bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of Evaluation of Genetic Variability of Gladiolus Cultivars under Agro-climatic Conditions of Prayagraj, India
Authors: Singh Veenu , Singh Devi , Wesley John
Published: August 2023

A field experiment was carried out to “Study of Evaluating Genetic Variability of Gladiolus (Gladilous grandiflorus L.) Cultivars Under Agro –Climatic conditions of Prayagraj” was conducted at the Departmental research field of Horticulture, Naini, Agriculture Institute during Rabi season of 2022-2023. The experiment involved 15 cultivars arranged in randomized block design with three replication. The analysis of the data showed that  phenotypic coefficient of variation (PCV) was higher than genotypic coefficient of variation (GCV) for all characters studied, indicating that environmental factors had a significant influence on these characters. Several traits, including number of leaves at 30DAS, corm yield per plant, number of cormels per hectare, cormel diameter, number of corms per hectare, and number of corms per plant, exhibited high PCV and GCV. Furthermore, the study found high heritability coupled with high genetic advance as a percentage of the mean for traits such as the number of leaves at 30DAS, corm yield per plant, number of cormels per hectare, cormel diameter, number of corms per hectare, and number of corms per plant. This suggests that these traits are under strong genetic control and have the potential for effective selection and improvement. Moreover, positive and highly significant correlations were observed between corm yield per plant (in grams) and various other traits, including the number of leaves at 30DAS, 60DAS, and 90DAS, number of shoots per plant, days to first flowering, rachis length, number of florets per spike, number of spikes per plant, floret length, floret diameter, number of corms per plant, corm diameter, weight of corm, number of corms per hectare, and number of cormels per hectare. These correlations indicate that these traits have a strong influence on corm yield. Based on the study's results, genotypes Yellow stone, followed by Joshka, Pusa suhagan, and Arka Naveen, were identified as high spike and corm-yielding genotypes under the agro-climatic conditions of Prayagraj.Overall, the study highlights the significant impact of environmental factors on the observed traits and provides valuable insights into the selection of gladiolus genotypes with desirable characteristics for cultivation in the Prayagraj region.
Impact of Nutritional Interventions on Epigenetic Influences in the Gestational and Puerperium Period: A Systematic Review
Authors: Santos Mateus Silva , Santos Ketle dos , Silva Jaqueline de Paula e
Published: August 2023

Background: Epigenetic analyzes associated with maternal and child nutrition are the subject      of several studies due to their crucial role in fetal development. Significant changes in diet during the gestational period or even in the puerperium can lead to metabolic diseases or even neuropsychiatric disorders.

Aims: The present study sought to carry out a systematic review of such interactions in the pre- and post-pregnancy periods.

Study Design: Systematic review.

Methodology: Bibliographic research was used as a method and data were obtained from the VHL information portal from 2017 to 2021. Original articles published in the last 6 years, related to nutritional impacts on epigenetic mechanisms, whether in women during the gestational and postpartum period or newborns, were included in this study. In the gestational period and puerperium or newborns.

Results: Nine studies that met the selection criteria and were associated with the topic were selected.

Conclusion: Based on this study, it was possible to understand the relationship between diet and the expression of epigenetic changes in order to promote studies in this area that facilitate the understanding of various diseases of genomic origin.
Economic Growth Implications of Inflation Targeting and Inflation Volatility: An Emerging Economy’s Perspective
Authors: Achiyaale Raymond Awonatezuaka , Adaletey Jennifer Ellah , Mbilla Simon Akumbo Eugene , Tsorhe Daniel Komla
Published: August 2023

Purpose: The purpose of this study was to comparatively examine the extent to which inflation targeting and inflation volatility impact on economic growth from an emerging economy’s perspective.

Methodology: Annual data from the World Development Indicator (WDI) and the Bank of Ghana (BoG) from 1985 to 2014 were used for the study. The data was interpolated into quarterly series using E-views. The stationarity characteristics of the variables were tested using the Augmented Dickey-Fuller and the Phillip-Perron unit root tests. The GARCH (1 1) and ARDL models were employed for the analysis.

Findings: The study found that inflation targeting had a positive significant effect on economic growth in Ghana. Also, despite the volatile nature of inflation in Ghana, inflation volatility had no significant effect on economic growth.

Implications: This scholarly work would aid policy makers in policy formulation pertaining to inflation targeting and inflation volatility on economic growth. It will also open up the circles of knowledge regarding inflation targeting monetary policy’s regime in empirical literature, institutions of higher learning and the understanding of the general public. The study recommends that the Bank of Ghana maintains its current monetary policy framework - Inflation Targeting, but should strengthen the preconditions and subsequent requirements of the monetary policy in order to maximize the gains to economic growth.
Posttraumatic Stress Disorder Symptoms Among First-Year Resident Physicians Working Before and During the COVID-19 Pandemic
Authors: Ptak Michelle K. , Frank Elena , Ross Katherine E. T. , Cleary Jennifer L. , Sen Srijan , Pereira-Lima Karina
Published: August 2023

This cohort study investigates differences in posttraumatic stress disorder (PTSD) symptoms among first-year resident physicians training before and during the first wave of the COVID-19 pandemic (March to June 2020).
Nucleocytoplasmic transport at the crossroads of proteostasis, neurodegeneration and neuroprotection
Authors: Ferreira Paulo A.
Published: August 2023

