Dorothea Terhorst

The Role of Toll-Like Receptors in Host Defenses and Their Relevance to Dermatologic Diseases

The family of toll-like receptors (TLRs) plays a central role in the cutaneous immune defense system. To date, different TLRs have been found on several major cell populations of the skin, such as keratinocytes, fibroblasts, antigen-presenting cells, and melanocytes.Activation of TLRs leads, via different intracellular signaling pathways, to the production of pro-inflammatory stimuli, and is considered a danger signal that should transform the skin in to the functional state of defense. However, TLRs have also been implicated in tissue homeostasis and renewal.Within the group of TLRs, two types have been identified: surface-expressed TLRs, which are predominantly active against bacterial cell wall compounds; and intracellular receptors, which preferentially recognize virus-associated pattern molecules. In addition, surface-expressed receptors trigger phagocytotic and maturation signals, while the intracellular TLRs lead to the induction of antiviral genes.Our review aims to outline the importance of TLRs in the pathogenesis of numerous skin diseases and the potential of TLR agonists as a treatment option for various skin diseases.

sentinel lymph node biopsy and risk factors for predicting metastasis in cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) is a common cancer capable of metastasis. Sentinel lymph node biopsy (SLNB) may be a valuable adjunct for patients with cSCC at high risk for metastasis. However, data on risk factors for metastasis and results of SLNB from patients with cSCC are limited.

Long-term outcome of intravenous therapy with rituximab in patients with primary cutaneous B-cell lymphomas.

The monoclonal antibody rituximab directed against the B‐cell antigen CD20 was approved for the treatment of B‐cell lymphomas and maintenance therapy in follicular lymphomas more than a decade ago. However, median follow‐up in case series of intravenous rituximab therapy in primary cutaneous B‐cell lymphomas (CBCL) lasts only up to 3 years. We retrospectively analysed a cohort of CBCL patients treated with rituximab to gain more long term information.

Applicability of confocal laser scanning microscopy for evaluation and monitoring of cutaneous wound healing

There is a high demand for noninvasive imaging techniques for wound assessment. In vivo reflectance confocal laser scanning microscopy (CLSM) represents an innovative optical technique for noninvasive evaluation of normal and diseased skin in vivo at near cellular resolution. This study was designed to test the feasibility of CLSM for noninvasive analysis of cutaneous wound healing in 15 patients (7 male/8 female), including acute and chronic, superficial and deep dermal skin wounds. A commercially available CLSM system was used for the assessment of wound bed and wound margins in order to obtain descriptive cellular and morphological parameters of cutaneous wound repair noninvasively and over time. CLSM was able to visualize features of cutaneous wound repair in epidermal and superficial dermal wounds, including aspects of inflammation, neovascularisation, and tissue remodelling in vivo. Limitations include the lack of mechanic fixation of the optical system on moist surfaces restricting the analysis of chronic skin wounds to the wound margins, as well as a limited optical resolution in areas of significant slough formation. By describing CLSM features of cutaneous inflammation, vascularisation, and epithelialisation, the findings of this study support the role of CLSM in modern wound research and management.

Reflectance confocal microscopy for the evaluation of acute epidermal wound healing.

The dynamic process of wound healing is routinely evaluated by clinical or histological evaluation. Recently, a number of non‐invasive imaging techniques have been evaluated for their clinical applicability in dermatology. Among them, reflectance confocal microscopy (RCM) represents a non‐invasive imaging technique that allows the in vivo characterization of the skin at near‐histological resolution. The aim of this study was to monitor epidermal wound repair using RCM in a model of tissue damage induced by cryosurgery. For this purpose, contact cryosurgery was performed at −32 °C for 10 seconds on the volar forearm of five healthy volunteers. Clinical and RCM evaluations were performed at nine consecutive time points. RCM allowed the visualization of edema formation and blood vessel dilatation immediately after cryosurgery, as well as morphologic features of wound repair, including the formation of finger‐like protusions of keratinocytes into the wound bed, the appearance of hairpin‐like vessels, and inflammatory cells. This pilot study illustrates that RCM represents a promising technique for quasi‐real‐time monitoring the kinetics of wound repair non‐invasively and over time, thus offering new insights into in vivo processes of cutaneous wound repair and angiogenesis, as well as potential effects of topically applied drugs on the process of tissue repair.

