Investigation of gamma secretase gene complex mutations in German population with Hidradenitis suppurativa designate a complex polygenic heritage.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease affecting apocrine gland-bearing skin in the axilla, groin and under the breasts. Mutations of the gamma secretase gene complex, which is essential in the activation of Notch signalling pathways, were shown in some families with HS and in a few sporadic cases. Although an imbalance in Notch signalling is implicated in the pathogenesis, the exact mechanism of HS development is yet unknown. OBJECTIVES: We aim to investigate the genetic basis of HS by determining the presence of mutations of gamma secretase gene complex in a cohort of HS patients and by searching for a disease-causing pathogenic variant in a multi-generational HS family using parametric linkage analysis. METHODS: Thirty-eight patients clinically diagnosed with HS were included in this study. All exons and exon-intron boundaries of the genes encoding gamma secretase complex consisting of six genes: APH1A, APH1B, PSENEN, NCSTN, PSEN1 and PSEN2 were sequenced by Sanger technique. Genetic mapping with parametric linkage analysis for the patients in the family was performed with eight affected and four healthy individuals. The logarithm of odds was calculated. RESULTS: In a sporadic patient with early-onset, severe lesions in axilla and groin, a novel single-nucleotide deletion causing frameshift in exon 1 of the NCSTN gene was identified ((NM_015331.3): c.38delG, p.(Gly13Glufs*15)). The LOD score of 1.5 was never exceeded in any region of the genome, pointing towards intricate multi-genic inheritance pattern within the affected family. CONCLUSIONS: The gamma secretase gene complex mutations were rare in our cohort (3.2%). Besides, our analysis indicates a possible complex multi-genic inheritance in a seemingly autosomal dominantly inherited large HS family. Genetics of both familial and sporadic HS may be complicated in most cases, and the role of other potential genes such as autoinflammatory and modifier genes as well as environmental factors may influence the pathogenesis.

European S1 guidelines on the management of lichen planus: a cooperation of the European Dermatology Forum with the European Academy of Dermatology and Venereology.

Lichen planus (LP) is a chronic inflammatory and immune-mediated disease that affects the skin, hair, nails and mucous membranes. Although there is a broad clinical spectrum of lichen planus manifestations, the skin and oral cavity remain the major sites of involvement. A group of European dermatologists with a long-standing interest and expertise in lichen planus has sought to define therapeutic guidelines for the management of patients with LP. The clinical features, diagnosis and possible medications that clinicians can use, in order to control the disease, will be reviewed in this manuscript. The revised final version of the lichen planus guideline was passed on to the European Dermatology Forum (EDF) for a final consensus with the European Academy of Dermatology and Venereology (EADV).

Cryosurgery combined with topical interventions for actinic keratosis: a systematic review and meta-analysis.

BACKGROUND: Actinic keratoses (AKs) are early in situ carcinomas of the skin caused by cumulative sun exposure. Cryosurgery is an easy and practicable lesion-directed approach for treatment of isolated lesions. OBJECTIVES: To investigate whether an upfront combination of cryosurgery with a topical intervention is superior to cryosurgery alone for treatment of AK. METHODS: We performed a systematic literature search in MEDLINE, Embase and CENTRAL and hand searched pertinent trial registers for eligible randomized controlled trials until 17 July 2018. Results from individual studies were pooled using a random effects model. The risk of bias was estimated with the Cochrane Risk of Bias Tool and the quality of evidence of the outcomes with the GRADE approach. RESULTS: Out of 1758 records initially identified, nine studies with a total sample size of 1644 patients were included. Cryosurgery in combination with a topical approach showed significantly higher participant complete clearance rates than monotherapy [risk ratio (RR) 1·74, 95% confidence interval (CI) 1·25-2·43, I2 = 73%, eight studies]. The participant partial clearance rate was not statistically different (RR 1·64, 95% CI 0·88-3·03, I2 = 77%, three studies). The number of patients who completed the study protocol and did not withdraw due to adverse events was equal in both groups (RR 0·98, 95% CI 0·95-1·01, I2 = 75%, seven studies). The studies were estimated to have high risk for selective reporting bias. CONCLUSIONS: Our results suggest the superiority of a combination regimen for AK clearance, with equal tolerability. This study highlights the importance of a field-directed approach in patients with multiple AKs or field cancerization.

