The millennium criteria for the diagnosis of atopic dermatitis

Abstract: Atopic dermatitis forms an active area of basic and clinical research, where important new knowledge about genetics and immunopathogenesis has surfaced over the past years, and where simultaneous development of new and innovative therapies is under way. However, the inclusion of any patient in an atopic dermatitis study, whether it is on its genetics, pathogenesis or therapy, requires a diagnosis which is irrefutable. Since there is no simple and also no complicated laboratory procedure to reach a diagnosis of atopic dermatitis, different sets of clinical criteria have been developed for the purpose of making the diagnosis uniformly in different studies as well as in different study centers. The most commonly used are Hanifin and Rajka's set of diagnostic features, which have major and minor clinical criteria to be fulfilled in order to establish a diagnosis of atopic dermatitis. Recent developments in the immunology of atopy have clearly established the major abnormality in this syndrome, the preferential production of allergen-specific IgE. In this contribution, it is suggested that the presence of such antibodies in a given patient should be a mandatory criterium for the diagnosis of atopic dermatitis. Such a diagnostic test however establishes a diagnosis of atopic syndrome, not atopic dermatitis. Thus, for atopic dermatitis we have to rely, for the time being, on additional clinical criteria. The clinical features described in the literature are critically evaluated, and it is suggested that in addition to the mandatory presence of allergen-specific IgE, 2 of 3 principal criteria (pruritus, typical morphology and distribution, chronic or chronically relapsing) should be present for such a diagnosis. Finally, the minor features originally described by Hanifin and Rajka and later evaluated by others are revised and divided over 4 subcategories; a) related to subclinical eczema; b) related to dry skin; c) extra skin folds; and d) ophthalmological pathology. They are suggested to be used as additional criteria only, needed when clinical suspicion is high but the new mandatory and principal diagnositic criteria described here are inconclusive. For study purposes, we suggest that the mandatory and principal criteria are sufficient. They are now evaluated and validated in ongoing atopic dermatitis treatment studies.     

SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis

BACKGROUND: SDZ ASM 981 is a selective inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro. It is the first ascomycin macrolactam derivative under development for the treatment of inflammatory skin diseases. OBJECTIVES: This study was designed to determine the safety and efficacy of SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6% and 1.0% in the treatment of patients with atopic dermatitis and to select the concentration to be used in phase III studies. METHODS: This was a double-blind, randomized, parallel-group, multicentre dose-finding study. A total of 260 patients were randomly assigned to treatment with SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6%, or 1.0%, matching vehicle cream, or the internal control 0.1% betamethasone-17-valerate cream (BMV). Treatment was given twice daily for up to 3 weeks. RESULTS: A clear dose-response relationship for SDZ ASM 981 was evident, with 0.2%, 0.6% and 1.0% SDZ ASM 981 creams all being significantly more effective than vehicle (P = 0.041, 0.001 and 0.008, respectively) in terms of baseline to end-point changes in the Eczema Area Severity Index (EASI) and pruritus score. The 1.0% cream was the most effective SDZ ASM 981 concentration. BMV was more effective than the SDZ ASM 981 creams tested in this study. It appears that the efficacy plateau was not reached with the SDZ ASM 981 creams within 3 weeks treatment. SDZ ASM 981 was well tolerated. Burning or a feeling of warmth were the only adverse events reported more frequently in the 0.6% and 1.0% SDZ ASM 981 treatment groups than in the vehicle treatment group (42.9%, 48.9% and 34.9%, respectively). Few systemic adverse events were reported during the study (headache was the most frequent systemic event reported by 15 of 252 patients) and none was considered to be related to treatment. The local tolerability profile of the 1.0% cream was similar to that of the lower concentrations. CONCLUSIONS: 1.0% SDZ ASM 981 cream, which was shown to be safe, well tolerated and the most effective concentration in this study, was selected as the concentration to be further developed in phase III studies.     

