Nonmelanoma skin cancer – from actinic keratosis to cutaneous squamous cell carcinoma

Actinic keratoses (AKs) are defined as intraepithelial proliferation of atypical keratinocytes. Given their potential for progression to invasive squamous cell carcinoma, they may eventually evolve into a life‐threatening disease. In recent decades, there has been a significant increase in the incidence of AKs, primarily due to changes in recreational activities and demographic trends in industrialized countries. As it is currently impossible to predict if and when a given AK might progress to invasive carcinoma, rigorous treatment of field cancerization is a key component in preventing potential progression. In addition to a broad armamentarium of procedures as well as pharmaceutical treatment options, primary prevention through diligent UV protection likewise plays a crucial role. New clinical, histomorphological, or molecular classifications are needed to be able to reliably stratify patients based on their individual risk. Especially in light of socio‐economic aspects, such a step might prevent over‐ and undertreatment of an ever‐growing patient population and help develop treatment concepts based on individual patient needs.     

Mastocytosis – an update

Mastocytosis (MC) encompasses a range of disorders characterized by a clonal, pathological accumulation of mast cells having a somatic activating mutation of the tyrosine kinase receptor Kit (exon 17, codon 816; D816V) in more than 90 % of adult patients. The mutation is much less common in children. Skin and bone marrow are most often affected. Symptoms and clinical course are very heterogeneous due to a variable degree of local or systemic mediator release or organ dysfunction as a result of mast cell infiltrates. Pruritus, wheals, flushing and gastrointestinal symptoms are often reported. The majority of pediatric patients experience spontaneous remission of MC. Adults usually have chronic disease, rarely transforming into an aggressive or lethal type. Indolent systemic MC with involvement of skin and bone is the most common type. In MC the risk for anaphylactic reactions following an insect sting (and other causes of mast cell activation) is increased significantly. Diagnostic hallmarks are biopsies from skin and bone marrow using tryptase antibodies for staining as well as serum tryptase levels. At present a curative treatment for MC is not available. Systemic histamine H₁ receptor antagonists are widely used. Aggressive types of MC respond partially to IFN‐α or cladribine. A variety of receptor tyrosine kinase inhibitors is still under critical evaluation for systemic treatment of MC. After introduction of the WHO classification for MC and the development a German MC guideline, as well as the foundation of national and international competence networks for MC, a significantly improved quality of medical care for MC patients can be expected for the future.     

Vascular anomalies – a practical approach

Vascular anomalies are common clinical problems (around 4.5% of all patients) in pediatric dermatology. A correct diagnosis is possible on clinical grounds in around 90% of cases; the remaining patients may require radiologic evaluations (duplex ultrasonography, MRI scan) and, rarely, histology. Vascular anomalies are divided into tumors and vascular malformations. This clear division reflects the different biological behaviors of these two groups. The infantile hemangioma represents by far the most common vascular tumor and is characterized by a typical growth cycle consisting of rapid proliferation, plateau phase, and finally slow regression. The discovery in 2008 of the efficacy of beta blockers in this disease is a therapeutic milestone. Vascular malformations can affect all types of vessels (capillaries, veins, arteries and lymphatic vessels). They usually manifest at birth and grow proportionally with the affected child. Some show marked progression especially during puberty. Considerable progress has been made with innovative interventional therapies in recent years, but surgery remains an important option. Basic knowledge of these diseases is important to every dermatologist in order to be able to counsel and manage affected patients correctly.     

Bexarotene – an alternative therapy for progressive cutaneous T‐cell lymphoma? First experiences

Background: A standard therapy for advanced cutaneous T‐cell lymphomas has not yet been defined. Bexarotene is a new retinoid x receptor‐specific retinoid that has been approved for systemic second‐line therapy for cutaneous T‐cell lymphomas in the USA and Europe. In order to evaluate the efficacy of bexarotene in cutaneous T‐cell lymphomas, a pilot trial was initiated. Patients and methods: In a pilot project 10 patients with advanced cutaneous T‐cell lymphomas, who had received a variety of previous treatments, were treated with bexarotene at the departments of dermatology in Münster, Minden and Charité Berlin, Germany. The patients received bexarotene at a dose of 300 mg/m² body surface daily. According to the percentage of tumour reduction and affected body surface, the response rates were divided in complete and partial remission, stable disease and progressive disease. Laboratory parameters i. e. cholesterol, triglycerides transaminases, T3, T4, and TSH were screened regularly. Results: In 2 patients a short partial remission was achieved; however, after a few weeks progression followed. In 4 patients a lasting stabilisation was obtained. The other 4 patients showed a progressive disease during therapy. 6 patients developed hypertriglyceridemia with levels up to 2000 mg/dl; therapy had to be suspended in 3 patients because of these adverse drug events. Conclusion: Weighing benefits and risks, bexarotene can at present not be recommended as standard therapy in the treatment of patients with progressive cutaneous lymphomas.     

