Psoriasis is a Th17-mediated chronic inflammatory skin disease with aberrant keratinocyte proliferation and differentiation. Th17 cytokines like IL-17, IL-22 and IL-23 are critically involved in psoriasis pathogenesis that results in epidermal thickening and production of innate factors such as antimicrobial peptides. Topical treatment of psoriasis with anthralin is highly effective although the exact mode of action of this drug in psoriasis is not fully understood. We aimed to study the direct effects of anthralin on keratinocyte proliferation, differentiation and production of innate factors like antimicrobial factors. To test the effects of anthralin we used (1) primary keratinocytes, (2) a 3D psoriasis tissue models and (3) skin biopsies from patients treated with anthralin. In addition we studied the effects of anthralin in monolayer and multilayer keratinocyte cultures stimulated with IL-17A and IL-22. Anthralin directly induced cell apoptosis in vitro in monolayer cultures but not in multilayer cultures treated with IL-17A and IL-22. Yet, keratinocyte proliferation was impaired by anthralin in vitro and in vivo. In lesional skin anthralin rapidly normalized cytokeratin (CK)16 expression. Moreover, anthralin suppressed DEFB4 expression in vitro and in vivo, while other antimicrobial peptides and innate cytokines studied like IL-6 and IL-8 were regulated differently in vitro and in vivo. Taken together anthralin has direct effects on keratinocytes beyond the impairment of proliferation. CK16 and DEFB4 expression by keratinocytes were both suppressed by anthralin.

BackgroundEarly paediatric dermatosurgery reveals excellent cosmetic results due to high skin elasticity and pronounced capacity to recover from trauma. Furthermore, the size of skin lesions increases during life proportionally to skin growth and therefore early removal is of major importance. Selected local anaesthetics like prilocaine can cause methaemoglobinemia. However, in contrast to general anaesthesia, many other local anaesthetics do not bare any major risks for infants. ObjectiveIn this retrospective study, we analysed infants aged less than 7months receiving tumescent local anaesthesia (TLA) followed by dermatosurgery at our department between 2005 and 2015. The analysis is mainly based on our records. Additional information for a subset of patients was gained by a postoperative survey. MethodsNinety-two infants (39 male, 53 female) with a median age of 4.2months (range: 1.5months; 6.7months) were included in this study. Additional postoperative information was available for 33 of the 92 studied patients (35%). ResultsInfants were mainly operated for removal of a melanocytic naevus (n=54), followed by haemangioma (n=23), naevus sebaceous (n=6) and other lesions (n=9). The lesions were located on the scalp or neck (n=31), on the extremities (n=31), on the trunk (n=21), in the face (n=6) or on the buttocks (n=3). The median size of excision was 509mm(2) (range: 16mm(2); 3600mm(2)). Primary defect closure was performed by intracutaneous (n=68) or extracutaneous (n=24) suture techniques. No side-effects of local anaesthesia were observed in any patient. Postoperative complications include pain (1/33; 3%), wound-healing disorder (1/33; 3%) and visible severe scarring (2/33; 6%). ConclusionsThe combination of TLA and dermatosurgery in infants is a suitable outpatient treatment option for small lesions without any major risks or side-effects and the benefit of prolonged postoperative analgesia.

Einleitung: Aufgrund steigender Inzidenzraten von Hautkrebs besteht die dringende Notwendigkeit für eine schnelle, zuverlässige und kosteneffiziente Therapie. In der mikroskopisch kontrollierten Chirurgie (MKC) werden die lückenlosen Exzisatschnittränder an Gefrier- oder Paraffinschnitten untersucht. Neuere Verfahren sind die ex vivo konfokale Laser-Scanning-Mikroskopie und optische Kohärenztomografie, welche im Prinzip optische Schnitte erstellen. Im Gegensatz dazu wird bei der „Rapid Lump Examination“ (RLE) das native Tumorgewebe bzw. die Tumorränder unmittelbar mikroskopisch betrachtet. In einer Pilotstudie zeigte die RLE eine hohe Sensitivität und Spezifität.

Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) rarely express T-cell-associated antigens (TCA), but the clinical significance of this finding is uncertain. Fifty cHLs expressing any TCA on the HRS cells (TCA-cHL) were identified in two cohorts (National Cancer Institute, n = 38; Basel, n = 12). Diagnostic pathology data were examined in all cases with additional T-cell receptor γ rearrangements (TRG@) polymerase chain reaction (PCR) in a subset of cases. The outcome data were compared with a cohort of cHLs negative for TCA (n = 272). Primary end points examined were event-free survival (EFS) and overall survival (OS). The median age in the TCA-cHL group was 40 years (range, 10-85 years). Seventy percent presented in low stage (stage I/II) at presentation with nodular sclerosis (NS) histology predominating in 80% of cases. Among the TCA, CD4 and CD2 were most commonly expressed, seen in 80.4% and 77.4% of cases, respectively. TRG@ PCR was negative for clonal rearrangements in 29 of 31 cases. During a median follow up of 113 months, TCA expression predicted shorter OS (adjusted hazard ratio [HRadj] = 3.32 [95% confidence interval (CI): 1.61, 6.84]; P = .001) and EFS (HRadj = 2.55 [95% CI: 1.45, 4.49]; P = .001). TCA-cHL often display NS histology, lack T-cell genotype, and are independently associated with significantly shorter OS and EFS compared with TCA-negative cHLs.

An association between classical Hodgkin lymphoma (cHL) and mycosis fungoides (MF) or lymphomatoid papulosis has been reported in the literature. However, there can be considerable morphologic and immunophenotypic overlap between cHL and nodal involvement by CD30-positive T-cell lymphoproliferative disorders (CD30-T-LPD). To examine this potential association, biopsies from patients with a history of MF or primary cutaneous CD30-T-LPD and lymph node biopsies reported as either CD30-positive T-cell lymphoma (TCL) with Hodgkin-like cells or cHL were retrieved from the authors' institution. Of 11 cases identified, 10 were considered CD30-positive TCL with Hodgkin-like cells, whereas 1 was confirmed as cHL upon review. Five cases originally diagnosed as cHL were revised as CD30-positive TCL. Cases of CD30-positive TCL with Hodgkin-like cells showed a male predominance (M:F, 4:1) with a median age of 53 years (range, 44 to 72 y). Nearly all patients (9/10) initially presented with skin lesions. In 7/10 patients the draining lymph node was involved, whereas in 3 cases this could not be confirmed. Tumor cells morphologically resembled Hodgkin/Reed-Sternberg cells; they were uniformly strongly positive for CD30, and CD15 was expressed in 9/10 (90%) cases. A T-cell derivation was confirmed by T-cell antigen expression (7/10) and clonal rearrangement of T-cell receptor genes (9/10). In 3 cases a common T-cell clone was identified in skin and lymph node. B-cell markers (CD20/PAX5) were consistently negative. In 1 case the diagnosis of cHL followed by lymphomatoid papulosis was confirmed, with Hodgkin/Reed-Sternberg cells expressing PAX5, CD30, and CD15. In situ hybridization studies for Epstein Barr virus were negative. We show that cHL is less often associated with MF and primary cutaneous CD30-T-LPD than previously thought and that the coexpression of CD30 and CD15 in these TCLs may lead to a mistaken diagnosis of cHL.