ABSTRACT
Increasing age alters innate immune-mediated responses; however, the mechanisms underpinning these changes in humans are not fully understood. Using a human dermal model of acute inflammation, we found that, although inflammatory onset is similar between young and elderly individuals, the resolution phase was substantially impaired in elderly individuals. This arose from a reduction in T cell immunoglobulin mucin receptor-4 (TIM-4), a phosphatidylserine receptor expressed on macrophages that enables the engulfment of apoptotic bodies, so-called efferocytosis. Reduced TIM-4 in elderly individuals was caused by an elevation in macrophage p38 mitogen-activated protein kinase (MAPK) activity. Administering an orally active p38 inhibitor to elderly individuals rescued TIM-4 expression, cleared apoptotic bodies and restored a macrophage resolution phenotype. Thus, inhibiting p38 in elderly individuals rejuvenated their resolution response to be more similar to that of younger people. This is the first resolution defect identified in humans that has been successfully reversed, thereby highlighting the tractability of targeting pro-resolution biology to treat diseases driven by chronic inflammation.
Subject(s)
Inflammation/etiology , Inflammation/metabolism , Phagocytosis/immunology , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , Age Factors , Aged , Animals , Apoptosis , Blister/immunology , Blister/metabolism , Blister/pathology , Cantharidin , Gene Expression , Humans , Immunity, Innate , Inflammation/pathology , Macrophages/immunology , Macrophages/metabolism , Macrophages/pathology , Male , Membrane Proteins/genetics , Membrane Proteins/metabolism , Neutrophils/immunology , Neutrophils/metabolism , Neutrophils/pathology , Receptors, Cell Surface/metabolism , Signal TransductionABSTRACT
Dystrophic epidermolysis bullosa is a rare genetic disease caused by damaging variants in COL7A1, which encodes type VII collagen. Blistering and scarring of the ocular surface develop, potentially leading to blindness. Beremagene geperpavec (B-VEC) is a replication-deficient herpes simplex virus type 1-based gene therapy engineered to deliver functional human type VII collagen. Here, we report the case of a patient with cicatrizing conjunctivitis in both eyes caused by dystrophic epidermolysis bullosa who received ophthalmic administration of B-VEC, which was associated with improved visual acuity after surgery.
Subject(s)
Collagen Type VII , Epidermolysis Bullosa Dystrophica , Genetic Therapy , Humans , Blister/etiology , Cicatrix/etiology , Collagen Type VII/genetics , Epidermolysis Bullosa Dystrophica/complications , Epidermolysis Bullosa Dystrophica/genetics , Epidermolysis Bullosa Dystrophica/therapy , Conjunctivitis/etiologyABSTRACT
Here, we introduce the full functional reconstitution of genetically validated core protein machinery (SNAREs, Munc13, Munc18, Synaptotagmin, and Complexin) for synaptic vesicle priming and release in a geometry that enables detailed characterization of the fate of docked vesicles both before and after release is triggered with Ca2+. Using this setup, we identify new roles for diacylglycerol (DAG) in regulating vesicle priming and Ca2+-triggered release involving the SNARE assembly chaperone Munc13. We find that low concentrations of DAG profoundly accelerate the rate of Ca2+-dependent release, and high concentrations reduce clamping and permit extensive spontaneous release. As expected, DAG also increases the number of docked, release-ready vesicles. Dynamic single-molecule imaging of Complexin binding to release-ready vesicles directly establishes that DAG accelerates the rate of SNAREpin assembly mediated by chaperones, Munc13 and Munc18. The selective effects of physiologically validated mutations confirmed that the Munc18-Syntaxin-VAMP2 "template" complex is a functional intermediate in the production of primed, release-ready vesicles, which requires the coordinated action of Munc13 and Munc18.
