Efficacy and safety of adjuvant immunoadsorption in pemphigus vulgaris and pemphigus foliaceus (IA-Pem Study): a multicentre randomized controlled trial.

BACKGROUND: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially life-threatening autoimmune blistering diseases. Treatment is based on long-term immunosuppression with high doses of glucocorticosteroids in combination with potentially corticosteroid-sparing agents and/or rituximab. Immunoadsorption (IA) has emerged as a fast-acting adjuvant treatment option. OBJECTIVES: To assess the clinical efficacy of IA in addition to best medical treatment (BMT). METHODS: We conducted a multicentre (26 centres from Germany and Austria) randomized controlled trial in 72 patients with newly diagnosed, relapsed or chronic active PV or PF (34 female patients and 38 male patients, aged 42-72 years) comparing BMT (prednisolone 1.0 mg kg-1 per day plus azathioprine or mycophenolate) with adjuvant IA (BMT + IA). Central 1 : 1 randomization was done at the coordinating centre for clinical trials (KKS Marburg). The primary endpoint was analysed using Kaplan-Meier and Cox regression methods. RESULTS: The study was ended prematurely owing to safety concerns after random allocation of 72 patients to BMT + IA (n = 34) or BMT (n = 38). The primary endpoint, time to complete remission on therapy, was not significantly different for the two groups [hazard ratio (HR) 1.35, 95% confidence interval (CI) 0.68-2.69; P = 0.39]. The cumulative dose of prednisolone was significantly lower in the BMT + IA group compared with BMT alone (difference -1214, 95% CI -2225 to -70; P = 0.03). In a post hoc analysis, patients with more extensive PV/PF showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group (HR 1.87, P = 0.17 in patients with baseline Pemphigus Disease Area Index ≥ 15). While more adverse events were observed in patients in the BMT group (29 vs. 25), severe adverse events were more frequent in patients in the BMT + IA group (17 events in 10 patients vs. 11 events in 8 patients). CONCLUSIONS: In this study, adjuvant IA did not demonstrate a shorter time to clinical remission, but a corticosteroid-sparing effect was observed. In patients with extensive PV/PF, post hoc analysis suggests that adjuvant IA may lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.

Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoantibody-driven blistering diseases, which present with erosions or blisters on skin and/or mucous membranes. Treatment is based on long-term immunosuppressive agents. Immunoadsorption (IA) is a procedure that removes autoantibodies from the blood and has emerged as a fast-acting treatment option for pemphigus.We conducted a trial comparing best medical treatment (BMT) (prednisolone 1.0 mg kg per day plus azathioprine or mycophenolate) with best medical treatment plus IA (BMT + IA). A total of 26 centres from Germany and Austria recruited 72 patients with active pemphigus (34 women and 38 men, aged 42­72 years) who were randomly allocated in a ratio of 1 : 1 to the treatment groups.Following inclusion of 72 patients in the BMT + IA (n = 34) or BMT (n = 38) groups, the study ended prematurely owing to safety concerns. The main outcome, time to complete remission (relief of all symptoms) while still receiving therapy, was not significantly different for the two groups. In contrast, the cumulative dose of prednisolone was significantly lower in the BMT + IA compared with BMT alone. In an additional analysis, patients with more extensive pemphigus showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group. While more adverse events were observed in the BMT group (29 vs. 25), severe adverse events were more frequent in the BMT + IA group (17 vs. 11). In this study, IA did not show a shorter time to clinical remission, but a prednisolone-sparing effect was observed. In patients with extensive pemphigus, adjuvant IA may possibly lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.

[Acne]. / Akne.

Acne vulgaris is one of the most frequent dermatological diseases with a lifetime prevalence of about 85%. The clinical spectrum shows a great variety. Key factors of pathogenesis are increased sebum production, hyperkeratinization of the follicular infundibulum, inflammatory processes, and a dysbiosis of the skin microbiome. In addition to endogenous factors (e.g., disturbances of the androgen metabolism) or other hormonal changes, exogenous factors (e.g., diet, mechanical irritation or the use of inappropriate cosmetics) can also play an important role. The clinical spectrum is broad, extending from neonatal Acne (A.) to adult A., from comedonal A. to fulminant A., from cosmetic A. to A. excoriée (skin picking disorder). The psychological effects of acne can be profound and can cause a severe reduction in quality of life. Therefore, in addition to an effective therapy with regular medical check-ups and good adherence, it is always necessary to consider psychological aspects.

