Epidemiology of patch tested patients with permanent tattoos-A comparative analysis of 9693 IVDK patients (2020-2022).

BACKGROUND: Permanent tattooing is the invasive introduction of tattoo ink (pigments) into the dermis. The ink and aftercare cosmetics applied on pre-damaged skin may contain skin sensitisers. OBJECTIVES: To identify patient characteristics and the pattern of sensitisation in tattooed patients patch tested within the Information Network of Departments of Dermatology (IVDK). PATIENTS AND METHODS: Comparative analysis of patient characteristics and reaction frequencies to baseline series allergens in 1648 consecutive patients with and 8045 consecutive patients without permanent tattoos. Non-overlapping 95%-confidence intervals were considered as significant. RESULTS: Having permanent tattoos was related with female sex, age <40 years, tobacco smoking, atopic dermatitis, (occupational) hand dermatitis and being employed in particular occupational groups (e.g., healthcare workers, mechanics, hairdressers). Sensitisation to nickel was increased in tattooed patients and associated with female sex (OR 4.23 [95%-CI, 3.48-5.18]), age ≥40 years (OR 1.26 [95%-CI, 1.08-1.49]), tobacco smoking (OR 1.19 [95%-CI, 1.01-1.40]) and having permanent tattoos (OR 1.27 [95%-CI, 1.05-1.53]). CONCLUSIONS: The association between nickel sensitisation and permanent tattoos is probably confounded by past reactions to pierced costume jewellery. Socio-economic factors most probably contribute to the connection between tattoos, tobacco smoking, occupational or hand dermatitis, and being employed in particular occupational groups.

Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia.

Mutations in SCN2A cause epilepsy syndromes of variable severity including neonatal-infantile seizures. In one case, we previously described additional childhood-onset episodic ataxia. Here, we corroborate and detail the latter phenotype in three further cases. We describe the clinical characteristics, identify the causative SCN2A mutations and determine their functional consequences using whole-cell patch-clamping in mammalian cells. In total, four probands presented with neonatal-onset seizures remitting after five to 13 months. In early childhood, they started to experience repeated episodes of ataxia, accompanied in part by headache or back pain lasting minutes to several hours. In two of the new cases, we detected the novel mutation p.Arg1882Gly. While this mutation occurred de novo in both patients, one of them carries an additional known variant on the same SCN2A allele, inherited from the unaffected father (p.Gly1522Ala). Whereas p.Arg1882Gly alone shifted the activation curve by -4 mV, the combination of both variants did not affect activation, but caused a depolarizing shift of voltage-dependent inactivation, and a significant increase in Na(+) current density and protein production. p.Gly1522Ala alone did not change channel gating. The third new proband carries the same de novo SCN2A gain-of-function mutation as our first published case (p.Ala263Val). Our findings broaden the clinical spectrum observed with SCN2A gain-of-function mutations, showing that fairly different biophysical mechanisms can cause a convergent clinical phenotype of neonatal seizures and later onset episodic ataxia.

Contact allergy induced by bisphenol A diglycidyl ether leachables from aluminium tubes for pharmaceutical use.

BACKGROUND: Aluminium tubes for pharmaceutical use are internally lacquered with epoxy resins (ER) based on bisphenol A diglycidyl ether (BADGE). Recently, it was shown that remnants of ER polymerization like BADGE are extractable from epoxy-based coatings of commercially available tubes and may leach into semi-solid drug preparations. We aimed to evaluate the safety of BADGE-contaminated macrogol ointments in individuals sensitized to ER based on BADGE by use tests. METHODS: Repeated open application testing (ROAT) in 11 patients sensitized to ER based on BADGE with BADGE in macrogol ointments (3 mg/kg; 30 mg/kg, equivalent to BADGE concentration determined in macrogol ointment after storage in a commercially available tube; 300 mg/kg). RESULTS: The 30 mg/kg BADGE ointment elicited reactions in three patients, and another three patients reacted to 300 mg/kg BADGE ointment. No reactions to the vehicle control and 3 mg/kg BADGE were observed. CONCLUSIONS: Elevated BADGE concentrations in ER-coated aluminium tubes pose a risk of developing contact dermatitis to patients sensitized to ER based on BADGE. Quality standards are deemed necessary for the production of ER-coated aluminium tubes intended for pharmaceutical use and should consider the results of the present ROAT study.