Subject(s)
Diglycerides , Synaptic Vesicles , Humans , Exocytosis , Synaptic Transmission , Synaptotagmins , BlisterABSTRACT
Low-intensity loading maintains or increases bone mass, whereas lack of mechanical loading and high-intensity loading decreases bone mass, possibly via the release of extracellular vesicles by mechanosensitive bone cells. How different loading intensities alter the biological effect of these vesicles is not fully understood. Dynamic fluid shear stress at low intensity (0.7 ± 0.3 Pa, 5 Hz) or high intensity (2.9 ± 0.2 Pa, 1 Hz) was used on mouse hematopoietic progenitor cells for 2 min in the presence or absence of chemical compounds that inhibit release or biogenesis of extracellular vesicles. We used a Receptor activator of nuclear factor kappa-Β ligand-induced osteoclastogenesis assay to evaluate the biological effect of different fractions of extracellular vesicles obtained through centrifugation of medium from hematopoietic stem cells. Osteoclast formation was reduced by microvesicles (10 000× g) obtained after low-intensity loading and induced by exosomes (100 000× g) obtained after high-intensity loading. These osteoclast-modulating effects could be diminished or eliminated by depletion of extracellular vesicles from the conditioned medium, inhibition of general extracellular vesicle release, inhibition of microvesicle biogenesis (low intensity), inhibition of ESCRT-independent exosome biogenesis (high intensity), as well as by inhibition of dynamin-dependent vesicle uptake in osteoclast progenitor cells. Taken together, the intensity of mechanical loading affects the release of extracellular vesicles and change their osteoclast-modulating effect.
Subject(s)
Cell-Derived Microparticles , Extracellular Vesicles , Animals , Mice , Osteoclasts , Bone Marrow , Hematopoietic Stem Cells , BlisterABSTRACT
BACKGROUND: Otosclerosis is a common cause of adult-onset progressive hearing loss, affecting 0.3%-0.4% of the population. It results from dysregulation of bone homeostasis in the otic capsule, most commonly leading to fixation of the stapes bone, impairing sound conduction through the middle ear. Otosclerosis has a well-known genetic predisposition including familial cases with apparent autosomal dominant mode of inheritance. While linkage analysis and genome-wide association studies suggested an association with several genomic loci and with genes encoding structural proteins involved in bone formation or metabolism, the molecular genetic pathophysiology of human otosclerosis is yet mostly unknown. METHODS: Whole-exome sequencing, linkage analysis, generation of CRISPR mutant mice, hearing tests and micro-CT. RESULTS: Through genetic studies of kindred with seven individuals affected by apparent autosomal dominant otosclerosis, we identified a disease-causing variant in SMARCA4, encoding a key component of the PBAF chromatin remodelling complex. We generated CRISPR-Cas9 transgenic mice carrying the human mutation in the mouse SMARCA4 orthologue. Mutant Smarca4+/E1548K mice exhibited marked hearing impairment demonstrated through acoustic startle response and auditory brainstem response tests. Isolated ossicles of the auditory bullae of mutant mice exhibited a highly irregular structure of the incus bone, and their in situ micro-CT studies demonstrated the anomalous structure of the incus bone, causing disruption in the ossicular chain. CONCLUSION: We demonstrate that otosclerosis can be caused by a variant in SMARCA4, with a similar phenotype of hearing impairment and abnormal bone formation in the auditory bullae in transgenic mice carrying the human mutation in the mouse SMARCA4 orthologue.
Subject(s)
Hearing Loss , Otosclerosis , Adult , Humans , Mice , Animals , Otosclerosis/genetics , Otosclerosis/surgery , Blister/complications , Genome-Wide Association Study , Reflex, Startle , Phenotype , Mice, Transgenic , Mutation , DNA Helicases/genetics , Nuclear Proteins/genetics , Transcription Factors/geneticsABSTRACT
Antibody-secreting cells (ASCs) produce immunoglobulin (Ig) G and IgE autoantibodies in secondary lymphoid organs. Evidence also suggests their existence in the skin in various chronic inflammatory conditions, and in association with CXCL12 and CXCL13, they regulate the recruitment/survival of ASCs and germinal center formation to generate ASCs, respectively. However, the presence of IgG and IgE in bullous pemphigoid (BP) lesions needs to be addressed. Here, we aimed to analyse BP skin for the presence of IgG and IgE and the factors contributing to their generation, recruitment, and persistence. Skin samples from 30 patients with BP were stained to identify ASCs and the immunoglobulin type they expressed. The presence of tertiary lymphoid organ (TLO) elements, which generate ASCs in non-lymphoid tissues, and the chemokines CXCL12 and CXCL13, which regulate the migration/persistence of ASCs in lymphoid tissues and formation of TLOs, respectively, were evaluated in BP skin. BP skin harboured ASCs expressing the two types of antibodies IgG and IgE. ASCs were found in high-grade cellular aggregates containing TLO elements: T cells, B cells, CXCL12+ cells, CXCL13+ cells and high endothelial venules. IgG+ ASCs were detected among these aggregates, whereas IgE+ ASCs were dispersed throughout the dermis. CXCL12+ fibroblast-like cells were located close to ASCs. The inflammatory microenvironment of BP lesions may contribute to the antibody load characteristic of the skin of patients with BP by providing a site for the presence of ASCs. CXCL13 and CXCL12 expression may contribute to the generation and recruitment/survival of ASCs, respectively.
