[Diagnosis of suspected superficial fungal infections]. / Diagnostiek bij vermoeden van een schimmelinfectie.

Most medical microbiology laboratories in the Netherlands have switched from direct potassium hydroxide microscopy and culture to polymerase chain reaction (PCR) testing when diagnosing dermato- and onychomycoses and Candida species in human dander, hair and nails. The predictive value of a PCR test is in most cases higher than the predictive value of KOH microscopy and culture in diagnosing or ruling out a fungal infection and should therefore replace traditional diagnostics in routine care. KOH microscopy and culture should be reserved in cases of therapy failure and suspected false negative PCR testing. An application for a PCR should be performed if there is any doubt about the clinical diagnosis. The application must be accompanied by sufficient clinical information from the patient to enable the microbiologist to determine whether the PCR test used is appropriate.

[Persisting itching? Consider scabies]. / Persisterende jeuk? Denk aan scabiës.

Scabies is a common skin condition, which is accompanied by severe itching and a high degree of contagiousness. Rapid diagnosis and adequate treatment for the patient and his contacts is therefore important. Recognizing scabies is not always easy. Patients may present with atypical skin lesions. Persistent itching, more intense at night, and itching in relatives can then lead to the clinical (probable) diagnosis. Demonstration of the mite and/or eggs in the skin can confirm the diagnosis, either by dermatoscopy or direct microscopy of skin scrapings. Treatment consists of applying permethrin cream and/or taking ivermectin tablets. Although resistance to these agents has been suggested, treatment failure is mainly caused by failure to properly implement the treatment recommendations by the patient and/or his or her contacts. We present three patients with scabies in which the diagnosis and treatment could have been performed better.

Measuring sensory and pain thresholds by Semmes-Weinstein monofilaments in patients with leg ulcers: a pilot study.

OBJECTIVE: Pain is a common and disabling symptom in patients with leg ulcers. Clinical quantification of pain mostly depends on subjective pain reports, which do not reveal underlying mechanisms. The aim of this pilot study is to identify mechanisms underlying the pain in patients with leg ulcers by documenting alterations in pain processing using quantitative sensory testing. METHODS: In nine ulcer patients the mechanical sensory thresholds and the mechanical pain thresholds were determined by Semmes-Weinstein monofilaments (SWM) at three different sites: on the contralateral (unaffected) leg, on the skin of the affected leg 10cm from the ulcer margin, and on the affected leg, close (1-2cm) to the ulcer margin. Besides the mechanical sensory thresholds and mechanical pain thresholds, pain at the site of the ulcer, using an 11-point numeric rating scale (NRS), was documented. RESULTS: Mechanical sensory thresholds were increased in all subjects. Almost half (44%) of patients consistently showed allodynia at the unaffected site. The lowering of mechanical pain thresholds correlated with higher scores on the NRS. CONCLUSION: All patients showed diminished touch and/or protective sensation, which might have contributed to ulcer development via (partial) loss of protective function. The allodynia at the unaffected site suggests the presence of central sensitisation of pain processing.

[Paraneoplastic syndromes]. / Paraneoplastische syndromen.

A paraneoplastic syndrome is a phenomenon or complex of symptoms that can occur with malignancy, without this being the result of tumour cells in the affected area. In this article, we describe the following paraneoplastic syndromes: thrombophlebitis migrans, clubbing, pemphigus, acanthosis nigricans, blue fingers, dermatomyositis, and myasthenia gravis.

[Overtreatment of premalignant and malignant skin lesions.] / Overbehandeling van premaligne en maligne huidafwijkingen.

The incidence of malignant and premalignant skin lesions has been increasing in recent decades. It concerns a spectrum of lesions, from relatively benign to highly malignant disease. The nomenclature does not always do justice to the biological character of the specific condition. We have to pay attention to avoid unnecessary diagnostics, overtreatment of conditions with little chance of progression of disease, and unnecessary follow-up. Besides better understanding about the biology of the various premalignant and malignant skin lesions, renaming of some of the conditions can be of help. The concept of applying the term 'indolent lesion of epithelial origin' for this purpose may be beneficial.