Skin irritability to sodium lauryl sulfate is associated with increased positive patch test reactions.

BACKGROUND: As previous observations have indicated an inter-relationship between irritant and allergic skin reactions we analysed data of synchronous allergen and sodium lauryl sulfate (SLS) patch tests in terms of a relationship between SLS responsiveness and allergic patch test reactions. OBJECTIVES: To analyse differences in terms of allergen-specific and overall reaction profiles between patients with vs. those without an irritant reaction to SLS. METHODS: Clinical data of 26 879 patients patch tested from 2008 to 2011 by members of the Information Network of Departments of Dermatology were analysed. After descriptive analyses, including the MOAHLFA index, the positivity ratio and the reaction index, a negative binomial hurdle model was adopted to investigate the correlation between SLS reactivity and positive patch test reactions. RESULTS: Men, patients aged ≥ 40 years and patients with an occupational dermatitis background were over-represented in the SLS-reactive group. Patients with an irritant reaction to SLS showed a higher proportion of weak positive reactions, as well as more questionable and irritant reactions to contact allergens than patients not reactive to SLS. The risk of an additional positive patch test reaction increased by 22% for SLS-reactive patients compared with those who were SLS negative. CONCLUSIONS: The marked association between SLS reactivity and the number of positive reactions in patch test patients may be due to nonspecific increased skin reactivity at the moment of patch testing only. However, increased SLS reactivity could also be due to longer-lasting enhanced skin irritability, which may have promoted (poly-)sensitization. Further studies, for example with longitudinal data on patients repeatedly patch tested with SLS and contact allergens, are necessary.

[Cancer of unknown primary. Epidemiology and pathogenesis]. / CUP-Syndrom. Epidemiologie und Pathogenese.

DEFINITION: The term cancer of unknown primary (CUP) describes by definition epithelial malignancies for which no primary tumor can be found after primary diagnostics have been performed. EPIDEMIOLOGY: The CUP syndrome constitutes 2-3% of all fatal cases of malignancies in both men and women. The proportion of women has increased in parallel to the increase of tobacco consumption in women. PATHOGENESIS: The most frequent origin appears to lie in the lungs or upper abdominal organs, while notable differences can be found between older autopsy findings and recent gene expression data with respect to identified primary tumors or tissue assignation. The fact that a primary tumor cannot be identified is probably based on various reasons: a complete regression of a primary tumor in isolated cases seems to be just as plausible as the misclassification of a primary tumor as a metastasis. CONCLUSION: In combination with the fact that a primary tumor cannot be identified by autopsy in more than 20 % of cases, the important conclusion can be drawn that curative approaches seem appropriate for localized CUP cases.

[Structured diagnostics and therapy of the CUP syndrome]. / Strukturierte Diagnostik und internistische Therapie des CUP-Syndroms.

BACKGROUND: In the majority of cases, patients with cancer of unknown primary (CUP) have a poor prognosis with no prospect of being cured. Hence, a reasonable focus of diagnostics on its essential targets seems appropriate. PATIENTS: Particularly important is the identification of all patients who can be assigned to subgroups with a favorable prognosis and who might benefit from a specific therapy. For all other patients, platinum-based combination therapy is the standard cytostatic therapy. THERAPY: In addition to platinum derivatives, taxanes, gemcitabine and irinotecan can also be used. Promising innovative approaches include targeted therapies, in particular bevacizumab and erlotinib, and identification of the tissue origin with micro-RNA or gene expression analyses which can help identify the most suitable organ-specific therapy for individual patients. PERSPECTIVES: It would be desirable if the group of patients treated with unspecific therapy could be reduced by improved diagnostics so that these patients could be treated with organ-specific therapy or with molecularly targeted approaches. Micro-RNA and gene expression analyses appear to be interesting for this purpose. Another complementary approach is to improve the treatment results of patients receiving an unspecific standard combination therapy by additional administration of new targeted substances.

