects of antihelix and scapha require special reconstructive techniques, taking into account skin structure and the three-dimensional architecture of the ear. The reconstruction usually consists of full-thickness skin grafting or anterior transposition flap, requiring an extended skin resection. The authors describe a one-stage technique that uses a pedicled retroauricular skin flap turned over the anterior defect, followed by immediate closure of the donor site with a transposition or a bilobed retroauricular skin flap. The one-stage combined retroauricular flap reparation optimizes cosmetic outcome and reduces the risk of successive surgical procedures.

Auricular leishmaniasis mimicking squamous cell carcinoma of the pinna.

Cutaneous leishmaniasis can occur on any exposed area of the body; however, the pinna is an exceptionally rare site for the disease. Caused by the parasite Leishmania, cutaneous leishmaniasis has a wide range of presentations and thus is very easy to misdiagnose or mistake for a neoplastic lesion. Here, we report the case of a middle-aged male patient presenting with a painful, ulcerated lesion on the left auricle initially suspected to be a malignancy with histopathology eventually revealing a diagnosis of auricular leishmaniasis. The patient received appropriate therapy and was found to be disease free at follow-up. These isolated lesions of the pinna often resemble neoplastic lesions and thus may escape diagnosis for months at a time, increasing patient stress as well as expenditure. In addition, prompt recognition may also help mitigate recurrence of the disease, making it worthwhile to include cutaneous leishmaniasis as part of the differential, especially in endemic areas.

Frank's Sign: A Link Between Dermatovenerology, Cardiac Pathology, and Neurology.

Dear Editor, Although some of my colleagues may find this surprising, as a neurologist, I have noticed many connections between dermatology and neurology. Neurological and dermatological signs and symptoms are common in many clinical entities, especially in the so-called phakomatoses or neurocutaneous syndromes (Von Recklinghausen's disease type 1 and 2, Bourneville-Pringle syndrome, Sturge-Weber syndrome, Von Hippel-Lindau syndrome, Louis-Bar syndrome) (1). The terms "neurodermatitis" and "neurodermatology" also confirm the above. Inspection is the basis of every clinical examination and an integral part of both dermatological and neurological propaedeutics. Therefore, I would like to remind your readers of Frank's sign, another link between dermatology and neurology. Frank's sign is a diagonal earlobe crease (DELC) that extends backwards from the tragus at a 45-degree angle across the lobule to the auricular edge of the ear (Figure 1). It has been described as a dermatological marker for atherosclerosis. Frank's sign is named after Dr. Sanders T. Frank, who observed this crease in 20 patients with coronary artery disease and published his findings in The New England Journal of Medicine in 1973 (2). Although this sign has been known for more than 50 years, it is still not routinely employed in clinical practice. Histopathological examination of DELC-positive earlobes revealed myoelastofibrosis in the arterial vessel at the base of the earlobe, indicating that DELC is not a coincidental finding but is directly related to atherosclerosis (3). Following the finding of DELC in patients with coronary artery disease, numerous studies have confirmed the presence of DELC in peripheral vascular disease as well as cerebrovascular disease. I encountered the description of this sign as a student in the textbook of Internal Medicine in 1991 (4). This sign was also the subject of research by Croatian authors. In 1998, Miric et al. found that a positive Frank's sign carried a higher risk of heart attack (5,6). In 2008, Glavic et al. found a statistically significant association between Frank's sign and an increase in intima media thickness (IMT) of the common carotid artery as a surrogate marker of atherosclerosis, thus confirming the hypothesis that Frank's sign is an uncontrollable risk factor for cerebrovascular disease (such as gender or age) (7). In clinical practice, earlobe inspection should be considered an integral part of the physical examination. In the case of a positive Frank's sign, a color Doppler ultrasound examination of the neck arteries and a cardiologist's examination are recommended. The determination of Frank's sign can be used as a method of primary prevention for cardiovascular and cerebrovascular diseases.

Effectiveness of fractional carbon dioxide laser combined with botulinum toxin type A in a rabbit ear model with the underlying mechanism.

