Developments and challenges in dermatology: an update from the Interactive Derma Academy (IDeA) 2019.

The 2019 Interactive Derma Academy (IDeA) meeting was held in Lisbon, Portugal, 10-12 May, bringing together leading dermatology experts from across Europe, the Middle East and Asia. Over three days, the latest developments and challenges in relation to the pathophysiology, diagnosis, evaluation and management of dermatological conditions were presented, with a particular focus on acne, atopic dermatitis (AD) and actinic keratosis (AK). Interesting clinical case studies relating to these key topics were discussed with attendees to establish current evidence-based best practices. Presentations reviewed current treatments, potential therapeutic approaches and key considerations in the management of acne, AK and AD, and discussed the importance of the microbiome in these conditions, as well as the provision of patient education/support. It was highlighted that active treatment is not always required for AK, depending on patient preferences and clinical circumstances. In addition to presentations, two interactive workshops on the diagnosis and treatment of sexually transmitted infections/diseases (STIs/STDs) presenting to the dermatology clinic, and current and future dermocosmetics were conducted. The potential for misdiagnosis of STIs/STDs was discussed, with dermoscopy and/or reflectance confocal microscopy suggested as useful diagnostic techniques. In addition, botulinum toxin was introduced as a potential dermocosmetic, and the possibility of microbiome alteration in the treatment of dermatological conditions emphasized. Furthermore, several challenges in dermatology, including the use of lasers, the complexity of atopic dermatitis, wound care, use of biosimilars and application of non-invasive techniques in skin cancer diagnosis were reviewed. In this supplement, we provide an overview of the presentations and discussions from the fourth successful IDeA meeting, summarizing the key insights shared by dermatologists from across the globe.

[Andrology in oncological diseases]. / Andrologie bei onkologischen Erkrankungen.

In dermato-oncological treatment there are many gonadotoxic interventions. Alkylating and hormonally active substances as well as gonadal irradiation, in particular, are known to have a fertilization-limiting effect in men. Since 2017 certified skin cancer centers in Germany therefore have the task to implement counselling on preservation of fertility. This is supported by the S2k guidelines on preservation of fertility in oncological treatment. Because recommendation of the various interventions from the dermato-oncological guidelines are dependent on the stage, the authors advocate at least the question "Is the desire to have children of interest to you?" when patients reach the appropriate stage. Fertility protection of men via cryopreservation of ejaculates or testicular tissue is then a simple and safe option. The procedure is standardized and usually available. In addition, the possibility of cryopreservation of testicular tissue from prepubertal male children and infants is now available via the new Androprotect project. If signs of hypogonadism occur during therapy, a treatment can be considered by weighing up the effects of testosterone but in this case it is important to take the anabolic and immunomodulating effects into account.

[Acne and rosacea in pregnancy]. / Akne und Rosazea in der Schwangerschaft.

Acne and rosacea are common chronic inflammatory skin diseases. During pregnancy these skin disorders may become aggravated, in rare cases occurring for the first time. There are no data available for rosacea and little data for acne concerning the course of these skin disorders during pregnancy. Up to 42% of the pregnant women suffer from acne. In 90% of these women the disease existed before pregnancy. In 1/3, however, acne relapsed during pregnancy after a prior disease-free period. In 60% acne deteriorated during pregnancy. Randomized controlled trials for the treatment of acne or rosacea during pregnancy do not exist. In this article the recommendations of current guidelines are modified, so that effective treatments can be recommended without harming the embryo or fetus.

[Cutaneous changes in long-standing erythropoietic protoporphyria]. / Hautveränderungen bei lange bestehender erythropoetischer Protoporphyrie.

Erythropoietic protoporphyria results in highly increased photosensitivity of the skin. Solar irradiation causes sunburn-like symptoms with erythema, edema and wheals. We report the case of a 60-year-old man suffering from erythropoietic protoporphyria since his childhood who additionally developed chronic cutaneous lichenoid papules in sun-exposed skin areas. Vaporization with both electrocautery and carbon dioxide laser proved to be a successful treatment option.

Clindamycin phosphate 1.2% / tretinoin 0.025%: a novel fixed-dose combination treatment for acne vulgaris.

