Dermatological Aspects Research Articles

Editorial

Editorial

Quality of life in patients with anogenital warts

Anogenital warts (GW) are among the most common sexually transmitted diseases. Few studies have investigated the quality of life (QoL) of GW patients. We undertook an exhaustive description of the health status of GW patients and assessed disease impact on QoL. GW patients enrolled at the Sexually Transmitted Diseases service of Rome Catholic University were administered the SF-36 questionnaire to assess health status, the Skindex-29 to evaluate the impact of dermatological aspects and the GHQ-12 questionnaire to identify patients with probable minor psychiatric non-psychotic conditions. Clinical severity was assessed with the Physician Global Assessment (PGA) and through quantitative measures. There was a significant association between greater disease severity and lower SF-36 values (reflecting a worse QoL). The severity parameters showed no significant differences in any of the Skindex-29 scales except for Emotions, which showed higher values (reflecting a worse QoL) in patients with severe disease assessed by PGA. The GHQ-positive patients (23.7%) consistently showed worse QoL scores on all the SF-36 scales and on all the Skindex-29 scales compared to GHQ-negative patients. To the best of our knowledge, this is the first study of the impact of GW on QoL to use a range of validated tools, both generic and dermatology-specific. We observed a strong influence of GW on the mental and physical components of QoL in terms of general health status (SF-36). The effects in terms of specific dermatological aspects (Skindex-29) were less significant, but still reflected an impact on patients' emotional state.

Chronic pruritus associated with dermatologic disease in infancy and childhood: Update from an interdisciplinary group of dermatologists and pediatricians

An effective treatment strategy for chronic pruritus in children with dermatologic disorders should consider the multidimensional aspects of pruritus, the unique challenges associated with treating pruritic skin disorders in the pediatric population, and evidence-based therapies with demonstrated antipruritic benefits and clinically relevant effects on patient/family quality of life (QoL). The Course of Advanced Learning for the Management of ITch (CALM-IT) Task Force is an interdisciplinary group of experts specializing in core aspects of pruritus treatment, integrating pediatrics, dermatology, psychotherapy, pruritus management, and sleep. CALM-IT recently convened to provide updated guidance on managing chronic pruritus associated with dermatologic diseases in pediatric patients, with a special focus on atopic dermatitis (AD) and chronic spontaneous urticaria (csU). This review highlights the updated concepts and best practices, which were built upon international PRACTALL consensus and modified for children and infants with AD and csU. CALM-IT supports the routine use of basic skin therapy and the escalation of topical medications, according to severity and focused on rapid itch control. Anti-inflammatory agents should be appropriate for infants and children (i.e., with an optimized therapeutic index) and have proven antipruritic properties, such as those demonstrated by methylprednisolone aceponate. New experimental findings do not support the use of non-sedating oral antihistamines as adjuvant antipruritic therapy for AD. In csU, oral H1 -antihistamine use is justified, consistent with the distinct pathophysiologic mechanisms of itch underlying AD and csU. All encompassing QoL assessments should consider the burden of both patient and caregiver and should address outstanding unmet clinical needs of pediatric patients. Future research areas include integrated QoL assessments and multidisciplinary treatment programs with pediatric-targeted pruritic therapies providing rapid itch control.

SP0061 How to treat psoriatic arthritis?

Psoriatic arthritis (PsA) is an inflammatory rheumatic condition usually associated with skin and/or nail psoriasis. The articular manifestations are quite heterogeneous, with arthritis being the most frequent manifestation, but with...

