Disruption of the endopeptidase ADAM10-Notch signaling axis leads to skin dysbiosis and innate lymphoid cell-mediated hair follicle destruction.

Hair follicles (HFs) function as hubs for stem cells, immune cells, and commensal microbes, which must be tightly regulated during homeostasis and transient inflammation. Here we found that transmembrane endopeptidase ADAM10 expression in upper HFs was crucial for regulating the skin microbiota and protecting HFs and their stem cell niche from inflammatory destruction. Ablation of the ADAM10-Notch signaling axis impaired the innate epithelial barrier and enabled Corynebacterium species to predominate the microbiome. Dysbiosis triggered group 2 innate lymphoid cell-mediated inflammation in an interleukin-7 (IL-7) receptor-, S1P receptor 1-, and CCR6-dependent manner, leading to pyroptotic cell death of HFs and irreversible alopecia. Double-stranded RNA-induced ablation models indicated that the ADAM10-Notch signaling axis bolsters epithelial innate immunity by promoting ß-defensin-6 expression downstream of type I interferon responses. Thus, ADAM10-Notch signaling axis-mediated regulation of host-microbial symbiosis crucially protects HFs from inflammatory destruction, which has implications for strategies to sustain tissue integrity during chronic inflammation.

Lessons from a scoping review: Clinical presentations of central centrifugal cicatricial alopecia.

BACKGROUND: Central centrifugal cicatricial alopecia (CCCA) nomenclature describes a typical clinical presentation of cicatricial hair loss that begins on the vertex scalp with progressive, symmetric, and centrifugal evolution. However, atypical presentations have been noted clinically by the authors and reported in the literature. OBJECTIVE: We sought to characterize the distribution of hair loss in published cases of adult patients with CCCA. METHODS: A 3-step search process was used to evaluate research articles in Cumulative Index to Nursing & Allied Health, EMBASE, Google Scholar, MEDLINE, Scopus, and Web of Science databases. Studies with scalp photography or description of hair loss distribution were included. Three researchers evaluated eligible studies for clinical subtypes. Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review was used to report results. RESULTS: Ninety-nine studies consisting of 281 cases of CCCA were included. Hair loss distributions included variants of the classic presentation along with distinct subtypes such as patchy, occipital, parietal, frontal, temporal, and trichorrhexis. LIMITATIONS: Studies had significant homogeneity, as the classic distribution of CCCA was commonly reported. Additionally, clinically diagnosed cases may have concurrent diagnoses, and numerous studies did not report trichoscopy findings. CONCLUSION: CCCA terminology may not always be reflective of clinical presentation. Understanding atypical presentations is essential to inform appropriate and targeted treatment.

Treatment for central centrifugal cicatricial alopecia-Delphi consensus recommendations.

BACKGROUND: There is no established standard of care for treating central centrifugal cicatricial alopecia (CCCA), and treatment approaches vary widely. OBJECTIVE: To develop consensus statements regarding the use of various pharmacological therapies in treating adults with CCCA. METHODS: We invited 27 dermatologists with expertise in hair and scalp disorders to participate in a 3-round modified Delphi study between January and March 2023. Statements met strong consensus if 75% of respondents agreed or disagreed. Statements met moderate consensus if 55% or more but less than 75% agreed or disagreed. RESULTS: In round 1, 5 of 33 (15.2%) statements met strong consensus, followed by 9 of 28 (32.1%) in round 2. After the final round 3 meeting, strong consensus was reached for 20 of 70 (28.6%) overall statements. Two statements achieved moderate consensus. LIMITATIONS: This study included only English-speaking, US-based dermatologists and did not consider nonpharmacological therapies. CONCLUSION: Despite varying opinions among dermatologists, consensus was reached for several statements to help clinicians manage CCCA. We also highlight areas that lack expert consensus with the goal of advancing research and therapeutic options for CCCA.

Resolution of Pityriasis rubra pilaris induced ectropion with oral dexamethasone. A case report.

