Annette Pfahlberg

Current clinical diagnosis in Creutzfeldt‐Jakob disease: Identification of uncommon variants

According to the recently established molecular basis for phenotypic heterogeneity of sporadic Creutzfeldt‐Jakob disease (CJD), six different phenotypes are characterized by the size of the protease‐resistant fragment of the pathological prion protein (types 1 and 2) and homozygosity or heterozygosity for methionine or valine at codon 129 of the prion protein gene (designated by MM1, MM2, MV1, MV2, VV1, and VV2). In the present investigation, we analyzed the value of commonly used clinical tests (electroencephalogram [EEG], detection of 14‐3‐3 protein in cerebrospinal fluid [CSF], and hyperintensity of the basal ganglia in magnetic resonance imaging) for the clinical diagnosis in each CJD phenotype. The detection of periodic sharp and slow wave complexes in the EEG is reliable in the clinical diagnosis of MM1 and MV1 patients only. The CSF analysis for 14‐3‐3 protein showed high sensitivity in all analyzed subgroups with the exception of MV2 patients. Valine‐homozygous patients had a negative EEG, but most had detectable levels of neuronal proteins in the CSF. The sensitivity of the magnetic resonance imaging was 70%, irrespective of the subgroup, but was particularly reliable in the clinical diagnosis of MV2 patients. The widening spectrum of diagnostic techniques in CJD is not only useful in the increased accuracy of the clinical diagnosis but should also lead to the identification of more atypical cases of sporadic CJD. Ann Neurol 2000;48:323–329

Timing of excessive ultraviolet radiation and melanoma: epidemiology does not support the existence of a critical period of high susceptibility to solar ultraviolet radiation- induced melanoma

Background  The existence of a ‘critical period’ early in life characterized by a high susceptibility to melanoma initiation due to excessive ultraviolet (UV) radiation has been suggested by various authors based on epidemiological findings from migration studies and some case–control studies. However, the evidence so far is controversial as several epidemiological investigations failed to corroborate these results.

Diagnosis of Creutzfeldt-Jakob disease by measurement of S100 protein in serum: prospective case-control study

Abstract Abstract Objective: To analyse serum concentrations of brain specific S100 protein in patients with Creutzfeldt-Jakob disease and in controls. Design: Prospective case-control study. Setting: National Creutzfeldt-Jakob disease surveillance unit. Subjects: 224 patients referred to the surveillance unit with suspected Creutzfeldt-Jakob disease and 35 control patients without dementia. Main outcome measure: Serum concentration of S100 protein in patients with Creutzfeldt-Jakob disease, in patients with other diseases causing dementia, and in the control group. Results: Of the 224 patients with suspected Creutzfeldt-Jakob disease, 65 were classed as definitely having the disease after neuropathological verification, an additional 6 were classed as definitely having the disease as a result of a genetic mutation, 43 as probably having the disease, 36 as possibly having the disease, and 74 patients were classed as having other disease. In the 108 patients classed as definitely or probably having Creutzfeldt-Jakob disease the median serum concentration of S100 was 395 pg/ml (SD 387 pg/ml). This was significantly higher than concentrations found in the 74 patients classed as having other diseases (median 109 pg/ml; SD 177 pg/ml; P=0.0001). At a cut off point of 213 pg/ml sensitivity for the diagnosis of the disease was 77.8% (95% confidence interval 68.8% to 85.2%) and specificity was 81.1% (70.3% to 89.3%). There was a significant difference in survival at different concentrations of S100 in Kaplan-Meier curves (P=0.023). Conclusion: Measurement of serum concentrations of S100 is a valuable tool which can be used more easily than tests on cerebrospinal fluid in the differential diagnosis of Creutzfeldt-Jakob disease. More studies are needed to determine whether serial testing of serum S100 improves diagnostic accuracy. Key messages Creutzfeldt-Jakob disease is a rare, fatal neurodegenerative disease. Diagnosis is made clinically and neuropathologically There is no serum test which allows the diagnosis to be made while the patient is alive In this study raised serum concentrations of S100 protein were found in patients with Creutzfeldt-Jakob disease Serum concentrations of S100 could be used with a sensitivity of 77.8% and a specificity of 81.1% to confirm Creutzfeldt-Jakob disease in the differential diagnosis of diseases that cause dementia Serial measurement of S100 concentrations will enhance diagnostic accuracy

Hand dermatitis in a prospectively-followed cohort of hairdressing apprentices:nal results of the POSH study

The incidence of hand dermatitis is high in the hairdressing trade; the individual disease burden is substantial, as are the costs of treatment, workers compensation and retraining programs. To evaluate the risk of developing occupational irritant hand dermatitis associated with several potential risk factors, namely constitution (atopy) and occupational exposure, an observational prospective population‐based cohort study set in vocational training schools in northwest Germany, recruiting 2352 hairdressing apprentices, was performed. Unprotected wet work of more than 2 h per day is the major signicant risk factor; low ambient absolute humidity is equally associated with a signicantly increased risk. Compared to the youngest age group, risk diminishes with increasing age. Constitutional risk factors are difcult to evaluate because of selective dropout of atopic participants. For primary prevention, a population approach, improving working conditions and skin protection for all exposed, appears to be the most beneficial.