BACKGROUND: Hypertrophic scar (HS) is a common disease in plastic and cosmetic surgery, with limited treatment options, and is a challenge for clinicians. OBJECTIVES: This study aimed to evaluate the efficacy of fractional carbon dioxide (CO2 ) laser combined with botulinum toxin type A (BTXA) in treating HSs in rabbit ears and to provide new strategies for treating HS. METHODS: Twenty-four New Zealand white rabbits with induced HSs were randomly divided into one control and three treatment groups. After 4 weeks of modeling, BTXA (2.0 U) was injected into the HS of the BTXA and combination groups, whereas a fractional CO2 laser (combo mode, deep energy: 12.5 mJ; super energy: 90 mJ) was used in the fractional CO2 laser and combination groups. The laser treatments were repeated after 2 weeks. The HSs in the rabbit ears were observed and photographed 5 weeks after the first treatment. The scar thickness in each group was measured and compared, and the scar elevation index (SEI) was determined using hematoxylin and eosin staining. Collagen content and alignment were observed using Masson's trichrome staining. Western blotting and immunohistochemistry were performed to analyze scar-related protein levels. RESULTS: Hypertrophic scars were reduced in all treatment groups compared with the control group. The combination group had lower scar thickness, SEI, and expression of scar-related proteins in HSs, with an appearance similar to that of normal rabbit ear skin. Furthermore, the fibroblast content and collagen deposition decreased significantly in the combination group (p < 0.001). CONCLUSIONS: Fractional CO2 laser combined with BTXA more effectively reduced HSs by inhibiting fibroblast proliferation, decreasing transforming growth factor-ß1 and α- smooth muscle actin expression, and causing collagen remodeling.

Long-Term Clinical Results of Two-Stage Total Ear Reconstruction of Microtia Using Autologous Cell-Engineered Chondrocytes.

BACKGROUND: Microtia repair requires a large volume of reconstruction material.In pediatric patients, the collectable volume of autologous cartilage is limited, and the impact of surgical invasion and donor-site morbidity can be particularly severe. The authors developed a new treatment method using cultured autologous human auricular chondrocytes that provides a sufficiently large volume of reconstruction material. METHODS: Approximately 1 cm2 of auricular cartilage was collected from the affected site. Chondrocytes were isolated and cultured with autologous serum to accelerate cell proliferation. The cells were subcultured and formed a gel-form mass without a scaffold. In our two-stage implantation, the cultured chondrocytes were first injected into the patient's lower abdomen, where the cells grew into a large, newly generated cartilage in 6 months. Thereafter, this cartilage was sculpted into an ear framework and subcutaneously reimplanted into the new ear location. Clinical outcomes were assessed over a long-term follow-up. RESULTS: Eight patients underwent surgery using cultured autologous auricular chondrocytes from 2002 to 2008. The patients' ages ranged from 6 to 10 years. The follow-up period ranged from 11 to 18 years. None of the patients experienced absorption of cultured chondrocytes after the second stage. Complications included one case of absorption and one case of allergic reaction in the first stage. CONCLUSIONS: The authors' patients represent the first successful cases of regenerative surgery for microtia using cultured chondrocytes. No malignant transformation, change in size, deformation, or other abnormalities were observed during the long-term follow-up, demonstrating the safety of cultured cartilage. No major complications occurred. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Presentation of External Ear Rosai-Dorfman Disease With Laryngeal Involvement.

Rosai-Dorfman disease (RDD) is a rare benign systemic histiocytic proliferation characterized by massive lymph node enlargement and sometimes associated with extranodal involvement. Even though it is considered to be benign, death can occur depending on the extent and location. Our case highlights a primary extranodal site of the right pinna with extension through the Eustachian tube to the subglottis. A previously healthy 15-year-old female presented with 1-year right pinna swelling, slowly enlarging and becoming more bothersome. An incisional biopsy was performed on the ear along with S100 staining yielding a diagnosis. After multidisciplinary case discussion, clofarabine monotherapy and systemic therapy for Langerhans cell histiocytosis has started. Rosai-Dorfman disease can be a general disorder, often affecting the lymph nodes. Unlike a nodal disease, extranodal disease could involve any site on the patient's anatomy. Head and neck lesions are the most common extranodal lesions. Rosai-Dorfman disease is self-limited in more than 20% of the cases with spontaneous regression without intervention; 70% of the patients have noticeable symptoms and vital organ involvement requiring treatments such as surgery, steroids, radiation, and chemotherapy. In our case, the patient had wide involvement and presented without any serious breathing difficulties; we decided to start with monotherapy with chemotherapy and systematic glucocorticoid treatment.

Pathology Clinic: Nodular Fasciitis Involving the External Ear.

Nodular fasciitis is a rare, benign lesion characterized by the pseudosarcomatous proliferation of fibroblasts and myofibroblasts. Accurate diagnosis presents a unique challenge for otolaryngologists, as nodular fasciitis frequently mimics malignancy clinically; however, it can be distinguished from malignancy by subtle findings on pathology. A diagnosis of nodular fasciitis should be considered for any irregular or rapidly growing lesion of the head and neck area, as accurate diagnosis is particularly important to avoid overtreatment in cosmetically sensitive regions.

Extensive Keloid and Hypertrophic Mixed Scarring Pattern in Ear Lobes of a 14-Year-Old African Female: A Case Report.