Book review

WOUND HEALING & SKIN INTEGRITY: PRINCIPLES AND PRACTICE Editor: M. Flanagan Publisher: Wiley-Blackwell Location: Oxford Pages: 312 Price: £32.99 Wiley-Blackwell has recently published a book entitled Wound Healing & Skin Integrity: Principles and Practice, edited by Madeleine Flanagan. This text provides three distinct sections: (1) Principles of Best Practice; (2) Challenging Wounds and (3) Improving Skin Integrity Services. The first section provides a good grounding in the importance of evidence and clinical decision making through skin, structure, function, integrity and related complications including the principles of wound management. The second section presents a more aetiological approach to different wound types, their complications and management. The more common wound types are covered but a focus on unusual and challenging wounds provides a valuable resource to those in the front lines dealing with wounds on a daily basis. This section also covers lymphoedema and also skin health and dermatological aspects. A broadening of the normal aetiological coverage provides a more up-to-date focus on skin health and skin integrity. The third section provides insight into evolving practice, cost reduction strategies and the evolution to date for our therapeutic armoury and where it might develop in the future. Wound Healing & Skin Integrity provides a truly international perspective as authors come from around the globe. This text provides an up to date resource that provides all necessary background to those who see patients with both acute and chronic wounds. It also provides a valuable resource to those involved in the maintenance of skin integrity. The global wound care community is a tight-knit group of dedicated and enthusiastic health professionals who are keen to share their knowledge and experience to improve the life of patients with compromised skin integrity. I am pleased to observe that this community is growing year on year as practitioners, researchers and the healthcare industry gain knowledge and push the boundaries about what is possible to improve the lives of patients with non healing wounds.

Editorial(Hot Topic: New Directions in Management of Sapho Syndrome)

To talk about SAPHO syndrome means to discuss its entity. It is a great honour to me as guest editor to greet you and to present to you the following scientific articles dealing with different aspects of the SAPHO syndrome. We are pleased to welcome experts in the fields of epidemiology, etiology, clinical aspects, imaging procedures and treatment modalities. Furthermore, I have been grateful to be able to invite a review board to read the articles and to support the authors with scientific remarks and interesting corrections. First, we will start with the introduction by Prof. Dr. Koehler, University of Saarland, Germany, entitled "From sternoclavicluar hyperostosis (SCCH) to SAPHO syndrome - a European story?". Afterwards, Dr. Colina, PhD, Imola, Italy, with co-authors will discuss "the latest state of the art" concerning essential clinical and radiological characteristics of the SAPHO syndrome. The following chapter by Dr. Pfoehler, PhD, University of Saarland, Germany, describes in detail the important dermatological aspects of psoriatic disease and its subentity of palmoplantar pustolosis against a etiological, diagnostic, and therapeutic background to better understand the arthro-osteo-cutaneous character of the SAPHO syndrome. In this context, Dr. Gilles, PhD, University Hospital of Paris, France, with co-authors then discuss the different hypotheses of immunology and the possible autoimmune etiology of SAPHO syndrome. Furthermore, Prof. Dr. Wollheim, University of Lund, Sweden, concludes and elucidates the genetic aspects of the disease. With the regard to different SAPHO manifestations in the childhood, I am thankful that Prof. Dr. Girschick, Pediatric Rheumatology Vivantes Center, Berlin, Germany, has contributed a scientific article dealing with "non-bacterial osteomyelitis in childhood". Last but not least, the article "Trends of SAPHO therapy: should we content?" from Dr. Rozin, PhD, Technion Haifa, Israel, focuses on the antirheumatic treatment modalities, including antibiotic treatment modalities which have been investigated in case series over the last 20 years. It was my intention that all authors touch on the genetic, diagnostic, and therapeutic aspects of SAPHO syndrome not to cause redundancies in the presentation but to discuss the central role of these aspects from a respectively different viewpoint - with the aim of gaining a deep insight into the etiopathogenesis and clinical aspects of SAPHO syndrome.

