The Treat-to-Target Project in Atopic Dermatitis: One Year On.

Atopic dermatitis is a chronic skin condition for which a range of systemic treatments have recently been approved. A treat-to-target strategy has been developed previously alongside an algorithm to guide the management of patients with atopic dermatitis. Here, we review the strategy and algorithm in the context of the evolving therapeutic landscape, and identify areas for further refinement and development.

Treat-to-Target in Atopic Dermatitis: An International Consensus on a Set of Core Decision Points for Systemic Therapies.

Currently no treat-to-target framework to guide systemic treatment in adults with moderate-to-severe atopic dermatitis exists. We sought to reach international consensus through an eDelphi process on a core set of recommendations for such an approach. Recommendations were developed by an international Steering Committee, spanning 3 areas (Guiding Principles, Decision Making, and Outcome Thresholds) and 2 specific time-points; an initial acceptable target at 3 months and an optimal target at 6 months, each based on improvements in patient global assessment plus at least one specific outcome domain. These treat-to-target- orientated recommendations were evaluated by an extended international panel of physicians, nurses and patients. Proposed recommendations were rated using a 9-point Likert scale; for each recommendation, consensus agreement was reached if ≥ 75% of all respondents rated agreement as ≥ 7. Consensus on 16 core recommendations was reached over 2 eDelphi rounds. These provide a framework for shared decision-making on systemic treatment continuation, modification, or discontinuation.

The safety profile of biologic agents in comparison with non-biologic systemic agents, and topical compounds in the management of psoriasis-A 30-month prospective, observational cohort study.

BACKGROUND: Although biologic agents (BAs) are very effective, solid data proving they are safer than other therapies in psoriasis are still lacking. METHODS: A total of 289 psoriatic patients were followed for 30 months; of which number 118 were treated with topical agents alone, 112 received BAs, and the remaining 59 patients were on non-biologic systemic agents (NBSAs). The rates of adverse events in these groups were recorded and statistically analysed. RESULTS: Patients treated with BAs had higher rates of adverse events (P = .017), including overall infections (P = .003), respiratory infections (P < .001), renal, urinary (P < .001), musculoskeletal, connective tissue (P < .001, and P = .021) and oral cavity-related (P = .046) disorders. Except for the incidence of infections, all the above adverse events occurred more often in our study than in clinical trials. The occurrence of serious adverse events was P = .066, with the incidence of serious infections being P = .164. Unlike patients on topical therapy and NBSAs, patients treated with BAs were forced to discontinue their therapies (P = .001). The Psoriasis Area Severity Index (PASI) and body surface area (BSA) scores were the lowest among patients on BAs. CONCLUSION: While BAs were the most effective therapies, they were associated with higher rates of treatment discontinuation and adverse events in comparison with other forms of therapy.

Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae co-infections among patients with newly diagnosed syphilis: a single-centre, cross-sectional study.

OBJECTIVES: The aim of the study was to determine the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae co-infections among patients with newly diagnosed syphilis. METHODS: In patients with any stage of newly diagnosed syphilis swabs were performed from urethra, rectum, pharynx and cervix according to the gender and type of sexual intercourse. From these smears standard validated nucleic acid amplification tests (NAATs) for Chlamydia trachomatis and Neisseria gonorrhoeae infections were done. RESULTS: From 548 (488 men, 60 women) screened patients co-infection was detected in 15.9% of the cases. The majority of the co-infections (86.2%) were asymptomatic. The overall prevalence of chlamydial infection was 11.1% and 8.8% for gonococcal infections. In men who have sex with men (MSM) the prevalence of co-infections was significantly higher (20.0%) than in heterosexual men and women (4.2%) (p < 0.001). In MSM patients the presence of co-infection was significantly associated with HIV infection (p < 0.001). Among MSM 9.6% of the tests detected infection in anorectal site, while prevalence in urethral (2.8%) and pharyngeal (2.4%) localization was significantly lower. In heterosexual patients prevalence was less than 2.0% in all anatomic sites. CONCLUSIONS: The implementation of screening tests in case of sexually transmitted infections in patients with newly diagnosed syphilis is an important part in the management of this disease. These results suggest that screening of asymptomatic heterosexual patients leads to detection of minimum co-infections, but in MSM (especially HIV positive) should always be performed at least in anorectal site, where asymptomatic co-infections are common.

Primavera: A new therapeutical approach to vulvo-vaginal atrophy.