Risk factors for contact allergy to nickel – results of a multifactorial analysis

To quantify the independent impact of potential risk factors for nickel contact allergy (NCA), a multifactorial Poisson regression analysis of standardized anamnestic and patch test data (with nickel sulfate, 5% in petrolatum) was performed, comprising 74 940 patients assessed in the 33 German and Austrian contact dermatitis units of the Information Network of Departments of Dermatology (IVDK) between 1992 and 2000. NCA was observed in 15.5% patients. Female sex was the strongest risk factor (prevalence ratio 3.74, 95% CI: 3.51–3.98). Risk increased monotonically and significantly with decreasing age. Atopic dermatitis was not a risk factor. The year of patch test had no influence on NCA risk. Significant variation of risk between occupations was observed. In conclusion, our multifactorial analysis was able to quantify the impact of established risk factors and additionally address other, e.g. occupational, factors yet unidentified.

A multifactorial analysis of concurrent patch-test reactions to nickel, cobalt, and chromate.

Background:  Previous research indicates that positive patch tests to nickel (II) sulphate, cobalt (II) chloride and potassium dichromate commonly occur together.

Association between occupation and contact allergy to the fragrance mix: a multifactorial analysis of national surveillance data

OBJECTIVES To assess the role of potential (occupational) risk factors for fragrance contact allergy (FCA). Most studies assessing the range of contact sensitisation in various clinical populations found the fragrance mix, a good screening tool for the detection of FCA in general, to be one of the leading allergens. The role of occupational exposure to fragrances is, however, yet unclear. METHODS Firstly, crude analyses of the prevalence of FCA in various occupational fields including all 57 779 patients patch tested in the participating centres of the Information Network of Departments of Dermatology (IVDK) between January 1992 and December 1998. Secondly, a multifactorial Poisson regression analysis of these patients, including several potential risk factors. RESULTS (a) The proportion of patients with FCA varied greatly between different occupational groups from 2.5% to 17.4%, (b) the highest occupational risk of FCA was associated with work as a masseur or physiotherapist, metal furnace operator, potter or glass maker etc, or geriatric nurse, (c) non-occupational factors that influenced risk of FCA included atopy, female sex, several sites, in particular the axillae, and increasing age. CONCLUSIONS Occupations with a high risk of FCA were identified as targets of preventive action—that is, the substitution of scented products with fragrance free materials with which to work (skin disinfectants, cleaning solutions, personal care products) wherever possible.

Effectiveness of skin protection measures in prevention of occupational hand eczema: results of a prospective randomized controlled trial over a follow-up period of 1 year

Background  We recently found a very low adherence to a generally recommended skin protection regimen in a sample of 1355 metalworkers.

The spectrum of contact allergy in elderly patients with and without lower leg dermatitis.

Background: There is a strong influence of lower leg dermatitis on the spectrum of allergic contact sensitivity in elderly patients. Objective: To quantitatively assess the impact of this factor which confounds the age-related pattern of allergic contact sensitivity. Methods: Stratified analysis of allergic contact sensitivity data collected between 1996 and 1999 in the 32 centres of the Information Network of Departments of Dermatology (three age groups: ≤60, 61–75, ≧76 years), both as crude and as directly standardised (for sex and leg dermatitis) proportions. Results: Among the 36,070 patients tested with the German standard series, allergic contact sensitivity to neomycin, lanolin, cetostearylic alcohols, colophony, fragrance mix and balsam of Peru, among others, was (much) more common in the elderly, with proportions more or less affected by standardisation. Conclusion: The comparison of crude and standardised proportions provides evidence that allergic contact sensitivity to several allergens strongly depends not only on age itself, but on age-related and thus confounding co-morbidity.

Infections and melanoma risk: results of a multicentre Eortc case-control study

Immune function plays a prominent role in the defence against cutaneous malignant melanoma and the increased risk of melanoma development during immunosuppression. Since the immune system is challenged beyond its routine activity by an infection, the effect of previous infectious diseases on the risk of melanoma may also be crucial. In a European Organization for Research and Treatment of Cancer (EORTC) case-control study performed in six European countries and Israel, we compared the history of severe infections in 603 melanoma patients with that in 627 population controls. We calculated adjusted odds ratios (ORs) to estimate the effect of infectious diseases on melanoma risk. The ORs for melanoma risk were below 1 for nearly all types of infections (except two) if body temperature was not taken into consideration, and for all infections with a body temperature above 38.5 degrees C. In the latter category significantly lowered ORs were found for pulmonary tuberculosis (0.16; 95% confidence interval [CI] 0.01-0.98), Staphylococcus aureus infections (0.54; 95% CI 0.31-0.94), sepsis (0.23; 95% CI 0.06-0.70), influenza and related infections (0.65; 95% CI 0.48-0.86) and pneumonia (0.45; 95% CI 0.27-0.73). Analysis of the cumulative influence revealed a consistent pattern of results pointing to a reduction in melanoma risk with increasing numbers of recorded infections and fever height. This apparent dose-response relationship suggests a causal association. Speculations on the underlying mechanism include a Shwartzman-like phenomenon when melanoma formation precedes the infection and/or an infection-related Th1-cell activation preventing the establishment of the tumour.