The Global Alliance to Improve Outcomes in Acne Group recommends retinoid-based combination therapy as first-line therapy and the preferred treatment approach for almost all acne patients except those with the most severe disease. Clindamycin 1% (as clindamycin phosphate 1.2%)/tretinoin 0.025% (Clin-RA) is a new fixed-dose retinoid-based combination therapy. The aqueous-based gel formulation of Clin-RA was designed to minimize skin irritation and optimize adherence with the therapy. It contains both solubilized and crystalline tretinoin which allows the retinoid to be slowly released onto the skin surface and decreases the potential for cutaneous irritation. A pooled analysis of three pivotal studies involving 4550 acne patients showed that Clin-RA is well tolerated and effective at treating both inflammatory and non-inflammatory acne lesions. The onset of action of Clin-RA is rapid occurring within 2 weeks of treatment initiation. It is not associated with acne flaring or an increase in clindamycin-resistant Propionibacterium acnes counts. Clin-RA is considered as effective as adapalene 0.1%/benzoyl peroxide (BPO) 2.5%, whereas Clin-RA has a more favourable tolerability profile. Clin-RA may be more effective than clindamycin 1%/BPO 5% at treating non-inflammatory acne lesions since the latter does not contain a retinoid to target comedones. Clin-RA is also easy for patients to handle and apply, and has the advantage of not containing BPO which can bleach hair and fabrics. Taken together, the profile of Clin-RA suggests Clin-RA to be a first-line treatment for patients with facial acne.

Macrophage metalloelastase-12 is detectable in human seminal plasma and represents a predictor for inflammatory processes in the male genital tract.

Macrophage metalloelastase-12 (MMP-12), a protein of the matrix metalloproteinase family, is involved in the breakdown of extracellular matrix in normal physiological processes as well as in disease processes. MMP-12 is almost exclusively produced by macrophages and is associated with inflammatory disorders. Giving the fact that inflammation negatively influences ejaculate parameters, we investigated a possible presence and correlation of MMP-12 in seminal plasma with parameters of the ejaculate, especially in leucocytospermic ejaculates. Forty-two patients who presented for semen analysis were assigned into four groups depending on the result of semen analysis according to the WHO guidelines 2010: normozoospermia (n = 11), OAT (n = 10), azoospermia (n = 10) and leucocytospermia (>1 mio. peroxidase-positive cells per ml) (n = 11). MMP-12 was detected by ELISA and was measurable in nearly all seminal plasma samples. Generally, MMP-12 concentrations were significantly higher in leucocytospermic samples than in nonleucocytospermic ones (P = 0.001). The MMP-12 levels between the latter nonleucocytospermic groups did not differ. Moreover, MMP-12 levels correlated with the presence of peroxidase-positive leucocytes. No correlation with CD 14 positive monocytes/macrophages was detected. In this study, we demonstrate that MMP-12 is present in seminal plasma and is correlated with inflammatory conditions in human semen and therefore may serve as predictor of ongoing inflammatory processes.

[The "obese" and "old" male patient in dermatological practice. When should hypogonadism be considered?]. / Der "dicke" und der "alte" Patient in der dermatologischen Praxis. Wann muss man an Hypogonadismus denken?

Hypogonadism refers to reduced endocrine function of the testicles and leads to testosterone deficiency. It is often observed in older and obese men. Symptoms with the highest predictive value are reduced sexual thoughts, decreased spontaneous erections, and erectile dysfunction. After excluding contraindications (e.g., desire for children), various forms of replacement therapy are available. Studies have shown that testosterone therapy is safe if regularly checked.

[Semen analysis in involuntary childlessness. What information does it provide?]. / Spermiogramm bei unerfülltem Kinderwunsch. Was sagt es aus?

Involuntary childlessness is a common problem. In about 50% of cases, inadequate semen quality plays a relevant role. A semen analysis provides information regarding exocrine function of the male reproductive organs of the testes, epidydimis, seminal vesicles, prostate gland, and vas deferens. These parameters can only be interpreted in conjunction with medical history and physical examination. Then they can be useful to identify relevant disorders or the causes of these disturbances. The fundamental principles for the interpretation of a semen analysis are easily learned and traditionally belong to the field of dermatology. This article explains the variables which are examined in a routine semen analysis as well as the reference values. Furthermore, common causes for deviations from the normal values are discussed to allow decision-making for further diagnostic workup. The interpretation of these values must always take into account the situation of the couple.

[Topical therapy of inflammatory dermatoses, pruritus and pain, as well as hyperhidrosis]. / Topische Therapie von entzündlichen Dermatosen, Juckreiz und Schmerz sowie Hyperhidrose.

In this review, substances suitable for the topical treatment of inflammatory dermatoses, pruritus, pain and hyperhidrosis are presented. Both non-specific and specific topical treatments are discussed with respect to their mode of action, indications and side effects; included are corticosteroids, calcineurin inhibitors, dithranol, coal tar, liquor carbonis detergens, vitamin D analogues, metronidazole, azelaic acid, retinoids, and benzoyl peroxide. Additionally, practical directions for the treatment of these common skin diseases are provided.

[Topical treatment of infections, tumors and hyperkeratotic disorders]. / Topische Therapie von Infektionen, Hauttumoren und Hyperkeratosen.