Nucleocytoplasmic transport comprises the multistep assembly, transport, and disassembly of protein and RNA cargoes entering and exiting nuclear pores. Accruing evidence supports that impairments to nucleocytoplasmic transport are a hallmark of neurodegenerative diseases. These impairments cause dysregulations in nucleocytoplasmic partitioning and proteostasis of nuclear transport receptors and client substrates that promote intracellular deposits – another hallmark of neurodegeneration. Disturbances in liquid–liquid phase separation (LLPS) between dense and dilute phases of biomolecules implicated in nucleocytoplasmic transport promote micrometer‐scale coacervates, leading to proteinaceous aggregates. This Review provides historical and emerging principles of LLPS at the interface of nucleocytoplasmic transport, proteostasis, aging and noxious insults, whose dysregulations promote intracellular aggregates. E3 SUMO‐protein ligase Ranbp2 constitutes the cytoplasmic filaments of nuclear pores, where it acts as a molecular hub for rate‐limiting steps of nucleocytoplasmic transport. A vignette is provided on the roles of Ranbp2 in nucleocytoplasmic transport and at the intersection of proteostasis in the survival of photoreceptor and motor neurons under homeostatic and pathophysiological environments. Current unmet clinical needs are highlighted, including therapeutics aiming to manipulate aggregation‐dissolution models of purported neurotoxicity in neurodegeneration.
A logical model of Ewing sarcoma cell epithelial‐to‐mesenchymal transition supports the existence of hybrid cellular phenotypes
Authors: Silveira Daner A. , Gupta Shantanu , da Cunha Jaeger Mariane , Brunetto de Farias Caroline , Mombach José Carlos Merino , Sinigaglia Marialva
Published: August 2023

Ewing sarcoma (ES) is a highly aggressive pediatric tumor driven by the RNA‐binding protein EWS (EWS)/friend leukemia integration 1 transcription factor (FLI1) chimeric transcription factor, which is involved in epithelial–mesenchymal transition (EMT). EMT stabilizes a hybrid cell state, boosting metastatic potential and drug resistance. Nevertheless, the mechanisms underlying the maintenance of this hybrid phenotype in ES remain elusive. Our study proposes a logical EMT model for ES, highlighting zinc finger E‐box‐binding homeobox 2 (ZEB2), miR‐145, and miR‐200 circuits that maintain hybrid states. The model aligns with experimental findings and reveals a previously unknown circuit supporting the mesenchymal phenotype. These insights emphasize the role of ZEB2 in the maintenance of the hybrid state in ES.
Canagliflozin mediates tumor suppression alone and in combination with radiotherapy in non‐small cell lung cancer (NSCLC) through inhibition of HIF‐1α
Authors: Biziotis Olga‐Demetra , Tsakiridis Evangelia Evelyn , Ali Amr , Ahmadi Elham , Wu Jianhan , Wang Simon , Mekhaeil Bassem , Singh Kanwaldeep , Menjolian Gabe , Farrell Thomas , Abdulkarim Bassam , Sur Ranjan K. , Mesci Aruz , Ellis Peter , Berg Tobias , Bramson Jonathan L , Muti Paola , Steinberg Gregory R , Tsakiridis Theodoros
Published: August 2023

Non‐small cell lung cancer (NSCLC) has a poor prognosis, and effective therapeutic strategies are lacking. The diabetes drug canagliflozin inhibits NSCLC cell proliferation and the mammalian target of rapamycin (mTOR) pathway, which mediates cell growth and survival, but it is unclear whether this drug can enhance response rates when combined with cytotoxic therapy. Here, we evaluated the effects of canagliflozin on human NSCLC response to cytotoxic therapy in tissue cultures and xenografts. Ribonucleic acid sequencing (RNA‐seq), real‐time quantitative PCR (RT‐qPCR), metabolic function, small interfering ribonucleic acid (siRNA) knockdown, and protein expression assays were used in mechanistic analyses. We found that canagliflozin inhibited proliferation and clonogenic survival of NSCLC cells and augmented the efficacy of radiotherapy to mediate these effects and inhibit NSCLC xenograft growth. Canagliflozin treatment alone moderately inhibited mitochondrial oxidative phosphorylation and exhibited greater antiproliferative capacity than specific mitochondrial complex‐I inhibitors. The treatment downregulated genes mediating hypoxia‐inducible factor (HIF)‐1α stability, metabolism and survival, activated adenosine monophosphate‐activated protein kinase (AMPK) and inhibited mTOR, a critical activator of hypoxia‐inducible factor‐1α (HIF‐1α) signaling. HIF‐1α knockdown and stabilization experiments suggested that canagliflozin mediates antiproliferative effects, in part, through suppression of HIF‐1α. Transcriptional regulatory network analysis pinpointed histone deacetylase 2 (HDAC2), a gene suppressed by canagliflozin, as a key mediator of canagliflozin's transcriptional reprogramming. HDAC2 knockdown eliminated HIF‐1α levels and enhanced the antiproliferative effects of canagliflozin. HDAC2‐regulated genes suppressed by canagliflozin are associated with poor prognosis in several clinical NSCLC datasets. In addition, we include evidence that canagliflozin also improves NSCLC response to chemotherapy. In summary, canagliflozin may be a promising therapy to develop in combination with cytotoxic therapy in NSCLC.
Histopathology of the Skin: General Principles
Authors: Calonje Eduardo , Bhogal Balbir S.
Published: August 2023