An 82-year-old male presented with generalised Pityriasis rubra pilaris (PRP) managed initially by dermatology team. The patient did not respond to first- and second-line treatment, including oral acitretin, steroid creams, and methotrexate, and developed bilateral cicatricial ectropion, for which he was referred to oculoplastic team for surgical management. A head injury resulting in subacute subdural haematoma, managed with a week course of low dose oral dexamethasone, resulted in the improvement of his skin condition and complete resolution of the cicatricial ectropion within a few weeks. Thus, systemic treatment of PRP with oral dexamethasone may be considered sooner in the treatment of cicatricial ectropion in similar cases.

Ocular cicatricial pemphigoid: is there an association with autoimmune diseases?

PURPOSE: To assess the prevalence of autoimmune diseases (ADs) associated with ocular cicatricial pemphigoid (OCP) and analyze clinical, laboratory, and treatment associations between these entities. METHODS: A multicentre cross-sectional study of patients with an OCP diagnosis. The population was divided into two groups according to their association with other ADs or not. Clinical, laboratory and treatment variables were described and compared between groups. A multivariable logistic regression analysis was performed to identify variables that could suggest the association between OCP and ADs. RESULTS: Eighty-eight patients were recruited, with a mean age at diagnosis of 64.3 years (SD 11.9). Biopsy was performed in 86.8% of the patients. There was a median delay of 2 years from the onset of symptoms to diagnosis. Extraocular involvement was evidenced in 11.5%. The group associated with ADs included 24 patients (27.3%). The most prevalent diagnosis was Sjögren´s syndrome. Hypergammaglobulinemia was associated with ADs and OCP, adjusted for age, sex, smoking, skin and mucosal involvement, and erythrocyte sedimentation rate (OR 8.7; 95%CI 1.6-46.8; p = 0.012). CONCLUSIONS: Due to OCP's autoimmune nature, it could coexist with other ADs. This study observed that more than a quarter of the population presented with this association, and hypergammaglobulinemia could suggest it.

The current alternative for ocular surface and anophthalmic socket reconstruction, cryopreserved umbilical amniotic membrane (cUAM).

PURPOSE: This report presents the results of using cryopreserved umbilical amniotic membrane (cUAM) as an alternative mucosal graft for ocular surface reconstruction in cases of anophthalmic socket contracture (ASC), cicatricial entropion (CE), and conjunctival-scleral defects. METHODS: The study included patients who underwent non-commercial implantation of cUAM grafts (prepared by corneal banking methods) for ASC, CE, conjunctival defect, and scleral melting. The main success criteria for this study were the comfortable fitting of the ocular prosthesis in ASC patients, the natural eyelid position in CE patients, and the degree of conjunctivalisation in melting patients. RESULTS: cUAM transplantation was performed in 2 patients who could not use a prosthetic eye due to conjunctival contracture, 2 patients with CE, and 1 patient with conjunctival defect and 1 patient with conjunctival-scleral melting. The primary outcome was achieved in 83.3% (5/6) of patients. In one patient with CE, partial healing was achieved due to the persistence of CE in the medial upper eyelid. CONCLUSIONS: cUAM is a viable alternative to mucosal grafting for reconstructing the bulbar and palpebral conjunctival surface, fornix, and orbit, with reduced donor morbidity and shorter surgical time. Its regenerative ability allows for tissue defect healing and improves cosmetic appearance through epithelialization within weeks.

[Improving surgical technique for tracheal resection with anastomosis]. / Usovershenstvovanie khirurgicheskoi tekhniki pri rezektsii lineinoi chasti trakhei s posleduyushchim anastomozom.

OBJECTIVE: To present modern aspects of improving surgical techniques in tracheal resection developed in recent years. MATERIAL AND METHODS: The authors have the most extensive experience in tracheal surgery (>2.000 patients over the past 50 years). Diagnostic capabilities, perioperative management and surgical techniques have changed over such a long period. This concerns the proposed classification of cicatricial tracheal stenosis, features of endoscopic and X-ray diagnostics, indications for various surgeries, choice of surgical approach, technique of tracheal tube mobilization and anastomosis after tracheal excision. Preventive measures for severe postoperative complications are described. CONCLUSION: Such an extensive experience allowed the authors to develop an algorithm for the treatment of patients with tracheal stenosis. This significantly reduced the incidence of postoperative complications and mortality. Replication of such equipment is associated with technical support of hospitals and professional level of specialists consisting of endoscopist, anesthesiologist, intensive care specialist and thoracic surgeon.

