A survey among dermatologists: diagnostics of superficial fungal infections - what is used and what is needed to initiate therapy and assess efficacy?

BACKGROUND: Superficial fungal infections are common. It is important to confirm the clinical diagnosis by mycological laboratory methods before initiating systemic antifungal treatment, especially as antifungal sensitivity and in vitro susceptibility may differ between different genera and species. For many years, the gold standard for diagnosis of superficial fungal infections has been direct fungal detection in the clinical specimen (microscopy) supplemented by culturing. Lately, newer molecular based methods for fungal identification have been developed. OBJECTIVE: This study was initiated to focus on the current usage of mycological diagnostics for superficial fungal infections by dermatologists. It was designed to investigate whether it was necessary to differentiate between initial diagnostic tests and those used at treatment follow-up in specific superficial fungal infections. METHODS: An online questionnaire was distributed among members of the EADV mycology Task Force and other dermatologists with a special interest in mycology and nail disease. RESULTS: The survey was distributed to 62 dermatologists of whom 38 (61%) completed the whole survey, 7 (11%) partially completed and 17 (27%) did not respond. Nearly, all respondents (82-100%) said that ideally they would use the result of direct microscopy (or histology) combined with a genus/species directed treatment of onychomycosis, dermatophytosis, Candida- and Malassezia-related infections. The majority of the dermatologists used a combination of clinical assessment and direct microscopy for treatment assessment and the viability of the fungus was considered more important at this visit than when initiating the treatment. Molecular based methods were not available for all responders. CONCLUSION: The available diagnostic methods are heterogeneous and their usage differs between different practices as well as between countries. The survey confirmed that dermatologists find it important to make a mycological diagnosis, particularly prior to starting oral antifungal treatment in order to confirm the diagnose and target the therapy according to genus and species.

Towards global consensus on core outcomes for hidradenitis suppurativa research: an update from the HISTORIC consensus meetings I and II.

BACKGROUND: A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items. OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains. METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey. RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments. CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings.

Low and high body mass index in hidradenitis suppurativa patients-different subtypes?

INTRODUCTION: Overweight is a well-established risk factor for hidradenitis suppurativa (HS). In this cross-sectional study, we compare HS patients with a high body mass index (BMI) with HS patients with a low BMI to investigate differences in disease characteristics. MATERIALS AND METHOD: Patients were recruited from 17 dermatological centres from four continents. A total of 246 patients with a BMI below 25 were compared to 205 patients with a BMI of above 35. RESULTS: Patients with a high BMI suffered more severe disease (Hurley, physician global assessment, number of areas affected and patient-reported severity (PRS), P < 0.001 for all). There was no difference in smoking (P = 0.783) nor in family history (P = 0.088). In both low and high BMI patients, early onset of HS was a predictor of positive family history (P < 0.001, for each). For low BMI patients, an increase in BMI significantly increased PRS (P < 0.001). For patients with a high BMI, number of pack-years significantly increased PRS (P = 0.001). Cluster analysis of eruption patterns was location specific for low BMI patients but severity specific for high BMI patients. DISCUSSION: Patients with a low and high BMI could represent two clinically different subtypes. We suggest a non-linear relationship between BMI and impact of HS. As patients go from a low BMI patient to a high BMI patient (or from high to low), eruption patterns and risk factors may change.

European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa.

Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body, most commonly the axillae, inguinal and anogenital regions. A mean disease incidence of 6.0 per 100,000 person-years and an average prevalence of 1% has been reported in Europe. HS has the highest impact on patients' quality of life among all assessed dermatological diseases. HS is associated with a variety of concomitant and secondary diseases, such as obesity, metabolic syndrome, inflammatory bowel disease, e.g. Crohn's disease, spondyloarthropathy, follicular occlusion syndrome and other hyperergic diseases. The central pathogenic event in HS is believed to be the occlusion of the upper part of the hair follicle leading to a perifollicular lympho-histiocytic inflammation. A highly significant association between the prevalence of HS and current smoking (Odds ratio 12.55) and overweight (Odds ratio 1.1 for each body mass index unit) has been documented. The European S1 HS guideline suggests that the disease should be treated based on its individual subjective impact and objective severity. Locally recurring lesions can be treated by classical surgery or LASER techniques, whereas medical treatment either as monotherapy or in combination with radical surgery is more appropriate for widely spread lesions. Medical therapy may include antibiotics (clindamycin plus rifampicine, tetracyclines), acitretin and biologics (adalimumab, infliximab). A Hurley severity grade-relevant treatment of HS is recommended by the expert group following a treatment algorithm. Adjuvant measurements, such as pain management, treatment of superinfections, weight loss and tobacco abstinence have to be considered.

