Topical resiquimod dosing regimens in patients with multiple actinic keratoses: a multicentre, partly placebo-controlled, double-blind clinical trial.

BACKGROUND: Topical immune response modifiers are established for actinic keratosis (AK) treatment and efforts are underway to make further improvements to their efficacy and safety. OBJECTIVES: To investigate the optimal dosing regimens of the Toll-like receptor 7/8 agonist resiquimod in terms of efficacy, safety and tolerability. METHODS: In a multicentre, partly placebo-controlled, double-blind clinical trial, we randomized 217 patients with AK lesions to 0·03% resiquimod gel once-daily application three times per week for 4 weeks or seven times within 2 weeks or five times for 1 week (arms 1/2/3) followed by a treatment-free interval of 8 weeks and one repetition of the cycle. In two additional arms (arms 4/5), patients applied either resiquimod gel 0·01% or 0·03% three times per week up to a biological end point defined by skin erosion or for a maximum duration of 8 weeks. Clearance was assessed clinically and histologically. RESULTS: Complete clinical clearance ranged from 56% to 85% with the highest rate observed in arm 2. Resiquimod 0·03% gel was more effective than 0·01% gel. Clearance rates in arms 1/2/3 were comparable and higher than with placebo and were reached with 24, 14 and 10 gel applications, respectively. Overall, 128 patients (59%) experienced treatment-related adverse reactions. CONCLUSIONS: Resiquimod 0·03% gel is more effective than 0·01% gel. From the perspectives of safety and tolerability, the lower concentration and shorter duration are preferable. The clinical response in arms 2/3 was reached with fewer gel applications. The dosing regimens that used the biological end point (arms 4/5) proved equally efficacious as predefined treatment durations and may therefore be suitable for personalized AK treatment.

[Off-label indications for topical tacrolimus]. / Off-label-Indikationen für topisches Tacrolimus.

The topical calcineurin antagonist tacrolimus plays an important role in the treatment of different forms of eczema because of its favorable risk profile. In addition, different off-label indications have been clinically tested where tacrolimus ointment has achieved clinical improvement. This article discusses off-label treatment of vitiligo, seborrheic dermatitis, steroid rosacea, perioral dermatitis, rosacea and lichen sclerosus.

Human papillomavirus genotype distribution and risk factors for infection in women from a small municipality in north east Brazil.

In order to assess the prevalence of human papillomavirus (HPV) infection, the HPV genotypes and factors associated with infection, we conducted a population-based survey in a small municipality in north east Brazil among women aged between 12 and 49 years. A questionnaire regarding socioeconomic variables, reproductive life and sexual behaviour was used, and women were examined gynaecologically, followed by collection of vaginal lavage with saline solution for HPV DNA determination. HPV DNA was detected by the Digene(®) SHARP Signal(TM)-System, and further genotyped by INNO-LiPA Genotyping System(®). Of 579 women, HPV infection was present in 68 (prevalence: 11.7%; 95% CI: 9.3-14.7). The most common HPV types were 16, 31 and 74, each accounting for 14.7% of infections. Of all HPV-positive women, 35.3% showed multiple HPV genotypes. Variables independently associated with HPV infection were: ≥3 partners in life (adjusted OR [aOR]: 3.06; 95% CI: 1.68-5.60) and the use of oral contraception in the last 12 months (aOR: 2.39; 95% CI: 1.33-4.30). Previous participation in a cervical cancer screening programme was protective (aOR: 0.28; 95% CI: 0.13-0.60). HPV infection is common among women from rural Brazil, and HPV genotypes identified indicate that immunization could be an important preventive measure in this population.

[Important viral and bacterial infections of the skin and mucous membrane]. / Wichtige virale und bakterielle Infektionen der Haut und Schleimhäute.

Skin infections are more frequent in immunodeficient patients, seniors and infants than in healthy individuals with an intact immune system. The severity of infections ranges from localized, self-limiting cutaneous infections to widespread necrosis of the skin, muscle, and fascia. The most frequent infections of the skin and mucous membranes are caused by bacterial and viral infectious agents. Fungal infection are also important especially in immunocompromised patients. In particular, viruses play an important and increasing role in the development of several tumors including HPV-associated cervical, anal and penile cancer or HHV-8-induced Kaposi sarcoma.