The histopathologic diagnosis of traction alopecia: An evidence-based model.

BACKGROUND: Traction alopecia (TA) is common, but histopathologic criteria for TA have not been objectively defined. OBJECTIVE: Determine whether the pauci-follicular unit (PFU) can be used as a diagnostic criterion for TA. Compared to a normal follicular unit (NFU), the PFU is a noninflamed follicular unit with an intact sebaceous gland but fewer than 2 follicles. METHODS: A retrospective review of 25 cases of TA and 25 cases of "normal scalp" was performed. Data included all follicles (by size and phase), sebaceous glands, and total follicular units. RESULTS: Comparing data (traction vs normal), we found a significantly higher number of PFUs in cases of TA (median 6 vs 0, P < .001), which can be used as a helpful and easily recognizable diagnostic tool in diagnosing cases of TA. LIMITATIONS: Comparison to other forms of alopecia was not performed. CONCLUSIONS: The number of PFUs in an alopecia biopsy can be used to establish the diagnosis of TA.

Central centrifugal cicatricial alopecia in males.

BACKGROUND: Central centrifugal cicatricial alopecia (CCCA) is a scarring alopecia seen primarily in women of African descent but rarely reported in men. The etiology of CCCA is unknown, but genetic variants, type 2 diabetes mellitus, and bacterial infections may play a role. OBJECTIVES: We aimed to characterize the demographics, medical histories, and clinical findings of male patients with CCCA with the hypothesis that features may differ from women. METHODS: This was a case series of adult male patients with biopsy-confirmed CCCA seen at an academic dermatology department between 2012 and 2022. RESULTS: In total, 17 males had a scalp biopsy and clinical findings consistent with CCCA. The average age was 43 years, and 88.2% of cases identified as Black race. Scalp pruritus was the most common symptom, and few patients endorsed high-risk hair care practices. None of the cases had diagnosis of type 2 diabetes mellitus, but 17.6% had history of latent tuberculosis, and 47.1% had a positive family history of alopecia. We observed 8 patients with atypical CCCA, and 29.4% had an overlapping scalp diagnosis. LIMITATIONS: This study is limited by the single center, retrospective design and small sample size. CONCLUSIONS: It is important to consider CCCA in the differential diagnosis of alopecia in adult Black males.

Treatment modalities for lymphocytic and neutrophilic scarring alopecia.

Primary cicatricial alopecia can result in permanent hair loss from the destruction of hair follicles. Early intervention is key in controlling disease progression, reducing symptoms, and optimizing hair density. Treatment modalities range from topical and intralesional therapies to oral medications and light therapy.

Alopecia - New building blocks.

Hair loss is devastating to the patient, but the diagnosis and treatment of alopecia are also difficult for primary care providers and even dermatologists. Given recent advances in the field, there has never been a more pressing time to reevaluate and improve upon the significant clinical skills needed to accurately diagnose and treat our patients with hair loss. This CME activity on alopecia is designed to (1) educate dermatologists in a simple, succinct fashion on the identification of, and the distinction between, the diverse types of hair loss and (2) discuss how to manage them.

The dermatoscope in the hair clinic: Trichoscopy of scarring and nonscarring alopecia.

Trichoscopy is currently regarded as an essential part of the hair loss consultation. It allows visualization of morphologic structures that are not obvious to the naked eye, including peri- and interfollicular skin surface abnormalities and changes to hair shaft thickness and shape. In this paper, we aim to discuss current knowledge on trichoscopy of the most common forms of scarring and nonscarring alopecias.

Ischemic alopecia as a complication from therapeutic embolization of the middle meningeal artery.

Selective endovascular embolization using microspheres is a widely used, relatively low-risk procedure to control intracranial bleeding. Side effects such as cranial nerve palsies and stroke have been reported in the literature. Skin necrosis and alopecia are exceedingly rare complications of endovascular embolization with a reported incidence of less than 1%. We report a case of a 55-year-old female who developed alopecia following a therapeutic embolization of the middle meningeal artery using microspheres. The clinical-histopathologic diagnosis and relevant literature are reviewed.

Pulmonary syphilis with a cicatricial variant of organizing pneumonia: a case report.