[Phlebology in German departments of dermatology. An analysis on behalf of the German Society of Phlebology]. / Phlebologie an deutschen Hautkliniken. Eine Bestandsaufnahme im Auftrag der Deutschen Gesellschaft für Phlebologie.

BACKGROUND: Phlebologic diseases have become extremely common and have major socio-economic impact. However, the percentage of dermatologists working in phlebology appears to be decreasing according to the data of the German Society of Phlebology (DGP). METHODS: To investigate the reasons for this development, we--on behalf of the DGP--sent a questionnaire to 120 German Departments of Dermatology in autumn 2012. RESULTS: In 76 returned questionnaires, the number of physicians with additional fellowship training in phlebology averaged 1.5; the average number of those who fulfill the criteria for training fellows in phlebology was 0.9. In 71.1 % of the departments there was a phlebologist. A special phlebologic outpatient clinic existed in 73.7 % of the departments. Sonography with Doppler (89.5 %) and duplex (86.8 %) was used as the most frequent diagnostic tool. For therapy, compression (94.7 %), sclerotherapy (liquid 78.9 %, foam 63.2 %, catheter 18.4 %), endoluminal thermic procedures (radio wave 28.9 %, laser 17.1 %) and surgery (especially crossectomy and stripping 67.1 %, phlebectomy of tributaries 75 %) were used. The average number of treatments was very heterogenous in the different departments. CONCLUSIONS: Phlebology definitely plays an important role in dermatology. Most departments fulfill the formal criteria for the license to conduct advanced training in phlebology. A wide spectrum of phlebological diagnostic and therapeutic procedures is available.

DNA damage-induced centrosome amplification occurs via excessive formation of centriolar satellites.

Centrosome amplification is a frequent phenomenon in malignancies and may facilitate tumorigenesis by promoting chromosomal instability. On the other hand, a centrosome inactivation checkpoint comprising centrosome amplification leading to elimination of cells by mitotic catastrophe has been described in response to DNA damage by ionizing radiation or cytostatic drugs. So far, the exact nature of DNA damage-induced centrosome amplification, which might be overduplication or fragmentation of existing centrosomes, has been controversial. To solve this controversy, we have established a method to distinguish between these two possibilities using A549 cells expressing photoconvertible CETN2-Dendra2. In response to various DNA-damaging treatments, centrosome amplification but not fragmentation was observed. Moreover, centrosome amplification was preceded by excessive formation of centrin-containing centriolar satellites, which were identified as de novo-generated atypical centrin dots staining positive for centriolar satellite markers but negative or only weakly positive for other established centrosomal markers, and which could be verified as centriolar satellites using immunogold electron microscopy. In line with this notion, disruption of dynein-mediated recruitment of centrosomal proteins via centriolar satellites suppressed centrosome amplification after DNA damage, and excessive formation of centriolar satellites could be inhibited by interference with Chk1, a known mediator of centrosome amplification in response to DNA damage. In conclusion, we provide a model in which a Chk1-mediated DNA damage checkpoint induces excessive formation of centriolar satellites constituting assembly platforms for centrosomal proteins, which subsequently leads to centrosome amplification.

Effects of acute psychological stress on glucose metabolism and subclinical inflammation in patients with post-traumatic stress disorder.

During acute psychological stress, the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system are activated. The released stress hormones influence glucose metabolism, can activate immune cells, and modulate subclinical inflammation. The aim of our study was to analyze the effect of acute psychological stress on glucose metabolism and the inflammatory status in patients with post-traumatic stress disorder (PTSD). We included 15 overweight male Bosnian war refugees with PTSD into the study (mean age 44+/-11 years, BMI 29.3+/-4.3 kg/m (2)). All subjects underwent an oral glucose tolerance test (OGTT) with either acute stress (trauma script exposure) or a resting period in a cross-over design. Blood was drawn over 2.5 h and metabolic markers were measured. Systemic levels of immune markers were determined using high-sensitive ELISA or bead-based multiplex assay. Immune gene expression was quantified by RT-PCR. After being exposed to acute stress, cortisol levels and heart frequency tended to be increased. Higher blood glucose and insulin levels after stress exposure were observed (p<0.05). Systemic levels of the chemokines interferon-gamma-inducible protein-10 and macrophage chemoattractant protein-1 were decreased compared to the control day (both p<0.05) and the expression of the proinflammatory regulator IKK beta was significantly reduced after stress exposure (p<0.001). In conclusion, acute stress induces postprandial blood glucose peaks and elevated insulin levels and a selective decrease of systemic immune markers and the proinflammatory regulator of the NF kappaB cascade, which are associated with type 2 diabetes. This points towards an independent effect of acute psychological stress on glucose metabolism and inflammation.