The Assessment of Disease Activity in Rheumatic Diseases

Disease activity in the rheumatic diseases can be defined as a reversible state, manifested by clinical, laboratory, or radiographical features. Disease activity occurs principally as a result of immunologic and inflammatory processes involving specific organs at a specific point in time. The multifaceted nature of clinical presentations in adults as well as in pediatric rheumatic diseases makes the assessment of disease activity challenging. Nevertheless, this assessment is fundamental in patient care and based on the use of valid, reliable, and interpretable instruments. The use of disease activity instruments enables clinicians, patients, and researchers to quantify and evaluate disease activity in a standardized way. The application of these instruments in a clinical care and research setting presents several challenges: namely, the administrative burden of the instrument, including the preparedness and skillfulness of the assessor, the mode of administration, the time required to complete the instrument, and the complexity of scoring. All of these factors need to be taken into consideration when choosing an instrument applicable in a particular setting. In the last decade, we have witnessed the emergence of a plethora of instruments developed to measure disease activity in the rheumatic diseases. This special issue contains five papers: four related to the assessment of activity in adult rheumatic diseases and one paper with a focus on pediatric rheumatic disease. Wong et al. “Measuring disease activity in psoriatic arthritis” provide a detailed review of the assessment of disease activity in psoriatic arthritis. Their paper highlights the currently available tools for the assessment of the various rheumatologic and dermatologic aspects of the disease and discusses the composite indices that have been developed, or are still under development. Dowsey and Choong “The utility of outcome measures in total knee replacement surgery” discuss the utility of outcome measures for total knee replacement surgery, most commonly performed to treat osteoarthritis. While the majority of patients have a substantial improvement in symptoms following this procedure, a proportion of patients report ongoing pain and poor function. The authors remind us that accurate and reproducible measurement of residual pain and functional impairment in patients undergoing arthroplasty forms an important basis for optimizing outcomes of this procedure. The paper by Dowsey et al. challenges our perception of disease “activity” in the rheumatic diseases and allows us to consider the overlap with the broader concept of “severity,” particularly in osteoarthritis, which does not traditionally follow a relapsing-remitting course. In an original research article, Ohrndorf et al. “Detailed joint region analysis of the 7-joint ultrasound score: evaluation of an arthritis patient cohort over one year” use ultrasound technique, specifically the 7-joint ultrasound (US7) score, to evaluate disease activity and the presence of erosions over one year in a cohort of patients with predominantly rheumatoid and psoriatic arthritis. They demonstrate a high synovitis score at baseline in the majority of patients, which diminishes over one year of treatment, corresponding with a decline in the DAS28 score. The responsiveness over time of ultrasound-based assessment of disease activity in inflammatory arthritis, compared with clinical-laboratory based assessment, and the prognostic significance of mild persistent synovitis detectable on ultrasound are yet to be conclusively demonstrated and quantified. However, the study by Ohrndorf et al. highlights the potential usefulness of imaging modalities in assessment of activity in the rheumatic diseases. Quimby et al. “Comparison of the systemic lupus erythematosus activity questionnaire and the systemic lupus erythematosus disease activity index in a black barbadian population” evaluate the use of the Systemic Lupus Activity Questionnaire (SLAQ), vis-a-vis the internationally accepted and validated Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and the physician global assessment (PGA). They conclude that SLAQ results in over-reporting of symptoms and is an inadequate disease monitoring tool. They underscore the use of laboratory measurements and highlight the need for a modified version that would be valid, feasible, and available to countries most burdened by SLE, yet least equipped to diagnose and manage the disease. Finally, Luca's and Feldman's “Disease activity measures in paediatric rheumatic diseases” provide a comprehensive review of assessment of disease activity in the pediatric population. Their paper explains the theoretical framework required for the development of disease activity measures citing the challenges encountered in this particular patient population. In addition, they summarize the most common disease activity measures used for Juvenile Idiopathic Arthritis (JIA), Juvenile Systemic Lupus Erythematosus (JSLE), and Juvenile Dermatomyositis (JDM) reminding us that more research is needed to determine the most appropriate measures to be used in clinical practice and the research environment. The assessment of disease activity in rheumatic diseases is very challenging but essential. Significant achievements have been made in improving the measurement properties of the instruments. Further research is needed to identify the measurement tools that are of the highest quality and can be conveniently used in clinics and in research studies.

Stevens–Johnson syndrome: An oral viewpoint

The Stevens–Johnson syndrome (SJS) is a severe variant of erythema multiforme (EM) that occasionally can rise to systemic upset and possibly compromise life. In this report, we described important oral and dermatologic aspects of a case of SJS triggered by Mycoplasma pneumoniae infection.