Association of pyrin mutations and autoinflammation with complex phenotype hidradenitis suppurativa: a case-control study.

BACKGROUND: Hidradenitis suppurativa (HS) is a rare, debilitating neutrophilic dermatosis characterized by chronic inflammation of hair follicles. Many inflammatory conditions may accompany HS. OBJECTIVES: To investigate the association of variants of the MEFV gene with a complex HS phenotype. METHODS: Firstly, we identified the clinical characteristics of 119 patients with HS with a complex phenotype (Hurley stage III disease and/or additional inflammatory symptoms). Then, we searched for MEFV variants among these patients. The odds ratios (ORs) for pathogenic MEFV mutations were calculated using data from these patients with HS and 191 healthy controls. RESULTS: The male/female ratio was higher, and the mean age of onset was earlier, in our complex HS group compared with patients with HS in general. Five of the patients with HS (4·2%) had a diagnosis of familial Mediterranean fever (FMF) with a standardized morbidity ratio of 45 [95% confidence interval (CI) 16·50-99·84, P < 0·001] when compared with the frequency of FMF in the general Turkish population. Of the patients with complex HS, 38% were positive for pathogenic variants of MEFV. The OR for carrying a pathogenic MEFV allele was 2·80 (95% CI 1·31-5·97, P < 0·001). CONCLUSIONS: The frequency of MEFV mutations in the group of patients with complex HS was higher than that in healthy controls, suggesting that MEFV mutations may contribute to the pathogenesis of HS. Understanding the role of autoinflammation in HS is of fundamental importance for the development of novel therapies.

Distribution of high-risk α-genus human papillomavirus genotypes impacts cutaneous neoplasms.

BACKGROUND: High-risk α-genus human papillomaviruses (α-HPVs) are linked to cervical and genital carcinomas; however, their correlation with cutaneous squamous cell carcinoma (cuSCC) or premalignant skin lesions remains controversial. OBJECTIVE: We evaluated the contribution of high-risk α-HPV to the occurrence of cuSCC, Bowen's disease and actinic keratosis (AK), and the distribution of high-risk α-HPV genotypes in these cutaneous tumours. METHODS: HPV genotypes were determined using a commercial PCR-based microarray on skin tissue samples collected from 76 [38 young (<60 years) and 38 elderly (>60 years)] cuSCC, 34 Bowen's disease, 48 AK patients and 10 young controls. Associations between α-HPV prevalence and relevant risk factors were analysed. RESULTS: High-risk α-HPV was more frequently detected in cuSCC patients (57.9%) than in the patients with Bowen's disease (38.2%), AK (0.0%) and control patients (10.0%). The high-risk α-HPV prevalence was higher in young than in elderly cuSCC patients (65.8% vs. 50.0%, P = 0.031). The most common HPV type was 16, present in 90.9% of all HPV-carrying cuSCC patients. Multiple infections with different high-risk α-HPV types were found in 20.5% of HPV-related cuSCC, whereas only single infection with type 16 was found in Bowen's disease. Although sun exposure is known as a major risk factor for cuSCC, high-risk α-HPVs were more frequently found in non-exposed sites rather than in sun-exposed sites of cuSCC. CONCLUSION: Multiple infections, as well as single infection with high-risk α-HPV may link to cuSCC. In spite of the involvement of high-risk α-HPV at high levels in cuSCC and Bowen's disease, no high-risk α-HPV was detected in AK patients, suggesting that Bowen's disease rather than AK might be involved in the development of HPV-related cuSCC as a precursor.

Ex vivo confocal laser scanning microscopy for bullous pemphigoid diagnostics: new era in direct immunofluorescence?