Millimeter wave silicon micromachined waveguide probe as an aid for skin diagnosis--results of measurements on phantom material with varied water content.

BACKGROUND: More than 2 million cases of skin cancer are diagnosed annually in the United States, which makes it the most common form of cancer in that country. Early detection of cancer usually results in less extensive treatment and better outcome for the patient. Millimeter wave silicon micromachined waveguide probe is foreseen as an aid for skin diagnosis, which is currently based on visual inspection followed by biopsy, in cases where the macroscopical picture raises suspicion of malignancy. AIMS: Demonstration of the discrimination potential of tissues of different water content using a novel micromachined silicon waveguide probe. Secondarily, the silicon probe miniaturization till an inspection area of 600 × 200 µm2, representing a drastic reduction by 96.3% of the probing area, in comparison with a conventional WR-10 waveguide. The high planar resolution is required for histology and early-state skin-cancer detection. MATERIAL AND METHODS: To evaluate the probe three phantoms with different water contents, i.e. 50%, 75% and 95%, mimicking dielectric properties of human skin were characterized in the frequency range of 95-105 GHz. The complex permittivity values of the skin are obtained from the variation in frequency and amplitude of the reflection coefficient (S11), measured with a Vector Network Analyzer (VNA), by comparison with finite elements simulations of the measurement set-up, using the commercially available software, HFSS. The expected frequency variation is calculated with HFSS and is based on extrapolated complex permittivities, using one relaxation Debye model from permittivity measurements obtained using the Agilent probe. RESULTS: Millimeter wave reflection measurements were performed using the probe in the frequency range of 95-105 GHz with three phantoms materials and air. Intermediate measurement results are in good agreement with HFSS simulations, based on the extrapolated complex permittivity. The resonance frequency lowers, from the idle situation when it is probing air, respectively by 0.7, 1.2 and 4.26 GHz when a phantom material of 50%, 75% and 95% water content is measured. DISCUSSION: The results of the measurements in our laboratory set-up with three different phantoms indicate that the probe may be able to discriminate between normal and pathological skin tissue, improving the spatial resolution in histology and on skin measurements, due to the highly reduced area of probing. CONCLUSION: The probe has the potential to discriminate between normal and pathological skin tissue. Further, improved information, compared to the optical histological inspection can be obtained, i.e. the complex permittivity characterization is obtained with a high resolution, due to the highly reduced measurement area of the probe tip.

Treatment of distal subungual onychomycosis with a topical preparation of urea, propylene glycol and lactic acid: results of a 24-week, double-blind, placebo-controlled study.

Onychomycosis is difficult to cure as this requires eradication of the primary infection and protection of new areas of growth from reinfection. A new topical treatment (K101) has been developed. The aim of this study was to assess the efficacy, safety and tolerability of K101 treatment of distal subungual onychomycosis. This was a 24-week (plus 2-week washout), multicentre, randomised, double-blind, placebo-controlled study in 493 patients with distal subungual onychomycosis (K101, n = 346; placebo, n = 147), stratified according to degree of nail involvement. More patients with ≤50% nail involvement achieved the primary endpoint (mycological cure after 26 weeks) in the K101 group (27.2%) than placebo (10.4%; P = 0.0012). Proportions for patients with 51-75% involvement were 19.1% for K101 and 7.0% for placebo (not significant). More patients applying K101 than placebo judged that their condition had improved from week 2 (P = 0.0148) to week 24 (P = 0.0004). No safety issues were identified. K101 provides early visible improvements in nail appearance and a clinically meaningful antifungal activity.