[Successful use of allogeneic stem cell transplantation for treatment-refractory mycosis fungoides]. / Erfolgreicher Einsatz einer allogenen Stammzelltransplantation bei therapierefraktärer Mycosis fungoides.

Mycosis fungoides is the most common type of cutaneous T-cell lymphoma and characterized by a chronic progressive course spanning decades. The choice of treatment options should be tailored to the stage depending on the extent and aggressiveness of the disease and taking the individual situation of the patient into consideration. Long-term complete remissions can only be achieved in the early phase of the disease, while there is no therapy that results in a cure or long-term remission in advanced stages. In young patients with a treatment-refractory course of mycosis fungoides, allogeneic stem cell transplantation represents an important alternative option to manage the disease since complete clinical remission can be obtained even in advanced stages.

[Trombiculiasis in humans]. / Trombidiose des Menschen.

Trombiculiasis is an epizoonosis that occurs worldwide and is caused by various types of chiggers. Clinical findings after accidental contact with the parasitic mite larvae include erythematous papules and urticarial plaques, to some extent with vesicular transformation, which can lead to excoriations due to the intense pruritus. Prophylaxis against exposure is recommended when visiting areas known to be colonized by mites. Reactions to bites can be treated by local application of alcohol compresses or zinc lotions and external application of agents containing polidocanol or glucocorticosteroid. Systemic antihistamines are indicated to control itching.

[Considerable variation in the range of time for complications to appear after tattoos]. / Erhebliche zeitliche Variationsbreite von Komplikationen nach Tätowierungen.

Side effects after tattoos are being observed with greater frequency in dermatological practice. The complications that occur can be classified into systemic and local reactions. The time course of cutaneous side effects ranges from direct complications during or following tattooing to reactions that first appear several years thereafter. The majority of allergic complications can be explained by the delayed degradation of the color pigment used for the tattoo and then release of potent allergens sometimes not until years later.

[Cutaneous leishmaniasis]. / Kutane Leishmaniose.

Leishmaniasis includes a spectrum of different diseases that differ in their clinical appearance and severity and influence the patient's health to varying degrees. All the diseases are caused by parasites of the genus Leishmania. The simplest and most widely used classifications use the clinical features and the geographic distribution. Cutaneous leishmaniasis can be divided into localized, diffuse, recurrent or post-kala-azar. Using the geographic distribution leishmaniasis of the Old World, is found in Africa, Asia, Middle East, Mediterranean basin and India. Both, cutaneous and visceral leishmaniasis, may develop. In contrast, New World leishmaniasis is caused by leishmania found in Central and South America and cause may cutaneous, mucocutaneous and visceral findings.

[Cutaneous larva migrans]. / Kutane Larva migrans.

As a result of the rise of mass tourism with increasingly cheap and exotic destinations, tropical diseases are becoming an increasingly important part of dermatology. Infection with cutaneous larva migrans is one of the most common "souvenirs" from the tropics. The disease is caused by the nematode infection with dog or cat hookworm parasites (Ancylostoma braziliense or A. caninum). The characteristic manifestation is a gyrated, serpiginous and in some cases vesicular erythema, which appears after penetration of the epidermis by the parasite and the subsequent intraepidermal migration of the larva. This is often accompanied by intense pruritus in the affected skin. The infection is usually found in those areas of the foot, calf or buttocks exposed by walking or sitting on sand. Although subjectively very unpleasant, the disease is self-limiting and resolves after several weeks; it is treated locally in most cases (e.g. using cryotherapy). The prognosis of the disease is excellent, but a prolonged course or complications have been observed, e.g. due to superinfection.

[Arthropod bite reactions and pyodermias]. / Iktusreaktionen und Pyodermien.

Tourists in the tropics often develop reactions to bites or stings of mosquitoes, fleas, mites, ants, bedbugs, beetles, larva, millipedes, spiders and scorpions. In addition, they may have fresh or salt water exposure to sponges, corals, jellyfish and sea urchins with resultant injury and inflammation. Bacterial skin infections (pyodermias) can follow bites or stings as well as mechanical trauma. The most common bacteria involved in skin infections are staphylococci and streptococci. For tourists, bacterial infections are often complicating a pruritic bite reaction and scratching. It is important to know the cause of the bite reaction and pyoderma in order to take appropriate therapeutic measures.