Frontiers in epidermal barrier homeostasis – an approach to mathematical modelling of epidermal calcium dynamics

Intact epidermal barrier function is crucial for survival and is associated with the presence of gradients of both calcium ion concentration and electric potential. Although many molecules, including ion channels and pumps, are known to contribute to maintenance of these gradients, the mechanisms involved in epidermal calcium ion dynamics have not been clarified. We have established that a variety of neurotransmitters and their receptors, originally found in the brain, are expressed in keratinocytes and are also associated with barrier homeostasis. Moreover, keratinocytes and neurons show some similarities of electrochemical behaviour. As mathematical modelling and computer simulation have been employed to understand electrochemical phenomena in brain science, we considered that a similar approach might be applicable to describe the dynamics of epidermal electrochemical phenomena associated with barrier homeostasis. Such methodology would also be potentially useful to address a number of difficult problems in clinical dermatology, such as ageing and itching. Although this work is at a very early stage, in this essay, we discuss the background to our approach and we present some preliminary results of simulation of barrier recovery.     

Multiple erythema migrans – manifestation of systemic cutaneous borreliosis

Erythema migrans is the clinical hallmark lesion of a stage I infection with Borrelia burgdorferi. Multifocal lesions are rarely observed in Europe and thus may be missed, in particular when the typical clinical appearance of the pronounced advancing margin is missing.We present three patients with such a clinical appearance which caused differential diagnostic problems. Multiple erythema migrans represent an early stage of systemic infection. Thus early diagnosis and rapid initiation of therapy are warranted.     

Panniculitis–an unusual cutaneous manifestation of systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune systemic disease characterized by small vessel involvement that leads to tissue ischemia and fibroblast stimulation resulting in accumulation of collagen (fibrosis) in the skin and internal organs. Lipomembranous panniculitis is a peculiar type of fat necrosis and has been reported with clinical conditions, commonly with peripheral vascular diseases. We describe a case of a 43‐year‐old woman with SSc manifestations, who presented with black scaly skin plaques, associated with thickening of the subcutaneous fat tissue, on the lateral surface of her thighs, her calves, gluteal area and lower abdomen. Biopsy revealed lipomembranous panniculitis. Lipomembranous changes have been seen in connective tissue disorders such as lupus profundus, morphea, systemic sclerosis and panniculitis associated with dermatomyositis, but rarely in thighs, calves, gluteal area and lower abdomen. Almeida MSTM, Lima SCB, Carvalho LL, Almeida JVM, Santos LG, Rolim JRA, Rocha TE. Panniculitis–An unusual cutaneous manifestation of systemic sclerosis.     

An algorithmic approach to esthetic facial volume restoration

ABSTRACT:  The growing availability of treatment options for facial restoration has created a need for a more organized approach to combination treatments. This article presents considerations from one practice to assessing the aging face and tailoring treatments to specific deficiencies.     

Vasculitis in childhood – a dermatological approach

Vasculitis, an inflammatory condition affecting the blood vessels, may be restricted to a single organ or involve several organ systems. The size of the involved vessels is an important criterion for categorization of vasculitides, which is a prerequisite for rapid diagnosis and initiation of treatment. In pediatric patients, this particularly applies to Kawasaki disease. However, making the diagnosis can be challenging for dermatologists as skin involvement may be variable and non‐specific. In contrast, Henoch‐Schönlein purpura (IgA vasculitis) presents with the classic picture of palpable purpura. It predominantly affects postcapillary venules frequently following upper respiratory tract infections. Severe organ involvement is relatively rare in children and the prognosis is good. As renal involvement may occur during the course of disease, continuous monitoring is required. Acute hemorrhagic edema of infancy is considered as a distinct type of immune complex vasculitis and is characterized by a triad of fever, edema and rosette‐shaped purpura. The clinical course of this rare disease is usually benign and self‐limited. Due to the variability of clinical symptoms and manifestations, management of childhood vasculitides represents a special challenge requiring interdisciplinary collaboration. Dermatologists should be aware of their important role especially for making an early diagnosis.     