In this review substances for the topical treatment of skin infections, skin tumors and hyperkeratotic disorders are presented. Substances with specific actions as topical antimycotic, antibiotic, antiseptic, antiviral and antiparasitic agents as well as diclofenac in hyaluronic acid, 5-fluoruracil, imiquimod, ingenol mebutate, bexarotene, mechlorethamine, BCNU, alitretinoin, silicone gel, salicylic acid and urea are discussed with respect to their mode of action, indication and side effects.

Peroxisome proliferator-activated receptor activators protect sebocytes from apoptosis: a new treatment modality for acne?

BACKGROUND: The main function of the human sebaceous gland is sebum excretion. Increased sebum levels combined with follicular hyperkeratinization are a prerequisite of acne vulgaris. As peroxisome proliferator-activated receptors (PPARs) are known to control lipid metabolism in several human tissues they have been considered to be involved in the pathogenesis of acne vulgaris. OBJECTIVES: To investigate the effect of activators of PPAR-α (WY14643), PPAR-γ (rosiglitazone) and PPAR-δ (L-165.041) on basal and staurosporine-induced apoptosis in the human sebocyte cell line SZ95 in vitro. METHODS: After defining the basal effects of PPAR activators on membrane integrity (lactate dehydrogenase release) and DNA synthesis (5-bromodeoxyuridine incorporation), apoptosis was determined by the release of histone-associated DNA fragments. The underlying signalling events were detected by Western blotting and the use of specific inhibitors against p44/42 and protein kinase B (PKB)/Akt. RESULTS: PPAR activators of all three subsets offer antiapoptotic effects, with L-165.041 being the most potent. This compound induced the activation of PKB/Akt and p44/42, two kinases involved in antiapoptosis and proliferation, respectively. An inhibition of these kinases by specific inhibitors reversed the suppression of histone-associated DNA fragments by L-165.041, indicating that these signalling pathways participate in the observed antiapoptotic effect. CONCLUSIONS: The present data suggest that activators of PPAR, in particular of the δ subset, might have beneficial effects on acne vulgaris by inhibiting the release of lipids in the context of sebocyte apoptosis.

Treatment of cutaneous lupus erythematosus.

In patients with cutaneous lupus erythematosus (CLE) and mild skin involvement, local therapy consisting of topically applied pharmacological agents, e.g., topical/intralesional steroids, may be sufficient. Recent reports have also shown efficacy of topical calcineurin inhibitors in patients with CLE, particularly on the face. Special attention receives consistent sun protection through photoresistant clothing and application of light-shielding substances with highly potent chemical or physical UVA- and UVB-protective filters. These substances should be applied in sufficient amount (ca. 2 mg/cm(2)) at least 20-30 minutes before sun exposure in order to avoid induction and exacerbation of cutaneous lesions. The mainstay of treatment for disfiguring and widespread skin manifestations in patients with CLE, irrespective of the subtype of the disease, is antimalarial agents. Our understanding of the use of combinations of antimalarials and proper dosing according to the ideal bodyweight limits problems with toxicity. Further therapies, such as methotrexate, or retinoids, dapsone, mycophenolate mofetil, and thalidomide in selected cases, can be helpful for patients with resistant disease; however, side effects need to be taken into consideration. Recent advances in biotechnology resulted in the development of novel systemic agents, but randomized controlled trials are necessary for the approval of new therapeutic strategies in CLE.

C-terminally truncated kindlin-1 leads to abnormal adhesion and migration of keratinocytes.

BACKGROUND: The Kindler syndrome (KS) protein kindlin-1 is a member of a protein complex that links cortical actin to integrins on the surface of basal keratinocytes. Loss of kindlin-1 leads to abnormalities of cell adhesion and motility, and to skin blistering and progressive poikiloderma as clinical symptoms. OBJECTIVES: Here we investigated a severely affected patient, disclosed the mutation that caused the disease and delineated its biological consequences. METHODS: Mutation screening of the kindlin-1 gene, KIND1 (now called FERMT1), was performed with polymerase chain reaction (PCR) amplification of all exons and sequencing. Mutated kindlin-1 was characterized by reverse transcriptase (RT)-PCR and immunoblotting, and genotype-phenotype correlations were analysed using immunohistochemical staining of skin biopsies and keratinocytes from the patient's skin. Cell adhesion and motility were assessed with functional tests. RESULTS: We disclosed a splice site mutation in the first position of intron 13 of the FERMT1 gene, which caused skipping of exon 13. The short transcript partially escaped nonsense-mediated mRNA decay and was translated into a truncated protein. CONCLUSION: A C-terminally truncated kindlin-1 in keratinocytes could not function correctly even if it were expressed.