Effectiveness of a risk-based visitor-prioritizing system at a sexually transmitted infection outpatient clinic

OBJECTIVE: The objective of this study was to study the efficacy/effectiveness of a risk-based visitor-prioritizing system at a sexually transmitted infection (STI) clinic aimed to improve screening capacity by providing tailored service. STUDY DESIGN: In April 2004, a prioritizing system was implemented that classifies visitors as high or low risk depending on reported sexual behavior and previous STI events. The high- and low-risk groups are assigned to standard and short screening protocols, respectively. Both protocols include diagnostic testing for syphilis, urogenital gonorrhea, chlamydia, and optional for HIV. To assess the effectiveness of the system, differences in prevalence of STI diagnoses in the standard and short protocol were analyzed by chi test. RESULTS: In total, 14,391 visitors (64%) received standard screening and 8,056 visitors (36%) received short screening. The STI prevalence in both groups was 18.1% and 7.6%, respectively (P <0.001); prevalence of HIV was 1.8% and 0.3%, respectively (P <0.001). The sensitivity of the prioritizing system was 74%. Specificity was substantially lower (42%). CONCLUSIONS: This prioritizing system is effective in differentiating between visitors at high and low risk for STI, contributing to provision of tailored STI service, increasing efficiency, and client access to STI service.     

Inguinal lymphogranuloma venereum in a man having sex with men: perhaps an example of the missing link to explain the transmission of the recently identified anorectal epidemic

A 38-year-old man who had sex with men, presented at the outpatient department for Sexually Transmitted Diseases in Amsterdam with a painful, red, fluctuating swelling in the left groin and general discomfort. He had been sexually active in the population of men who have sex with men, in which an anorectal lymphogranuloma venereum (LGV) epidemic has recently been discovered. Unlike other cases where there was anorectal involvement, this patient was the first case of LGV with the classical inguinal presentation although he had not visited the tropics where the inguinal form of LGV occurs as an STD. Routine investigation using PCR on material from urethra and rectum and from the urine, repeatedly failed to detect LGV. However, PCR on pus aspirated from the enlarged lymph node demonstrated Chlamydia trachomatis serovar type L2. Treatment with doxycycline 100 mg twice daily was started. This case illustrates that routine analysis from urethra and rectum and of urine may fail to detect LGV. Furthermore, this case of a patient who probably had LGV initially in the urethra may be the missing link in explaining the route of transmission of the anorectal LGV epidemic.     

High time for wide application of an opting-out strategy for HIV testing

--Despite the current active HIV test policy, the effects of the former policy are still visible, i.e. a relatively low number of individuals that have ever been tested for HIV. --The number of HIV tests and knowledge of current HIV status has increased among visitors to the STI clinic in Amsterdam. --Nevertheless, anonymous HIV surveillance among visitors to the STI clinic shows that a considerable proportion of HIV-infected individuals (24% of men who have sex with men (MSM) and 80% of heterosexuals) are unaware of the infection. --A new opting-out strategy for HIV testing in STI clinics is recommended. --The opting-out strategy may also be applicable to other medical settings, especially those that treat target populations such as MSM, heterosexuals with STI-related symptoms, and persons originating from AIDS-endemic regions. --The opting-out system was initiated in the Amsterdam STI clinic in 2007 in order to further reduce the number of undiagnosed HIV infections.     