Interobserver variability of clinical scores in hidradenitis suppurativa is low.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic recurrent disease with scars and sinus tract formation that causes substantial impact on quality of life. For evaluation of HS and treatment results, a scoring system for disease severity (Hidradenitis Suppurativa Score, HSS) has been proposed. OBJECTIVES: To describe the interobserver reliability of the HSS and further to document its correlation with risk factors and other measures of disease severity. METHODS: Sixty-one consecutive patients with HS, referred to a clinical centre with special interest in the disease, were scored according to the HSS protocol: eight patients by four dermatologists together, 23 patients by all four observers independently and 30 patients by a single observer. Interobserver variability in HSS between the four observers was investigated in the group of 23 patients. Patients' reports of weight and height, smoking habits etc., were collected, as well as Dermatology Life Quality Index (DLQI) questionnaires. RESULTS: The interobserver concordance of HSS was 0·95. Median (interquartile range, IQR) HSS for all patients was 40 (18-73); women 39 (16-68); men 60·5 (30-95). Median (IQR) HSS for nonsmokers was 26 (12-65); former smokers 30 (10-56); smokers 44 (26-108). Median (IQR) HSS for normal weight patients was 12 (10-30); overweight 43 (25-58); obese 51 (24-95). Mean ± SD DLQI for all patients was 11·3 ± 8·6. CONCLUSIONS: HSS is simple to use and shows low interobserver variability. The score correlates with suggested risk factors, indicating that it reflects a valid estimation of disease severity.

Objective scoring of hidradenitis suppurativa reflecting the role of tobacco smoking and obesity.

BACKGROUND: Hidradenitis suppurativa (HS) is a long-standing disease with abscess and often fistula formation, predominantly in the axillae and groins. The disease is difficult to treat and has a severe impact on quality of life. A clinically relevant system for scoring disease severity is lacking in HS. OBJECTIVES: To evaluate the modified Hidradenitis Suppurativa Score (HSS) and to study the impact of body mass index (BMI) and smoking habits on disease severity. METHODS: Two hundred and fifty-one consecutive patients with HS referred to a clinic with special interest in the disease were included, of whom 115 were scored. Points were given for regions involved, types of lesion (nodules, fistulas), total area involved and whether lesions were separated by normal skin. Background characteristics included BMI and smoking habits. Two hundred and forty-six patients completed the Dermatology Life Quality Index (DLQI). RESULTS: The median (interquartile range, IQR) HSS for all patients was 38 (18-66): women 38 (18-71) and men 37 (19-51). Median (IQR) HSS for smokers was 41 (22-75.5), former smokers 27 (16-53) and nonsmokers 22 (10-57). Median (IQR) HSS for patients with BMI < 25 kg m(-2) was 32 (12-54), BMI 25-30 kg m(-2) 44 (22-56) and BMI > or = 30 kg m(-2) 50 (18-86). Mean +/- SD DLQI for the whole group of patients was 10.3 +/- 7.5, median 9, and showed no significant differences between the groups studied. There was a significant positive correlation of fair degree between HSS and DLQI. There were significant differences in HSS between nonsmokers and smokers as well as between women of normal weight compared with obese women. CONCLUSIONS: The modified HSS is simple and practical and it extracts important clinical information. A connection between disease severity and BMI as well as smoking habits in patients with HS is presented. The results suggest that the HSS may be a relevant outcome measure in future therapeutic trials in HS.

What causes hidradenitis suppurativa?