Background Massive earlobe scarring/keloid formation can occur after ear piercing in individuals of African descent. Case report: A 14-year-old African girl with pierced ears in childhood presented with two progressively growing and disfiguring tumors on both earlobes. The maximum diameter of each lesion was 5.5 centimeters, and the weight of each lesion was approximately 20 grams. Histologically, there was a mixed pattern of keloid and hypertrophic scarring. Discussion: Massive keloids can occur after ear piercing in childhood. It is unclear why some individuals develop these massive keloids.

Contour first-retrospective study of an algorithmic approach of auricular keloids.

BACKGROUND: Auricular keloids are difficult to treat, and recurrent keloids are more aggressive and more likely to develop aural deformities. Surgical excision, injections, or radiotherapy alone have high recurrence rates. An algorithmic approach of auricular keloid remains to be explored. AIMS: To investigate the sequential treatment protocol for the treatment of auricle keloids to maintain auricle morphology and reduce the postoperative recurrence rate. PATIENTS/METHODS: A retrospective analysis of 42 patients who attended the scar minimally invasive treatment center of the Hospital of Plastic Surgery, Chinese Academy of Medical Sciences for serial treatment from January 2019 to June 2021. According to the size and involvement of the keloid, the core excision of the scar was excised under the condition of ensuring the priority of the auricular contour, and the scar flap was repaired to reconstruct the auricular appearance, and electron beam treatment was performed within 24 h after the operation, ray energy: 6-7 MeV, dose: Dt18Gy/2f; regular trimethoprim combined with 5-Fu injection treatment and the application of silicone ear clips for local compression treatment were performed 1 month after the operation. RESULTS: Thirty-five patients were followed up from 12 to 40 months after surgery, and three of them showed a tendency of recurrence, and early local treatment with trimethoprim and 5-Fu injection achieved favorable results. CONCLUSION: A standardized and sequential treatment plan for keloids with different morphology and anatomical locations can achieve remodeling of the auricular morphology and maintain long-term results.

A successful reconstruction of the upper antihelix defect via postauricular pull-through pedicle flap.

The auricle is a complex anatomic structure with a three-dimensional configuration proper reinstating that poses a substantial reconstructive challenge. The postauricular pull-through flap is perfectly suitable method for the reconstruction of helical and antihelical auricle defects; however, due to its difficult harvest technique, it is not commonly used in a practice. Here we describe a case of a patient with an antihelix defect following basal cell carcinoma (BCC). In our case, the reconstruction was performed via postauricular pull-through pedicle flap, and a satisfactory result was achieved.

Keloids in Darkly Pigmented Skin: Clinical Pattern and Presentation at a Tertiary Health Facility, Southwest Nigeria.

BACKGROUND: Keloids are chronic dermal fibro-proliferative disorders resulting from excessive collagen deposition. Although it is commonly seen in the dark skin, it occurs in other races. It is a disfiguring dermatosis whose epidemiology and clinical pattern should be put into proper perspective in an area where it has not been extensively documented. SUBJECTS AND METHOD: A cross-sectional design that included 120 consenting keloids patients was made at the dermatology and plastic surgery clinics of a tertiary hospital over one year. Keloid was diagnosed clinically, risk factors, locations and patterns of affectation were documented. RESULTS: 120 patients with 192 keloids were seen. The mean age of the patients was 36.3±16.0 years with a slight female preponderance (M: F, 1:1.9). The chest was the commonest site 37 (19.3%), then earlobe 27 (14.1%) and face 21(11.0%). The buttock/feet were the least affected areas. Trauma including ear piercing, shaving, lacerations/cuts were the commonest risk factors 108 (56.2%) for keloid. The commonest observed morphological patterns in descending order of occurrence include flat 61 (31.8%), nodular 54 (28.1%) and superficial spreading 51 (26.6%) type. Flat pattern was commonest in breast and chest areas 35 (71.4%), nodular pattern on earlobes 17 (63.0%), face 11 (52.3%), scalp 3 (50.0%), neck 5 (38.5%), and guttate pattern on the face 3 (14.0%) and back 2 (22.0%). The shoulder 5 (50.0%), arms 7 (58.3%) and back 4 (44.4%) had more of the superficial spreading pattern when the morphology/patterns of keloid in these areas were compared. CONCLUSION: Keloids affects predominantly young adults with single anatomical site being the commonest presentation, with the chest mostly affected and the flat pattern commonly observed. The morphological distinction of keloids and location may influence the choice of treatment modality.