Online-mediated syphilis testing: feasibility, efficacy, and usage

OBJECTIVES: To determine the feasibility and efficacy of an online-mediated syphilis screening among men who have sex with men. METHODS: We developed a Web site that offered information about syphilis and motivated users to download a referral letter with which they could test for syphilis in a nonclinical setting. A week after the blood test, participants could retrieve their results online. To assess the feasibility and efficacy of the Web site we followed the users through the online procedure and compared the percentage of syphilis infected men detected online with those diagnosed at the local sexually transmitted infection (STI) clinic, during the same time frame. The trial was divided into an initial period of online advertising (4 months) and no advertising (11 months) to examine how advertisements affect usage. RESULTS: During 15 months, 898 visitors downloaded a referral letter. Of these, 93 (10%) men tested and 96% (90 of 93) obtained their test results online. Through the Web site we found a significantly higher percentage of men who needed treatment for syphilis compared with the STI clinic (50% online vs. 24% STI clinic, P <0.01). Of the Online users who tested positive 33% (3 of 10) had never visited the STI clinic before. In the bannered period there was a monthly average of 15 testers compared with 3 per month in the nonbannered period. CONCLUSION: Online-mediated testing for syphilis is feasible and was more successful in detecting men who have sex with men with an early or late syphilis infection than standard procedures. However, longer promotion periods are needed to generate more usage of the online service.     

Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone acetate ointment in children with atopic dermatitis

BACKGROUND: Vehicle-controlled studies have demonstrated the efficacy and safety of tacrolimus ointment in the treatment of patients with atopic dermatitis (AD). OBJECTIVE: This study was undertaken to compare 0.03% and 0.1% tacrolimus ointment with 1% hydrocortisone acetate ointment in children 2 to 15 years of age with moderate-to-severe AD. METHODS: Treatment was twice daily to affected areas for 3 weeks in this multicenter, randomized, double-blind, parallel-group study. The primary endpoint was the modified eczema area and severity index (mEASI) mean area under the curve (mAUC) as a percentage of baseline. RESULTS: Five hundred sixty patients were randomized and received at least one application of ointment. Discontinuations included 21 of 189 patients from the 0.03% tacrolimus group, 13 of 186 patients from the 0.1% tacrolimus group, and 20 of 185 patients from the hydrocortisone acetate group. The median mEASI mAUC as a percentage of baseline showed 0.03% and 0.1% tacrolimus to be significantly more effective than 1% hydrocortisone acetate (P <.001) and 0.1% tacrolimus to be more effective than 0.03% tacrolimus (P =.006). The mEASI mAUC as a percentage of baseline was 44.8%, 39.8%, and 64.0% for patients who received 0.03% tacrolimus, 0.1% tacrolimus, and 1% hydrocortisone acetate, respectively. Transient skin burning was the only adverse event to show a higher incidence in the tacrolimus treatment groups than in the hydrocortisone acetate group (P <.05). Laboratory parameters showed no treatment differences and no marked changes over time. CONCLUSION: Tacrolimus, 0.03% and 0.1%, was significantly more effective than 1% hydrocortisone acetate and 0.1% tacrolimus was more effective than 0.03% tacrolimus in the treatment of moderate-to-severe AD in children. No safety concerns were identified.     

Low systemic exposure after repeated topical application of Pimecrolimus (Elidel), SD Z ASM 981) in patients with atopic dermatitis

BACKGROUND: Pimecrolimus is a cell-selective inhibitor of inflammatory cytokine release developed specifically for the treatment of inflammatory skin diseases. AIM: The objective of this study was to evaluate blood concentrations and tolerability of pimecrolimus during topical treatment. METHODS: Twelve adult patients with extensive atopic dermatitis were enrolled in an open-label, noncontrolled, pharmacokinetic study. The patients were treated twice daily for 3 weeks with pimecrolimus cream 1% on all lesions. Pimecrolimus blood concentrations were measured at regular time points, and the safety and tolerability were monitored throughout the study. RESULTS: In 78% of the 444 blood samples evaluated, pimecrolimus concentrations remained below the limit of quantitation (0.5 ng/ml). The highest concentration measured was 1.4 ng/ml. There was no indication of drug accumulation. Pimecrolimus was well tolerated locally and systemically. CONCLUSION: The 3-week twice daily treatment with pimecrolimus cream 1% results in consistently low pimecrolimus blood concentrations with no accumulation. Pimecrolimus cream appears suitable for the long-term management of atopic dermatitis.