Biologic Therapy for Hidradenitis Suppurativa Plus Conglobate Acne Associated with SAPHO Syndrome: A Case Report.

is missing (Short Communication).

Safety and Efficacy of Topically Applied Selected Cutibacterium acnes Strains over Five Weeks in Patients with Acne Vulgaris: An Open-label, Pilot Study.

Imbalance in skin microflora, particularly related to certain Cutibacterium acnes strains, may trigger acne. Application of non-acne-causing strains to the skin may modulate the skin microbiome and thereby lead to a reduction in acne. This pilot study evaluates the safety and efficacy of microbiome modulation on acne-prone skin. The study had 2 phases: active induction (5% benzoyl peroxide gel, 7 days) and interventional C. acnes strains treatment (5 weeks). Patients were randomized to either topical skin formulations PT1 (2 strains of C. acnes Single Locus Sequence Typing [SLST] type C3 and K8, 50% each) or PT2 (4 strains of C. acnes SLST type C3 [55%], K8 [5%], A5 [30%] and F4 [10%]). Safety and efficacy was evaluated in 14 patients (PT1=8/14, PT2=6/14). Skin microbiome composition shifted towards study formulations. No untoward adverse events, visible irritation, or significant flare-up were observed. Non-inflamed lesions and skin pH were reduced. Comedone counts improved clinically with no deterioration in inflammatory lesions.

Practical management of acne for clinicians: An international consensus from the Global Alliance to Improve Outcomes in Acne.

Scientific advances are continually improving the knowledge of acne and contributing to the refinement of treatment options; it is important for clinicians to regularly update their practice patterns to reflect current standards. The Global Alliance to Improve Outcomes in Acne is an international group of dermatologists with an interest in acne research and education that has been meeting regularly since 2001. As a group, we have continuously evaluated the literature on acne. This supplement focuses on providing relevant clinical guidance to health care practitioners managing patients with acne, with an emphasis on areas where the evidence base may be sparse or need interpretation for daily practice.

Eczema in Psoriatico: An Important Differential Diagnosis Between Chronic Allergic Contact Dermatitis and Psoriasis in Palmoplantar Localization.

Differential diagnosis of palmoplantar non-pustular psoriasis and chronic allergic contact dermatitis (ACD) and the combination of these conditions, termed "eczema in psoriatico" (EIP), is difficult, especially in cases of isolated involvement. A blind re-evaluation of 63 archived formalin-fixed palmoplantar samples, previously diagnosed clinically as either psoriasis or chronic ACD, was performed. Samples were allocated to histopathological diagnoses of psoriasis, contact dermatitis or EIP. Immunohistological stainings were performed for better characterization. Immunochemistry of EIP revealed features that overlapped contemporarily with psoriasis (cytokeratin 17 (CK17), Ki67, interleukin (IL)-8, IL-17, IL-23) and with ACD (CD1a, major histocompatibility complex (MHC) class I, MHC class II, epidermal T-cell subsets). Surprisingly, a significantly much higher number of dermal CD8+ T cells was found in EIP than in ACD and psoriasis. In conclusion, this study provides insight into the immunohistological differentiation of palmoplantar psoriasis, chronic ACD and EIP.

Female type of adult acne: Physiological and psychological considerations and management.

