Tacrolimus: the drug for the turn of the millennium?

BACKGROUND: Tacrolimus has been shown to be a powerful suppressor of the immune system. It was introduced into clinical use to prevent allograft rejection and is now routinely used in kidney, liver, and heart transplantation. Recently, 2 double-blind multicenter studies demonstrated the therapeutic efficacy of topical and systemic tacrolimus in the inflammatory skin diseases atopic dermatitis and psoriasis. DATA SOURCE: MEDLINE was searched for relevant publications and combined with our own clinical, in vitro, and in vivo studies. STUDY SELECTION: All studies dealing with tacrolimus and dermatology were reviewed. DATA EXTRACTION: Publications with clinically relevant data were included in this review. CONCLUSIONS: Topical tacrolimus is a safe and effective therapeutic agent that may open a new era in the treatment of inflammatory skin diseases, particularly for patients with atopic dermatitis. Before its full potential in dermatology can be assessed, more clinical experience in treating children and comparison with the criterion standard of anti-inflammatory therapy, glucocorticosteroids, are needed.     

Is baldness bad for the heart?

Various skin conditions are considered to be characteristic markers for elevated coronary disease risk. Over and above these established signs there are reports on other skin signs with possible associations with elevated coronary disease risk, i.e. the horizontal earlobe crease, high breast hair density, precocious graying and male pattern hair loss. A review of the literature is presented in this article, and the relevance of these symptoms is discussed as they are related to the possible myocardial disease risk. The available data on this topic are impressive, but on close assessment most of the studies are marred by methodical errors.     

What is the most promising strategy for the treatment of metastasizing melanoma?

The treatment of patients with metastasizing melanoma, still one of the most deadly diseases in modern medicine, ranks among the greatest challenges that a clinician has to face. Metastatic melanoma also is one of the most profound sources of clinical frustration, since it provides far more ultimately defeating experiences than clinical victories. At the same time, the fascinating biology of melanoma has invited the study of this neuroectodermal tumor as a model system for dissecting many of the key problems of modern oncology, ranging from molecular oncogenesis via the controls of tumor proliferation, apoptosis, invasion, metastasis, and angiogenesis to tumor immunosurveillance and tumor drug resistance. Together with the dire need to develop more effective treatment modalities for improving both life expectancy and quality of life of affected patients, this has made metastatic melanoma a favorite model for the exploration of innovative strategies for tumor management. Encouragingly, many of these have already generated very promising results in animal models. However, this impressive level of research progress in conquering melanoma in the animal room contrasts rather pitifully with the actual progress made on the ward. This CONTROVERSIES feature, therefore, critically and soberly reviews the state of the art of treating metastatic melanoma today (distinguishing between nodal and distant metastases), and sharply defines unresolved or comparatively neglected key problems. In addition, this feature highlights several novel, provocative, hitherto underappreciated, yet potentially promising treatment approaches that deserve systematic exploration. Hopefully, this will offer further inspiration for the design and pursuit of innovative anti-melanoma strategies off-the-beaten-track.     

Are combined same-day treatments the future for photorejuvenation?

Background: Skin rejuvenation requires a treatment combination including lasers, intense pulsed light (IPL), radiofrequency, botulinum toxin (BT) and fillers. A combined approach is considered optimum but usually same-day combined treatments are avoid and lasers are performed prior to filler or toxin injections owing to the concern that the light may inactivate or degrade them. Objective: To review the literature on the use of combination treatments with radiofrequency, IPL, non ablative and ablative lasers plus fillers or BT. Results: review of the literature identified 15 studies of combination treatments: three of them on animal models and 12 were clinical studies. Seven studies contained combined light system treatments with fillers and eight studies combined physical therapies with botulinum toxin injection. In all of them treatments were used as standard protocols. Six studies documented no histological changes in fillers injected after applying radiofrequency, IPL or laser treatments and one studied documented improvement in collagen after IPL treatment and toxin injection. These studies reported clinical improvement in various features of photodamaged skin, no increase of adverse effects and neither decrease on efficacy of substances injected. Conclusions: review of the literature demonstrates safety of same day combined treatments for rejuvenation, which improve clinical results, are more comfortable for patients have no loss of efficacy or other apparent adverse effect.     

How adequate is adequate for the collection of endocervical specimens for Chlamydia trachomatis testing?