Dermatological exposure to coal tar and bladder cancer risk: a case-control study.

OBJECTIVE: Coal tar ointments are used as treatment of various skin diseases, especially psoriasis and eczema. These ointments contain several carcinogenic polycyclic aromatic hydrocarbons. Metabolites of these polycyclic aromatic hydrocarbons are excreted in the urine and therefore, dermatological use of coal tar may be associated with an increased risk of bladder cancer. The objective of this study was to evaluate the association between dermatological use of coal tar ointments and bladder cancer. MATERIAL AND METHODS: A population-based case-control study was conducted including 1,387 cases diagnosed with bladder cancer and 5,182 population controls. Information on the use of coal tar, history of skin disease, and known risk factors for bladder cancer was obtained through postal questionnaires. Logistic regression analyses were performed to estimate the risk of bladder cancer after coal tar treatment, adjusted for age, gender, smoking status, duration of smoking, and intensity of smoking. RESULTS: The use of coal tar ointments was approximately equal among cases and controls (3.8% vs. 3.0%, respectively). Dermatological application of coal tar was not significantly associated with bladder cancer (adjusted odds ratio = 1.37, 95% CI: 0.93-2.01). An inverse association between bladder cancer and a history of skin disease was observed (adjusted odds ratio = 0.74, 95% CI: 0.61-0.90). CONCLUSION: This is the first study with a specific aim to study the association between the use of coal tar preparations and bladder cancer. The results suggest that there is no reason for safety concerns with respect to the risk of bladder cancer after the use of coal tar preparations in dermatological practice.

Technical and radiological image quality comparison of different liquid crystal displays for radiology.

BACKGROUND: To inform cost-effective decisions in purchasing new medical liquid crystal displays, we compared the image quality in displays made by three manufacturers. METHODS: We recruited 19 radiologists and residents to compare the image quality of four liquid crystal displays, including 3-megapixel Barco(®), Eizo(®), and NEC(®) displays and a 6-megapixel Barco display. The evaluators were blinded to the manufacturers' names. Technical assessments were based on acceptance criteria and test patterns proposed by the American Association of Physicists in Medicine. Radiological assessments were performed on images from the American Association of Physicists in Medicine Task Group 18. They included X-ray images of the thorax, knee, and breast, a computed tomographic image of the thorax, and a magnetic resonance image of the brain. Image quality was scored on an analog scale (range 0-10). Statistical analysis was performed with repeated-measures analysis of variance. RESULTS: The Barco 3-megapixel display passed all acceptance criteria. The Eizo and NEC displays passed the acceptance criteria, except for the darkest pixel value in the grayscale display function. The Barco 6-megapixel display failed criteria for the maximum luminance response and the veiling glare. Mean radiological assessment scores were 7.8±1.1 (Barco 3-megapixel), 7.8±1.2 (Eizo), 8.1±1.0 (NEC), and 8.1±1.0 (Barco 6-megapixel). No significant differences were found between displays. CONCLUSION: According to the tested criteria, all the displays had comparable image quality; however, there was a three-fold difference in price between the most and least expensive displays.

Economic evaluation of an integrated care programme for patients with hand dermatitis.