BACKGROUND: Ex vivo confocal laser scanning microscopy (ex vivo CLSM) is a novel diagnostic method allowing rapid, high-resolution imaging of excised skin samples. Furthermore, fluorescent detection is possible using fluorescent-labelled antibodies. OBJECTIVE: To assess the applicability of ex vivo CLSM in the detection of basement membrane (BM) fluorescence in bullous pemphigoid (BP) and to compare its diagnostic accuracy with direct immunofluorescence (DIF) microscopy. METHODS: A total of 81 sections of 49 BP patients with positive DIF microscopy findings were examined using ex vivo CLSM in reflectance and fluorescence mode following staining with fluorescent-labelled IgG and C3 antibodies. RESULTS: Ex vivo CLSM showed an overall performance of 65.3% in identifying BM fluorescence in BP patients. IgG and C3 deposition along the BM was detected in 50% and 45.5% of the patients, respectively. The sensitivity of ex vivo CLSM in detecting BM fluorescence was low (IgG: 50%, C3: 45.5%), but the specificity was high (IgG: 100, C3: 90%). In addition to immunoreactivity, ex vivo CLSM could display subepidermal inflammatory cells similar to histological examination in 84% of patients. CONCLUSIONS: Basement membrane fluorescence could be identified with ex vivo CLSM in the skin sections of BP patients. Ex vivo CLSM enables simultaneous and rapid detection of histopathological and immunofluorescence findings in the same session, albeit with a lower sensitivity than DIF in detecting BM fluorescence.

Increased sensitivity and high specificity of indirect immunofluorescence in detecting IgG subclasses for diagnosis of bullous pemphigoid.

BACKGROUND: Indirect immunofluorescence (IIF) microscopy on monkey oesophagus is an important assay for the diagnosis of bullous pemphigoid (BP). Its relatively low sensitivity (60-80%) may be partly due to insufficient detection of minor IgG subclasses. AIM: To determine the operating characteristics of an IgG subclass in IIF. METHODS: We designed a retrospective, dual-centre, controlled cohort study on sera from 64 BP sera that had been rated as false negatives by traditional IIF microscopy, and assessed circulating IgG1 , IgG3 and IgG4 autoantibodies. RESULTS: The sensitivities of IIF in detecting IgG1 , IgG3 , IgG4 and all three in combination were 45.3%, 18.8%, 32.8% and 48.4%, respectively. Specificities were > 97%. CONCLUSION: Detection of IgG subclass (especially IgG1 and IgG4 ) autoantibodies by IIF on monkey oesophagus can significantly improve diagnostic performance of IIF microscopy for diagnosis of BP.

Efficient isolation and observation of the most complex human commensal, Demodex spp.

Demodex spp. mites are an often neglected member of the human skin microbiome. Mostly they are commensals, although their pathophysiological role in rosacea, spinulosis folliculorum, and other skin diseases is recognized. Little is known about their life cycle, biology, and physiology. Demodex mites cannot be cultivated in vitro, thereby complicating research immensely. The manual extraction from human sebum is laborious and death can only be detected by surrogate markers like ceased movement or loss of fluorescence. Here we present a new approach for the extraction of larger mite numbers and the hitherto most precise way to detect death. The extraction of mites from sebum and debris by hand can be accelerated by a factor 10 using sucrose gradient centrifugation, which is well tolerated by the mites. Staining with propidium iodide allows for easy identification of dead mites, excluding frail mites that stopped moving, and has no negative effect on overall mite survival. We anticipate our methods to be a starting point for more sophisticated research and ultimately in vitro cultivation of Demodex spp. mites.

A practical approach to ichthyoses with systemic manifestations.

Inherited ichthyoses are rare disorders in terms of patient numbers, but abundant in terms of clinical-genetic subtypes. These disorders are often associated with severe systemic manifestations, in addition to significant medical, cosmetic and social problems. There are 17 subtypes of syndromic ichthyosis identified so far and most patients with these syndromes are living in countries with high consanguinity rates. Frequently, clinicians cannot make a definitive diagnosis and patients are not managed properly owing to the rarity and complexity of these disorders. These difficulties make this group of ichthyosis and the patients living with them 'orphan'. After skin and skin appendages, nervous system is the most frequently involved system in ichthyosis syndromes. Thus, association of ichthyosis with neurological symptoms provides an important clue for diagnosis. In this article, we aim to increase clinicians' comprehension of ichthyosis syndromes by providing a symptomatology-based approach based on this observation. Additionally, we provide a review of ichthyosis syndromes, with special emphasis on neurological symptoms, hoping to attract interest to this complicated field.