BACKGROUND: Endocervical specimen adequacy has been assessed by subjective criteria that are based on arbitrarily chosen thresholds for the presence of target cells observed on microscopic slide examinations. GOAL OF THIS STUDY: To assess the relationship of chlamydia test positivity to specimen adequacy with the use of a semi-quantitative cytologic staining method for assessing endocervical specimen collection cellularity. STUDY DESIGN: Endocervical specimens for chlamydia testing (PACE 2, GenProbe, San Diego, CA) and for a slide cytologic examination (n = 3,500) were collected in parallel. A semi-quantitative cytologic examination to determine a specimen adequacy (SA) score was performed for every chlamydia-positive result (n = 163) and approximately every fifth negative result (n = 626). The Chi-square test for linear trends was used to assess the relationship between SA scores and chlamydia positivity. The median SA scores for chlamydia-positive and negative slides were compared. RESULTS: The median SA scores for chlamydia-positive and -negative slides were 27 and 20, respectively (P < 0.001). Chlamydia positivity rates increased with increasing specimen adequacy scores (0-9, 2.7%; 10-19, 15.1%; 20-29, 24.8%; and 30-45, 31.3%; Chi-square for linear trend: P < 0.001). CONCLUSION: These results demonstrate a linear relationship between the numbers of cells observed on an endocervical smear and chlamydia positivity rather than the threshold concept in practice. The semiquantitative cytologic technique offers an objective method for further evaluating specimen adequacy for Chlamydia trachomatis testing.     

Optimising the design of a broad‐band light source for the treatment of skin

Phototherapy has become a treatment of choice in many areas of medicine. Light can be used to deliver energy to tissue selectively targeting specific structures in order to induce the desired therapeutic outcome. The choice of optical parameters for a specific application is not simple. Wavelength, energy, exposure time and fluence can be varied and induce a wide range of tissue effects. The treatment of the skin with light is probably the one phototherapy application that is most developed in terms of technology and market maturity. White light systems are extensively used to address a range of skin conditions. However, different conditions have different physiology and hence require differing optical parameters. The technology standard is based upon systems, which have a number of different optical filters allowing the output to be tailored to the specific application. This paper discusses the advantages of a diferent type of system, namely the iPulse i300 (Cyden Ltd, Swansea, UK), which uses a single dichroic reflectance filter and whose optical output is changed by varying other parameters in a carefully controlled manner.     

What are the most promising strategies for the therapeutic immunomodulation of allergic diseases?Note

Abstract: Specific immunotherapy and other immunomodulatory strategies have long been a stronghold in the management of allergic diseases. In particular, “immunodeviation‐therapy” or “vaccination for allergies”, i.e. the redirection of Th2‐type immune responses towards a Th1‐response pattern, has become an ever more popular concept. The present feature of CONTROVERSIES complements our previous discussion of atopy (Röcken et al., Exp Dermatol 7: 97–104, 1998), and is dedicated to a critical analysis of the general problems and limitations one faces with the main immunomodulatory strategies traditionally considered in this context. We also explore alternative approaches that appear promising in order to achieve both a more effective and/or a more specific immunotherapy of allergic diseases. Given that the mast cell remains a key protagonist in the pathogenesis of allergic diseases finally, this feature examines how innovative, more selectively mast cell‐targeted strategies may be developed for the management of allergic diseases.     

Intertriginous bullous morphea: A clue for the pathogenesis?

Bullae occurring in lesions of morphea are uncommon. The cause of bullae formation in morphea is multifactorial, although lymphatic obstruction from the sclerodermatous process is considered the likeliest cause. Bullous morphea may be confused clinically with lichen sclerosus et atrophicus since both diseases may cause bullae in sclerodermatous plaques. A 69-year-old woman presented with a history of generalized morphea diagnosed 9 years earlier; and a 1-month history of pruritic bullae on her inframammary folds, axillary regions, lower abdomen, upper extremities and inguinal folds. Physical examination revealed multiple erythematous erosions, hemorrhagic vesicles and eroded bullae with slight scale or crusts overlying hypopigmented, indurated, shiny plaques. Skin biopsy revealed prominent edema in the papillary dermis, resulting in bulla formation and thickening of collagen fibers within the dermis. Direct immunofluorescence was negative. According to histologic and clinical features, the diagnosis of bullous morphea was established.     

Is the Hair Follicle Necessary for Normal Wound Healing?

The hair follicle contributes cells to the interfollicular epidermis after wounding, but the functional role of these cells has not been resolved. To address this question, Langton et al. (this issue, 2008) take advantage of the Edaradd mutant mouse, which lacks hair follicles on its tail. They discover an initial sluggish response of the hairless tail epidermis to wounding that is rapidly compensated for by recruitment of epidermal cells from outside the normally responsive area. This suggests that the hair follicle is important but not necessary for normal wound healing.