BACKGROUND: Hand dermatitis has a large impact on society as a whole. OBJECTIVES: To evaluate the cost-effectiveness of integrated, multidisciplinary care as compared with usual care (UC) for patients with moderate to severe chronic hand dermatitis after 52 weeks. METHODS: Patients (n = 196) visiting the dermatology department at one of the participating hospitals for hand dermatitis were randomized to integrated care (IC) or UC. IC was provided by a multidisciplinary team, and integrated clinical and occupational care to optimize treatment of hand dermatitis. Effect outcomes were clinical assessment of hand dermatitis with the Hand Eczema Severity Index (HECSI), and disease-specific quality of life, work performance and quality-adjusted life-years with the EQ-5D. Incremental cost-effectiveness ratios (ICERs) were calculated. The ICER indicates the additional investment needed to gain one unit of effect. RESULTS: The HECSI difference between both groups after 52 weeks was 8.7 (standard error 5.3, 95% confidence interval -1.8-18.9). No differences were found on secondary outcome measures. Mean total costs with IC (€ 3613; SD 798) were significantly higher than with UC (€ 1576, SD 430). The ICER for improvement in HECSI score was -247. IC was not considered to be cost-effective as compared with UC. The probability that IC was cost-effective was 90% at a ceiling ratio of € 1500 per additional point improvement in HECSI score. CONCLUSION: Integrated care was neither cost-effective, nor effective after 12 months follow-up, in contrast to our findings after 6 months. Decision makers should decide whether the clinical benefits of integrated care on the short term outweigh the higher costs compared to usual care.

A simple tool with which to study the course of chronic hand eczema in clinical practice: a reduced-item score.

BACKGROUND: Physicians need a simple, disease-specific tool with which to assess disease severity and the effect of therapeutic intervention in patients with chronic hand eczema. The currently available clinical scoring systems include numerous items, which makes them laborious to complete and limit their use in daily practice. OBJECTIVE: To develop a simple tool with which to assess disease severity of patients with chronic hand eczema. METHODS: We evaluated two tools, the Hand Eczema Severity Index (HECSI) and the Hand Eczema Area and Severity score, to determine their ability to predict the Investigator's Global Assessment (IGA) of disease severity in patients with moderate to severe hand eczema. We used a stepwise reduction analysis to determine a minimal set of significantly contributing items for predicting IGA. RESULTS: A three-item score, based on the highest observed value of induration, fissuring, and scaling, predicted IGA with a correlation of 0.667. The HECSI predicted the IGA with a correlation of 0.675. CONCLUSION: On the basis of this analysis, we propose a simple tool for clinical decision-making and evaluation of therapeutic intervention in daily practice.

Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis.

Topical application of coal tar is one of the oldest therapies for atopic dermatitis (AD), a T helper 2 (Th2) lymphocyte-mediated skin disease associated with loss-of-function mutations in the skin barrier gene, filaggrin (FLG). Despite its longstanding clinical use and efficacy, the molecular mechanism of coal tar therapy is unknown. Using organotypic skin models with primary keratinocytes from AD patients and controls, we found that coal tar activated the aryl hydrocarbon receptor (AHR), resulting in induction of epidermal differentiation. AHR knockdown by siRNA completely abrogated this effect. Coal tar restored filaggrin expression in FLG-haploinsufficient keratinocytes to wild-type levels, and counteracted Th2 cytokine-mediated downregulation of skin barrier proteins. In AD patients, coal tar completely restored expression of major skin barrier proteins, including filaggrin. Using organotypic skin models stimulated with Th2 cytokines IL-4 and IL-13, we found coal tar to diminish spongiosis, apoptosis, and CCL26 expression, all AD hallmarks. Coal tar interfered with Th2 cytokine signaling via dephosphorylation of STAT6, most likely due to AHR-regulated activation of the NRF2 antioxidative stress pathway. The therapeutic effect of AHR activation herein described opens a new avenue to reconsider AHR as a pharmacological target and could lead to the development of mechanism-based drugs for AD.

The effectiveness of integrated care for patients with hand eczema: results of a randomized, controlled trial.

