Keloids – clinical diagnosis,pathogenesis, and treatment options

Keloids are defined as excessive scar tissue formation extending beyond the area of the original skin injury and occurring in predisposed individuals. They are considered to be a result of abnormal wound healing. The pathogenetic mechanisms that cause keloids remain unknown. Experiments with cells derived from keloid tissue revealed a number of abnormalities in cellular functions, such as in proliferation, apoptosis, or expression of growth factors and extracellular matrix proteins. Furthermore, several studies have reported altered keratinocyte‐fibroblast interactions in keloids. Despite the diverse pathological changes in cellular functions and expression profiles of cells derived from keloid tissue, recent genetic studies have provided evidence that single genes may act as major regulators of keloid formation. We provide an overview of the pathogenetic mechanisms of keloid formation in the context of their clinical characteristics and current therapeutic approaches.     

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.     

肥大细胞增生症病因与治疗研究进展

2016年WHO更新了肥大细胞增生症（mastocytosis, MC）的分型和诊断标准，一些方法已经得到验证并应用于临床，包括：酪氨酸激酶抑制剂，单克隆抗体靶向治疗，细胞减灭术，造血干细胞移植等。本文对该病的分型、发病机制、目前常用和新兴治疗方法进行综述。     

Extramammary Paget disease – clinical appearance,pathogenesis, management

Extramammary Paget disease is a rare malignant neoplasm. With regard to the pathogenesis, two prognostically different forms can be distinguished. The primary form of extramammary Paget disease is an in situ carcinoma of the apocrine gland ducts. In contrast, the secondary form is characterized by an intraepithelial spread due to an underlying carcinoma of the skin or other organ systems. Extramammary Paget disease occurs in older patients. The predilection sites include the entire anogenital skin and less often the axillary region. We present five different patients with this disease, thereby demonstrating its variation in clinical morphology. The lesion usually presents as an erythematous sharply defined spot. The polygonal borders, caused by the centrifugal growth of the tumor, may provide a diagnostic clue. The treatment of choice for extramammary Paget disease remains Mohs’ microscopic surgery. However, radiotherapy or topical applications may be alternative treatment options in selected cases. In patients with the secondary form of extramam‐mary Paget disease, treatment of the primary tumor is the main approach.     

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.     

Leprosy – an overview of clinical features,diagnosis, and treatment

Leprosy is a chronic infectious disease caused by Mycobacterium (M.) leprae. Worldwide, 210,758 new cases were diagnosed in 2015. The highest incidence is found in India, Brazil, and Indonesia. While the exact route of transmission remains unknown, nasal droplet infection is thought to be most likely. The pathogen primarily affects the skin and peripheral nervous system. The disease course is determined by individual host immunity. Clinically, multibacillary lepromatous variants are distinguished from paucibacillary tuberculoid forms. Apart from the various characteristic skin lesions, the condition is marked by damage to the peripheral nervous system. Advanced disease is characterized by disfiguring mutilations. Current treatment options are based on WHO recommendations. Early treatment frequently results in complete remission without sequelae. While paucibacillary forms are treated with rifampicin and dapsone for at least six months, multibacillary leprosy is treated for at least twelve months, additionally requiring clofazimine. Leprosy reactions during therapy may considerably aggravate the disease course. Besides individual treatment, WHO‐supported preventive measures and strategies play a key role in endemic areas.     