Today we see more cases of acne after adolescence, with a greater prevalence in females than males. Adult female acne has a distinct clinical presentation and is associated with a number of specific pathophysiological features and gender-specific triggers. The psychological impact of acne is generally significant and largely underestimated; stress during professional and private life, anxiety and sleep quality, in particular, have a reciprocal relationship with disease susceptibility and severity. It is essential to compare with males. Acne in females often causes greater distress in adults than in adolescents. The impact of disease may therefore be greater for female patients, triggering higher levels of psychosocial anguish and increasing the likelihood of sequelae such as skin picking and the risks of cutaneous superinfection, scarring and PIH and acne recurrence. The management of adult female acne should encompass not just medical treatment of the symptoms, but also a comprehensive, holistic approach to the patient as a whole, her individual lifestyle factors and the impact of acne on her quality of life. Future management of this disease should aim to improve patient adherence to therapy and to develop validated outcomes of treatment regarding overall skin appearance and quality of life.

Sentinel-Lymphknoten-Biopsie des Melanoms mittels Indocyaningrün und "FOVIS"-System.

HINTERGRUND: Der Nachweis metastatischer Infiltrate im Sentinel-Lymphkoten (SLN) gilt als wesentlicher prognostischer Faktor des Melanoms. Alternativ zur Farbstoffmethode mit Patentblau zum Goldstandard der SLN-Biopsie (SLNB) mittels Radiokolloid wird die fluoreszenzoptische Darstellung mit Hilfe von Indocyaningrün (ICG) und Nahinfrarot (NIR)-Kamerasystem kommuniziert. Im Vergleich zur konventionellen Methode wurde die Wertigkeit des ICG-/NIR-Verfahrens in Abhängigkeit vom Body-Mass-Index (BMI) des Patienten und der Konzentration von ICG bezüglich der Visualisierung des Lymphabstroms und des SLNs untersucht. PATIENTEN UND METHODIK: An zehn Patienten wurde die SLNB mittels Technetium-99m, Patentblau und ICG durchgeführt. Die Fluoreszenz-Darstellung von Lymphbahnen und SLN erfolgte in Echtzeit mittels der NIR-Kameratechnik "FOVIS". Je nach erzielter Bildqualität wurde ICG in einer Dosis von 0,25 mg bis 2,5 mg intrakutan appliziert. ERGEBNISSE: Neun der zehn SLN wurden fluoreszenzoptisch identifiziert (90 %), alle zehn radioaktiv (100 %), nur acht (80 %) mittels ICG-Grünfärbung bzw. Patenblau-Markierung. Transdermal wurde ein SLN dargestellt (10 %). In Korrelation zum BMI waren höhere ICG-Mengen, bis zu 2,5 mg intrakutan absolut, in der Darstellung der Lymphbahnen von Vorteil. SCHLUSSFOLGERUNGEN: Die SLN-Fluoreszenzmarkierung mit dem ICG/NIR-Kamera-System "FOVIS" stellt eine sichere Alternative zur Farbstoffmethode mit Patentblau ergänzend zur Radiokolloidmethode mit Technetium-99m dar. Weitere Studien zur optimalen Dosierung von ICG und transdermalen Bildgebung in Relation zum BMI sind notwendig.

Indocyanine green-assisted sentinel lymph node biopsy in melanoma using the "FOVIS" system.

BACKGROUND: Metastatic involvement of the sentinel lymph node (SLN) represents a key prognostic factor in melanoma. The combined use of a radiocolloid (technetium-99m) and blue dye is the gold standard in sentinel lymph node biopsy (SLNB). In this context, near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) has been suggested as an alternative. The objective of the present study was to examine the potential advantages of fluorescence-guided SLNB - compared to the conventional method - with respect to the visualization of lymphatic drainage pathways and the SLN. Particular focus was on the impact of the ICG dose used and the body mass index (BMI). PATIENTS AND METHODS: The study included ten patients who underwent the SLNB procedure using technetium-99m, blue dye, and ICG. Real-time fluorescence imaging of lymphatic drainage pathways and the SLN was done using the "FOVIS"-NIR system. Depending on the quality of the images achieved, ICG was intradermally administered at a dose ranging from 0.25 to 2.5 mg. RESULTS: Nine SLNs were identified by fluorescence (90 %); (100 %) ten, by gamma probe; eight (80 %), by ICG or blue dye. Transdermal SLN detection was possible in one case (10 %). In correlation to the BMI, higher intradermal ICG doses - up to 2.5 mg overall - proved to be advantageous in the visualization of lymphatic vessels. CONCLUSIONS: Supplementing the technetium-99m method, fluorescence SLNB using ICG and the "FOVIS"-NIR system is a safe alternative to the blue-dye technique. Further studies on the optimal ICG dose and transdermal imaging in correlation to the BMI are required.

