[Papular drug eruption along the lines of Blaschko caused by lenalidomide]. / Papulöse Arzneimittelreaktion entlang der Blaschko-Linien durch Lenalidomid.

Cutaneous drug reactions can take many forms. In rare cases these reactions can occur along the lines of Blaschko. A 60-year-old patient received lenalidomide in 3-weeks-cycles for the treatment of a plasmocytoma. After four months of treatment, red papules appeared on the extremities and the trunk following the lines of Blaschko. The lesions nearly disappeared during drug-free intervals and appeared with renewed intensity after restart of a therapy cycle.

The importance of context information in the diagnostic rating of digital images of patch test reactions.

BACKGROUND: Patch test (PT) guidelines recommend classifying PT reactions based on morphological criteria only, i.e. irrespective of context information such as substance, concentration and vehicle. OBJECTIVES: To analyse reclassification of PT reactions after revelation of context information subsequent to an initial blinded reading. METHODS: One hundred and twenty-two participants (experienced dermatologists and researchers) rated 20 digital images of different PT reactions twice, first blinded, then unblinded regarding substance, concentration and vehicle. Agreement between both ratings was quantified with Cohen's kappa, and systematic differences statistically examined with tests for marginal homogeneity. RESULTS: Mostly, ratings remained stable, e.g. in > 90% of cases of images showing typical strong or extreme positive PT reactions. Reclassification was comparatively often observed in images depicting irritant reactions. Conversely, 16 of 122 participants re-rated doubtful reactions to thiuram mix and dichromate, respectively, as 'allergic' (weak or strong positive) after knowing the substance. CONCLUSIONS: The considerable proportion of participants who choose an 'allergic' rating, despite a morphological presentation definitely not justifying this, points to a conceptual problem of the PT reading scale: the mixing up of morphological classification and interpretation. We therefore suggest amending the scale. Moreover, standardization of PT reading can be improved by continual PT training sessions.

Hand eczema classification: a cross-sectional, multicentre study of the aetiology and morphology of hand eczema.

BACKGROUND: Hand eczema is a long-lasting disease with a high prevalence in the background population. The disease has severe, negative effects on quality of life and sometimes on social status. Epidemiological studies have identified risk factors for onset and prognosis, but treatment of the disease is rarely evidence based, and a classification system for different subdiagnoses of hand eczema is not agreed upon. Randomized controlled trials investigating the treatment of hand eczema are called for. For this, as well as for clinical purposes, a generally accepted classification system for hand eczema is needed. OBJECTIVES: The present study attempts to characterize subdiagnoses of hand eczema with respect to basic demographics, medical history and morphology. METHODS: Clinical data from 416 patients with hand eczema from 10 European patch test clinics were assessed. RESULTS: A classification system for hand eczema is proposed. CONCLUSIONS: It is suggested that this classification be used in clinical work and in clinical trials.

para-Phenylenediamine: the profile of an important allergen. Results of the IVDK.

BACKGROUND: para-Phenylenediamine (PPD) is an important contact allergen and primarily used in hair dyeing. OBJECTIVES: To quantify cases of contact allergy (CA) to PPD attributed to sources of exposure. METHODS: Patients with PPD CA, diagnosed by the Information Network of Departments of Dermatology (IVDK; n = 3307 of 83 030 patients tested), were divided into five subgroups of exposure. Demographic variables and pattern of concomitant reactions were used to characterize the subgroups further. The impact of individual factors on the risk of PPD CA was examined with a logistic regression analysis. Clinical epidemiology and drug utilization research (CE-DUR) methods were employed to estimate the 10-year prevalence of PPD CA in the general population. RESULTS: The 4% prevalence of PPD CA in patients was extrapolated to a prevalence of 0.96% in the general population. The defined profiles were found to 'explain' the following percentages of PPD CA: (i) hair dyeing in clients 22% (0.2% of the general population); (ii) different occupational exposures, namely hair dyeing by hairdressers, paint- and rubber-associated exposures 23% (0.22% of the general population); (iii) clothing/shoes 12% (0.12% of the general population). A probable causal exposure to PPD could not be identified in about 44% of patients with PPD CA. CONCLUSIONS: In more than 50% of cases of PPD CA, a (very) probable causal exposure was identified. In the large remainder (44%) this was not possible. 'Historical' CA without current relevance and active sensitization through patch testing (a further important exposure to PPD) must be considered in these patients.

Surfactants cause in vitro chemotaxis and chemokinesis of human neutrophils.