The impact of sentinel node dissection on disease-free and overall tumour-specific survival in melanoma patients: a single centre group-matched analysis of 1192 patients.

BACKGROUND: Sentinel lymph node dissection (SLND) is considered a standard staging procedure providing important prognostic information on melanoma patients. It remains a matter of debate, whether SLND and hence, removal of potential lymph node micrometastasis will alter survival outcome. OBJECTIVE: The aim of this group-matched analysis was to compare survival data of a large cohort of melanoma patients who were treated by wide local excision only (WLE) and nodal observation (WLE group) to a group of patients treated with WLE plus SLND group to investigate the potential therapeutic benefit of SLND in the treatment of patients with melanoma. METHODS AND MATERIALS: A total of 596 consecutive patients who had undergone WLE plus SLND between 1996 and 2003 were assessed. As a historical control group 596 patients treated with WLE and nodal observation but without SLND between 1986 and 1995 were selected. The groups were matched according to sex, age, Breslow tumour thickness and localization of primary tumour. The adjuvant treatment and follow-up examinations were performed according to protocols of the German Dermatologic Cooperative Oncology Group (DeCOG) and applicable study protocols that our clinic participated in; and hence, subject to change over time. RESULTS: Kaplan-Meier testing revealed significant differences in survival in favour of the SLND group. Mean overall tumour-specific survival (OS) was 102.7 months in the SLND group vs. 97.0 months in the WLE group respectively (P-value: 0.024). Disease-free survival (log-rank test: 0.003) and time to lymph node progression (P-value: <0.01) also differed significantly between the two groups. CONCLUSION: SLND is not only an important diagnostic procedure, but might also be of therapeutic benefit in terms of disease-free and overall tumour-specific survival of melanoma patients.

[Stable disease or complete response? : A critical evaluation of the radiologic response to immune checkpoint blockade in advanced melanoma]. / Stabile Erkrankung oder vollständiges Ansprechen? : Evaluation der radiologischen Interpretation des Therapieansprechens auf Immune-Checkpoint-Blockade im metastasierten malignen Melanom.

BACKGROUND: Rating the response of melanoma to immune checkpoint blockade (ICB) by conventional CT proves to be difficult, since response patterns and kinetics differ from the classical responses seen with other therapies. Hence, immune-related response criteria were developed. However, they are mainly based on the alteration of the diameter of lesions over time but do not include metabolic activity. OBJECTIVE: The aim of this study was to search for additional criteria to improve the interpretation of the radiologic images of patients with metastatic melanoma after ICB. MATERIALS AND METHODS: We retrospectively analysed 7 patients with metastatic melanoma over a period of 13-41 months after treatment with ICB using contrast enhanced CT scans from the neck region to the lower abdomen and compared the results in the follow ups with 18F-FDG PET/CT. RESULTS: Metastatic lesions in 5 of 7 patients rated as stable disease (SD) in CT staging showed no metabolic activity in 18F-FDG PET/CT. The size of these lesions did not increase or show metabolic activity in the further follow-up, even after discontinuation of ICB. In contrast, tumor lesions in the other 2 patients rated as SD in CT staging showed metabolic activity in 18F-FDG PET/CT. These tumor lesions expanded significantly in the further course of the disease. CONCLUSION: In addition to the size of a tumor lesion, its metabolic activity adds important information regarding treatment response. Thus, we propose that the metabolic activity assessed with 18F-FDG-PET/CT should be included in the immune response criteria. No FDG uptake in a lesion should be rated as inactive tumor rather than SD and further treatment may not be required.

The first trial of CIM331, a humanized antihuman interleukin-31 receptor A antibody, in healthy volunteers and patients with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single dose in a randomized, double-blind, placebo-controlled study.