BACKGROUND: Syphilis is a chronic disease that progresses in the primary, secondary, latent, and tertiary stages. Pulmonary manifestations of syphilis are rare, and their histological features have not been well-described. CASE PRESENTATION: A 78-year-old man was referred to our hospital because of a solitary nodular shadow in the right middle lung field on a chest radiograph. Five years prior, a rash appeared on both legs. He was tested for syphilis at a public health center, and the non-treponemal test result was negative. When he was approximately 35 years old, he had unspecified sexual intercourse. Chest computed tomography showed a 13-mm nodule with a cavity in S6 of the right lower lobe of the lung. Robot-assisted resection of the right lower lobe was performed because of suspected localized right lower lobe lung cancer. A cicatricial variant of organizing pneumonia (CiOP) was observed, and immunohistochemistry identified Treponema pallidum inside the macrophages in the nodule cavity. The rapid plasma regain (RPR) value was negative, and the Treponema pallidum hemagglutination assay was positive. The patient was diagnosed as having secondary syphilis with pulmonary involvement. Insidious progression of secondary syphilis may result in CiOP and a negative RPR test result. CONCLUSIONS: We report the first case of pulmonary syphilis with a histological pattern of CiOP. It may be asymptomatic and difficult to diagnose because the RPR test may be negative for a long period of time. When either non-treponemal or treponemal test results are positive, the possibility of pulmonary syphilis should be considered along with appropriate medical treatment.

Mucous membrane grafting for cicatricial entropion repair: review of surgical techniques and outcomes.

Mucous membrane graft (MMG) is used for moderate-to-severe cicatricial entropion repair either in primary or recurrent cases. We conducted a review to comprehensively summarize the various surgical techniques, outcomes, and complications of using MMG for cicatricial entropion. Though the comparison between different techniques is limited by multiple factors like small numbers of cicatricial entgropion patients, variable severity and success criteria across studies, and different underlying cicatricial entropion etiologies, the author has brought forth the nuances of the use of MMG for cicatricial entropion repair along with its outcomes and complications. MMG use in moderate-to-severe cicatricial entropion gives favourable outcomes. The shortened tarsoconjunctiva is lengthened using MMG, which is used either with terminal tarsal rotation or anterior lamellar recession (ALR) or tarsotomy alone. Non-trachomatous entropion has poor outcomes compared to trachomatous entropion. The most common source of MMG is labial or buccal mucosa and the exact size of MMG harvested is variable according to the defect, and very few prefer oversizing the graft by 10-30%. The outcomes of ALR+MMG appear similar to tarsal rotation and MMG for severe cicatricial entropion. The recurrences of trichiasis or entropion can occur for up to one year after surgery, irrespective of the technique used. Factors affecting the outcomes of cicatricial entropion repair are not well known. There is a non-uniformity in data reporting across literature; hence, future studies with details on severity of entropion, ocular surface changes, forniceal depth and ocular surface inflammation, and the degree of dry eye disease would be informative.

[Cicatricial tracheal stenosis in elderly and senile patients: immediate and long-term results of treatment]. / Rubtsovyi stenoz trakhei v pozhilom i starcheskom vozraste: neposredstvennye i otdalennye rezul'taty lecheniya.

OBJECTIVE: To present treatment outcomes in elderly and senile patients with cicatricial tracheal stenosis (CTS) and features of their perioperative management. MATERIAL AND METHODS: The study included 46 elderly and senile patients with CTS. We analyzed their gender and age, body mass index, etiology, extent and degree of stenosis, comorbidity index and ASA grade, postoperative complications according to TMM grading system. RESULTS: Age of patients varied from 61 to 95 years (mean 66.38±8.65). Post-intubation stenosis was detected in 7 (15.2%) patients, post-tracheostomy CTS - in 39 (84.8%) patients (2 (4.3%) ones with tracheoesophageal fistula and 18 (39.1%) ones with tracheomalacia). CTS length ranged from 8 to 65 mm. The causes of invasive mechanical ventilation were traumatic brain and spinal trauma in 6 cases, emergency surgery in 11 cases and therapeutic diseases in 29 cases. CTS of cervical trachea was found in 21 patients, subglottic larynx and cervical trachea - 8 patients, cervical and upper thoracic trachea - 12 patients, thoracic segment - 3 patients, multifocal lesions - 2 patients. The Charlson index ranged from 5 to 12 points. ASA grade II was observed in 8 (17.4%) patients, III - 28 (60.9%), IV - in other ones. Circular resection was performed in 5 patients, laryngotracheoplasty - in 37 patients. CTS repair and tracheoesophageal fistula closure with laryngotracheoplasty were carried out in 2 patients. Postoperative complications occurred in 18 (39.1%) patients, mortality was 2.17%. In 21.7% of cases, complications were associated with tracheal suture. Endoscopic procedures, cryosurgery and hyperbaric oxygenation were used for correction. Good and satisfactory treatment outcomes were achieved in 86.5% of patients. CONCLUSION: Surgical treatment of CTS in elderly and senile patients requires participation of interdisciplinary team with special experience. Laryngotracheoplasty is safe and effective in these patients, and indications for circular resection are still limited.