Subject(s)
Pemphigoid, Bullous , Humans , Immunoglobulin E/metabolism , Blister , Autoantibodies/metabolism , Immunoglobulin G/physiology , B-Lymphocytes , Dermis/metabolism , Autoantigens , Non-Fibrillar CollagensABSTRACT
OBJECTIVES: To compare clinical image quality and perceived impact on diagnostic interpretation of chest CT findings between ultra-high-resolution photon-counting CT (UHR-PCCT) and conventional high-resolution energy-integrating-detector CT (HR-EIDCT) using visual grading analysis (VGA) scores. MATERIALS AND METHODS: Fifty patients who underwent a UHR-PCCT (matrix 512 × 512, 768 × 768, or 1024 × 1024; FOV average 275 × 376 mm, 120 × 0.2 mm; focal spot size 0.6 × 0.7 mm) between November 2021 and February 2022 and with a previous HR-EIDCT within the last 14 months were included. Four readers evaluated central and peripheral airways, lung vasculature, nodules, ground glass opacities, inter- and intralobular lines, emphysema, fissures, bullae/cysts, and air trapping on PCCT (0.4 mm) and conventional EIDCT (1 mm) via side-by-side reference scoring using a 5-point diagnostic quality score. The median VGA scores were compared and tested using one-sample Wilcoxon signed rank tests with hypothesized median values of 0 (same visibility) and 2 (better visibility on PCCT with impact on diagnostic interpretation) at a 2.5% significance level. RESULTS: Almost all lung structures had significantly better visibility on PCCT compared to EIDCT (p < 0.025; exception for ground glass nodules (N = 2/50 patients, p = 0.157)), with the highest scores seen for peripheral airways, micronodules, inter- and intralobular lines, and centrilobular emphysema (mean VGA > 1). Although better visibility, a perceived difference in diagnostic interpretation could not be demonstrated, since the median VGA was significantly different from 2. CONCLUSION: UHR-PCCT showed superior visibility compared to HR-EIDCT for central and peripheral airways, lung vasculature, fissures, ground glass opacities, macro- and micronodules, inter- and intralobular lines, paraseptal and centrilobular emphysema, bullae/cysts, and air trapping. CLINICAL RELEVANCE STATEMENT: UHR-PCCT has emerged as a promising technique for thoracic imaging, offering improved spatial resolution and lower radiation dose. Implementing PCCT into daily practice may allow better visibility of multiple lung structures and optimization of scan protocols for specific pathology. KEY POINTS: ⢠The aim of this study was to verify if the higher spatial resolution of UHR-PCCT would improve the visibility and detection of certain lung structures and abnormalities. ⢠UHR-PCCT was judged to have superior clinical image quality compared to conventional HR-EIDCT in the evaluation of the lungs. UHR-PCCT showed better visibility for almost all tested lung structures (except for ground glass nodules). ⢠Despite superior image quality, the readers perceived no significant impact on the diagnostic interpretation of the studied lung structures and abnormalities.
Subject(s)
Cysts , Lung Diseases , Pulmonary Emphysema , Humans , Pulmonary Emphysema/diagnostic imaging , Blister , Phantoms, Imaging , Lung/diagnostic imaging , Tomography, X-Ray Computed/methods , PhotonsABSTRACT
Recognising the need for objective imaging-based technologies to assess wound healing in clinical studies, the suction blister wound model offers an easily accessible wound model that creates reproducible epidermal wounds that heal without scarring. This study provides a comprehensive methodology for implementing and evaluating photography-based imaging techniques utilising the suction blister wound model. Our method encompasses a protocol for capturing consistent, high-quality photographs and procedures for quantifying these images via a visual wound healing score and a computer-assisted colour analysis of wound exudation and wound redness. We employed this methodology on 16 suction blister wounds used as controls in a clinical phase-1 trial. Our method enabled us to discern and quantify subtle differences between individual wounds concerning healing progress, erythema and wound exudation. The wound healing score exhibited a high inter-rater agreement. There was a robust correlation between the spectrophotometer-measured erythema index and photography-based wound redness, as well as between dressing protein content and photography-based dressing yellowness. In conclusion, this study equips researchers conducting clinical wound studies with reproducible methods that may support future wound research and aid in the development of new treatments.