BACKGROUND: The cytokine interleukin-31 (IL-31) is considered to be responsible for the development of pruritus in humans. At present, no available evidence has been provided on the safety and efficacy of blocking the IL-31 signal in humans for the amelioration of pruritus in atopic dermatitis (AD). CIM331 is a humanized antihuman IL-31 receptor A (IL-31RA) monoclonal antibody, which binds to IL-31RA to inhibit subsequent IL-31 signalling. OBJECTIVES: To assess the tolerability, safety, pharmacokinetics and preliminary efficacy of CIM331 in healthy Japanese and white volunteers, and Japanese patients with AD. METHODS: In this randomized, double-blind, placebo-controlled phase I/Ib study, CIM331 was administered in a single subcutaneous dose. The primary outcomes were safety and tolerability; the exploratory analysis was efficacy. RESULTS: No deaths, serious adverse events (AEs) or discontinuations due to AEs were reported in any part of the study. No dose-dependent increase in the incidence of AEs occurred in any part of the study. In healthy volunteers, all AEs occurred once in the placebo groups, and increased creatine phosphokinase was more common in the CIM331 groups. In patients with AD, CIM331 reduced pruritus visual analogue scale score to about -50% at week 4 with CIM331 compared with -20% with placebo. CIM331 increased sleep efficiency and decreased the use of hydrocortisone butyrate. CONCLUSIONS: A single subcutaneous administration of CIM331 was well tolerated in healthy volunteers and patients with AD. It decreased pruritus, sleep disturbance and topical use of hydrocortisone. CIM331 may become a novel therapeutic option for AD by inhibiting IL-31.

Atypical discrete papular lichen myxedematosus associated with monoclonal gammopathy: report of four cases and review of the literature.

BACKGROUND: Discrete papular lichen myxedematosus (DPLM) is a rare form of localized lichen myxedematosus that presents with skin involvement only and without systemic involvement. OBJECT: To describe our experience with atypical cases of DPLM associated with monoclonal gammopathy. METHODS: Data were collected from patients with clinicopathological evidence of DPLM associated with monoclonal gammopathy who presented to the Department of Dermatology of two tertiary university-affiliated medical centres from 2000 to 2015 and were followed prospectively. RESULTS: The sample included four patients (three males) with a mean age of 58 years. No clinicopathological differences from typical cases of DPLM were observed, except for the presence of monoclonal gammopathy. The patients were followed up for a mean of 34 months (6-72 months) and no progression to scleromyxedema, multiple myeloma or systemic involvement was observed. No therapy was applied, except for topical tacrolimus or steroids, and the eruptions remained stable. CONCLUSION: Our experience indicates an excellent prognosis of DPLM even for atypical cases in spite of the presence of monoclonal gammopathy.

Maintenance of remission following successful treatment of papulopustular rosacea with ivermectin 1% cream vs. metronidazole 0.75% cream: 36-week extension of the ATTRACT randomized study.

BACKGROUND: There are a limited number of approved treatments for papulopustular rosacea (PPR) and remission is difficult to maintain after successful treatment. OBJECTIVES: To investigate remission over a 36-week extension period in patients with moderate to severe PPR successfully treated with 16 weeks' treatment with ivermectin 1% cream once daily (QD) or metronidazole 0.75% cream twice daily (BID) in a randomized, parallel-group Phase III study. METHODS: Treatment was discontinued in patients initially successfully treated [Investigator's Global Assessment (IGA) score of 0 or 1] with ivermectin 1% cream QD (n = 399) or metronidazole 0.75% cream BID (n = 365; Part A) and patients were followed every 4 weeks for up to 36 weeks (Part B). Treatment with the same study treatment as used in Part A was only re-initiated if patients relapsed (IGA ≥ 2). Efficacy assessments were: time to first relapse; relapse rate; and number of days free of treatment. Safety assessments included incidence of adverse events and local cutaneous signs and symptoms. RESULTS: The median time to first relapse was significantly longer (115 days vs. 85 days) and relapse rates at the end of the study period significantly lower (62.7% vs. 68.4%) for patients initially successfully treated with ivermectin 1% compared with metronidazole 0.75%; Kaplan-Meier plot demonstrated a statistically significant difference between the two arms (P = 0.0365). The median number of days free of treatment was higher for ivermectin compared with metronidazole (196 days vs. 169.5 days; P = 0.026). The percentage of patients who experienced a related adverse event was equally low in both groups. CONCLUSION: The results of this relapse study showed that an initial successful treatment with ivermectin 1% cream QD significantly extended remission of rosacea compared with initial treatment with metronidazole 0.75% cream BID following treatment cessation.