This chapter describes in detail the steps followed from the moment a skin biopsy is taken through to the final step when interpretation of the changes is performed by the histopathologist. It emphasizes laboratory methods including special techniques useful to reach a diagnosis, potential artefacts and the approach to the interpretation of skin biopsies.
Diagnosis of Skin Disease
Authors: Coulson Ian H. , Benton Emma C. , Ogden Stephanie
Published: August 2023

This chapter deals with the essentials of arriving at a diagnosis of skin disease by the process of history taking and clinical examination, supplemented by simple both bedside procedures (e.g. Wood's light, diascopy, dermoscopy and confocal microscopy) and laboratory investigations. It includes a glossary of dermatological terms and their definitions. The roles of teledermatology, mobile telephone and Internet technology are also covered.
Health Economics and Skin Disease
Authors: Augustin Matthias , Krensel Magdalene
Published: August 2023

This chapter contains a brief introduction to the basic methods of health economic analysis followed by a presentation of the results of international cost‐of‐illness studies for psoriasis and skin cancer. The validity of the presented results and limitations in their comparison are discussed. In conclusion, the impact of health economic findings on decision making in dermatology practice is discussed.
Inflammation, Immunology and Allergy
Authors: Steinhoff Martin
Published: August 2023

Inflammation can be defined as a complex body defence mechanism responding to dangerous endogenous or exogenous stimuli in order to restore body homeostasis. Thus, the skin is continuously challenged to prevent inflammation, and inflammatory skin diseases are very common worldwide. Similarly, allergic reactions (types 1–4) are inflammatory processes created by the body system to respond to ‘danger signals’ of various origins. Very early in phylogenesis, inflammation is associated with the host defence against infectious, allergic or toxic agents, UV radiation, noxious heat and cold, or other injury. Innate and later adaptive immune mechanisms have been established that, uncontrolled, potentially lead to chronic disease or death, as in anaphylactic shock. The body system responds with the induction of various inflammatory pathways such as radical oxygen species, nitric oxide derivatives, complement compounds, adenosine monophosphate, antimicrobial peptides, cytokines, chemokines, prostaglandins, leukotrienes, proteases, neuropeptides and growth factors, just to name a few. This chapter systematically covers the various mechanisms that regulate inflammatory and allergic responses and refers in a translational setting to the diseases that are involved in order better to understand the clinical characteristics of a skin disease, its differential diagnoses and optimal treatment options.
Photobiology
Authors: Young Antony R.
Published: August 2023

The main source of human skin exposure to ultraviolet radiation (UVR) is the sun, but people are also exposed to UVR in phototherapy and through the use of tanning devices. UVR has many important acute and long‐term effects on the skin. The most evident acute effects are erythema and tanning; skin cancer and photoageing are the long‐term effects. Acute and long‐term effects are dependent on the genetically determined skin type. All photobiological effects are initiated by the absorption of UVR energy by molecules in the skin called chromophores, of which DNA is an important example. Most of the effects of UVR on the skin are considered to be detrimental, but the synthesis of vitamin D is the only well‐established beneficial effect. Adequate photoprotection, which includes shade seeking, sunscreens and clothing, can reduce the adverse effects of UVR, whilst still allowing vitamin D synthesis.
Cutaneous Response to Injury and Wound Healing
Authors: O'Toole Edel A.
Published: August 2023

Wound healing is a complex and dynamic response to injury that can be divided into three phases: inflammation, re‐epithelialization and matrix remodelling. Interactions are required between keratinocytes, fibroblasts, endothelial and inflammatory cells, growth factors, extracellular matrix and enzymes called proteases. Fetal wounds can heal without scarring; however wounds in children and adults heal with a remodelling phase resulting in a scar. Non‐healing or chronic wounds occur because of infection or pressure as well as systemic factors such as ischaemia or diabetes. Abnormal scarring results in hypertrophic or keloid scars. The effect of secreted heat shock proteins, regulation by microRNAs, manipulation of macrophage polarization and wound treatment with mesenchymal stem cells (by direct application or mobilization from bone marrow) are new areas of interest.
Psychological and Social Impact of Long‐Term Dermatological Conditions
Authors: Bundy Christine , Cordingley Lis
Published: August 2023

An altered appearance associated with skin conditions may confer significant additional emotional and social burdens on patients. For some conditions, this burden is substantial and enduring. It is crucial to recognize that the degree of impact is not necessarily directly related to the severity of the underlying skin pathology but is more likely to be associated with people's beliefs about the condition, about its treatment and their perceived ability to cope. In routine clinical management, the life impact is rarely acknowledged or managed explicitly and this can have repercussions for self‐management, in particular adherence to prescribed treatment. This chapter summarizes current knowledge about the psychological and social impacts of a range of common skin conditions dermatologists will encounter and provides an understanding of an evidence‐based psychological approach to supporting and addressing patient needs in routine dermatological consultations.
Clinical Pharmacology
Authors: Smith Catherine H.
Published: August 2023