OBJECTIVES: To evaluate the effectiveness of integrated, multidisciplinary care as compared with usual care for patients with moderate to severe, chronic hand eczema after 26 weeks of follow-up. BACKGROUND: This study was designed as a randomized, controlled trial. METHODS: Patients who visited one of the participating hospitals were randomized to integrated care or usual care. Integrated care was carried out by a multidisciplinary team, and integrated clinical and occupational care to optimize treatment, and the patient's quality of life and social functioning. Outcome variables were clinical assessment of hand eczema with the Hand Eczema Severity Index (HECSI) (primary outcome), quality of life, patient's global assessment of hand eczema, and sick leave. RESULTS: Average improvement on the HECSI was 22.4 points in the intervention group and 11.7 points in the control group. The mean difference in improvement on the HECSI between both groups after 26 weeks was 10.7 points in favour of the integrated care group (standard error 5.3, 95% confidence interval 0.3-21.1, p = 0.044). No differences in improvement between the groups were found for any of the other outcomes. CONCLUSIONS: The integrated care programme significantly improved clinical outcome measures as compared with usual care, and was effective for treating patients with chronic hand eczema.

Process evaluation of an integrated, multidisciplinary intervention programme for hand eczema.

UNLABELLED: BACKGROUND. Over the last decade, few randomized controlled trials of high methodological quality have been carried out to evaluate the effectiveness of interventions for patients with hand eczema. Little to no attention has been paid to the feasibility of these interventions. This process evaluation was carried out to gain insight in the barriers to and facilitators for implementation of an intervention for hand eczema. The aims of this process evaluation were to examine the feasibility and the satisfaction of the patients and the professionals with the integrated care programme, and the perceived barriers to and facilitators for the use of the programme. METHODS: Eligible for this study were patients with moderate to severe chronic hand eczema who completed the integrated care programme. This programme is an intervention provided by a multidisciplinary team, consisting of a dermatologist, a specialized nurse, and a clinical occupational physician. Data were collected from the patients and the healthcare professionals, by means of semistructured telephone interviews, questionnaires, and a patient tracking system. Implementation, satisfaction and expectations were investigated. RESULTS: Ninety-three patients completed the integrated care programme. Compliance with the integrated care programme was good. The results indicate good satisfaction of both patients and healthcare professionals with the integrated care programme. However, with regard to the process and feasibility of the integrated care programme, there is room for improvement. The clinical occupational physician was only involved in a very limited number of cases, the protocol was not flexible, and the intervention period was too compact. Most of the perceived barriers in the present study are at the organizational level. CONCLUSION: Satisfaction with the integrated care programme was high among both patients and healthcare professionals. The involvement of the clinical occupational physician in the treatment, when indicated, should be optimized. With the multidisciplinary approach and good communication as a basis for the programme, and a more flexible protocol to avoid unnecessary consultations by the healthcare professionals, integrated care could be a useful treatment from a process evaluation perspective.

Dutch randomized trial comparing standard catheter-directed thrombolysis versus ultrasound-accelerated thrombolysis for thromboembolic infrainguinal disease (DUET): design and rationale.

BACKGROUND: The use of thrombolytic therapy in the treatment of thrombosed infrainguinal native arteries and bypass grafts has increased over the years. Main limitation of this treatment modality, however, is the occurrence of bleeding complications. Low intensity ultrasound (US) has been shown to accelerate enzymatic thrombolysis, thereby reducing therapy time. So far, no randomized trials have investigated the application of US-accelerated thrombolysis in the treatment of thrombosed infra-inguinal native arteries or bypass grafts. The DUET study (Dutch randomized trial comparing standard catheter-directed thrombolysis versus Ultrasound-accElerated Thrombolysis for thrombo-embolic infrainguinal disease) is designed to assess whether US-accelerated thrombolysis will reduce therapy time significantly compared with standard catheter-directed thrombolysis. METHODS/DESIGN: Sixty adult patients with recently (between 1 and 7 weeks) thrombosed infrainguinal native arteries or bypass grafts with acute limb ischemia class I or IIa, according to the Rutherford classification for acute ischemia, will be randomly allocated to either standard thrombolysis (group A) or US-accelerated thrombolysis (group B). Patients will be recruited from 5 teaching hospitals in the Netherlands during a 2-year period. The primary endpoint is the duration of catheter-directed thrombolysis needed for uninterrupted flow in the thrombosed infrainguinal native artery or bypass graft, with outflow through at least 1 crural artery. DISCUSSION: The DUET study is a randomized controlled trial that will provide evidence of whether US-accelerated thrombolysis will significantly reduce therapy time in patients with recently thrombosed infrainguinal native arteries or bypass grafts, without an increase in complications. TRIAL REGISTRATION: Current Controlled Trials ISRCTN72676102.