The surfactant sodium lauryl sulfate (SLS) and alkyldimethylbenzylammonium chloride (ADB) cause erythema and leukocyte infiltration on epicutaneous application. To elucidate the mechanism of this inflammatory response, the in vitro effect of the same agents was studied on human neutrophil migration, basophil histamine release, and leukocyte lysosomal enzyme (beta-glucuronidase) release. At concentrations of greater than 0.02%, both surfactants were cytotoxic, as was evident by decreased eosin exclusion, massive histamine and beta-glucuronidase-release, and absent migration of cells. At dilutions of less than 0.002% of both surfactants, viability of cells was normal, and small amounts of histamine and beta-glucuronidase were released at a dilution of 0.001%. The most striking finding was a dose-dependent chemotactic and chemokinetic response at dilutions from 10(-3) to 10(-8)%. These observations offer a possible explanation for the pathomechanisms of irritant dermatitis due to surfactants.

Response of cutaneous mast cells to PUVA in patients with urticaria pigmentosa: histomorphometric, ultrastructural, and biochemical investigations.

In six patients with urticaria pigmentosa, population density and ultrastructure of the cutaneous mast cells and histamine levels of the lesional skin were studied before, immediately after, and again 5-8 months after photochemotherapy (PUVA). Immediately after PUVA, the total mast cell number was not reduced, but on separate analysis of the intradermal distribution, significantly fewer mast cells were found in the papillary dermis and correspondingly more mast cells in the adjacent upper dermis. On electron microscopic examination, 4% of the mast cell granules were immature before and 27% after PUVA therapy, based on the lower electron density of the granular matrix. This was associated with a markedly lower histamine content of the lesional skin. Five to eight months after recovery from PUVA, the morphologic changes and the histamine levels had all returned to the pre-PUVA status. These findings were paralleled by a reversal of all clinical beneficial effects that had been observed with PUVA.

Anti-P. acnes antibody in comedonal extracts.

Extracts of comedonal material obtained from patients with acne vulgaris were analyzed for albumin, IgG, IgM, IgA, and anti-Propionibacterium acnes antibodies using immunodiffusion and anti-immunoglobulin hemagglutination tests. Extracts were obtained from comedones of patients with (1) comedonal, (2) papulopustular, (3) nodular-cystic, (4) "burned out" acne, (5) patients under oral tetracycline treatment, and (6) with pustules. In all comedonal extracts analyzed, albumin and IgG (ratio approximately 1:2.5) could be detected. IgM, IgA, and C3 could not be found in noninflamed comedones by the techniques used; pustules, however, contained all immunoglobulin classes and albumin in ratios found in serum as well as C3. The anti-P. acnes antibody activity in the comedonal extracts was associated with the IgG class. Immunofluorescence microscopical examination of material from single comedones obtained by the cyano-acrylate technique showed IgG antibody on rod-shaped bacteria. The amount of IgG and albumin in comedonal extracts from the various patient groups was not different. It is concluded that IgG (and antibody of the IgG class) in comedones is derived from the serum and selectively accumulated in the follicle by an unknown mechanism.

Effect of neutrophil-derived eosinophil chemotactic factor (ECF) in human and guinea pig skin.

The in vivo effectiveness of eosinophil chemotactic factor (ECF), secreted in vitro by human neutrophils (PMN) during phagocytosis, is tested in 2 model systems. Injection of ECF into guinea pig ears causes a preferential attraction of eosinophils with time that is more marked in animals with preexisting eosinophilia. In the same model system, activated serum attracts fewer eosinophils and more PMN. In human skin windows, ECF and activated serum are equally effective on a quantitative basis, but ECF is more selective for eosinophils in patients with eosinophilia. With normal controls, ECF and activated serum attract PMN equally well. The studies confirm previous in vitro observations on the properties of ECF and suggest a potentially significant role of this factor during pathological processes.

Expression of 1,25-dihydroxyvitamin D3 receptors in normal and psoriatic skin.

Increasing evidence suggests an immunoregulatory function of the potent steroid hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) which has been successfully applied for treatment of psoriasis. The skin is both a site of production and a target of 1,25(OH)2D3. In vitro, 1,25(OH)2D3 inhibits proliferation and stimulates differentiation of keratinocytes. We investigated the in situ expression of vitamin D-receptors (VDR) in normal and psoriatic skin by immunochemical methods. The VDR were visualized using the monoclonal antibody (MoAb) 9A7g to the VDR and the labeled avidinbiotin technique. Immunoreactivity was consistently confined to nuclei in all skin biopsies. In normal skin specimens (n = 10) VDR antigens were expressed in keratinocytes of all epidermal layers (except those of the stratum corneum) and in cells of the epidermal appendages. Double labeling experiments with MoAb to cluster-defined antigens indicated that melanocytes and approximately 75% of Langerhans cells exhibit 1,25(OH)2D3 receptors in normal skin biopsies (n = 5). Depending on their localization in skin compartments 42-62% of CD11b+ positive macrophages and 45-75% of CD3+ T lymphocytes expressed VDR. Non-lesional psoriatic skin specimens (n = 8) revealed nearly identical staining patterns. Lesional psoriatic skin specimens (n = 8) exhibited a significant increase of VDR expression both in basal and suprabasal epidermal layers as measured by computer-assisted morphometry and showed a remarkable change of the immune cell pattern: the densitity and proportion of VDR positive T lymphocytes and macrophages were higher in the epidermal and the perivascular papillary loop compartment. These in vivo findings strongly support the hypothesis that 1,25(OH)2D3 modulates immune response and cell proliferation/differentiation in human skin.