[Propranolol therapy to treat problematic hemangiomas : a new standard therapy makes its debut]. / Die Propranolol-Therapie in der Behandlung problematischer Hämangiome : Eine neue Standardtherapie kündigt sich an.

Small hemangiomas sometimes produce large findings. Depending on localization, local therapy is not always possible. According to a case described in the literature, a hemangioma in an infant regressed following cardiologically indicated Propranolol. This experience has been used in numerous other cases since then and Propranolol has been administered for the indication of a hemangioma. Even in cases of very large hemangiomas rapid improvement has been observed; successful results persisted even after discontinuation. Particularly in cases of problematic localisation, such as in the eye area, prompt therapeutic success is important in order to prevent blindness. Relevant studies are in the preparatory phase.

[Blastic plasmacytoid dendritic cell neoplasm - a rare differential diagnosis of neoplastic skin infiltrations associated with systemic symptoms]. / Blastische plasmozytoide Neoplasie dendritischer Zellen - seltene Differenzialdiagnose neoplastischer Hautinfiltrate mit systemischer Beteiligung.

HISTORY AND CLINICAL FINDINGS: A 70-year-old female patient developed a non-pruritic, indolent rash associated with infections and peripheral blood abnormalities. A skin biopsy was suggestive of malignant lymphoma of the skin. INVESTIGATIONS: The peripheral blood count showed mild pancytopenia and 12 % blasts. Additional immunohistochemistry of the skin specimen as well as cytologic and flow cytometric examination of the bone marrow revealed an immature cell population expressing CD4 and CD56 which infiltrated both the dermis and, with an infiltration grade of about 85 %, the bone marrow. DIAGNOSIS: Blastic plasmacytoid dendritic cell neoplasm (formerly known as blastic NK cell lymphoma). TREATMENT AND COURSE: After the first course of induction chemotherapy with daunorubicin and cytarabin, both the rash and the hematologic findings of bone marrow and peripheral blood showed a complete remission. CONCLUSION: The blastic plasmacytoid dendritic cell neoplasm is a rare, aggressive hematopoietic neoplasm most likely related to acute myeloid leukemia (AML). Since cutaneous involvement is regularly present at diagnosis, the differential diagnosis of unexplained skin lesions should include this disease entity, especially if peripheral blood abnormalities are present. Despite the initial response to cytostatic therapy being mostly excellent, the prognosis is poor. Hence, treatment as high-risk AML seems advisable.

AML with translocation t(8;16)(p11;p13) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features.

Balanced chromosomal rearrangements define distinct entities in acute myeloid leukemia (AML). Here, we present 13 AML cases with t(8;16)(p11;p13) with observed low incidence (13/6124 patients), but more frequent presentation in therapy-related AML than in de novo AML (7/438 versus 6/5686, P=0.00001). Prognosis was poor with median overall survival of 4.7 months. Cytomorphology was characterized by parallel positive myeloperoxidase and non-specific esterase staining, therefore, French-American-British (FAB)-classification was impossible and origin of the AML with t(8;16) from an early stem cell with myeloid and monoblastic potential is hypothesized. Erythrophagocytosis was observed in 7/13 cases. Using gene expression profiling on 407 cases, patients with t(8;16) were compared to AML FAB subtypes with normal karyotype. Principal component analyses demonstrated that AML with t(8;16) were distinct from FAB subtypes M1, M4, M5a/b. When further compared to AML showing balanced rearrangements, that is, current WHO categories t(15;17), t(8;21), inv(16) and t(11q23)/MLL, AML with t(8;16) cases were clustered close to t(11q23)/MLL sharing commonly expressed genes. Subsequently, a pairwise comparison discriminated AML with t(8;16) from AML with t(11q23)/MLL, thus defining a highly unique signature for AML with t(8;16). In conclusion, AML with t(8;16) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features and is a specific subtype of AML.