Lyme borreliosis – an update

Lyme borreliosis is the most common tick‐borne, infectious disease in the northern hemisphere. Disease manifestations in the United States and Europe vary as a result of geographic distribution of different species within the genospecies Borrelia burgdorferi sensu lato, which in turn are host‐specific. Certain toxigenic B. burgdorferi strains cause early disseminated disease. The ability of Borrelial organisms to break down the extracellular matrix also promotes dissemination. B. burgdorferi are eliminated by complement‐mediated lysis and by T and B cell activity of the specific immune response. Yet, B. burgdorferi can evade humoral immunity by means of type of protective mechanism by which it adheres to the proteoglycan decorin in the joints and skin. A further factor in the persistence of the pathogen is altered antigen expression. Re‐infection usually occurs with a different strain, although repeated infection with the same strain is also possible after a certain period of latency. New developments in serologic testing include the use of recombinant native antigen as well as antigens produced in vivo such as VlsE (variable major protein‐like sequence, expressed) or decorin‐binding protein A. Diagnosis continues to be complicated by seropositivity of healthy individuals, the persistence of antibodies after therapy, and a lacking humoral immune response in patients with erythema migrans.     

Extragenital cutaneous warts – clinical presentation,diagnosis and treatment

Extragenital cutaneous warts are benign epidermal tumors caused by human papillomaviruses (HPVs) and a frequent reason for patients to consult a dermatologist. Depending on wart type and site involved, the clinical presentation is highly varied. Given that warts represent a self‐limiting condition, a wait‐and‐see approach may be justified. However, treatment is always indicated if the lesions become painful or give rise to psychological discomfort. Factors to be considered in this context include subjective disease burden, patient age, site affected, as well as the number and duration of lesions. Destructive treatment methods involve chemical or physical removal of diseased tissue. Nondestructive methods consist of antimitotic and antiviral agents aimed at inhibiting viral proliferation in keratinocytes. Some of the various immunotherapies available not only have localized but also systemic effects and are thus able to induce remission of warts located at any distance from the injection site. Especially patients with warts at multiple sites benefit from this form of treatment. Intralesional immunotherapy using the mumps‐measles‐rubella (MMR) vaccine is a particularly promising option for the treatment of recalcitrant warts in adult patients. For children, on the other hand, HPV vaccination is a novel and promising approach, even though it has not been approved for the treatment of cutaneous warts. At present, there is no universally effective treatment available. Moreover, many frequently employed therapies are currently not supported by conclusive clinical trials.     

Histiocytosis – cutaneous manifestations of hematopoietic neoplasm and non‐neoplastic histiocytic proliferations

Histiocytoses are rare disorders characterized by the accumulation of cells derived from macrophages, dendritic cells or monocytes in various tissues. There is a broad spectrum of disease manifestations with some subtypes commonly showing skin lesions, while in others, the skin is rarely involved. Here, we describe cutaneous manifestations of histiocytoses belonging to the Langerhans group (L group), the group of cutaneous and mucocutaneous histiocytoses (C group) and the group of Rosai–Dorfman disease (RDD) and related histiocytoses (R group) according to the current classification. Characteristic clinical presentations noted were a rust‐brown colour or xanthomatous aspect in many cases of histiocytoses. Histological criteria for differentiation are described. Immunohistochemistry shows positivity for S100 and CD1a in Langerhans‐cell histiocytoses (LHCH) of the L group, while CD68 positivity with S100 and CD1a negativity are typical in histiocytoses of the C group of cutaneous and mucocutaneous histiocytoses. RDD in the R group shows positivity for S100 and CD68, while CD1a is negative. We further review the pathogenesis of LHCH based on insights on the central role of the mitogen‐activated protein (MAPK) kinase pathway. Common mutations in various histiocytic populations of diverse ontogeny and at different stages of differentiation may be responsible for the diverse clinical picture of this neoplastic entity. For histiocytoses of the C group and R group, a reactive origin is discussed with the exception of the disseminated form of juvenile xanthogranuloma. We suggest exploring the role of an origin from skin residing histiocytes for the isolated cutaneous manifestation in some types. With regard to therapeutic options, skin‐directed therapies are the first choice in limited disease, while systemic chemotherapy has traditionally been used in extensive disease. In Langerhans‐cell histiocytoses and related entities, therapy by BRAF inhibition has led to a breakthrough especially in patients with an activation of the MAPK pathway.