Systemic sclerosis – focus on dermatological aspects. Part 2: Diagnostics, therapy

Systemic sclerosis is a chronic inflammatory multiorgan disease which may involve the skin and internal organs to a varying extent. Pathogenetically the vasculature, connective tissue and the immune system are involved in a yet to be defined sequence and impact. Case history and results of physical as well as laboratory examinations will determine individually adapted further organ imaging or invasive procedures. Based on their results therapy is initiated which may include supportive measures such as physiotherapy as well as basic skin care and avoidance of any trauma. Many agents are available for the circulatory problems including Raynaud phenomenon and digital ulcers such as calcium channel blockers, ACE inhibitors and intravenous prostacyclin derivatives, as well as endothelin receptor blockers and phosphodiesterase inhibitors. Immunosuppressive and immunomodulatory agents are of varying efficacy depending on organ involvement. Though various therapeutic measures are available, beneficial effects are limited and associated with various unwanted effects. In any case, the therapy has to be individually adapted to the disease stage and course of the disease.

Isolation of human epidermal layers by laser capture microdissection: application to the analysis of gene expression by quantitative real‐time PCR

We describe, for the first time, an efficient protocol based on laser capture microdissection (LCM) for the isolation of human epidermal layers for gene expression profiling using quantitative real-time PCR. Two areas enriched either in basal or granular layers were isolated by LCM. Skin biopsies were fixed in dry ice-cooled isopentane, cryosectioned and stained before the laser procedure. High-quality total RNA was extracted from each microdissected sample, which allowed the analysis of the spatial distribution of mRNA transcripts from 10 innate immunity-related genes within the epidermal layers. Using integrin alpha-6/integrin beta-4 and corneodesmosin/filaggrin-2 sets as gene markers for the basal and granular layers, respectively, we showed that Toll-like receptor 2, RNase 7, human beta-defensin-2 and -3, psoriasin and nucleotide-binding oligomerization domain 1 are upregulated in the suprabasal layer of normal human epidermis. Our protocol, which is based on the rapid isolation of epidermal layers, can be used to follow transcriptional processes in specific areas of the epidermis and is a very promising tool to use in the study of numerous aspects of dermatology.

Dermatologic aspects of ectodermal dysplasias

Ectodermal dysplasias are a large group of heterogeneous heritable conditions characterized by congenital defects of ectodermal structures and their appendages: hair (hypotrichosis, partial or total alopecia), nails (dystrophic, hypertrophic, abnormally keratinized), teeth (enamel defect or absent) and sweat glands (hypoplastic or aplastic). The ectodermal dysplasias, as a rule, are not pure “one-layer diseases”. Mesodermal and occasionally endodermal dysplasias may coexist. Embryogenesis occurs in distinct tissue fields and specific interactions among the germ layers that may lead to a wide range of ectodermal dysplasias exist when genes important for development are mutated or otherwise altered in expression. Of the approximately 200 different ectodermal dysplasias, about 50 have been characterized at the molecular level with identification of the causative gene. Modern molecular genetics will increasingly elucidate the basic defects of the different syndromes and yield more insight into the regulatory mechanisms of embryogenesis. This lecture focuses on the fact that with molecular diagnosis it is possible to diagnose oligosymptomatic forms of ectodermal dysplasia. These are much more common than earlier anticipated. Cutaneous key features which give hints for the presence of some type of ectodermal dysplasia will be presented.

Nanotechnology in medicine and relevance to dermatology: Present concepts

Nanotechnology and nanomedicine are complementary disciplines aimed at the betterment of human life. Nanotechnology is an emerging branch of science for designing tools and devices of size 1–100 nm, with unique functions at the cellular, atomic and molecular levels. The concept of using nanotechnology in medical research and clinical practice is known as nanomedicine. Today, nanotechnology and nanoscience approaches to particle design and formulations are beginning to expand the market for many drugs and forming the basis for a highly profitable niche within the industry, but some predicted benefits are hyped. Under many conditions, dermal penetration of nanoparticles may be limited for consumer products such as sunscreens, although additional studies are needed on potential photooxidation products, experimental methods and the effect of skin condition on penetration. Today, zinc oxide and titanium dioxide nanoparticles (20–30 nm) are widely used in several topical skin care products such as sunscreens. Thus, in the present scenario, nanotechnology is spreading its wings to address the key problems in the field of medicine. The benefits of nanoparticles have been shown in several scientific fields, but very little is known about their potential to penetrate the skin. Hence, this review discusses in detail the applications of nanotechnology in medicine with more emphasis on the dermatologic aspects.