Drug therapy forms a critical component of the management of skin disease, and the advent of targeted biological therapy has led to transformational improvements in outcomes for many patients. Clinical pharmacology deals with the actions, mechanisms of action, uses, adverse effects and fate of drugs in humans, and underpins all aspects of drug therapy from novel drug development through to safe, effective prescribing. Knowledge of these principles is essential to ensure optimal use of drug therapy in dermatology.
Principles of Holistic Management of Skin Disease
Authors: Gibbs Sam
Published: August 2023

In the last 50–100 years medical practice has become increasingly shaped and influenced by technological advances. The idea of holistic management is in part a reaction against what is perceived as the increasingly technical and impersonal nature of medical care, particularly in so‐called developed societies. Holistic practice embraces a range of concepts but essentially refers to the appreciation and inclusion of broader social, psychological and spiritual factors in medical practice. Thus the holistic management of skin disease involves considering the whole patient and not just their disease and the technical aspects of its diagnosis and treatment. Social, psychological and spiritual factors can have a direct influence on the effectiveness of treatments, particularly in dermatological practice, although there is a dearth of good research in this area. Patient education and empowerment, including the involvement of patients in self‐help groups, is also an increasingly important component of holistic care.
Principles of Photodynamic Therapy
Authors: Ibbotson Sally , McKenna Kevin
Published: August 2023

Topical photodynamic therapy is widely used for the treatment of superficial non‐melanoma skin cancer and dysplasia and has been shown to be at least as effective as non‐surgical standard comparators such as topical fluorouracil and cryotherapy. British and European guidelines are available for its use, and treatment is undertaken on an out‐patient basis and is generally well tolerated, with the exception of pain during irradiation in a significant proportion of patients. Optimization of treatment regimens to improve efficacy and reduce side effects have included refinements in pro‐drug development and delivery and in the methods of light delivery, in particular using reduced irradiance regimens. The use of topical photodynamic therapy (PDT) has also been applied to a wide range of other diverse skin diseases including acne vulgaris and recalcitrant viral warts and it may have a role in some of these conditions, although further studies are required. It is important that topical PDT services are widely available in dermatology, particularly to those involved in skin cancer management, through the multidisciplinary team, and that standards and clinical governance for PDT are established.
Principles of Radiotherapy
Authors: Kelly Charles G. , Frew John
Published: August 2023

The clinical effects of ionizing radiation on the skin have been known since the discovery of X‐rays in 1895. Initially, both benign and malignant skin conditions were irradiated, and dose and clinical indications were chosen empirically with little knowledge of the late effects of radiation on the skin and subcutaneous tissue. Indications for treating benign disease by irradiation have declined since the advent of topical steroids. It is in the best interest of patients suffering from skin tumours to be seen in a clinic where the expertise of specialists in radiotherapy and oncology, plastic surgery and micrographic surgery as well as dermatology are present. This is being achieved with the mandatory development of multidisciplinary team meetings and clinics in the UK as described in the National Institute for Health and Care Excellence guidelines of 2006.
Bacterial Infections
Authors: Hay Roderick J. , Morris‐Jones Rachael
Published: August 2023

This chapter starts by considering the resident bacterial population of the skin and how this has altered with our growing understanding of the skin microbiome. It then reviews the whole range of bacterial skin infections from primary Gram‐positive infections due to staphylococci and streptococci to the less common infections caused by Gram‐negative and anaerobic bacteria. The cutaneous manifestations of common and rare systemic bacterial infections such as staphylococcal septicaemia and melioidosis are described in practical detail. Using new work on antibiotics, the spread of drug resistance amongst skin bacterial pathogens is reviewed and its relevance clarified in the treatment algorithms. Rickettsial infections are also considered.
Mycobacterial Infections
Authors: Yates Victoria M. , Walker Stephen L.
Published: August 2023

Infections of the skin caused by mycobacteria have a wide geographical distribution. The clinical manifestations are varied and not necessarily species‐specific.Mycobacterium tuberculosisinfection of the skin is often a chronic infection but may present as immunological phenomena – tuberculids. An increasing number of species are recognized as causing non‐tuberculous mycobacterial infections. Immunosuppression appears to increase the risk of some mycobacterial infections and the role of HIV and iatrogenic immune modulation are notable risk factors. Molecular diagnostics have increased the ability to identify specific organisms but prolonged antimicrobial therapy is often required.
Leprosy
Authors: Lockwood Diana N. J.
Published: August 2023

Leprosy is a chronic granulomatous disease caused by infection of the skin and nerves withMycobacterium lepraeand about 250 000 new cases are diagnosed annually, 60% of which are in India. The patient's host immune response to the mycobacteria determines clinical presentation and the occurrence of immune‐mediated reactions and neuritis. Skin lesions range from anaesthetic macules to nodules. Diagnosis is clinically based on the type of skin lesion, peripheral nerve thickening and the presence of mycobacteria in the skin. A skin biopsy is often useful in diagnosing leprosy. Nerve damage causes sensorimotor damage affecting the hands, feet and eyes. The infection is readily treatable with a combination of antibiotics (e.g. rifampicin, dapsone, clofazimine) but the associated nerve damage and inflammation is difficult to switch off and patients may need repeated courses of steroid treatment. Leprosy patients are still stigmatized and this needs combatting at all levels; most patients are not infectious.
Syphilis and Congenital Syphilis
Authors: Kinghorn George R. , Omer Rasha
Published: August 2023