Kinetic Profile of Inflammation Markers in Human Skin In vivo Following Exposure to Ultraviolet B Indicates Synchronic Release of Cytokines and Prostanoids.

Ultraviolet B (UVB) irradiation affects epidermal cells, which respond via a cascade of inflammation markers. After initial in vitro and ex vivo experiments, this study used cutaneous microdialysis to generate a kinetic profile for 16 cytokines and 4 prostanoids in human skin in vivo. Skin areas 9 cm2 were irradiated with UVB (2× minimal erythematous dose) 16 h after catheter placement in the dermis of the volar forearms of healthy volunteers. Dialysates were collected at 4-h intervals up to 64 h and analysed for 5- and 8-iso-PGF2α, 9α,11α-PGF2α and PGE2 by gas chromatography-mass spectrometry (GC/MS). Dialysates were also analysed for interleukin (IL)-1ß, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-α, Fas ligand (FasL), interferon-γ-inducible protein-10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), RANTES, eotaxin, and granulocyte-macrophage colony-stimulating factor (GM-CSF) using a multiplex-based cytometric-bead-array. In conclusion, 3 peaks with synchronic release of T helper (TH) 1-directed inflammatory cytokines and prostanoids could be detected post-UVB: an early phase (4-12 h), an intermediate phase (16-24 h) and a late phase (32-40 h). A TH2-directed cytokine response was detectable at intermediate and late phases.

Effects of Topical Tacrolimus and Polyunsaturated Fatty Acids on In Vivo Release of Eicosanoids in Atopic Dermatitis During Dermal Microdialysis.

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease with release of distinct inflammatory signals. This study investigated the presence of eicosanoids in AD skin and the effect of topical agents with potential to suppress inflammation. Twelve patients with moderate AD received topical treatment on either arm with tacrolimus 0.1% ointment or a lotion containing 12% ω-6 fatty acids (polyunsaturated fatty acids; PUFA) twice daily for 5 consecutive days. Interstitial fluid was collected in vivo via dermal microdialysis from 4 defined skin areas: lesional, non-lesional and topically treated skin (tacrolimus or PUFA). Markers of oxidative stress (F2-isoprostanes; 5- and 8-prostaglandin F2α) and inflammation (9α,11α-prostaglandin F2α; and prostaglandin E2) were determined by gas chromatography-mass spectrometry. All eicosanoid levels were reduced in non-lesional and tacrolimus-treated skin. A significant reduction was observed in total F2-isoprostanes; 9α,11α-prostaglandin F2α; and prostaglandin E2 in non-lesional skin and in 9α,11α-prostaglandin F2α in tacrolimus-treated compared with untreated AD skin. In conclusion, treatment with tacrolimus compared with PUFA appears to suppress eicosanoids more efficiently in AD skin.

Verantwortlicher Umgang mit Antibiotika: Notwendigkeit der Antibiotikareduktion in der Aknetherapie.