Subject(s)
Blister , Photography , Wound Healing , Humans , Wound Healing/physiology , Photography/methods , Suction/methods , Erythema , Female , Male , Bandages , Exudates and Transudates , Image Processing, Computer-Assisted/methodsABSTRACT
BACKGROUND: Anti-p200 pemphigoid is a subepidermal autoimmune blistering disease (AIBD) characterized by autoantibodies against a 200 kDa protein. Laminin γ1 has been described as target antigen in 70% to 90% of patients. No diagnostic assay is widely available for anti-p200 pemphigoid, which might be due to the unclear pathogenic relevance of anti-laminin γ1 autoantibodies. OBJECTIVE: To identify a target antigen with higher clinical and diagnostic relevance. METHODS: Immunoprecipitation, mass spectrometry, and immunoblotting were employed for analysis of skin extracts and sera of patients with anti-p200 pemphigoid (n = 60), other AIBD (n = 33), and healthy blood donors (n = 29). To localize the new antigen in skin, cultured keratinocytes and fibroblasts, quantitative real-time polymerase chain reaction and immunofluorescence microscopy were performed. RESULTS: Laminin ß4 was identified as target antigen of anti-p200 pemphigoid in all analyzed patients. It was located at the level of the basement membrane zone of the skin with predominant expression in keratinocytes. LIMITATIONS: A higher number of sera needs to be tested to verify that laminin ß4 is the diagnostically relevant antigen of anti-p200 pemphigoid. CONCLUSION: The identification of laminin ß4 as an additional target antigen in anti-p200 pemphigoid will allow its differentiation from other AIBD and as such, improve the management of these rare disorders.
Subject(s)
Pemphigoid, Bullous , Humans , Autoantibodies , Autoantigens , Basement Membrane , Blister , Laminin , GiardiaABSTRACT
PURPOSE: In Europe, most medicines are taken orally and primarily packaged as single solid oral dosage forms (SODF) in blister chambers (alveoli) arranged on blister cards. Blister cards are constructed as multilayer laminates of aluminum (Al) foils and/or various plastic polymers bonded together, forming the alveoli, which are separated by more or less large gaps. We calculated the amount of packaging material (and thus waste) generated annually for the packaging of the most commonly prescribed SODF in Germany and estimated how much waste could be saved by rearranging the alveoli. METHODS: For this purpose, we analysed the SODF of the 50 most frequently prescribed medicines that were packaged in alveoli (N = 45; 13 of aluminum-aluminum blisters, 32 of mixed materials), measured and weighed their packaging material and content, calculated the annual amount of waste produced from them, and estimated how much waste could be saved if the alveoli were optimally positioned on the blister cards. In addition, we examined the variability of the blister packaging of eight groups of commonly prescribed generics of the same strength. RESULTS: Detailed analysis of the blister cards revealed that most of the material (69%) was used for the space between blisters and that aluminum-aluminum alveoli were more than four times larger than the packaged SODF. The (conservatively) estimated annual amount of composite waste generated for the primary packaging of these SODF was 3868 t (and extrapolated to the entire German pharmaceutical market 8533 t), of which an optimized arrangement of the blister chambers, i.e., a 2-mm sealing area around each alveolus and the arrangement of the SODF in 2 rows, would save approximately 37%. CONCLUSION: Considering that other ecological strategies are not yet mature, the optimal arrangement of blister chambers would be a captivatingly simple and, above all, immediately implementable strategy to avoid large amounts of avoidable waste.