No increased risk of cancer after coal tar treatment in patients with psoriasis or eczema.

Coal tar is an effective treatment for psoriasis and eczema, but it contains several carcinogenic compounds. Occupational and animal studies have shown an increased risk of cancer after exposure to coal tar. Many dermatologists have abandoned this treatment for safety reasons, although the risk of cancer after coal tar in dermatological practice is unclear. This large cohort study included 13,200 patients with psoriasis and eczema. Information on skin disease and treatment, risk factors, and cancer occurrence was retrieved from medical files, questionnaires, and medical registries. Proportional hazards regression was used to evaluate differences in cancer risk by treatment modality. Patients treated with coal tar were compared with a reference category of patients treated with dermatocorticosteroids (assumed to carry no increased cancer risk). The median exposure to coal tar ointments was 6 months (range 1-300 months). Coal tar did not increase the risk of non-skin malignancies (hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.78-1.09), or the risk of skin cancer (HR 1.09; 95% CI 0.69-1.72). This study has sufficient power to show that coal tar treatment is not associated with an increased risk of cancer. These results indicate that coal tar can be maintained as a safe treatment in dermatological practice.

Integrated, multidisciplinary care for hand eczema: design of a randomized controlled trial and cost-effectiveness study.

BACKGROUND: The individual and societal burden of hand eczema is high. Literature indicates that moderate to severe hand eczema is a disease with a poor prognosis. Many patients are hampered in their daily activities, including work. High costs are related to high medical consumption, productivity loss and sick leave. Usual care is suboptimal, due to a lack of optimal instruction and coordination of care, and communication with the general practitioner/occupational physician and people involved at the workplace. Therefore, an integrated, multidisciplinary intervention involving a dermatologist, a care manager, a specialized nurse and a clinical occupational physician was developed. This paper describes the design of a study to investigate the effectiveness and cost-effectiveness of integrated care for hand eczema by a multidisciplinary team, coordinated by a care manager, consisting of instruction on avoiding relevant contact factors, both in the occupational and in the private environment, optimal skin care and treatment, compared to usual, dermatologist-led care. METHODS: The study is a multicentre, randomized, controlled trial with an economic evaluation alongside. The study population consists of patients with chronic, moderate to severe hand eczema, who visit an outpatient clinic of one of the participating 5 (three university and two general) hospitals. Integrated, multidisciplinary care, coordinated by a care manager, including allergo-dermatological evaluation by a dermatologist, occupational intervention by a clinical occupational physician, and counselling by a specialized nurse on optimizing topical treatment and skin care will be compared with usual care by a dermatologist. The primary outcome measure is the cumulative difference in reduction of the clinical severity score HECSI between the groups. Secondary outcome measures are the patient's global assessment, specific quality of life with regard to the hands, generic quality of life, sick leave and patient satisfaction. An economic evaluation will be conducted alongside the RCT. Direct and indirect costs will be measured. Outcome measures will be assessed at baseline and after 4, 12, 26 and 52 weeks. All statistical analyses will be performed on the intention-to-treat principle. In addition, per protocol analyses will be carried out. DISCUSSION: To improve societal participation of patients with moderate to severe hand eczema, an integrated care intervention was developed involving both person-related and environmental factors. Such integrated care is expected to improve the patients' clinical signs, quality of life and to reduce sick leave and medical costs. Results will become available in 2011.

Uptake of pyrene in a breast-fed child of a mother treated with coal tar.