Nurses' perceptions of the benefits and adverse effects of hand disinfection: alcohol-based hand rubs vs. hygienic handwashing: a multicentre questionnaire study with additional patch testing by the German Contact Dermatitis Research Group.

BACKGROUND: Nurses have a high risk of developing hand eczema due to hand disinfection procedures. OBJECTIVES: To investigate the perception of nurses regarding the adverse effects of hand washing (HW) and alcoholic disinfection (ADI), and to obtain data on the prevalence of hand dermatitis and sensitization to alcohols and alcohol-based hand rubs (ABHRs). METHODS: A self-administered questionnaire survey, carried out as a pilot study (PS), followed by a modified multicentre study (MC) in five hospitals. Patch tests to ethanol (80%), 1-propanol (60%), 2-propanol (70%) and ABHRs were performed in a subsample. RESULTS: The majority (PS 60.1%; MC 69.5%) of nurses considered ADI to be more damaging than HW. Mostly, ADI and HW were suspected to have irritant effects (ADI 79.2%/52.1%; HW 65.5%/36.2%) compared with an allergenic potential (ADI 10.4%/5.8%; HW 7.8%/3.9%). The prevalence of hand dermatitis in the MC was 13.4% by self-diagnosis and 22.4% by symptom-based questions. In 50 tested individuals no sensitization and only two irritant reactions to alcohols and three single-positive reactions to ABHRs were observed, none of the latter related to alcohols. CONCLUSIONS: Although ADI is known to cause less skin irritation than HW, nurses perceive ADI as more damaging, resulting in: (i) a low compliance with ADI and (ii) a higher prevalence of hand dermatitis because the more deleterious HW is preferred. This may result in an increase in occupational disease and nosocomial infections. Educational programmes should promote ADI as a procedure with good efficiency and skin tolerability to reduce the prevalence of hand eczema in nurses and to enhance compliance with hand hygiene standards.

How irritant is alcohol?

BACKGROUND: Alcohol-based hand rubs are used worldwide to prevent transmission of nosocomial pathogens. OBJECTIVES: To investigate skin irritation caused by alcohols alone and in combination with detergent washing. METHODS: Single and repetitive patch testing with 60-100% alcohols [ethanol, 1-propanol, 2-propanol (synonyms: isopropyl alcohol, isopropanol)], a positive control [0.5% sodium lauryl sulphate (SLS)] and negative controls (empty chamber and water) were performed. Wash tests were performed with 80% ethanol and 0.5% SLS on the forearms with each agent alone and with both agents in a tandem design. Skin hydration, erythema and barrier disruption [measured as transepidermal water loss (TEWL)] were evaluated (always 15 volunteers). RESULTS: We found no significant change in skin barrier or erythema induced by the alcohols in the patch tests, whereas skin hydration decreased significantly. Application of alcohols to previously irritated skin did not show a stronger skin barrier disruption than application of SLS alone. Wash tests demonstrated that alcohol application caused significantly less skin irritation than washing with a detergent (TEWL, P < 0.001; skin hydration, P < 0.05; erythema, P < 0.05). Even on previously irritated skin, ethanol did not enhance irritation. By contrast, a protective effect of ethanol used after skin washing was observed (TEWL, P < 0.05; skin hydration, P < 0.05; erythema, P < 0.05). CONCLUSIONS: Alcohol-based hand rubs cause less skin irritation than hand washing and are therefore preferred for hand hygiene from the dermatological point of view. An alcohol-based hand rub may even decrease rather than increase skin irritation after a hand wash due to a mechanical partial elimination of the detergent.

Dose-dependent induction of IL-6 by plant-derived proteases in vitro.

