Targeting JAK/STAT signalling in inflammatory skin diseases with small molecule inhibitors.

For most inflammatory skin diseases topical glucocorticosteroids and traditional oral immunosuppressive drugs remain the principle treatment choices, but this has started to change. A deeper understanding in individual disease pathogenesis, basic immune mechanisms and molecular signalling pathways, together with advances in pharmaceutical drug development, allow us to interfere more precisely with disease-related factors. Some examples of inflammation-controlling interventions include antibodies neutralizing disease-associated cytokines, and small molecules targeting intracellular pathways relevant to cytokine production or cytokine signalling. So far, this is best established for psoriasis, an inflammatory skin disease dominated by Th17 cytokines. In this review, we focus on chronic inflammatory skin diseases where cytokines using type I/II cytokine receptors play a dominant role in disease pathogenesis and where novel treatments with inhibitors of the JAK/STAT pathway are already under clinical investigation. To better understand the rationale of using JAK/STAT inhibitors in the discussed skin diseases, we give an overview of important genetic and immunological associations with the JAK/STAT pathway and summarize the stage of clinical development of small molecular inhibitors. JAK/STAT inhibitors will presumably find wide application in dermatology, since they can be applied not only systematically but also topically for the treatment of inflammatory skin diseases.

Patterns of infiltration and local recurrences of various types of cutaneous sarcomas following three-dimensional histology.

BACKGROUND: Cutaneous sarcomas are rare and characterized by pathogenetic heterogeneity. Knowledge about local infiltration patterns and recurrence rates may be useful in improving patient care and outcomes. The objective of the present study was to compare these two characteristics in sarcomas that had been treated using the identical surgical procedure. PATIENTS AND METHODS: Between 2006-2010, 84 patients with various types of sarcoma underwent surgery followed by three-dimensional histology. Tumor entities included dermatofibrosarcoma protuberans (DFSP, 54 patients), leiomyosarcoma (ten patients), rhabdomyosarcoma (one patient), angiosarcoma (seven patients) as well as atypical fibroxanthoma (AFX, three patients) and cutaneous undifferentiated pleomorphic sarcoma (UPS, nine patients). Median follow-up was four years (range: 2-6 years). RESULTS: Local recurrence rates among patients with primary DFSP were 2.2 %. All patients undergoing re-excision were subsequently tumor free. Patients with leiomyosarcoma, rhabdomyosarcoma, AFX, and cutaneous UPS experienced no local recurrence; however, one individual developed in-transit metastasis (UPS) (8.3 %). Three patients with angiosarcoma developed local recurrence (43 %), two of whom remained tumor free following re-excision. Two angiosarcoma patients died from distant metastases (29 %). Both DFSP and especially angiosarcoma lesions exhibited extensive subclinical growth. CONCLUSIONS: Recurrence rates of cutaneous sarcomas following three-dimensional histology are low. Local recurrences are readily manageable by re-excision. Angiosarcoma is characterized by extensive superficial growth, aggressive biological behavior, and predominantly hematogenous spread.

Combination of ultra-low-dose isotretinoin and antihistamines in treating Morbihan disease - a new long-term approach with excellent results and a minimum of side effects.

Morbihan disease is characterized by erythema and solid edema in the two upper thirds of the face. Underlying factors are an imbalance in lymphatic drainage, chronic inflammation, and mast cells leading to fibrosis. Treatment options known thus far have led to unsatisfactory results and have often been associated with a greater risk of side effects; even invasive options have been applied. This study presents four patients treated with a combination of ultra-low-dose isotretinoin and antihistamines for a mean duration of 14 months. While no side effects other than dryness of the lips were noted, a significant reduction of the erythema and edema could be observed in all patients. Specialists evaluated the treatment's success by photodocumentation and measured a 91.5% alleviation of erythema, and 85% reduction of edema, respectively. Based on these results, this new regimen in the therapeutic approach toward Morbihan disease is suggested due to its anti-inflammatory features and low risk of side effects.