[The role of endosonography in the treatment of chemical ulcerative-necrotic burns of the esophagus]. / Rol' endosonografii v opredelenii taktiki lecheniya khimicheskogo yazvenno-nekroticheskogo ozhoga pishchevoda: klinicheskoe nablyudenie.

The authors present ultrasonography-assisted endoscopic diagnosis of chemical burn of the esophagus. This method early predicted decompensated cicatricial stenosis of the esophagus that was valuable to determine treatment strategy. Preventive mini-invasive endoscopic percutaneous gastrostomy provided adequate enteral nutrition in a patient with decompensated esophageal stenosis before reconstructive surgery.

[Surgical management of tracheal anastomosis failure and risk of arterial bleeding]. / O khirurgicheskoi taktike pri nesostoyatel'nosti trakheal'nogo anastomoza i ugroze arrozionnogo krovotecheniya.

OBJECTIVE: To determine the optimal algorithm for tracheal anastomotic insufficiency and prevention of arterial bleeding. MATERIAL AND METHODS: We present 2 patients with defects of tracheal anastomosis after tracheal resection and divergence of tracheal edges. We primarily analyzed appropriate emergency care and prevention of subsequent severe complications such as arterial bleeding and respiratory insufficiency. CONCLUSION: Tracheostomy may be preferable for complete late tracheal anastomotic insufficiency to restore breathing. However, surgery should be accompanied by prevention of arterial bleeding. Isolation of damaged area, particularly tracheostomy tube, from the mediastinum by well-vascularized tissues can prevent bleeding from major vessels (for example, innominate artery). Follow-up is unreasonable due to worsening of clinical situation, risk of hemorrhagic complications and fatal outcomes. General satisfactory clinical status of the patient is not of matter. Repeated tracheal anastomosis is justified only for early insufficiency, i.e. within 2-3 days when postoperative inflammation is mild.

[Treatment of cicatricial tracheal stenosis and tracheoesophageal fistula in patients with COVID-19 pneumonia]. / Lechenie rubtsovogo stenoza trakhei i trakheopishchevodnogo svishcha u bol'nykh, perenesshikh COVID-19-pnevmoniyu.