Hidradenitis suppurativa (HS)--a rather common, very chronic and debilitating inflammatory skin appendage disorder with a notoriously underestimated burden of disease--has long been a playground for the high priests of nomenclature: Ask a bunch of eminent dermatologists and skin pathologists to publicly share their thoughts on what causes HS, and they will soon get entrenched in a heated debate on whether this historical term is a despicable misnomer. Fortunately, the recently founded Hidradenitis Suppurativa Foundation (HSF; http://www.hs-foundation.org), to which EXP DERMATOL serves as home journal, has broken with this unproductive tradition and has encouraged publication of the current CONTROVERSIES feature. This is exclusively devoted to discussing the pathobiology of this chronic neutrophilic folliculitis of unknown origin. Although traces of terminological bickering remain visible, it does the HS experts in our virtual debate room credit that they engage in a constructive and comprehensive dissection of potential pathogenesis pathways that may culminate in the clinical picture we know under the competing terms HS or acne inversa. These experts sketch more often complementary than mutually exclusive pathogenesis scenarios, and the outlines of a conceivable consensus on the many open pathobiology questions begin to emerge in these CONTROVERSIES. Hopefully, this heralds a welcome new tradition: to get to the molecular heart of HS pathogenesis, which can only be achieved by a renaissance of solid basic HS research, as the key to developing more effective HS therapy.

HLA-DR, -DQ and -DP alleles in nickel, chromium, and/or cobalt-sensitive individuals: genomic analysis based on restriction fragment length polymorphisms.

The increased concordance rate of nickel sensitivity in monozygotic compared to dizygotic twins indicates a genetic causal component. We have previously described an association in nickel-sensitive subjects with an HLA-DQA restriction fragment length polymorphism (RFLP) (4.5-kb TaqI band, DQA1*0501). The purpose of the present study was to investigate if our previous finding could be confirmed in an independent study, and also to investigate the distribution of HLA class II alleles in chromium- and cobalt-sensitive individuals. Using TaqI- or MspI-digested DNA and DQA, DQB, DRB, DPA and DPB cDNA probes alleles were defined by RFLP analysis. The association with the DQA1*0501 allele was not confirmed in the new group of 37 nickel-sensitive subjects (compared to 150 new controls), nor when the two groups of patients were combined. The distribution of HLA class II alleles and DR-DQ haplotypes were similar in the pooled group of 70 nickel-sensitive subjects and the combined control groups (n = 250). No significant changes in the distribution of HLA class II allele among the chromium- (n = 26) and/or cobalt- (n = 38) sensitive individuals were found. Our results indicate that it is unlikely that the tendency to develop metal sensitivity is associated with alleles of the HLA class II region.

On assessment of skin reactivity using electrical impedance.

Pathophysiological events in biological tissue are characterized by a shift in electrical impedance spectra of the tissue under study. In this paper, techniques based on electrical impedance are reviewed with emphasis on their possible role in evaluating the skin reactivity of an individual, including results from impedance measurement studies on patients with allergic contact reactions, wheals, tuberculin tests, and irritant contact reactions and on an appropriate number of controls. The results show that, compared to relevant controls, at different types of experimental cutaneous reactions, both of allergic and irritant type, statistically significant changes of the impedance parameters have been detected. Each reaction type had a specific impedance index pattern. Data up to now indicate that the improved impedance technique offers not only a noninvasive alternative for characterization and perhaps differentiation between the skin responses induced by either an allergen or an irritant, but also a capability to distinguish responses induced by chemically different irritants.

Incidence of cancer among patients with hidradenitis suppurativa.

BACKGROUND: On the basis of some case reports, a relationship has been suggested between hidradenitis suppurativa (HS) and the development of nonmelanoma skin cancer. OBJECTIVES: To confirm this relationship and to explore the risk of other cancers among patients with HS. PATIENTS: Patients with a discharge diagnosis of HS were obtained from the computerized database of hospital discharge diagnoses from January 1, 1965, through December 31, 1997. A total of 2119 patients with HS were identified. SETTING: All hospitals in Sweden. DESIGN: With record linkage to the Swedish National Cancer Registry, standardized incidence ratios (SIR [the ratio of the observed to expected incidence]) were calculated to estimate relative risk. RESULTS: The risk of developing any cancer in the cohort with HS increased 50% (95% confidence interval of SIR, 1.1-1.8, based on 73 observed cases). Statistically significant risk elevations were observed for nonmelanoma skin cancer (5 cases; SIR, 4.6; 95% confidence interval, 1.5-10.7), buccal cancer (5 cases; SIR, 5.5; 95% confidence interval, 1.8-12.9), and primary liver cancer (3 cases; SIR, 10.0; 95% confidence interval, 2.1-29.2). CONCLUSIONS: This study confirms an increased risk of nonmelanoma skin cancer among patients with HS. The risk for buccal cancer and primary liver cancer was also elevated among this cohort, but these associations should be interpreted cautiously because the combination of multiple significance testing and the few observed cases may have generated chance findings.