Subject(s)
Aluminum , Blister , Humans , Drug Packaging , Tablets , EuropeABSTRACT
Amicrobial pustulosis of the folds (APF) is a rare neutrophilic dermatosis found in association with autoimmune diseases. We present a 49-year-old woman with a history of systemic lupus erythematosus and a recurrent pustular eruption in the cutaneous folds. Histologic examination revealed spongiform pustulosis and dermal neutrophilic infiltrate. The Gram and periodic acid-Schiff stains were negative for bacteria and fungi. A diagnosis of amicrobial pustulosis of the folds was given. While there is no standard treatment, our patient's symptoms resolved following an oral prednisone taper and have not recurred since starting colchicine. The presence of pustules and erosive plaques in skin folds in young women with autoimmune conditions should raise suspicion for APF. The combination of localized neutrophilic spongiosis with intraepidermal or subcorneal pustules in conjunction with dermal changes of a neutrophilic dermatosis is a helpful clue to the diagnosis. If the patient does not already have a diagnosis of an underlying autoimmune condition, a presentation of APF should prompt further screening consisting of a relevant review of symptoms and appropriate assessment for autoimmune antibodies, since APF may precede the diagnosis of autoimmune disorders.
Subject(s)
Autoimmune Diseases , Dermatitis , Lupus Erythematosus, Systemic , Humans , Female , Middle Aged , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Dermatitis/diagnosis , Autoimmune Diseases/complications , Autoimmune Diseases/diagnosis , Prednisone , Diagnosis, Differential , BlisterABSTRACT
Differentiating between giant pulmonary bullae and pneumothorax can pose a challenge in clinical settings. A chest CT scan during the patient's health assessment revealed that approximately 40% of the right chest cavity was filled with air, leading to incomplete expansion of the right lung. The patient was initially misdiagnosed with pneumothorax in the emergency department and subsequently underwent closed thoracic drainage without experiencing any improvement in symptoms. Upon further examination through thoracoscopy, the patient was correctly diagnosed with a giant pulmonary bulla. Upon reviewing the patient's chest CT scan, we were able to identify key distinguishing features between giant pulmonary bullae and pneumothorax.
Subject(s)
Blister , Diagnostic Errors , Pneumothorax , Tomography, X-Ray Computed , Humans , Pneumothorax/diagnostic imaging , Pneumothorax/diagnosis , Pneumothorax/etiology , Blister/diagnostic imaging , Male , Diagnosis, Differential , Lung Diseases/diagnostic imaging , Lung Diseases/diagnosis , Emergency Service, HospitalABSTRACT
ABSTRACT: Mucha-Habermann disease (MHD) is an inflammatory skin disease characterized by polymorphous eruptions of erythematous, necrotic macules that have been reported for similarities to cutaneous T-cell lymphoma. Febrile ulceronecrotic MHD (FUMHD) represents a severe variant of MHD, marked by ulcers, hemorrhagic bullae, and systemic symptoms. Herein, we report a case of a severely atypical lymphomatoid expression of FUMHD associated with hemophagocytic lymphohistiocytosis (HLH). A previously healthy 21-year-old woman was admitted to the hospital with a rapidly progressive necrotic papular rash. Physical examination revealed right orbital swelling, bilateral hemorrhagic auricular bullae, and multiple ulcerative purpuric papulonodules on the trunk, face, and extremities. Biopsy indicated a dermal and subcutaneous infiltrate of atypical CD8 + lymphocytes with loss of CD5 and reduction in CD7 expression, along with features of lymphomatoid vasculitis. A diagnosis of a severely atypical lymphomatoid expression of FUMHD was made. The patient also met 7 of 9 HLH-2004 criteria, leading to a diagnosis of HLH. Positron emission tomography/computed tomography, flow cytometry, and rheumatologic workup were unremarkable. Treatment with an eight-week course of etoposide and dexamethasone for HLH led to rapid clinical improvement. Over time, her skin lesions regressed and eventually scabbed over to leave hyperpigmented scars, confirming the diagnosis of MHD. She has remained stable, off therapy for 4 years. Although potentially fatal, FUMHD often exhibits favorable outcomes and may resolve without recurrence, as in our patient. FUMHD should be considered in the differential diagnosis for patients presenting with cutaneous CD8 + necrotizing angiocentric lymphoproliferative disease complicated by HLH.