A woman was treated for atopic dermatitis with coal tar containing ointments. Coal tar containing ointments contain genotoxic polycyclic aromatic hydrocarbons. Over a period of 50 days the accumulated dose of different coal tar containing ointments treatments corresponded to 993 mg of pyrene and 464 mg of benz[a]pyrene. During this treatment she gave breast milk to her 3-month-old daughter. Analysis of urine samples from the breast-fed child showed elevated levels of urinary excretion of a metabolite of pyrene (1-hydroxypyrene, 1-OHP). These levels were in the same range as urinary excretion levels of this metabolite observed in the mother's urine. As no pyrene was observed in breast milk at a limit of determination of 0.0035 micromol/L, transfer of pyrene from mother to child via breast milk is not likely. Also, a low level of 1-hydroxypyrene observed in the mother's milk did not account for the observed urinary excretion levels in the child. It must therefore be assumed that pyrene was transferred from mother to child via another route, presumably direct skin-to-skin or skin-to-mouth contact. Dermatologists should inform their patients who receive treatment with coal tar containing ointments of the risk of transfer of polycyclic aromatic hydrocarbons by skin-to-skin or skin-to-mouth contact.

The occupational exposure of dermatology nurses to polycyclic aromatic hydrocarbons - evaluating the effectiveness of better skin protection.

OBJECTIVES: We studied the uptake of polycyclic aromatic hydrocarbons (PAH) in nurses who apply ointments containing coal tar to patients and investigated the effectiveness of skin protection methods. METHODS: We determined gas-phase PAH on XAD-2 and particle-associated PAH on filters. We also used pads to determine PAH on the skin. Pyrene and benzo(a)pyrene were analyzed by gas chromatography/mass spectrometry and gas chromatography/tandem mass spectrometry; their respective urinary metabolites 1-hydroxypyrene and 3-hydroxybenzo(a)pyrene were analyzed using high performance liquid chromatography with fluorescence detection. RESULTS: We ruled out the inhalation of airborne pyrene and benzo(a)pyrene as the sources of PAH exposure. However, substantial amounts of pyrene and benzo(a)pyrene were observed on the hands of the nurses (median 33.0 and 16.4 ng/cm (2), respectively). Excretion of urinary 1-hydroxypyrene indicated an increased uptake of pyrene in 8 out of 12 nurses. We asked 35 nurses to perform a treatment with gloves followed by a second treatment without gloves. The use of gloves changed the excretion of 1-hydroxypyrene by -0.58 mumol (range -5.1-1.0 mumol), corresponding to a median reduction of 51.5% (P<0.001). Based on this finding, a new protocol was adopted, involving the permanent use of vinyl gloves and Tyvek sleeves. The effectiveness of this protocol was tested against pre-existing work practices and showed a 97% reduction in skin contamination with pyrene and benzo(a)pyrene, and a lowering in urinary excretion of 1-hydroxypyrene of 57%. CONCLUSION: Protecting the skin more stringently reduced pyrene and benzo(a)pyrene contamination of the hands, and lowered urinary excretion of 1-hydroxypyrene.

Effectiveness of a multidisciplinary itch-coping training programme in adults with atopic dermatitis.

The short- and longer-term effectiveness of a brief, multidisciplinary itch-coping group training scheme in adults with atopic dermatitis was evaluated. Clinical severity scores (Eczema Area and Severity Index) and validated self-report measures were obtained in a waiting-list control condition (n=30) and a treatment condition (n=61) at pre- and post-treatment and in the treatment condition at 3- and 12-month follow-ups. Relative to the control condition, all post-treatment measures showed improvements in terms of enhanced skin status, reduced itching and scratching and improved itch-coping patterns. In the treatment condition, the changes were sustained or further improved at both follow-ups. Also, the dermatological healthcare use was significantly reduced during the follow-up periods, in terms of fewer visits to the dermatologist and decreased use of topical corticosteroids and itch-relieving medication (histamine antagonists). The brief multidisciplinary itch-coping programme in adults with atopic dermatitis considerably reduced itch-scratching patterns, improved their skin status and reduced the use of dermatological care, both in the short and longer term.