Vulvovaginal atrophy is a condition that affects women, although it is mainly associated with the onset of menopause mainly due to hormonal changes vulvovaginal laxity and mucosal atrophy can also affect women at different life stages such as after pregnancy or for cancer patients who have undergone chemo or endocrine therapy. This condition negatively influence quality of life, sexual desire, and self-confidence. Many therapies have been considered mainly with inconclusive or transient results in terms of benefit factor. Recently, a new non-invasive product, containing hyaluronic acid, oligopeptides, and antioxidants was introduced to the market. Its name is "Primavera," by Renaissance, Italy. The aim of this product is to allow a vulvo-vaginal biostimulation and considered simple, safe, and satisfactory.

Concordance of HPV-DNA in cervical dysplasia or genital warts in women and their monogamous long-term male partners.

Transmission of human papillomavirus (HPV) is a premise for development of cervical dysplasia and genital warts (GWs). This cross-sectional study assesses concordance of HPV types present in GWs or cervical dysplasia in women and genital infection of their monogamous male partners in conjunction with seroprevalence of HPV-6, -11, -16, and -18 antibodies. Blood was taken from both women and men, as well a smear of the urogenital area of men. HPV DNA detection in women was done in fixed paraffin embedded tissues under histological control. Of 143 couples who agreed to participate in the study, 68 met inclusion criteria. Type-specific concordance was observed in 32.5% (13/40) of couples in which women had genital warts and in 32.1% (9/28) of couples in which women had cervical dysplasia. In multivariate analysis only smoking in women was associated with concordance (P < 0.05). Prevalence of HPV-specific antibodies was high in male partners, but was not associated with presence of the same HPV type on their genitals. The same type-specific HPV antibodies were detected in 81.8% of men in couples with HPV-6 concordant genital warts, but only in 14.3% of men in couples with HPV-16 concordant cervical dysplasia (P < 0.01). These results suggest that type-specific HPV concordance in genital warts and cervical dysplasia lesions of women and genital infection of their male partners is common and similar. Higher seroconversion in couples with HPV-6 concordant genital warts compared with couples with HPV-16 concordant cervical dysplasia may be explained by viral load exposure.

High prevalence of genital HPV infection among long-term monogamous partners of women with cervical dysplasia or genital warts-Another reason for HPV vaccination of boys.

We conducted a cross-sectional study on the occurrence of a specific type of genital human papillomavirus (HPV) among long-term monogamous male partners of women with cervical dysplasia and genital warts. The purpose of the study was to improve knowledge with regards to the management of these couples. The presence of genital HPV-DNA was detected by PCR with broad spectrum primers followed by hybridization. 82 males met the study criteria, 41 in each group. Genital HPV-DNA prevalence was 67.5% in the genital warts group and 72.2% in the cervical dysplasia group. The prevalence of high risk HPVs was higher in the cervical dysplasia group, while low risk HPVs were more prevalent in the genital warts group (p < .05). The prevalence of HPV in males was independent of the duration of the relationship (73.5% for 6-24 months and 66.7% for longer relationships). In conclusion, our results suggest that the prevalence of the genital HPV infection in both groups of male partners is comparable and very high, but the spectrum of HPV types varies significantly. The presence of the genital HPV infection in male sexual partners seems to be independent of the duration of the relationship. Applying the HPV vaccination to boys may prevent this phenomenon.

Immunosuppressive therapy in the posttransplant period and skin cancer.

AIMS: To determine the incidence of malignancies in renal transplant recipients (RTRs) and to analyze the association between the risk of skin cancer and immunosuppressive regiments used in the posttransplant period. MATERIALS AND METHODS: A cohort study was performed on 797 RTRs. Standardized morbidity ratio (SMR) was calculated for the most common types of cancer developed in the posttransplant period and different types of immunosuppressive therapy used in the cohort. RESULTS: 192 cases of malignancies were diagnosed in 86 RTRs (10.8%). Nonmelanoma skin cancer (NMSC) was the most frequent type of cancer (SMR = 6.42, p = 0.000), followed by renal cancer (SMR = 5.9, p = 0.000), malignant melanoma (SMR = 2.59, p = 0.080), and prostate cancer (SMR = 1.21, p = 0.593). The risk to develop NMSC was significantly higher in the group where cyclosporine has been used besides tacrolimus, mycophenolatemophetil and steroids as well as in the group treated with the combination without cyclosporine (SMR = 9.62, p = 0.001 and SMR = 5.18, p = 0.000). Furthermore, the risk was significantly higher in RTRs receiving anti-thymocyte globulin within induction therapy (SMR = 4.14, p = 0.000). CONCLUSION: The preliminary results indicate that the risk of NMSC in RTRs is significantly higher than in the general population and thus emphasize the need to improve preventive strategies in the Czech transplant population.