Syphilis is among the most fascinating of skin diseases. It may present to the dermatologist as a sexually acquired, contagious disease or as a congenitally acquired infection. When sexually acquired, it commonly coexists with at least one other sexually transmitted infection. Although syphilis is endemic worldwide, its steady decline over the last 400 years has been punctuated by epidemic peaks associated with unstable social conditions or upheavals. These changes include mass migrations and wars, as well as growing prosperity and economic reversals precipitating real or relative poverty. More recently, rates of primary and secondary syphilis have increased in the past decade, warranting renewed attention to the diagnosis and treatment of this disease.
Graft‐Versus‐Host Disease
Authors: Basu Tanya N.
Published: August 2023

Graft‐versus‐host disease is a major complication of allogeneic haematopoietic stem cell transplantation. It is a multiorgan disease process that results from the action of donor‐derived immunocompetent T‐lymphocyte cells against antigens expressed on the cells of the immunocompromised recipient host. The main organs affected are the skin, liver and gastrointestinal tract. Acute, chronic and overlap forms are recognized.
Atopic Eczema (Atopic Dermatitis)
Authors: Ardern‐Jones Michael R. , Flohr Carsten , Reynolds Nick J. , Holden Colin A.
Published: August 2023

Atopic eczema is a chronic, relapsing, inflammatory skin condition characterized by itch which affects 20–30% of schoolchildren and 5–10% of adults in the UK. The increased prevalence in both western industrialized countries and developing nations over the last 20 years highlights the strong role of environmental factors in mediating the disease. However, the identification of a strong association between atopic eczema and mutations in the gene encoding filaggrin in 2006 has provided a paradigm shift in our understanding of the role of genetics in this condition and the importance of the function of the epidermal barrier. Indeed, interventions to repair the epidermal barrier show promise in both the treatment and prevention of atopic eczema and its complications. T‐helper 2 cells are central to mediating atopic eczema inflammation and specific targeted interventions are progressing well in clinical trials. Further developments in our understanding of disease pathogenesis, including the role of thymic stromal lymphopoeitin, and recently discovered subsets of immunocytes, are exciting targets and provide an optimistic future for the management of this challenging disease. However, topical therapy with emollients, corticosteroids and calcineurin inhibitors remains the mainstay of treatment. Thus, for more severe disease, current therapeutic options remain limited. As a result, atopic eczema still contributes a significant quality of life and financial burden on society and health care systems worldwide.
Autoinflammatory Diseases Presenting in the Skin
Authors: Lipsker Dan , Grattan Clive E. H. , Lovell Christopher R.
Published: August 2023

Autoinflammatory diseases comprise a heterogeneous group of inherited monogenic and acquired polygenic multisystem disorders that may present in the skin and are therefore of importance to dermatologists. The inherited monogenic disorders typically present in childhood. Those that present with urticarial rashes are particularly important to differentiate from chronic urticaria since the pathogenesis, prognosis and treatment are completely different. Cryopyrin‐associated periodic syndrome should be suspected in children with a family history of chronic urticaria that does not respond to H1antihistamines and who have systemic symptoms of malaise and fever with persistently raised inflammatory indices. Autoinflammatory syndromes also may present with unexplained fever, erysipelas‐like rash (familial Mediterranean fever), oedema (tumour necrosis factor receptor‐associated periodic syndrome), pustulosis and lipoatrophy (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature), an aseptic pustular dermatosis (deficiency of interleukin 1 receptor antagonist) or pyoderma gangrenosum (pyogenic sterile arthritis, acne and pyoderma gangrenosum). Acquired autoinflammatory syndromes which present in adult life include Schnitzler syndrome and adult Still disease; the differential diagnosis includes urticarial vasculitis.
Mastocytosis
Authors: Grattan Clive E. H. , Radia Deepti H.
Published: August 2023

Mastocytosis is a rare multisystem disorder of increased mast cell numbers in the skin and other tissues. Molecular genetic analysis of bone marrow reveals a mutation ofKITin nearly all adult patients with systemic disease. Although mastocytosis is primarily a haematological disorder, it often presents with skin lesions to dermatologists or paediatricians. Patients may also present with symptoms or complications of the disease to allergists, metabolic bone disease specialists or accident and emergency departments. A diagnosis of mastocytosis can be confirmed by lesional skin biopsy. Systemic mastocytosis is usually diagnosed by bone marrow biopsy. Local or systemic symptoms from mast cell mediator release are common. Complications of adult disease include anaphylaxis, osteoporosis and the lifetime development of associated haematological non‐mast cell diseases. At least 50% of children will grow out of mastocytosis by puberty, particularly those with early‐onset disease. Treatment is aimed primarily at symptom control with antimediator drugs, including H1 antihistamines, but patients with advanced systemic disease may require cytoreductive drugs.
Reactive Inflammatory Erythemas
Authors: Rustin Malcolm , Cerio Rino
Published: August 2023