Oral administration of proteases such as bromelain and papain is commonly used in patients with a wide range of inflammatory conditions, but their molecular and cellular mechanisms of action are still poorly understood. The aim of our study was to investigate the impact of these proteases on the release of interleukin-6 (IL-6) and other cytokines in the recently described modified mixed lymphocyte culture (MMLC) test system which is based on the mutual interaction of cells of the innate and adaptive immunity. Bromelain and papain enhanced IL-6 production dose-dependently up to 400-fold in MMLC before and up to 30-fold after neutralization of LPS content of proteases using polymyxin B, indicating that IL-6 induction by protease treatment was attributable to both protease action and LPS content of enzyme preparations. The production of IFNgamma and IL-10 was not altered by bromelain or papain, indicating a selective and differential immune activation. Both proteases impaired cytokine stability, cell proliferation and expression of cell surface molecules like CD14 only marginally, suggesting no impact of these mechanisms on protease-mediated cytokine release. These findings might provide the mechanistic rationale for the current use of proteases in wound healing and tissue regeneration since these processes depend on IL-6 induction.

Quantitative patch and repeated open application testing in methyldibromo glutaronitrile-sensitive patients.

Contact allergy to methyldibromo glutaronitrile (MDBGN), often combined with phenoxyethanol (PE) (e.g., Euxyl K 400), increased throughout the 1990s in Europe. Consequently, in 2003, the European Commission banned its use in leave-on products, where its use concentration was considered too high and the non-sensitizing use concentration as yet unknown. The 2 objectives of the study are (a) to find a maximum non-eliciting concentration in a leave-on product in MDBGN/PE-sensitized patients, which could possibly also be considered safe regarding induction and (b) to find the best patch test concentration for MDBGN. We, therefore, performed a use-related test (ROAT) in patients sensitized to MDBGN/PE (n = 39) with 3 concentrations of MDBGN/PE (50, 100 and 250 p.p.m. MDBGN, respectively). A subset of these patients (n = 24) was later patch-tested with various concentrations (0.1, 0.2, 0.3 and 0.5% MDBGN, respectively). 15 patients (38%, 95% confidence interval (CI) = 23-55%) had a negative and 24 (62%; 95% CI = 45-77%) a positive overall repeated open application test (ROAT) result. 13 reacted to the lowest (50 p.p.m.), 8 to the middle (100 p.p.m.) and 3 to the highest concentration (250 p.p.m.) only. In those 13 reacting to the lowest ROAT concentration, dermatitis developed within a few days (1-7). The strength of the initial and the confirmatory patch test result, respectively, and the outcome of the ROAT were positively associated. Of the 24 patients with a use and confirmatory patch test, 15 reacted to 0.1% MDBGN, 16 to 0.2%, 17 to 0.3% and 22 to 0.5%. With the patch test concentration of 0.5%, the number of ROAT-negative patients but patch-test-positive patients increases considerably, particularly due to + reactions. A maximum sensitivity of 94% (95% CI = 70-100%) is reached with a patch test concentration of 0.2%, and is not further improved by increasing the concentration. However, the specificity decreases dramatically from 88 (95% CI = 47-100%) with 0.2% to a mere 12.5% (95% CI = 0-53%) with 0.5%. It can be concluded (a) that for MDBGN 0.2% is very likely the best patch test concentration and (b) that 50 p.p.m. in a leave-on product can elicit contact dermatitis in sensitized persons. We were, therefore, unable to find a safe, still microbicidal, concentration for leave-on products. By contrast, with other contact allergens, dose-response use tests may be able to identify a non-eliciting concentration, which could give valuable clues to a non-inducing (i.e., safe) concentration in products.

[Clinical trials in Germany and in the EU in the new legislative environment. An analysis from the industry's point of view]. / Klinische Prüfungen in Deutschland und der EU im neuen gesetzlichen Umfeld Eine Analyse aus Sicht der pharmazeutischen Industrie.

The European Union's (EU) Directive 2001/20/EC and its accompanying directives and guidance aim at approximating laws, regulations and administrative provisions relating to the implementation of Good Clinical Practice and Good Manufacturing Practice in the conduct of clinical trials on investigational medicinal products for human use in the EU member states. In addition, the establishment of two European databases for collecting information on clinical trials and suspected unexpected serious adverse events, respectively, should increase the transparency of clinical trials in the EU and thus improve patient safety. Some member states have not implemented the EU directive yet, others have implemented modified requirements, i.e. the pharmaceutical industry in the EU is confronted with different national solutions for specific aspects of the conduct of clinical trials. For industry, this creates additional work and expense. There is the hope that patient safety will be improved by these measures. The future task of all involved stakeholders will be to work on a harmonisation of the different requirements in order to achieve the original goals intended by the Directive 2001/20/EC.