Malignant melanoma in organ transplant recipients: incidence, outcomes, and management strategies: a review of literature.

Malignant melanoma is considered to be an immunogenic tumor, which is expected to change its behaviour in the field of immunosuppression. Although the incidence of melanoma in organ transplant recipients is increased to a smaller degree than in non-melanoma skin cancer, its potential morbidity and mortality has to be considered in the posttransplant care. The aim of this review is to investigate the relationship between melanoma and immunosuppression and to discuss management strategies for different melanoma scenarios in pre-transplant as well as posttransplant period.

Are Anti-TNF-α Agents Safe for Treating Psoriasis in Hepatitis C Virus Patients with Advanced Liver Disease? Case Reports and Review of the Literature.

Tumor necrosis factor-alpha (TNF-α) inhibitors represent an effective treatment for severe psoriasis in hepatitis C virus (HCV) patients. The literature reports mainly on short-term treatment in patients with chronic hepatitis with minimum-to-moderate activity with an acceptable safety profile. We report the first 2 cases of hepatocellular carcinoma (HCC) arising in HCV psoriatic patients with advanced liver disease during long-term treatment with etanercept. Our first patient, known to have had HCV infection for 41 years, developed an HCC after 21 months of therapy with etanercept (50 mg/week). The second patient, HCV+ for 20 years, was treated for 58 months with the same therapy, and despite no signs of liver function impairment was diagnosed with HCC. Both of them presented with cirrhosis, which was diagnosed 9 and 5 years earlier, respectively. It remains to be clarified whether there is any connection between psoriasis treatment with anti-TNF-α agents and the development of HCC in HCV-infected patients. Further long-term, follow-up studies and registries of HCV patients with mild/moderate activity may contribute to clarify this issue.

Penile Analogue of Stratified Mucin-Producing Intraepithelial Lesion of the Cervix: The First Described Case. A Diagnostic Pitfall.

The authors report a case where undifferentiated (classic) penile intraepithelial neoplasia was associated with the presence of goblet cells throughout the full epithelial thickness and which later progressed into an invasive carcinoma. The lesion evolved in three consecutive biopsies from only surface epithelium occupying numerous goblet cells in the first to variably sized solid nodules in the dermis composed of atypical squamous and/or basaloid cells intermixed with numerous goblet cells in the third biopsy. Both cellular components expressed CK7 and p16 protein. Human Papillomavirus (HPV) genotyping revealed high risk HPV type 16. To the best of our knowledge, this is the first description of such a lesion occurring on the penis, which can be considered the penile analogue of cervical stratified mucin-producing intraepithelial lesion (SMILE). The correct diagnosis was rendered retrospectively, after recognition of the existence of a vulvar lesion resembling cervical SMILE. The initial biopsy was misinterpreted as extramammary Paget disease, which also constitutes the main pitfall in the differential diagnosis. Another important differential diagnosis is penile/vulvar mucinous metaplasia. The finding of atypical squamous epithelial cells positive for p16 associated with mucinous cells present throughout the full epithelial thickness is a clue to the diagnosis of penile SMILE.

Steady increase of lymphogranuloma venereum cases, Czech Republic, 2010 to 2015.

Since the notification of the first case of lymphogranuloma venereum (LGV) in the Czech Republic in 2010, the numbers of LGV cases have steadily increased in the country. In 2015, 40 LGV cases were diagnosed, bringing the total for 2010-2015, to 88 cases. The profile of the most affected group, HIV-positive men who have sex with men with a previous sexually transmitted infection, matches that of those described in LGV outbreaks in western Europe.

Relative Importance of Traditional Risk Factors for Malignant Melanoma in the Czech Population.

AIM: The Czech Republic is one of the leading European countries in incident cases of malignant melanoma (MM), which is on the rise. The study objective was to assess the strength of associations between MM and the known generally accepted risk factors for MM in the population of the Czech Republic. METHODS: The study was designed as a case-control study where cases were incident cases of MM detected at the Department of Dermatology and Venereology of the Bulovka Hospital. Controls were selected from cancer-free patients admitted to departments other than Dermatology and Venereology. Validated questionnaires were used to collect demographic, epidemiological, and clinical data. RESULTS: The binary logistic model shows the main risk factors for MM: male, female (OR=0.292, 95% CI=0.175-0.486), a changed mole (OR=6.371, 95% CI=3.774-10.756), a history of skin cancer (OR=95.704, 95% CI=37.241-10.756), and sunbeds use (OR=3.594, 95% CI=1.288-10.028). Using sunscreen products was considered as a protective factor against MM (OR=0.253, 95% CI=0.137-0.466). CONCLUSION: The primary and secondary prevention increasingly emerges as a public health priority in the effort to reverse the negative trend in cases of MM and mortality from this disease in the Czech Republic. A prerequisite for an effective secondary prevention through screening is, among others, the identification of the population groups at highest risk for MM.