Multiple skin conditions can present with ring‐like or annular lesions for which a specific diagnosis can be made (e.g. tinea corporis, granuloma annulare, psoriasis or annular sarcoidosis). This chapter describes a group of conditions that do not necessarily lead to a specific underlying diagnosis and may pose diagnostic and therapeutic problems. It includes erythema multiforme, annular erythema of infancy, necrolytic migratory erythema (NME), erythema annulare centrifugum (EAC), erythema gyratum repens and erythema marginatum. EAC and subacute cutaneous lupus will be covered in separate chapters. Each eruption may have characteristic features and although diagnosis of erythema multiforme is often easy and there are a limited number of underlying causes, the diagnosis of NME may take time in view of the different manifestations of the disease. Physicians should be alert to the subtle eruption of erythema marginatum and the importance of diagnosing rheumatic fever. These cutaneous signs therefore present a challenge with heterogenous diseases presenting with varying morphologies.
Dermatomyositis
Authors: Gordon Patrick , Creamer Daniel
Published: August 2023

Dermatomyositis (DM) is an autoimmune disorder of skin and muscle characterized by a broad spectrum of cutaneous manifestations. The dermatosis of DM may occur in isolation (clinically amyopathic DM) but myositis is usual and can lead to profound weakness. Involvement of the oro‐pharynx and the upper oesophageal sphincter in DM causes dysphagia. Aspiration pneumonia, exacerbated by respiratory muscle weakness, is the life‐threatening complication of oro‐pharyngeal involvement. There is a strong association between DM and internal malignancy, with studies indicating that up to one‐third of adult patients have an underlying cancer. Pathogenetically, DM is a humorally mediated microvasculopathy; the majority of patients have disease‐associated autoantibodies, notably the myositis‐specific antibodies (MSAs), including anti‐Mi‐2, TIF‐1γ, MDA‐5, Jo‐1 and SUMO activating enzyme. MSAs are specific for myositis and help define phenotype. Systemic corticosteroids are the primary treatment when both skin and muscles are involved. An immunosuppressant agent, such as azathioprine, methotrexate or mycophenolate mofetil, is usually needed to control the inflammatory activity and limit corticosteroid requirements. Intravenous immunoglobulin infusions can be effective for both muscle and skin activity. Antimalarials, topical corticosteroid and topical tacrolimus are variably useful in the management of DM skin disease.
Mixed Connective Tissue Disease
Authors: Goodfield Mark
Published: August 2023

Mixed connective tissue disease (MCTD) refers to one of a number of conditions in which patients have symptoms or signs that suggest a number of different disease entities within the spectrum of the connective tissue diseases (CTDs). The original MCTD, Sharp syndrome, was associated with a specific autoantibody – anti‐U1‐RNP – occurring in a patient with elements of lupus erythematosus, systemic sclerosis and dermatomyositis, and was recognized as an identity in its own right. Subsequently, other combinations have been described, and may occur with other autoantibody profiles. These have been described as overlap syndromes, or as undifferentiated CTD, or as CTD in evolution because of the range of symptoms and signs and the sometimes changing nature of the condition. There is a tendency for the patient's condition to evolve in the direction of a single CTD over time, although many remain with overlapping features. The condition, however varied, is characterized by a generally good prognosis, and by a good response to therapy, although some patients may be severely affected, and may develop life‐threatening complications despite treatment.
Morphoea (Localized Scleroderma)
Authors: Orteu Catherine H.
Published: August 2023

Morphoea encompasses a group of related conditions characterized by varying degrees of sclerosis, fibrosis and atrophy in the skin and subcutaneous tissues, sometimes extending deeply into the muscle, bone, eye and brain. Extracutaneous manifestations occur in up to 25% of cases but in contrast to systemic sclerosis (SSc), no internal organ fibrosis or vascular changes occur. Antinuclear antibody positivity is common but the specific autoantibodies seen in SSc are rarely present. There is no increased mortality, but substantial morbidity may occur as a result of joint contractures, facial and limb asymmetry, extracutaneous manifestations and the psychological impact of the condition. Although previously considered self‐limiting, there is now emerging evidence that a protracted, relapsing–remitting course may be common. The key to successful treatment is the involvement of a multidisciplinary team and the initiation of therapy during the active inflammatory stage, before significant damage has occurred. Topical and phototherapies are appropriate in superficial forms of morphoea, whilst a majority of linear, generalized and deep forms require systemic therapy.
Nutritional Disorders Affecting the Skin
Authors: Chu Derek H. , Jen Melinda V. , Yan Albert C.
Published: August 2023

Balanced intake, absorption and utilization of macro‐ and micronutrients, including carbohydrates, protein, fat, vitamins and minerals, are necessary for the function of various physiological processes and metabolic reactions. Derangements in this critical balance may lead to disease states with significant cutaneous and systemic manifestations. This chapter provides a comprehensive overview of various essential nutrients and their associated biological significance, as well as the important clinical syndromes that result from their deficiency or excess.
Inherited Disorders of Cornification
Authors: Oji Vinzenz , Metze Dieter , Traupe Heiko
Published: August 2023