Subject(s)
Herpes Simplex , Lymphohistiocytosis, Hemophagocytic , Pityriasis Lichenoides , Skin Neoplasms , Skin Ulcer , Female , Humans , Young Adult , Blister , Fever/etiology , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/diagnosis , Necrosis , Pityriasis Lichenoides/complications , Pityriasis Lichenoides/diagnosis , Skin Neoplasms/complications , Skin Ulcer/pathologyABSTRACT
We describe a rare presentation of congenital bullous syphilis in a premature neonate born with extensive skin desquamation. The newborn was noted to have diffuse erythema with widespread, superficial skin desquamation in addition to plantar bullae and erosions, and an absence of mucosal involvement. Immunohistochemical syphilis diagnostic staining was performed on a blister roof, highlighting a novel diagnostic approach for congenital bullous syphilis.
Subject(s)
Infant, Newborn, Diseases , Syphilis, Congenital , Syphilis , Infant, Newborn , Humans , Blister/diagnosis , Syphilis, Congenital/diagnosis , ErythemaABSTRACT
Incontinentia pigmenti (IP) is a rare X-linked dominant, male-lethal disorder characterized by pathognomic skin lesions. As described in the literature the typical cutaneous changes follow the pattern of Blaschko's lines and develop in four stages that usually start at birth. Stage 1 is called vesicular, bullous or inflammatory. The vesicles are rapidly filled with eosinophils and thus turn into pustules. Thus, the term "pustular" is relevant to the first phase of IP, and the stage can be considered as "vesiculopustular/inflammatory" to be more precise than "vesicular" or "bullous."
Subject(s)
Incontinentia Pigmenti , Infant, Newborn , Humans , Male , Incontinentia Pigmenti/diagnosis , Incontinentia Pigmenti/pathology , Skin/pathology , Blister/pathology , Eosinophils/pathology , Rare Diseases/pathologyABSTRACT
Congenital syphilis is a serious, disabling, and life-threatening infection that is transmitted transplacentally from mother to fetus. Early diagnosis is often difficult because affected infants are usually asymptomatic at birth and clinical findings are often subtle and nonspecific. Pemphigus syphiliticus is an early presentation of congenital syphilis which is characterized by fluid-filled vesicles and bullae which appear mostly on the extremities and tend to rapidly desquamate and erode. Awareness of the clinicians to this early cutaneous manifestation and possible treatment reaction will allow for prompt diagnosis and adequate treatment of syphilis-infected patients.
Subject(s)
Exanthema , Pemphigus , Soft Tissue Injuries , Syphilis, Congenital , Syphilis, Cutaneous , Syphilis , Infant, Newborn , Infant , Female , Humans , Syphilis, Congenital/diagnosis , Syphilis, Congenital/drug therapy , Pemphigus/diagnosis , Pemphigus/drug therapy , Syphilis/diagnosis , BlisterABSTRACT
Lobsters and crayfish in Australasia can develop a condition known as Tail Fan Necrosis (TFN syndrome). Many attempts have been made to find a primary pathogen or link the syndrome to commercial activities, but a solution remains elusive. TFN syndrome is a 'wicked problem', a problem difficult or impossible to solve because of incomplete and contradictory information forming a matrix of potential outcomes with no simple solution. Reviewing the literature shows TFN syndrome is sometimes reported to develop in association with sterile blisters on the telson and uropods which may rupture permitting invasion by environmental fungal and/or bacterial flora. Whether blisters form prior to, or because of, infection is unknown. TFN syndrome sometimes develops in captivity, sometimes requires a previous insult to the telson and uropods, and prevalence is patchy in the wild. The literature shows the cause of blisters associated with TFN syndrome remains an enigma, for which we suggest several possible initiating factors. We strongly urge that researchers not 'jump to conclusions' as to the aetiology of TFN syndrome. It cannot be explained without carefully exploring alternative aetiologies whilst being cognisant of the age-old lesson that 'correlation does not equal causation'.