Cutaneous B‐cell lymphomas – pathogenesis,diagnostic workup,and therapy

Cutaneous B‐cell lymphomas (CBCLs) comprise a group of mature lymphoproliferative B‐cell disorders that primarily affect the skin. Characterized by great biological and clinical variability among its various subtypes, CBCLs fundamentally differ from primary nodal or systemic B‐cell lymphomas. Given their uncomplicated course and excellent prognosis, lymphoma classifications rank primary cutaneous marginal zone lymphoma (PCMZL) and primary cutaneous follicle center lymphoma (PCFCL) as indolent CBCLs. By contrast, diffuse large B‐cell lymphoma, leg type (DLBCL‐LT) in particular, represent more aggressive lymphoma variants associated with a poorer prognosis. Therapeutic decisions and diagnostic procedures are based on the exact histological and immunohistochemical classification as well as the exclusion of systemic involvement and thus differentiation from nodal and systemic lymphomas. In this context, the diagnostic workup should also include molecular biology methods. Primary therapeutic options for indolent CBCL lesions include surgery and radiation therapy, as well as systemic treatment with rituximab (anti‐CD20 antibody) in case of dissemination. More aggressive CBCLs usually require a combination of rituximab and polychemotherapy, primarily the CHOP regimen or modifications thereof. Given that the pathogenesis and biology of CBCLs has not been conclusively elucidated, and given the limited therapeutic armamentarium available, there is great need for comprehensive research, especially with respect to DLBCL‐LT.     

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.     

Psoriasis – a systemic inflammatory disorder: clinic,pathogenesis and therapeutic perspectives

Psoriasis has seen a dramatic change in its perception by dermatologists as well as other medical specialties. Its well‐recognized association with several other diseases makes a complete switch in its management necessary. This review summarizes current epidemiological data on the comorbidities of psoriasis. Subsequently, the evidence for insulin resistance as a cause for endothelial cell dysfunction with its relevant pathogenetic link to the development of cardiovascular comorbidity is discussed. Based on these novel insights, we propose a possible state‐of‐the‐art approach towards comprehensive psoriasis management.     

Eumycetoma and actinomycetoma – an update on causative agents,epidemiology, pathogenesis,diagnostics and therapy

Mycetoma is a chronic putrid infection of the cutaneous and subcutaneous tissue concerning predominantly the feet, and more rarely other body parts. Mycetoma can be caused by both fungi (eumycetoma) and bacteria (actinomycetoma). Mode of infection is an inoculation of the causative microorganism via small injuries of the skin. The clinical correlate of both forms of mycetoma is tumescence with abscesses, painless nodules, sinuses and discharge. The latter is commonly serous‐purulent and contains grains (filamentous granules) which can be expressed for diagnostic purposes. Distinctive for both eumycetoma and actinomycetoma, are the formation of grains. Grains represent microcolonies of the microorganism in vivo in the vital tissue. The most successful treatment option for eumycetomas offers itraconazole in a dosage of 200 mg twice daily. This triazole antifungal is considered as ‘gold standard’ for eumycetomas. Alternatively, the cheaper ketoconazole was widely used, however, it was currently stopped by the FDA. Actinomycetomas should be treated by the combination of trimethoprim‐sulphamethoxazole (co‐trimoxazole 80/400 to 160/800 mg per day) and amikacin 15 mg/kg body weight per day. Mycetomas are neglected infections of the poor. They are more than a medical challenge. In rural areas of Africa, Asia and South America mycetomas lead to socio‐economic consequences involving the affected patients, their families and the society in general.     

“Retronychia – clinical and pathophysiological aspects”

Retronychia represents proximal ingrowth of the nail that occurs when the nail embeds backwards into the proximal nail fold. It is suspected when there is a persistent paronychia, particularly in the setting of trauma. Important clinical criteria for diagnosis are inflammation of the proximal nail fold, granulation tissue emerging from under the nail fold, thickening of the proximal portion of the nail plate and interruption of nail growth. The condition is rarely diagnosed and often misinterpreted, and is therefore unnecessarily treated with systemic antibiotics and antifungals. Avulsion of the nail confirms the diagnosis and it is the curative treatment. Conservative treatment with an adhesive technique is a valid option in early cases. We report 20 cases of retronychia diagnosed in our department between 2010 and 2013.     