The majority of keratinization disorders are referred to as Mendelian disorders of cornification. This is a very broad group, clinically characterized by hyperkeratosis or visible scaling or both. This chapter deals with the ichthyoses, palmoplantar keratodermas (PPKs) and miscellaneous cornification disorders such as porokeratoses. It is aimed primarily at dermatologists and physician scientists who have to make a clinical diagnosis and provide adequate management for their patients. Therefore a nosology and classification scheme has been chosen that is based on clinicogenetic and morphological features. Clinical diagnoses are then discussed with their molecular pathology. Part of the chapter addresses the management of congenital ichthyoses. Various tables provide an overview on clinical and/or pathophysiologically related groups of diseases. Finally, several cornification disorders are discussed that do not have a genetic basis, but are acquired or are of unknown aetiology (e.g. acquired ichthyoses/PPKs or perforating keratotic disorders).
Inherited Acantholytic Disorders
Authors: Zamiri Mozheh , Munro Colin S.
Published: August 2023

Darier disease (DD) and Hailey–Hailey disease (HHD) are autosomal dominant disorders characterized by epidermal acantholysis. They have a similar molecular pathogenesis, with mutations in the intracellular calcium pumps of the endoplasmic reticulum (SERCA2) and Golgi (SPCA1), respectively. DD presents with persistent, hyperkeratotic papules in a seborrhoeic distribution, associated with nail changes and palmar pitting. HHD presents with painful, mainly flexural, erosions. In both, secondary infection is common and hypertrophic flexural disease can be disabling. Histologically, both are characterized by loss of epidermal intercellular adhesion (acantholysis). In DD, acantholysis is predominantly suprabasal and there is overlying dyskeratosis. In HHD, acantholysis is more diffuse. First line topical treatment is with emollients, antimicrobials and corticosteroids. Oral antibiotics are often necessary for exacerbations; other systemic options include retinoids and ciclosporin. Physical measures such as laser resurfacing, photodynamic therapy, botulinum toxin and surgical interventions can be considered in refractory cases.
Inherited Hair Disorders
Authors: Sprecher Eli
Published: August 2023

Inherited hair disorders form a highly phenotypically and genetically heterogeneous group, which result from abnormal regulation of hair growth and differentiation leading either to excessive or defective hair follicle development. Accurate diagnosis is essential as many of these disorders are indicative of sometimes occult and/or delayed systemic manifestations.
Genetic Blistering Diseases
Authors: McGrath John A.
Published: August 2023

Resilient in health, the structural integrity of skin can become impaired or break down in a collection of inherited skin diseases, referred to as the blistering genodermatoses. Most disorders are classified as a form of epidermolysis bullosa, although there is clinical and molecular heterogeneity. These conditions arise from gene mutations in a variety of structural and signalling proteins and manifest clinically as blisters or erosions following minor skin trauma, sometimes with extracutaneous manifestations including gastrointestinal, cardiac and ocular complications. In recent years, an improved understanding of the molecular basis of the blistering genodermatoses has led to better disease classification and advancement of translational research with the advent of new clinical trials of gene, protein, cell, drug and small molecule therapies.
Genetic Disorders of Collagen, Elastin and Dermal Matrix
Authors: Burrows Nigel
Published: August 2023

The inherited disorders of connective tissue are a heterogeneous group of conditions characterized by defects involving primarily one element of the connective tissue: collagen, elastic fibre or other extracellular matrix proteins. Multisystem involvement is common and can be fatal. There is variable skin involvement but recognition of characteristic skin findings may provide an early diagnosis and identify those at risk of internal complications. This chapter covers the inherited disorders of collagen and elastic fibres, infantile stiff skin and premature ageing syndromes, disorders of ectopic calcification and abnormal mineralization, as well as other syndromes related to abnormal connective tissue.
Congenital Naevi and Other Developmental Abnormalities Affecting the Skin
Authors: Kinsler Veronica A. , Sebire Neil J.
Published: August 2023

The understanding of congenital naevi has evolved rapidly in the last few years, with the discovery of many of the causative genes, and an increasing understanding of the phenotypic correlates of genotypic mosaicism in the skin. A new classification of all congenital naevi is proposed, based on phenotype, histology and genetics, which allows for the addition of new conditions as they are discovered, and for the regrouping of previously distinct disorders. The clinical features and extracutaneous associations of different congenital naevi are reviewed, as well as those of non‐naevoid developmental abnormalities of the skin.
Chromosomal Disorders
Authors: Irvine Alan D. , Mellerio Jemima E.
Published: August 2023

Chromosomal disorders may be due to abnormalities of chromosome number or structure and may involve autosomes or sex chromosomes. Somatic cells are diploid, with a complement of 46 chromosomes, whereas gametes (ova and sperm) are haploid, with only 23 chromosomes following reduction division in meiosis. Numerical abnormalities that involve the gain or loss of one or more chromosomes are known as aneuploidies. The traditional approach to studying chromosomal anomalies involved karyotype or fluorescentin situhybridization analysis. However, in recent years the development of array comparative genomic hybridization (or microarray) has been developed and is becoming the primary genetic tool in examining chromosomes for abnormalities of chromosome number (aneuploidy) and structure (deletions/duplications/inversions). This chapter reviews the common chromosomal abnormalities including Down syndrome and Turner syndrome, and their dermatological manifestations.
Poikiloderma Syndromes
Authors: Irvine Alan D. , Mellerio Jemima E.
Published: August 2023