Subject(s)
Decapoda , Fish Diseases , Animals , Tail , Blister/veterinary , Necrosis/microbiologyABSTRACT
Rashes in the newborn period are common and most are benign. Infections should be suspected in newborns with pustules or vesicles, especially in those who are not well-appearing or have risk factors for congenital infection. Congenital cytomegalovirus infection can cause sensorineural hearing loss and neurodevelopmental delay. Skin manifestations of cytomegalovirus may include petechiae due to thrombocytopenia. The most common skin manifestations of early congenital syphilis are small, copper-red, maculopapular lesions located primarily on the hands and feet that peel and crust over three weeks. Erythema toxicum neonatorum and neonatal pustular melanosis are transient pustular rashes with characteristic appearance and distribution. Neonatal acne is self-limited, whereas infantile acne may benefit from treatment. Milia can be differentiated from neonatal acne by their presence at birth. Cutis marmorata and harlequin color change are transient vascular phenomena resulting from inappropriate or exaggerated dilation of capillaries and venules in response to stimuli.
Subject(s)
Acne Vulgaris , Dermatitis, Exfoliative , Exanthema , Humans , Infant, Newborn , Skin , Exanthema/diagnosis , Exanthema/etiology , BlisterABSTRACT
BACKGROUND: Suction blister epidermal grafting (SBEG) is currently one of the most prevalent surgical methods for stable vitiligo. OBJECTIVE: To investigate the long-term outcomes of vitiligo patients who underwent SBEG and to explore risk factors associated with postoperative relapse. METHODS: A retrospective cohort study was conducted in patients who underwent SBEG in our department between January 2016 and December 2022. Treatment outcomes, including repigmentation rate, adverse events, and postoperative relapse, were surveyed via telephone interview or out-=patient visit. Multivariate logistic regression models were used to assess the potential risk factors for postoperative relapse. Statistical significance was assumed at P < .05. RESULTS: A total of 253 patients were included with a repigmentation rate of 96% (243/253) after grafting. Common adverse events included cobblestone-like appearance (73.1%, 185/253) in the donor site, perigraft halo (46.2%, 117/253), and cobblestone-like appearance (26.1%, 66/253) in the recipient site. Postoperative relapse occurred in 20.1% of patients over a mean time of 29.7 months after grafting. Nonsegmental type of vitiligo and coexistence of autoimmune diseases were risk factors for postoperative relapse. CONCLUSION: SBEG is an effective surgical treatment for vitiligo with high repigmentation rate and good safety profile. Nonsegmental vitiligo and comorbid autoimmune diseases may increase the risk of postoperative relapse.
Subject(s)
Recurrence , Skin Transplantation , Vitiligo , Humans , Vitiligo/surgery , Male , Retrospective Studies , Female , Adult , Skin Transplantation/methods , Adolescent , Middle Aged , Young Adult , Risk Factors , Suction/methods , Epidermis/transplantation , Prognosis , Blister/surgery , Child , Treatment OutcomeABSTRACT
BACKGROUND: Mayflies are basal winged insects of crucial importance for the understanding of the early evolution of Pterygota. Unlike all other insects, they have two successive winged stages, the subimago and the imago. Their forewings feature so-called bullae, which are desclerotized spots in the anterior main veins. Up to now, they have been considered to play a major role in wing bending during flight. RESULTS: We investigated bullae by multiple methods to reveal their structure and arrangement and to gain new information on the evolution of insect flight. Bullae are mostly present in the anterior negative wing veins, disrupting the otherwise rigid veins. High-speed videography reveals that mayfly wings do not bend during flight. Likewise, different arrangements of bullae in different species do not correlate with different modes of flying. Observations on the moulting of subimagines unravel that they are essential for wing bending during the extraction of the imaginal wing from the subimaginal cuticle. Bullae define predetermined bending lines, which, together with a highly flexible wing membrane enriched with resilin, permit wing bending during subimaginal moulting. Bullae are only absent in those species that remain in the subimaginal stage or that use modified modes of moulting. Bullae are also visible in fossil mayflies and can be traced back to stemgroup mayflies of the Early Permian, the 270 million years old Protereismatidae, which most probably had bullae in both fore- and hind wings. CONCLUSIONS: Bullae in mayfly wings do not play a role in flight as previously thought, but are crucial for wing bending during subimaginal moulting. Thus, the presence of bullae is a reliable morphological marker for a subimaginal life stage, confirming the existence of the subimago already in Permian Protereismatidae. A thorough search for bullae in fossils of other pterygote lineages may reveal wheather they also had subimagines and at what point in evolution this life stage was lost. In mayflies, however, the subimago may have been retained due to selective advantages in connection with the transition from aquatic to terrestrial life or due to morphological requirements for a specialized mating flight.