OBJECTIVE: To describe treatment of cicatricial tracheal stenosis and tracheoesophageal fistula in patients with COVID-19 pneumonia. MATERIAL AND METHODS: There were 91 patients with cicatricial tracheal stenosis for the period from August 2020 to April 2022 (21 months). Of these, 32 (35.2%) patients had cicatricial tracheal stenosis, tracheoesophageal fistula and previous coronavirus infection with severe acute respiratory syndrome. Incidence of iatrogenic tracheal injury following ventilation for viral pneumonia in the pandemic increased by 5 times compared to pneumonia of other genesis. Majority of patients had pneumonia CT grade 4 (12 patients) and grade 3 (8 patients). Other ones had pulmonary parenchyma lesion grade 2-3 or mixed viral-bacterial pneumonia. Isolated tracheoesophageal fistula without severe cicatricial stenosis of trachea or esophagus was diagnosed in 4 patients. In other 2 patients, tracheal stenosis was combined with tracheoesophageal fistula. Eight (25%) patients had tracheostomy at the first admission. This rate was almost half that of patients treated for cicatricial tracheal stenosis in pre-pandemic period. RESULTS: Respiratory distress syndrome occurred in 1-7 months after discharge from COVID hospital. All patients underwent surgery. In 7 patients, we preferred palliative treatment with dilation and stenting until complete rehabilitation. In 5 patients, stent was removed after 6-9 months and these ones underwent surgery. There were 3 tracheal resections with anastomosis, and 2 patients underwent tracheoplasty. Resection was performed in 3 patients due to impossible stenting. Postoperative course in these patients was standard and did not differ from that in patients without viral pneumonia. In case of tracheoesophageal fistula, palliative interventions rarely allowed isolation of trachea. Four patients underwent surgery through cervical approach. There were difficult surgeries in 2 patients with tracheoesophageal fistula and cicatricial tracheal stenosis. One of them underwent separation of fistula and tracheal resection via cervical approach at primary admission. In another patient with thoracic fistula, we initially attempted to insert occluder. However, open surgery was required later due to dislocation of device. CONCLUSION: Absolute number of patients with tracheal stenosis, tracheoesophageal fistula and previous COVID-19 has increased by several times compared to pre-pandemic period. This is due to greater number of patients requiring ventilation with risk of tracheal injury, non-compliance with preventive protocol for tracheal injury including anti-ischemic measures during mechanical ventilation. The last fact was exacerbated by involvement of allied physicians with insufficient experience of safe ventilation in the «red zone¼, immunodeficiency in these patients aggravating purulent-inflammatory process in tracheal wall. The number of patients with tracheostomy was 2 times less that was associated with peculiarity of mechanical ventilation in SARS-CoV-2. Indeed, tracheostomy was a poor prognostic sign and physicians tried to avoid this procedure. Incidence of tracheoesophageal fistula in these patients increased by 2 times compared to pre-pandemic period. In subacute period of COVID-associated pneumonia, palliative measures for cicatricial tracheal stenosis and tracheoesophageal fistula should be preferred. Radical treatment should be performed after 3-6 months. Absolute indication for circular tracheal resection with anastomosis is impossible tracheal stenting and ensuring safe breathing by endoscopic methods, as well as combination of cicatricial tracheal stenosis with tracheoesophageal fistula and resistant aspiration syndrome. Incidence of postoperative complications in patients with cicatricial tracheal stenosis and previous mechanical ventilation for COVID-19 pneumonia and patients in pre-pandemic period is similar.

[Surgical treatment of combined injuries of the neck and shoulder joints]. / Khirurgicheskoe lechenie sochetannykh porazhenii shei i plechevykh sustavov.

OBJECTIVE: To develop the algorithm for effective surgical restoration of shoulder joint and neck functions and acceleration of social and labor rehabilitation. MATERIAL AND METHODS: There were 116 patients with combined consequences of burns of the neck and shoulder joints between 2012 and 2021. These ones amounted to 29.4% of all patients with lesions of the neck or shoulder joints. Simultaneous surgeries with correction of post-burn cicatricial deformities and contractures were performed in 66 patients (56.9%). Age of patients ranged from 18 to 72 years, and 96% of them were employable. There were 89 (76.7%) women and 27 (23.3%) men. We assessed spread and localization of cicatricial process, as well as restriction of mobility of the neck and shoulder joint to select optimal surgical approach. Classification of neck deformities and contractures of shoulder joints considering severity of cicatricial lesion and functional impairment made it possible to systematize the approach to reconstructive procedures. Reconstructive surgery included repair with local tissues including skin-fatty flap, non-perforated split or full-thickness skin autograft, rotated flaps including those based on perforator vessels, as well as preliminary skin stretching. RESULTS: In general, 116 patients with combined lesions of the neck and shoulder joints underwent 314 surgeries. To accelerate rehabilitation, we performed simultaneous surgeries with correction of deformities and contractures in 66 patients (56.9%). Staged reconstructive surgeries were carried out in 50 patients. Acute dermotension and skin-fatty neck flap grafting were the most common for deformities and contractures of the neck. Skin-fatty axillary flap was used in most patients with contractures of shoulder joints. CONCLUSION: Simultaneous surgeries can accelerate rehabilitation. Correct algorithm of staged surgical treatment reduces rehabilitation period and eliminates functional disorders.