Molecular cloning of an echinococcal microtrichal antigen immunoreactive in Echinococcus multilocularis disease.

A cDNA expression library of the larval stage of the cestode worm Echinococcus multilocularis has been established in the phage lambda ZAPII system. By immunoscreening with pooled sera from patients with alveolar echinococcosis an immunoreactive clone, termed pEM13, was isolated. EM13 was expressed using the expression vector pGEX-3X, resulting in the synthesis of a glutathione S-transferase fusion protein. 82% of the sera from 28 patients suffering from E. multilocularis disease had antibodies against EM13, whereas none of the 55 sera obtained from Echinococcus granulosus-infected patients and none of the 15 sera from patients with other helminthic infections reacted with recombinant EM13. By use of a polyclonal rabbit anti-EM13 hyperimmune serum native EM13 protein could be detected only in the protoscolices of E. multilocularis, but not in E. granulosus larvae or hydatid fluid. Immunoelectron microscopy suggested that EM13 is located in the microtriches on the surface of the larvae. In contrast, EM13 mRNA could be detected by Northern blot analysis in both E. multilocularis and E. granulosus larval RNA preparations. Nucleotide and amino acid sequence analysis of a cDNA clone coding for the corresponding antigen of E. granulosus larvae, termed EG13, revealed a 21-bp insertion, a 51-bp deletion and additional 22 nucleotide exchanges resulting in a 96.3% identity at the nucleotide sequence level and a 96.6% identity at the amino acid sequence level to the coding region of the cDNA pEM13. Cross-reactivity of the polyclonal anti-EM13 serum with the recombinant EG13 indicates a posttranscriptional regulation mechanism, resulting in an EG13 negative phenotype in E. granulosus.

Cloning and characterisation of an immunodominant major surface antigen of Echinococcus multilocularis.

A lambda gt11 cDNA expression library from mRNA of Echinococcus multilocularis protoscolices has been constructed in Escherichia coli Y1090. Immunoscreening with pooled sera obtained from patients suffering from E. multilocularis disease revealed 5 reactive clones. By partial DNA sequence comparison all clones proved to encode the same gene. The complete cDNA sequence of the clone pEM10 with the largest insert of 2.2 kb was determined and an open reading frame of 1.7 kb could be described. The derived amino acid sequence shares 42.6% identity with human microvillar cytovillin found in the membranes of placenta and carcinoma tissues. The coding region of the cDNA of pEM10 was amplified by polymerase chain reaction (PCR) and cloned in frame into expression vector pGEX-3X. Immunoblot analysis revealed the expression of a recombinant antigen of 65 kDa and a protein with the same molecular weight was also found in the lysate of E. multilocularis protoscolices. In contrast, the protein was absent from hydatid fluid or larvae of Echinococcus granulosus. By means of immunofluorescence studies this immunodominant antigen could be located in the germinal layer of brood capsules and in the tegument of E. multilocularis protoscolices. The fusion protein was purified and used for diagnostic purposes in immunoblot. The diagnostic value of this antigen is discussed.

Hepatic failure in a patient treated with dacarbazine (DTIC) for malignant melanoma.

A 55-year-old white woman received chemotherapy with DTIC after surgery for malignant melanoma (stage I, SSM IV, depth of invasion 12 mm). She died suddenly during the second treatment cycle. Autopsy revealed massive necrosis of the liver and thrombosis of the hepatic veins. The cause of the fatal outcome is attributed to the adverse toxic effects of DTIC.

Cutaneous sensitivity to ultraviolet light and chemical irritants.