Non-invasive diagnosis of sweat gland dysplasia using optical coherence tomography and reflectance confocal microscopy in a family with anhidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome).

BACKGROUND: Anhidrotic ectodermal dysplasia (AED) is an inherited syndrome, which originates mainly from genetic alteration of the ectodysplasin A (EDA) gene. It regularly affects the adnexa of the skin which results in a characteristic phenotype of the patients including hypo- or anhidrosis leading to severe disturbances in the regulation of body temperature. OBJECTIVES: To prevent the development of the symptoms in early childhood promising therapeutic approaches are currently under clinical investigation. In this context, timely diagnosis of this genetic syndrome is crucial. The purpose of our study was the investigation of modern non-invasive imaging methods such as optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) in the immediate diagnosis of AED. METHODS: We examined a 3-year-old boy with the suspicion for an AED syndrome and his family members with RCM and OCT to document presence and characteristic features of sweat glands in comparison to non-affected individuals. RESULTS: The patient and the affected brother showed significantly reduced sweat glands in the imaging compared to the controls. The genetic analysis revealed a mutation of the EDA gene for hemizygosity previously associated with AED and the mother was revealed as the conductor of the genetic alteration. CONCLUSIONS: With the help of non-invasive imaging, we were able to detect sweat gland dysplasia in the affected family members without performing a biopsy which led us to the diagnosis of an AED. The application of modern dermatological imaging techniques might serve as valuable supplementary tools in the immediate, non-invasive diagnosis of genetic syndromes especially in newborns when early therapeutic approaches are planned.

Morphologic features of basal cell carcinoma using the en-face mode in frequency domain optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) has become a valuable non-invasive tool in the in vivo diagnosis of non-melanoma skin cancer, especially of basal cell carcinoma (BCC). Due to an updated software-supported algorithm, a new en-face mode - similar to the horizontal en-face mode in high-definition OCT and reflectance confocal microscopy - surface-parallel imaging is possible which, in combination with the established slice mode of frequency domain (FD-)OCT, may offer additional information in the diagnosis of BCC. OBJECTIVES: To define characteristic morphologic features of BCC using the new en-face mode in addition to the conventional cross-sectional imaging mode for three-dimensional imaging of BCC in FD-OCT. METHODS: A total of 33 BCC were examined preoperatively by imaging in en-face mode as well as cross-sectional mode in FD-OCT. Characteristic features were evaluated and correlated with histopathology findings. RESULTS: Features established in the cross-sectional imaging mode as well as additional features were present in the en-face mode of FD-OCT: lobulated structures (100%), dark peritumoral rim (75%), bright peritumoral stroma (96%), branching vessels (90%), compressed fibrous bundles between lobulated nests ('star shaped') (78%), and intranodular small bright dots (51%). These features were also evaluated according to the histopathological subtype. In the en-face mode, the lobulated structures with compressed fibrous bundles of the BCC were more distinct than in the slice mode. CONCLUSION: FD-OCT with a new depiction for horizontal and vertical imaging modes offers additional information in the diagnosis of BCC, especially in nodular BCC, and enhances the possibility of the evaluation of morphologic tumour features.

The invisible basal cell carcinoma: how reflectance confocal microscopy improves the diagnostic accuracy of clinically unclear facial macules and papules.