Clinical parameters in male genital lichen sclerosus: a case series of 329 patients

The dermatological aspects of male genital lichen sclerosus (MGLSc) have not received much prominence in the literature. Sexual morbidity appears under-appreciated, the role of histology is unclear, the relative places of topical medical treatment and circumcision are not established, the prognosis for sexual function, urinary function and penis cancer is uncertain and the pathogenesis has not been specifically studied although autoimmunity (as in women) and HPV infection have been mooted. To illuminate the above by analysing the clinical parameters of a large series of patients with MGLSc. A total of 329 patients with a clinical diagnosis of MGLSc were identified retrospectively from a dermatology-centred multidisciplinary setting. Their clinical and histopathological features and outcomes have been abstracted from the records and analysed by simple descriptive statistics. The collation and analysis of clinical data derived from the largest series of men with MGLSc ever studied from a dermatological perspective has been achieved. These data allow the conclusions below to be drawn. MGLSc is unequivocally a disease of the uncircumcised male; the adult peak is late in the fourth decade; dyspareunia is a common presenting complaint; non-specific histology requires careful interpretation; most men are either cured by topical treatment with ultrapotent steroid (50-60%) or by circumcision (>75%); effective and definitive management appears to abrogate the risk of developing penile squamous cell carcinoma; urinary contact is implicated in the pathogenesis of MGLSc; HPV infection and autoimmunity seem unimportant.

Biopolymers as Transdermal Drug Delivery Systems in Dermatology Therapy

The skin is considered a complex organ for drug delivery because of its structure. Drug delivery systems are designed for the controlled release of drugs through the skin into the systemic circulation, maintaining consistent efficacy and reducing the dose of the drugs and their related side effects. Transdermal drug delivery represents one of the most rapidly advancing areas of novel drug delivery. The excellent impervious nature of the skin is the greatest challenge that must be overcome for successful drug delivery. Today, polymers have been proven to be successful for long-term drug delivery applications as no single polymer can satisfy all of the requirements. Biopolymers in the field of dermal application are rare and the mechanisms that affect skin absorption are almost unknown. Biopolymers are widely used as drug delivery systems, but as such the use of biopolymers as drug delivery systems in dermatologic therapy is still in progress. Commonly used biopolymers include hydrocolloids, alginates, hydrogels, polyurethane, collagen, poly(lactic-co-glycolic acid), chitosan, proteins and peptides, pectin, siRNAs, and hyaluronic acid. These new and exciting methods for drug delivery are already increasing the number and quality of dermal and transdermal therapies. This article reviews current research on biopolymers and focuses on their potential as drug carriers, particularly in relation to the dermatologic aspects of their use.