CONTEXTE: Les chéloïdes sont des troubles dermiques chroniques fibro-prolifératifs résultant d'un dépôt excessif de collagène résultant d'un dépôt excessif de collagène. Bien qu'elle soit couramment dans les peaux foncées, elle se produit dans d'autres races. Il s'agit d'une dermatose défigurante dermatose dont l'épidémiologie et le profil clinique doivent être mis en perspective dans une région où elle n'a pas été largement documentée. SUJETS ET MÉTHODE: Une étude transversale incluant 120 patients consentants atteints de chéloïdes a été réalisée dans les cliniques de dermatologie et de chirurgie plastique d'un hôpital tertiaire sur une période d'un an. La chéloïde a été diagnostiquée cliniquement, les facteurs de risque, les localisations et les schémas d'affectation ont été documentés. RÉSULTATS: 120 patients présentant 192 chéloïdes ont été examinés. L'âge moyen des patients était de 36,3±16,0 ans avec une légère prépondérance féminine (M : F,1:1.9). La poitrine était le site le plus fréquent 37 (19,3%), puis le lobe de l'oreille 27 (14,1 %) et le visage 21 (11,0 %). Les fesses et les pieds étaient les zones les moins touchées zones les moins touchées. Les traumatismes, y compris le perçage des oreilles, le rasage, les lacérations/coupures, étaient les facteurs de risque les plus courants.les facteurs de risque les plus courants 108 (56,2 %) pour la chéloïde. Les formes morphologiques les plus courantes morphologiques les plus fréquemment observés, par ordre décroissant de fréquence sont le type plat 61 (31,8 %), le type nodulaire 54 (28,1 %) et le type d'extension superficielle 51 (26,6 %). La forme plate était la plus fréquente dans les zones du sein et de la poitrine.35 (71,4 %), le type nodulaire sur le lobe des oreilles 17 (63,0 %), le visage 11 (52,3 %), cuir chevelu 3 (50,0 %), le cou 5 (38,5 %), et le motif en gouttes sur le visage 3 (14,0 %) et le dos 2 (22,0 %). L'épaule 5 (50,0 %), les bras 7 (58,3 %) (58,3 %) et le dos 4 (44,4 %) présentaient davantage de motifs d'étalement superficiel morphologie/profil de la chéloïde dans ces zones. CONCLUSION: Les chéloïdes touchent principalement les jeunes adultes. site anatomique unique est la présentation la plus courante, le thorax étant le plus souvent touché. La poitrine est la plus touchée et le modèle plat est couramment observé. Le site distinction morphologique des chéloïdes et de leur localisation peut influencer le choix de la modalité de traitement. MOTS CLÉS: Chéloïde, Peau foncée, Épidémiologie, Profil Clinique.

[A man with a crease in his earlobe]. / Een man met een groef in zijn oorlel.

A 68-year-old man consulted his GP with a crease in his earlobe, running diagonally from the tragus over the earlobe backwards. This is the Frank's sign, which is a risk factor for the presence and prognosis of cardiovascular pathology, such as coronary sclerosis, cerebrovascular accident and peripheral arterial disease.

Radiation therapy of non-melanoma skin cancer of the pinna: an Italian 35-year experience.

BACKGROUND: Radiation therapy (RT) is a well-known alternative to surgery for the treatment of non-melanoma skin cancer (NMSC), especially in elderly people or in patients who cannot undergo or refuse surgical procedure. It has also a pivotal role in those areas, as pinna, where both function and cosmesis must be preserved. We report our experience in treating cutaneous carcinoma of the auricle with radiation therapy. METHODS: We conducted a retrospective monocentric study on 363 NMSC of the auricle treated by conventional energy radiation therapy as a primary treatment or with adjuvant and salvage purpose. Tumors involving the external canal of the ear or regional lymph node at diagnosis were excluded. RESULTS: A complete response has been obtained in 95.5% with a 2- and 5-year cure rate respectively of 84% and 76%. Fifty-two tumors developed a central or marginal relapse. Aesthetic result was good or acceptable in the majority of the cases. No cartilage necrosis has been registered. CONCLUSIONS: Our experience confirms safety and effectiveness of RT on selected auricle carcinoma, affording good cosmetic and functional results.

Frank's sign and paired ear creases of the helix : Current concepts of significance for morbidity.

Frank's sign (FS) was described in 1973 as an auricular marker for cardiovascular disease presenting as a crease of the auricular lobule. Since its first clinical description, there have been multiple studies underlining the role of FS in a myriad of conditions, such as atherosclerosis, hypertension, cerebrovascular disease, peripheral artery disease, metabolic diseases as well as studies looking at physiological differences in the auricular shape that may mimic FS; however, a complex study to comprehensively analyze the clinical, gross, and histological findings of patients with FS has not yet been performed. Most studies focused on a specific system, mechanism of disease entry. This short review tries to summarize the current knowledge of FS in relation to diseases as well as its clinical classification, histology, and association with the recently described paired ear creases of the helix, as an attempt to reveal the dubious role of FS as a possible prognostic and predictive marker.