Evaluation of different methods in the follow-up of patients with indolent types of primary cutaneous lymphomas

Background  Primary cutaneous lymphomas (CLs) are a heterogeneous group of diseases arising from B or T lymphocytes. CLs are grouped according to their clinical behaviour into indolent, intermediate and aggressive types. Indolent CLs respond well to therapy but frequently relapse, resulting in prolonged periods of follow‐up.

Treatment of indolent primary cutaneous B-cell lymphomas with subcutaneous interferon-alfa

BACKGROUND Interferon-alfa is used in the treatment of primary cutaneous B-cell lymphoma (PCBCL). Therapy with interferon-alfa has thus far been reported solely in case reports and small case series, mostly describing intralesional use. OBJECTIVE We sought to evaluate efficacy, response rate, time to response, duration of response, and safety of subcutaneously administered interferon-alfa for the treatment of cutaneous B-cell lymphoma. METHODS We conducted a retrospective chart analysis of patients given the diagnosis of PCBCL and treated with interferon-alfa subcutaneously at a tertiary referral center. RESULTS Fifteen patients with indolent subtypes of PCBCL were identified. The overall response rate was 66.7%; all responding patients went into complete remission. Response was not significantly associated with the maximum tolerated dose. Within the median follow-up time of 40 months, 90% of the responders experienced a relapse; median duration of response was 15.5 months. Adverse events were predominantly mild and in no case led to cessation of therapy. LIMITATIONS Retrospective nature of the analysis and small number of patients because of scarcity of the disease are limitations. CONCLUSION Treatment of indolent PCBCL with subcutaneously injected interferon-alfa demonstrated good response rates and tolerability. Response was not dose dependent. Relapses were observed in nearly all responding patients raising the question of interferon-alfa maintenance therapy in PCBCL.

Evaluation of blood parameters for the monitoring of erythrodermic cutaneous T‐cell lymphoma

Erythrodermic cutaneous T‐cell lymphomas are aggressive diseases posing diagnostic and therapeutic challenges. Numerous indicators for confirming diagnosis and disease‐monitoring have been proposed. CD26‐negativity of peripheral CD4+ T‐cells has been reported to have these properties. Our aim was to test, if the CD4+ T‐cell count, fraction of CD26‐ or CD7‐negative CD4+ T‐cells during the course of disease are valuable markers to predict therapeutic efficacy or disease progression in relation to changes in skin status.

Leishmaniasis: A Reminder in the Face of Forgotten Travel

Figure 2. Dermal lymphohistiocytic infiltrate with typical plasma cells (arrows). A 10-year old boy presented with a slowly growing (over 1 year) painless nodule on his left temple, pre-existing for 1 year (Figure 1). His general health was excellent; travel outside Germany was denied. The skin biopsy showed a diffuse granulomatous dermatitis mainly composed of epitheloid cells, and occasional multinucleated foreign body type giant cells. A granulomatous foreign body reaction after a ruptured epidermal cyst was diagnosed. After ineffective topical corticosteroid therapy, the first of a scheduled sequential excision was done. This specimen once more showed epitheloid granulomas now consuming the whole dermis. However, in contrast to the first biopsy, plasma cells were now spotted within the lymphohistiocytic infiltrate that prompted us to re-evaluate the diagnosis (Figure 2). Investigations for Borrelia and Mycobacteria were negative, but polymerase chain reaction revealed the presence of Leishmania donovani complex DNA. After confronting the patient and his mother with this result, the boy recalled a 2-week journey to a rural area near Barcelona, Spain, approximately 1 year before the skin lesion had occurred, thus, pointing at Leishmania infantum as the culprit infectious agent. Laboratory tests, clinical, and ultrasound investigations did not reveal any signs of systemic disease. Consequently, cutaneous leishmaniasis was diagnosed and topical 15% paromomycin/12% methylbenzethonium chloride in white petrolatum treatment under occlusion was initiated. After 2 months of treatment, the lesion completely resolved, leaving an atrophic scar.

In chronic spontaneous urticaria, high numbers of dermal endothelial cells, but not mast cells, are linked to recurrent angio‐oedema

Chronic spontaneous urticaria (CSU) is an inflammatory skin disorder characterized by recurrent weals, angio‐oedema or both. Recent studies have shown that the number of endothelial cells is increased in the skin of patients with CSU, but the underlying mechanisms and clinical implications of this are unclear.