Drug-induced lupus: an update on its dermatologic aspects

Drug-induced lupus erythematosus (DILE) is defined as an entity characterized by clinical manifestations and immunopathological serum findings similar to those of idiopathic lupus but which is temporally related to continuous drug exposure and resolves after discontinuation of the offending drug. Similar to idiopathic lupus, DILE can be divided into systemic lupus erythematosus (SLE), subacute cutaneous lupus erythematosus (SCLE) and chronic cutaneous lupus erythematosus (CCLE). Based on the literature review and retrospective analysis of our case series, we focused on the dermatological aspects of DILE. The cutaneous features of drug-induced SLE are protean, including particularly purpura, erythema nodosum and photosensitivity as well as the skin lesions characterizing both urticarial and necrotizing vasculitis. The typical laboratory profile of systemic DILE consists of positive antinuclear antibodies (ANA) and antihistone antibodies, the latter being regarded as the serum marker of this subset. The drugs most frequently implicated in the development of systemic DILE are hydralazine, procainamide, isoniazid and minocycline. Drug-induced SCLE usually presents with annular polycyclic or papulosquamous cutaneous manifestations as in the idiopathic form, but blisters or targetoid lesions mimicking erythema multiforme cannot rarely be associated. The clinical presentation is often generalized, with involvement of the lower legs that are usually spared in idiopathic SCLE. ANA and anti-Ro/SSA antibodies are usually present, whereas antihistone antibodies are uncommonly found. Drugs associated with SCLE include particularly calcium channel blockers, angiotensin-converting enzyme inhibitors, thiazide diuretics, terbinafine and the recently reported tumour necrosis factor (TNF)-alpha antagonists. Drug-induced CCLE is very rarely described in the literature and usually refers to fluorouracile agents or TNF-alpha antagonists. The picture is characterized by the occurrence of classic discoid lesions, but aspects of lupus tumidus can occasionally develop. ANA are demonstrated in around two-thirds of the cases. Management of DILE is based on the withdrawal of the offending drug. Topical and/or systemic corticosteroids and other immunosuppressive agents should be reserved for resistant cases.

Dermatological aspects of medicine: highly active antiretroviral therapy and the treatment of human immunodeficiency virus

This is the sixth in a series of CPD articles aimed at reviewing the recent general medical literature relating to topics that may be of interest to dermatologists. In this issue the new classes of anti-retroviral drugs will be described in the context of the replication cycle of human immunodeficiency virus (HIV). The regimens of drug treatments and the more common side-effects including HIV-lipodystrophy syndrome will be discussed along with the recommendations for testing of people for HIV from new guidelines.

Aesthetic and cosmetic dermatology

Auteur(s) : M Kerscher St. Williams Definitions Cosmetic/aesthetic dermatology focuses on the appearance-related aspects of dermatology and represents an overlap between the traditional medical treatment of skin diseases and cosmetology. Aspects of cosmetic dermatology include the maintenance of healthy skin, the prevention and treatment of skin ageing and photodamage, rejuvenation procedures and many others. Cosmetic dermatology also deals with skin diseases that have great impact on the patient’s appearance [...]

Diagnostic methods for confirming drug-allergy – the lymphocyte transformation test in dermatology

Recognizing the adverse drug reactions and confirming the role of the drug causing the symptoms is a great challenge for a medical team. The aim of this article is to review the diagnostic methods for confirming drug-allergy and to evaluate the lymphocyte transformation test according to dermatological aspect. Lymphocyte transformation test relies on the observation that specific T-cells divide and expand after encountering the antigen. T-cell sensitization is measured by 3H-thymidine uptake in dividing cells. The main advantage of this test is its applicability with many different drugs in different immune reactions, as drug-specific T-cells are almost always involved in drug hypersensitivity reactions. Its disadvantage is that the test is cumbersome and technically demanding. The method is not unequivocally accepted, it is necessary to carry out a systematic evaluation of its sensitivity and specificity to make the test more widely appreciated. Despite of its deficits, the lymphocyte transformation test plays an important role in diagnosing drug-hypersensitivities.

A case of acute radiation syndrome from the dermatological aspect

Accidental whole‐body overexposure of radiation occurs very rarely. Radiation exposure causes DNA breaks in the cells and shows various clinical features, which are time dependent, dose dependent and tissue dependent. Neutron rays are more destructive than gamma rays but their actual effect on humans have been under‐reported. We observed the time‐dependent and the dose‐dependent dermatological changes in a patient who was severely irradiated by neutron and gamma rays, with the aim of clarifying the clinicopathological features of severely irradiated skin. The detection of DNA breaks in keratinocytes was performed by the terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end labelling technique. The degenerative changes of the skin and the re‐epithelialization varied in a time dependent and dose dependent manner. DNA breaks were significantly higher in irradiated keratinocytes. Neutron rays caused depth‐dependent degeneration of the skin. Evaluation of DNA breaks in the skin cells might be a clue to estimate local dosimetry.

A case of acute radiation syndrome from the dermatological aspect

A case of acute radiation syndrome from the dermatological aspect