Roxithromycin compared to doxycycline in the treatment of genital chlamydial infection and non-specific urethritis.

A single-blind randomized follow-up study was conducted to evaluate the efficacy and tolerance of roxithromycin 300 mg once a day compared to doxycycline 200 mg day 1 and 100 mg day 2-10 in the treatment of genital chlamydial infection in men and women and non-specific urethritis (NSU) in men. A total of 211 patients (200 men and 11 women) between 18 and 46 years were enrolled. The women were excluded from the efficacy analysis because of the low number, but were included in the tolerance analysis. The clinical (clearance of polymorphonuclear leucocytes in urethral smears) and bacteriological response was evaluated one and 11 days after the treatment. Of 113 included men with chlamydial infection, 105 (93%) and 96 (85%) were evaluable on respective follow-up visits and of 87 included men with NSU, 74 (85%) and 64 (74%) were evaluable one and 11 days after treatment, respectively. The bacteriological eradication rate immediately after the treatment in chlamydia positive patients was 92.7% and 100% for roxithromycin and doxycycline, respectively, and 91.8% and 100% at follow-up. The clinical cure rate of all evaluable patients was 83.1% and 80.7% for roxithromycin and doxycycline, respectively, one day after the treatment and 80.5% and 85.3% for the two drugs, respectively, 11 days after treatment. None of these observed differences was statistically significant. The diagnosis did not influence the clinical response rate with either drug. Probable and possible drug-related side-effects were more common after doxycycline than after roxithromycin, 35% and 19% respectively (P = 0.0032).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of perorally administered pivmecillinam on the normal oropharyngeal, intestinal and skin microflora.

To study the ecological effects of pivmecillinam on the human oropharyngeal, intestinal and skin microflora, 15 healthy volunteers were given pivmecillinam tablets 400 mg twice daily for 7 days. Saliva, stool and skin specimens were taken before (days -3 and 0) and on the 2nd, 4th and 7th days during the administration period and 14 and 21 days after the start of administration. Mecillinam caused no major changes in the aerobic or anaerobic oropharyngeal microflora. In the aerobic intestinal microflora there was a decrease in the numbers of Escherichia coli while no changes occurred in the anaerobic microflora. In the skin microflora there was a transient decrease in the numbers of Propionibacterium spp. underneath the wing of the nose. The major effect of pivmecillinam was seen on E. coli and to some extent on Propionibacterium spp. No further ecological disturbances were noticed in the oropharyngeal, intestinal or skin microflora.

Treatment of psoriasis vulgaris with a synthetic metalloporphyrin and UVA light.

Sn-protoporphyrin is a synthetic heme analogue which inhibits the catabolism of natural heme to bilirubin and can suppress a wide variety of experimentally induced or naturally occurring forms of jaundice in animals and man. Ten patients, 9 of whom were substantially or completely unresponsive to other forms of therapy, received 2.0 mumol/kg body weight of Sn-protoporphyrin on day 0 of this study followed by UVA light treatment for 21 days. Severity of psoriatic plaques, clinically scored (erythema 0-3; scaling, 0-3; infiltration, 0-3;) declined from a mean +/- score of 7 +/- 0.3 on day 0 to 3.6 +/- 0.7 on day 21. Psoriatic lesions were improved in all patients and in some the effect was dramatic. No deleterious side effects were registered. As shown in this study, one-day treatment with Sn-protoporphyrin followed by conventional UVA light treatment may be a useful therapeutic modality for psoriasis patients and merits further investigation.