Characterized by mixed hypo‐ and hyperpigmentation, skin atrophy and telangiectasia, poikiloderma is a feature of a number of different genetic skin diseases including dyskeratosis congenita, Rothmund–Thomson syndrome, Kindler syndrome and poikiloderma with neutropenia. Systemic associations of these disorders may include developmental abnormalities, a predisopsition to malignancy or infection, or progressive fibrosis of the bone marrow and other organs. Clinical and, where possible, genetic evaluation are vital to anticipation of potential complications, targeted management and genetic counselling.
Hamartoneoplastic Syndromes
Authors: Irvine Alan D. , Mellerio Jemima E.
Published: August 2023

This chapter covers the four most common hamartoneoplastic syndromes, including neurofibromatosis type 1, tuberous sclerosis, Gardner syndrome and Cowden syndrome. These conditions have diverse clinical and genetic features and require detailed condition‐specific knowledge, along with specific treatment guidelines and plans. They are, however, united by the common features of extensive and diverse skin manifestations along with somatic hamartomas and a significant risk of cutaneous and non‐cutaneous neoplasia. The four conditions are reviewed in detail with respect to pathophysiology, clinical features, diagnosis and management. A brief review of the emerging field of disorders with the collective term ‘RASopathies’ is included.
Acquired Disorders of Hair
Authors: Messenger Andrew G. , Sinclair Rodney D. , Farrant Paul , de Berker David A. R.
Published: August 2023

Hair is a defining feature of mammals. In other species hair confers important functions that affect survival. Most have been lost or are irrelevant in humans but the role of hair in social and sexual signalling in women and in men survives and thrives. Departures from cultural norms, either physiological or due to pathology, can therefore cause much concern and anxiety. Following an introduction to hair biology, this chapter considers the approach to the diagnosis and management of the patient with hair loss before discussing specific hair disorders. These include the various forms of hair loss due to hair follicle pathology, disturbances in hair cycling and hair shaft dystrophies, and disorders associated with excessive hair growth. The chapter concludes with a discussion of acquired alterations in hair pigmentation.
Hidradenitis Suppurativa
Authors: Desai Nemesha , van der Zee Hessel H. , Jemec Gregor B. E.
Published: August 2023

Hidradenitis suppurativa is characterized by inflamed lesions and scars that are restricted to typical topography (axillae, inframammary folds and groin), with a chronic course with flares. The average age of onset is after puberty and it is estimated to affect 1–2% of the European population. The aetiology is not known, but hereditary factors, obesity, smoking, host defence mechanisms, sex hormones and bacterial colonization are each suspected to play a role. Histology shows it to be a disease of the hair follicle. Flares are characterized by pain and suppuration, and the disease has a strong negative impact on patients' quality of life. Basic treatment should include supportive measures (weight loss, bandages and analgesics) for all patients. It is recommended that patients are treated with a combination of medical and surgical therapies. Medical therapies include antibiotics and anti‐inflammatory drugs. Surgical therapies include non‐ablative and ablative lasers as well as excisions.
Acquired Disorders of the Nails and Nail Unit
Authors: de Berker David A. R. , Richert Bertrand , Baran Robert
Published: August 2023

This chapter deals with all aspects of the nails in health and disease apart from hereditary nail disorders and fungal infections of the nails which are addressed in Chapters 69 and 32, respectively. Nail biology and growth establishes the basis for an understanding of how the nail may be affected by disease processes and their treatment. The significance of nail signs, which may be an important indicator of systemic diseases, is fully discussed before individual disorders of the nail and perionychium are described. The section on dermatoses affecting the nails includes the main categories of inflammatory and neoplastic diseases seen at other sites in the skin, but as expressed in the nail unit. The diagnostic imaging of the nail and nail surgery sections highlight special considerations required in managing disorders of the nail. Finally, the reader is introduced to cosmetic procedures used on nails and problems which may arise from them.
Acquired Disorders of Dermal Connective Tissue
Authors: Lovell Christopher R.
Published: August 2023

The subject matter of this chapter comprises the major acquired disorders that affect mainly collagen and elastic tissue. The connective tissue of normal skin is discussed elsewhere. Heritable disorders of connective tissue, such as Ehlers–Danlos syndrome, are covered in another chapter, as are disorders of ground substance, such as the mucinoses and mucopolysaccharidoses. In addition, many disorders, including developmental defects, neoplasms and other reactive or scarring conditions, may involve the connective tissues. Although it can be convenient to separate conditions into disorders affecting collagen or elastic tissue, the distinction is somewhat artificial, as changes in these proteins are generally preceded by abnormal metabolism of other matrix components, such as fibronectin or periostin.
Granulomatous Disorders of the Skin
Authors: Bourke Johnny
Published: August 2023

Granulomatous inflammation is seen in a wide range of skin conditions including infections, neoplasms and inflammatory disorders. This chapter addresses three important idiopathic granulomatous disorders of the skin. The first two, granuloma annulare and necrobiosis lipoidica, are relatively common. Treatment is of uncertain value and is generally disappointing. Granuloma annulare usually resolves spontaneously over years but necrobiosis lipoidica tends to persist. Their association with systemic disorders is discussed. The third, cutaneous Crohn disease, is uncommon. It may affect the skin by direct extension causing swelling and ulceration or occasionally may involve distant sites, so‐called metastatic Crohn disease. Cutaneous sarcoidosis is addressed in another chapter.