Der übermäßige oder unkritische weltweite Einsatz von Antibiotika in der Medizin hat die Ausbreitung von Antibiotikaresistenzen beschleunigt. In einigen Bereichen sind viele Antibiotika bei bakteriellen Infektionen, die zuvor noch gut auf antibakterielle Wirkstoffe reagierten, mittlerweile wirkungslos geworden. Dermatologen/Venerologen setzten orale und topische Antibiotika bei der Behandlung von Acne vulgaris routinemäßig ein, obwohl Akne weder eine infektiöse Erkrankung ist noch alleine durch das Propionibacterium getriggert wird. Vielmehr ist sie eine komplexe, chronische entzündliche Hauterkrankung, die durch verschiedene pathogenetische Faktoren wie follikuläre Hyperkeratose, erhöhter Sebumproduktion, bakterielle Proliferation und Entzündung zustande kommt. Folglich sollte eine erfolgreiche Therapie auf die Bekämpfung verschiedener pathogenetischer Faktoren und nicht nur auf die von Propionibacterium acnes abzielen. Daher wurden topische Retinoide und Benzoylperoxid als Mittel der ersten Wahl definiert. Monotherapien mit lokalen Antibiotika sollten insgesamt vermieden werden. Systemische Antibiotika der Tetrazyklin-Gruppe haben bei bestimmen Krankheitsstadien ihren Sinn, ihre Wirkung könnte aber eher auf der antientzündlichen als auf der antibiotischen Reaktion beruhen. Gesundheitsbehörden ermahnen alle Gesundheitsdienstleister, den Einsatz von Antibiotika einzuschränken. Das Nutzen-Risiko-Verhältnis muss bei der Entscheidung für oder gegen eine antibiotische Therapie bei einem einzelnen Patienten immer auch in Bezug auf das öffentliche Interesse am Erhalt der Wirksamkeit von Antibiotika abgewogen werden. Im Folgenden werden das aktuelle Krankheitskonzept zu Acne vulgaris und die sich daraus ableitenden Konsequenzen für den Einsatz von Antibiotika vorgestellt.

S1-Guidelines on UV phototherapy and photochemotherapy.

Known in part since antiquity, the salutary effects of sunlight again garnered increasing attention in the second half of the 19(th) century. The development of a device for ultraviolet irradiation of cutaneous tuberculosis by Finnsen at the onset of the twentieth century truly marked the beginning of modern phototherapy. In dermatology, treatment methods almost exclusively use wavelengths below the visible light range (ultraviolet light). Since the early 1970s, increasingly powerful artificial light sources have become available for UVB and UVA therapy as well as the combination of UVA and photosensitizers (photochemotherapy). High structural and procedural quality standards are an essential prerequisite for the implementation of effective as well as safe phototherapy. The following guidelines outline the current consensus of leading experts in the field of phototherapy with respect to indications, contraindications, and side effects of various treatment options available. Particular focus is also on adequate UV doses at the beginning and over the further course of treatment as well as on management of side effects.

S1-Leitlinie zur UV-Phototherapie und Photochemotherapie.

Die heilsame Wirkung des Sonnenlichts war teilweise schon im Altertum bekannt und fand in der zweiten Hälfte des 19. Jahrhunderts wieder zunehmend Beachtung. Den Beginn der modernen Phototherapien markiert die Entwicklung einer Apparatur zur ultravioletten Bestrahlung der Hauttuberkulose durch Finnsen zu Beginn des zwanzigsten Jahrhunderts. Zur Therapie von Hauterkrankungen finden beinahe ausschließlich die spektralen Bereiche unterhalb des sichtbaren Lichtes (ultraviolett) Anwendung. Seit den 1970er Jahren stehen zunehmend leistungsfähige künstliche Strahlenquellen bereit für die Therapie mit UVB, UVA und die Kombination von UVA mit Photosensibilisatoren (Photochemotherapie). Hohe strukturelle und prozedurale Qualitätsstandards sind unabdingbare Voraussetzung für die Durchführung einer gleichermaßen wirkungsvollen wie auch sicheren Phototherapie. Die Leitlinie formuliert den aktuellen Konsens führender Experten auf dem Gebiet der Phototherapie in Bezug auf die Indikationen für die jeweiligen Therapieverfahren, deren Gegenanzeigen und Nebenwirkungen und insbesondere für die Wahl der korrekten Dosis zu Beginn und im Verlauf einer Therapie sowie das Management von Nebenwirkungen.

Aetiology, comorbidities and cofactors of chronic leg ulcers: retrospective evaluation of 1 000 patients from 10 specialised dermatological wound care centers in Germany.