Difficult to diagnose and early non-melanoma skin cancer lesions are frequently seen in daily clinical practice. Besides precancerous lesions such as actinic keratosis, basal cell carcinomas (BCCs) score the highest frequency in skin tumors. While infiltrative and nodular BCCs require a surgical treatment with a significant impact on the patients' quality of life, early and superficial BCCs might benefit from numerous conservative treatments, such as topical immune-modulators or photodynamic therapy. Dermoscopy has shown a high sensitivity and specificity in the diagnosis of early BCCs, and non-invasive imaging techniques like reflectance confocal microscopy (RCM) have proven to be helpful. The aim of our study was to investigate the importance of RCM in the diagnosis of BCCs with indistinct clinical and dermoscopic features. We retrospectively examined 27 histologically proven BCCs in which diagnosis was not possible based on naked eye examination; we separately reviewed clinical, dermoscopic, and confocal microscopy features and evaluated the lesions meeting the common diagnostic criteria for BCCs, and our diagnostic confidence. All lesions were clinically unclear, with no characteristic features suggestive for BCC; dermoscopy showed in most cases unspecific teleangiectasias (74 %) and micro-erosions (52 %). Confocal microscopy revealed in most of the cases the presence of specific criteria: peripheral palisading of the nuclei (89 %), clefting (70 %), stromal reaction (70 %), dark silhouettes (70 %), inflammatory particles (70 %), and tumor islands (67 %). In the absence of significant diagnostic clinical signs and with unclear dermoscopic features, specific confocal patterns were present in most of the lesions and enabled a correct diagnosis. In the absence of significant clinical features of BCC and in the case of uncertain dermoscopy, striking confocal features are detectable and easy to recognize in most cases. Confocal microscopy can therefore be instrumentful in the diagnosis of the so-called invisible BCCs.

[Severe acne in autoinflammatory diseases]. / Schwere Akne bei Autoinflammationskrankheiten.

BACKGROUND: In recent years, acne has been described as a symptom of autoinflammatory diseases, such as PASH (pyoderma gangrenosum - PG, acne and suppurative hidradenitis - SH) and PAPASH (PG, acne, pyogenic arthritis, and SH). The pathogenesis of autoinflammatory diseases is not fully understood; however, based on the possible involvement of IL-1ß, the recombinant human interleukin-1 receptor antagonist anakinra has been used in the treatment of certain autoinflammatory diseases. METHODS: We describe two patients with severe acne and associated symptoms which led to the diagnosis PAPASH and PASH syndrome and who were treated with anakinra. RESULTS: In the patient with PASH syndrome, inhibition of inflammation and almost complete healing of ulcers was observed. In the patient with PAPASH syndrome, partial response was achieved. CONCLUSION: The therapeutic effect of anakinra in PASH syndrome and partly in PAPASH syndrome indicates an involvement of IL-1ß in acne-associated autoinflammatory diseases.

State of the art: systemic rosacea management.

Based on numerous trials, oral tetracyclines and most commonly their second-generation derivative doxycycline have become the main pillar in systemic rosacea treatment. However, the only preparation that has been approved so far in this setting is 40 mg doxycycline in an anti-inflammatory dosage and with a modified release formulation. With the introduction of this once-daily, non-antibiotic dosing of doxycycline, oral therapy is more commonly prescribed as first-line treatment in moderate to severe papulopustular rosacea. In addition, topical and oral strategies are often used in combination due to the more substantial improvements compared to monotherapy. Although several other non-approved oral agents like macrolides, isotretinoin, and carvedilol have been evaluated for systemic treatment and showed promising results, yet the experience with these drugs in rosacea is limited, and thus they should be reserved for special situations.

Aktueller Stand der systemischen Rosazea-Therapie.

Basierend auf den Daten zahlreicher Studien sind orale Tetracycline - und hier insbesondere Doxycyclin als Tetracyclin der zweiten Generation - die Grundpfeiler der systemischen Rosazea-Therapie. Bisher ist dafür jedoch nur Doxycyclin 40 mg in antientzündlicher Dosierung mit veränderter Wirkstofffreisetzung zugelassen. Seit Einführung der Therapie mit Doxycyclin einmal täglich in nicht antibiotischer Dosierung wird die orale Therapie häufiger als Erstbehandlung bei mittelschwerer bis schwerer papulopustulöser Rosazea verschrieben. Oft wird diese Behandlung aufgrund der besseren Wirksamkeit im Vergleich zur Monotherapie auch mit einer topischen Behandlung kombiniert. Obwohl in der Systemtherapie weitere, nicht zugelassene Wirkstoffe wie Makrolide, Isotretinoin und Carvedilol mit viel versprechenden Ergebnissen untersucht wurden, ist die vorliegende Erfahrung bisher begrenzt, so dass diese Substanzen speziellen Situationen vorbehalten bleiben sollten.