Simultaneous sodium lauryl sulphate testing improves the diagnostic validity of allergic patch tests. Results from a prospective multicentre study of the German Contact Dermatitis Research Group (Deutsche Kontaktallergie-Gruppe, DKG).

BACKGROUND: There is evidence that a higher skin susceptibility may induce nonspecific erythematous or weak positive reactions to contact allergens in patch testing. OBJECTIVES: To evaluate whether simultaneous application of sodium lauryl sulphate (SLS) along with diagnostic patch tests with contact allergens can provide information regarding skin irritability which may help to discriminate allergic from nonspecific irritant reactions to contact allergens. METHODS: Between July 2001 and June 2003, this prospective study collected patch test data of 5971 patients from 19 centres in Germany and Austria in the Information Network of Departments of Dermatology (IVDK). In addition to contact allergens (standard series and eight known 'problematic' allergens with a low reaction index and a high positivity ratio: 1,3-diphenylguanidine, amerchol L-101, benzalkonium chloride, benzoyl peroxide, cocamidopropyl betaine, octyl gallate, phenyl mercuric acetate and propylene glycol), patches with SLS 0.5% and 0.25% aq. were applied. Reactions to the allergens and to SLS were analysed at the IVDK data centre. The association between an erythematous or positive reaction to a certain allergen and an irritant reaction to SLS was assessed with logistic regression analysis, at the same time controlling for the influence of age and sex. RESULTS: Of the 29 allergens of the standard series, 23 and 21 gave a higher percentage of nonspecific erythematous reactions in patients with an irritant reaction to 0.25% and 0.5% SLS, respectively, in comparison with SLS-negative patients. All eight 'problematic' allergens gave an increased percentage of nonspecific erythematous reactions. Similarly, 22 and 21 allergens of the standard series gave a higher percentage of positive allergic reactions in patients with an irritant reaction to 0.25% and 0.5% SLS, respectively, and seven of the eight 'problematic' allergens gave a higher percentage of positive allergic reactions (exception: octyl gallate). For most allergens, the markers of skin reaction (reaction index and positivity ratio) were worse in SLS-positive patients. Differences were more pronounced when testing with SLS 0.25% than with SLS 0.5%. CONCLUSIONS: Because there is a convincing association between skin irritability (evaluated by SLS test) and the degree of skin reaction to contact allergens, the SLS test may help in deciding whether a doubtful erythematous or weakly 'positive' skin reaction should be interpreted as allergic or irritant.

Gender aspects in chronic myeloid leukemia: long-term results from randomized studies.

Gender-related aspects in chronic myeloid leukemia (CML) have not been studied well. We therefore analyzed 856 patients with Ph/BCR-ABL-positive CML from the German randomized CML-studies I (interferon alpha (IFN) vs hydroxyurea (HU) vs busulfan) and II (IFN+HU vs HU alone). The median observation time was 8.6 years. A total of 503 patients (59%) were male. Female patients were older (51 vs 46 years; P<0.0001), presented with lower hemoglobin (11.7 vs 12.5 g/dl; P<0.0001), higher platelet counts (459 vs 355 x 10(9)/l; P<0.0001), smaller spleen size (3 vs 4 cm below costal margin; P=0.0097), a lower rate of additional cytogenetic aberrations (9 vs 15%; P=0.018) and a less favorable risk profile (P=0.036). The transplantation rate was 14% for female (n=48) and 22% for male patients (n=113). Median survival was longer in female patients (58 vs 49 months; P=0.035) mainly attributable to better survival in the low- and intermediate-risk groups and, independent from risk groups, in the HU group. These results were confirmed by matched-pair analyses based on German population data (n=496, 59 vs 45 months; P=0.0006). This is the first analysis of gender aspects in CML using randomized trials. It demonstrates the relevance of analyses of gender differences in CML and in malignant disease at large.