Systemic isotretinoin in the treatment of rosacea – doxycycline‐ and placebo‐controlled,randomized clinical study

Background: Systemic isotretinoin has been known for decades to be effective in the treatment of severe forms of rosacea, but it must be used off‐label because of the lack of evidence‐based data. Patients and Methods: 573 patients with rosacea subtype II and III received one of three different dosages of isotretinoin (0.1 mg, 0.3 mg, or 0.5 mg per kg body weight), doxycycline (100 mg daily for 14 days, then 50 mg daily) or placebo in a double‐blinded, randomized way for 12 weeks in 35 German centers. Results: Isotretinoin 0.3 mg/kg proved to be the most effective dose with significant superiority versus placebo. Isotretinoin 0.3 mg/kg showed also significant non‐inferiority versus doxycycline with reduction of lesions of 90 % compared to 83 % with doxycycline. Investigators diagnosed complete remission in 24 % and marked improvement in further 57 % of patients with isotretinoin treatment, in contrast to remission in 14 % and marked improvement in 55 % of patients treated with doxycycline. Isotretinoin 0.3 mg/kg revealed a similar safety profile as for the treatment of acne. Isotretinoin 0.5 mg/kg showed more dermatitis facialis as compared to 0.3 mg/kg. Conclusions: Isotretinoin 0.3 mg/kg is an effective and well‐tolerated therapy option for the treatment of rosacea subtype II and III and can therefore be used successfully as an alternative to therapy with oral antibiotics.     

S3 Guideline for the treatment of psoriasis vulgaris,update – Short version part 1 – Systemic treatment

The German guideline for the treatment of psoriasis vulgaris was updated using GRADE methodology. The guideline is based on a systematic literature review completed on December 1, 2016, and on a formal consensus and approval process. The first section of this short version of the guideline covers systemic treatment options considered relevant by the expert panel and approved in Germany at the time of the consensus conference (acitretin, adalimumab, apremilast, cyclosporine, etanercept, fumaric acid esters, infliximab, methotrexate, secukinumab and ustekinumab). Detailed information is provided on the management and monitoring of the included treatment options.     

银屑病伴瘙痒的临床特点、发病机制及治疗研究进展

【摘要】 以往认为银屑病属于非瘙痒性皮肤病,近年来,人们逐渐认识到瘙痒是加重银屑病患者疾病负担的因素之一。本文主要阐述瘙痒在银屑病中的临床特点,关注神经源性炎症中神经肽异常表达和神经末梢异常分布在瘙痒发病机制中作用,介绍治疗银屑病对瘙痒症状缓解的影响。     

Nail psoriasis – a treatment challenge

Nail involvement in psoriasis is common and mostly occurs with other lesions but can also occur alone. Besides psychosocial and aesthetic impairments, patients often complain about functional impairment. Nail psoriasis is a predictor for more severe psoriasis, decreased quality of life, and a higher risk for the development of psoriatic arthritis. Onychomycosis and other differential diagnoses should be excluded prior to treatment. This article presents an overview of different clinical appearances of nail psoriasis, the essential diagnostic assessment before treatment, important differential diagnoses, and published data on treatment options for nail psoriasis.     

Paediatric psoriasis – narrowband UVB treatment

Narrowband UV‐B is a safe and efficacious option for the treatment of adult psoriasis. However, the use of this therapy has been limited in children due to its long‐term carcinogenic potential. It has proven to be an adequate alternative in patients whose condition is refractory to topical treatment. Aims To evaluate the efficacy and short‐term safety of narrowband UV‐B in the treatment of paediatric psoriasis, and to compare our results with those obtained in other studies on paediatric psoriasis. Materials and methods Over a period of 2 years and 4 months, we administered narrowband UV‐B to 20 children diagnosed with psoriasis that was refractory to topical therapy. The therapeutic response was measured using the Psoriasis Area and Severity Index (PASI). Results Between August 2005 and December 2007, 20 children received narrowband UV‐B. Their median age was 13 years (range, 5–17 years), and the median initial PASI score was 8.25 (2.7–22.2). A median of 28 (10–59) sessions was required to achieve clearance, reaching almost complete or total remission (median final PASI) in all but two patients. Six patients required a new therapeutic course because of relapse, and the mean duration of remission was 8 months (4–18). No patients experienced severe adverse events during therapy, and only one discontinued treatment, for unrelated reasons. Discussion and conclusion Narrowband UV‐B for the treatment of paediatric psoriasis has received little attention in the literature. This treatment has been limited in children because of its potential long‐term carcinogenic effects, and most information has been extrapolated from adults. Nevertheless, narrowband UV‐B phototherapy is an effective and well‐tolerated therapeutic alternative in paediatric patients with severe psoriasis.