The BH3-only member Noxa causes apoptosis in melanoma cells by multiple pathways.

The molecular causes for resistance of melanoma to apoptosis are currently only partly understood. In the present study, we examined gene transfer and expression of the proapoptotic BH3-only protein Noxa as an alternative approach to chemotherapy and investigated the molecular mechanisms regulating Noxa-induced apoptosis. Noxa gene transfer caused dysregulation of both mitochondria and, as shown for the first time, also the endoplasmic reticulum, resulting in the accumulation of reactive oxygen species. Interestingly, expression of Noxa not only triggered the classical mitochondrial caspase cascade, but also resulted in the activation of apoptosis signal-regulating kinase1 and its downstream effectors c-Jun N-terminal kinase and p38. The activation of these kinases was abolished by antioxidants. Moreover, inhibition of the kinases by RNA interference or pharmacological inhibitors significantly attenuated Noxa-induced apoptosis. Thus, our data provide evidence for the involvement of multiple pathways in Noxa-induced apoptosis that are triggered at mitochondria and the endoplasmic reticulum, and suggest Noxa gene transfer as a complementary approach to chemotherapy.

[Topical therapy of squamous cell carcinoma]. / Lokale Therapie von Plattenepithelkarzinomen.

Many forms of topical chemo- and immunotherapy are employed to treat skin cancers. Topical treatment is particularly attractive for field cancerization involving multiple non-melanoma skin cancers. The dermatologist must identify such patients and lesions and provide the most suited therapy.

Methylation of SOCS-3 and SOCS-1 in the carcinogenesis of Barrett's adenocarcinoma.

BACKGROUND: The suppressors of cytokine signalling (SOCS) are inhibitors of cytokine signalling; methylation of SOCS-3 has been implicated in the tumorigenesis of liver as well as head and neck cancer. AIMS: This study was performed to elucidate the role of SOCS-1 and SOCS-3 in Barrett's adenocarcinoma and its precursor lesions. METHODS: DNA of specimens from 19 Barrett's adenocarcinomas, 56 Barrett's intraepithelial neoplasias (n = 29 low grade and n = 27 high grade), 30 Barrett's mucosa without neoplasia, 20 samples of normal squamous and gastric epithelium and four cell lines were studied using methylation specific PCR for the SOCS-1 and SOCS-3 promoter following microdissection. The presence of SOCS-3 mRNA transcripts was confirmed by semiquantitative real time PCR, and the SOCS-3 protein was analysed immunohistochemically. RESULTS: In normal squamous epithelium and normal gastric mucosa, neither SOCS-3 nor SOCS-1 methylation was observed. In Barrett's mucosa without intraepithelial neoplasia, SOCS-3 methylation occurred in 4/30 cases (13%) whereas SOCS-1 was unmethylated. A hypermethylated SOCS-3 promoter was found in 14/19 Barrett's adenocarcinomas (74%) and in 20/29 high and 6/27 low grade intraepithelial neoplasias (69% and 22%, respectively). SOCS-1 promoter hypermethylation occurred in 8/19 adenocarcinomas (42%) and in 6/29 high grade and 1/27 low grade intraepithelial neoplasias (21% and 4%, respectively). Methylation of the SOCS-3 promoter correlated with downregulation of SOCS-3 transcripts and protein expression in these tumours and various cell lines. In the cell lines tested, SOCS-3 and SOCS-1 transcripts increased after treatment with the demethylation compound 5-aza-2-deoxycytidine. CONCLUSIONS: These data indicate that promoter methylation and subsequent transcript downregulation of SOCS-3 transcripts and, to a much lesser extent, SOCS-1 are involved in the multistep carcinogenesis of Barrett's adenocarcinoma.

[Hand-foot syndrome with capecitabine therapy]. / Hand-Fuss-Syndrom bei einem Patienten unter Capecitabin-Therapie.

A 72-year-old patient with esophageal carcinoma developed a severe hand-foot syndrome during second-line therapy with the oral fluoropyrimidine capecitabine. We also summarize the current knowledge with regard to the hand-foot syndrome and distinguish it from palmoplantar erythrodysesthesia.