[The skin - a mirror of internal diseases]. / Kuze - zrcadlo vnitrních nemocí.

UNLABELLED: The knowledge of the relationship between dermatologic manifestations and disorders and internal diseases may facilitate early identification of general disease. The report aims to provide an overview of dermatologic manifestations of gastrointestinal disorders, non-specific inflammatory bowel disease and gastrointestinal stromal tumours, and skin alterations related to diabetes mellitus. The role of a dermatologist is primarily to diagnose dermatoses. KEY WORDS: diabetes mellitus - dermatoses - m. Crohn - gastrointestinal stromal tumours - inflammatory bowel disease - ulcerative colitis.

Dermatitis toxica faciei after boric acid.

An adverse toxic reaction to the topical application of a 2% boric acid solution is described in a 2-year-old girl. Topical boric acid is licensed for use in children above the age of 10 in the Czech Republic. However, it can be bought over the counter and it is very often used in younger children. Due to its fast absorption and slow elimination, there is a high risk of systemic side effects. On the other hand, topical side effects are not reported in the present literature.

Drug fever as an adverse effect of acitretin in complicated psoriasis patient.

We present a case of a 63-year old man with severe chronic plaque psoriasis and a recent history of lung cancer, wherein fever appeared suddenly after initiation of treatment with low dose acitretin. Tumor recurrence or infection was not found during extensive examinations, nevertheless the patient was empirically treated with broad-spectrum antibiotics without any effect on fever. Immediately after discontinuation of acitretin therapy, the fever disappeared. The patient was followed for next 2 years, during this period similar problems did not reappear, although there has been a relapse of psoriasis and the patient was switched later on biological treatment.

First case of pachyonychia congenita in the Czech Republic.

Pachyonychia congenita (PC) is a rare autosomal dominant skin disorder characterized predominantly by hypertrophic nail dystrophy, oral leukokeratosis, and painful palmoplantar keratoderma. It is associated with a mutation in one of five keratin genes, KRT6A, KRT6B, KRT6C, KRT16, or KRT17. The International PC Research Registry (IPCRR) confirms that as of January 2014 there have been 547 cases of PC genetically confirmed. It is estimated that there are between 2000 and 10,000 cases of PC in the world. However, the exact prevalence of PC is not yet established. We report a case of PC-K6a, p.Arg164Pro, in a 40-year-old man. Initially he was diagnosed with onychomycosis and was treated with systemic antifungals. This is the first genetically confirmed case of PC in the Czech Republic.

Molecular typing of Treponema pallidum in the Czech Republic during 2011 to 2013: increased prevalence of identified genotypes and of isolates with macrolide resistance.

From January 2011 to December 2013, a total of 262 samples, from 188 patients suspected of having syphilis were tested for the presence of treponemal DNA by PCR amplification of five chromosomal loci, including the polA (TP0105), tmpC (TP0319), TP0136, TP0548, and 23S rRNA genes. Altogether, 146 samples from 103 patients were PCR positive for treponemal DNA. A set of 81 samples from 62 PCR-positive patients were typeable, and among them, nine different genotypes were identified. Compared to a previous study in the Czech Republic during 2004 to 2010, the number of genotypes detected among syphilis patients in a particular year increased to six in both 2012 and 2013, although they were not the same six. The proportion of macrolide-resistant clinical isolates in this 3-year study was 66.7%.

Manifestation of Crohn's disease in a young woman during the course of treatment for severe form of chronic plaque psoriasis with etanercept.

With the growing number of patients with immune-modulated diseases treated with tumor necrosis factor (TNF) alpha inhibitors, we are more frequently encountering the occurrence of so-called paradoxical drug reactions. These are basically situations where during the course of the treatment of one disease, the manifestation of another with similar etiopathogenesis occurs, although under normal conditions this newly developed disease responds well to treatment with TNF alpha inhibitors and is indicated for this treatment. Skin reactions are most frequently recorded in the form of induced psoriasis and psoriasiform exanthems. A less common paradoxical reaction is the induction of Crohn's disease, which is most often described in association with the treatment of inflammatory joint diseases with etanercept. We present a case of induction of Crohn's disease during therapy with etanercept, where the primary disease being treated was psoriasis. In the literature, similar cases have only been described sporadically.