Numerous comorbidities and cofactors have been known to influence wound healing processes. In this multicentre study, clinical data of 1 000 patients with chronic leg ulcers from ten specialised dermatological wound care centers were analysed. The patient cohort comprised 567 females and 433 males with an average age of 69·9 years. The wounds persisted on average for 40·8 months and had a mean size of 43·7 cm(2) . Venous leg ulcers represented the most common entity accounting for 51·3% of all chronic wounds, followed by mixed-type ulcers in 12·9% and arterial ulcerations in 11·0% of the patients. Vasculitis was diagnosed in 4·5%, trauma in 3·2%, pyoderma gangrenosum in 2·8%, lymphoedema in 1·7%, neoplasia in 1·0% and delayed post-surgical wound healing in 0·6% of the included patients. In total, 70·5% of patients suffered from arterial hypertension, 45·2% were obese, 27·2% had non-insulin dependent diabetes, and 24·4% dyslipidaemia. Altogether 18·4% suffered from metabolic syndrome. Cofactors and comorbidities of patients with chronic leg ulcers have previously been studied but not in detail. Here, we were able to demonstrate the existence of several potentially relevant cofactors, comorbidities of their associations and geographical distributions, which should be routinely examined in patients with chronic leg ulcers and - if possible - treated.

Pimecrolimus in atopic dermatitis: consensus on safety and the need to allow use in infants.

Atopic dermatitis (AD) is a distressing dermatological disease, which is highly prevalent during infancy, can persist into later life and requires long-term management with anti-inflammatory compounds. The introduction of the topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, more than 10 yr ago was a major breakthrough for the topical anti-inflammatory treatment of AD. Pimecrolimus 1% is approved for second-line use in children (≥2 yr old) and adults with mild-to-moderate AD. The age restriction was emphasized in a boxed warning added by the FDA in January 2006, which also highlights the lack of long-term safety data and the theoretical risk of skin malignancy and lymphoma. Since then, pimecrolimus has been extensively investigated in short- and long-term studies including over 4000 infants (<2 yr old). These studies showed that pimecrolimus effectively treats AD in infants, with sustained improvement with long-term intermittent use. Unlike topical corticosteroids, long-term TCI use does not carry the risks of skin atrophy, impaired epidermal barrier function or enhanced percutaneous absorption, and so is suitable for AD treatment especially in sensitive skin areas. Most importantly, the studies of pimecrolimus in infants provided no evidence for systemic immunosuppression, and a comprehensive body of evidence from clinical studies, post-marketing surveillance and epidemiological investigations does not support potential safety concerns. In conclusion, the authors consider that the labelling restrictions regarding the use of pimecrolimus in infants are no longer justified and recommend that the validity of the boxed warning for TCIs should be reconsidered.

Efficacy of adapalene/benzoyl peroxide combination in moderate inflammatory acne and its impact on patient adherence.

BACKGROUND AND OBJECTIVES: Adapalene 0.1 %/benzoyl peroxide (BPO) 2.5 % (Epiduo®) is the first, fixed-dose topical combination gel developed for the once-daily treatment of acne. The objective of this observational study was to assess efficacy and patient adherence under daily clinical practice conditions in a large population of young adults and adolescents (12 to 20 years) with moderate inflammatory acne. PATIENTS AND METHODS: A total of 2 780 patients receiving adapalene-BPO were evaluated in this multicenter, open-label, prospective non-interventional observational study. Observation time per patient was approximately 12 weeks. Assessment parameters included changes in acne severity, treatment success, safety, and therapeutic adherence. RESULTS: After 12 weeks, the majority of patients (91.5 %) showed improvement of acne under adapalene-BPO treatment, with an initial therapeutic response noted after a median time of 14 days. Overall, 21.8 % of participants displayed complete resolution of visible acne lesions. Treatment adherence was assessed as good in 63.2 % of patients. The majority of individuals (69.5 %) experienced no or only mild local skin irritations. No serious adverse drug reactions (ADR) were reported during the course of the study. CONCLUSIONS: Adapalene-BPO is effective and safe in the treatment of moderate inflammatory acne. The fixed-dose combination and easy application simplifies the therapeutic regimen, leading to good treatment adherence in the majority of patients.