This investigation examines the relationship between the sun sensitivity of human skin and its response to chemical irritants. Forty-four Caucasoid subjects with normal back skin were studied. The minimal erythema dose (MED) was determined with the sunburning spectrum of a high-pressure mercury lamp. Cutaneous irritability was quantified using a series of seven irritants of different chemical structure, solubility, and concentrations. The response was either expressed as a threshold value of exposure time (ammonium hydroxide, sodium hydroxide) or was graded after a standard exposure in intensity of whealing (dimethyl sulphoxide) or erythema (sodium lauryl sulphate, quaternium 1, croton oil, kerosene). A significant correlation between the MED and the response to all seven primary irritants was found. The relationship was better for water-soluble irritants than for lipid-soluble ones. Despite marked individual variations the determination of the MED is suggested as a valuable tool in identifying hyperirritable skin. Skin typing based on complexion and sunburn history proved to be less reliable.

Effect of retinoids on wound healing in diabetic rats.

In order to clarify the effect of retinoids on wound healing, diabetic rats were treated with oral acitretin or isotretinoin at 1 mg/kg for 5 days prior to the setting of deep punch biopsies, 6 mm in diameter, and for 14 days thereafter. Wound care was done with either a dry or a wet dressing. Wound surface area and transepidermal water loss were measured twice weekly at the time of the change of dressings. Statistically significant increases of both test parameters were noted after 1 week in retinoid-treated animals, but only with dry dressings. No excessive granulation tissue was observed at any time. The data suggest that under certain unfavorable circumstances, problems in wound healing may arise under retinoid treatment.

A double blind trial of H1 and H2 receptor antagonists in the treatment of atopic dermatitis.

Eighteen patients with atopic dermatitis were randomly chosen for a clinical trial to compare the action of the H2 receptor antagonist cimetidine in combination with the H1 receptor antagonist chorpheniramine against the chlorpheniramine alone and against placebo. Each treatment period lasted for 4 weeks. Intensity of puritus was recorded daily by the patient on an analogue scale. Global clinical assessment was graded on a 5-point scale every 2 weeks by the investigators and weekly by the patient himself. Further study parameters were: quantity of the corticosteroid ointment used for 'emergencies'. immunoglobulin E level, and eosinophil count. The data of 16 patients was evaluated. There was no significant difference in any of the study parameters during the three treatment periods. On the basis of this study, the combined administration of H1 and H2 receptor antagonists is of no benefit in the treatment of atopic dermatitis.

Phototherapy of urticaria pigmentosa: clinical response and changes of cutaneous reactivity, histamine and chemotactic leukotrienes.

Ten patients with moderate to very severe urticaria pigmentosa were studied for the therapeutic effect of photochemotherapy (PUVA; six adults) and selective ultraviolet phototherapy (SUP; four adolescents). Despite a high mean PUVA dosage (138.6 +/- 63.4 J/cm2), only two patients had a very good response, while three had a good response and one had a fair response. On the reduction of the frequency of treatments, the symptoms gradually recurred, and several months after the discontinuation of therapy, the clinical status had reached the level prior to PUVA. The results with SUP were even less encouraging. A number of biophysical and biochemical parameters of the skin were studied in five patients before PUVA treatment, immediately after several months of PUVA treatment and again 5 months after the discontinuation of PUVA treatment. Weal and erythema reactions to intracutaneous skin tests remained unchanged after PUVA, while wealing with topically applied dimethylsulfoxide (DMSO) decreased. Transepidermal water loss was markedly reduced over DMSO weals. Histamine levels, which were elevated in lesional but not in normal skin, dropped with PUVA treatment, but after the discontinuation of treatment, they increased again in the lesions. On reverse-phase high-performance liquid chromatography, two main chemotactic factors, leukotriene B4 and 5-HETE, were identified in lesional skin. Chemotactic activity was elevated in both lesional and uninvolved patient skin, reached normal levels at both sites after PUVA and maintained these low levels for several months after the discontinuation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Contact allergy to propylene glycol. Do we use the appropriate test concentration?

The authors describe a case in which contact allergy to propylene glycol would have been missed if a concentration higher than 10 per cent in water had not been used for patch testing. They suggest raising the patch-test concentration to at least 20 per cent and using 50 or even 100 per cent in doubtful cases, although cautioning that further experience with larger numbers of patients is necessary.

Epidemiology of contact dermatitis. The information network of departments of dermatology (IVDK) in Germany.

In 1988, the multicenter project "Information Network of Departments of Dermatology (IVDK)", including eight university skin hospitals was founded. It now comprises 30 participating centers. At these centers, all patch test results are recorded, together with important anamnestic details and, twice a year, these are sent to the data center at the Göttingen University Skin Hospital. Regular, descriptive analyses of data collected by this epidemiological surveillance system serve the different purposes discussed in this paper: 1) observation of "sentinel events"; e.g. an increase in the proportion of patients tested who were sensitized to a certain allergen, or the identification of certain subgroups at particular risk as a starting point for further research or preventive action, and 2) advancement of good clinical practice in patch testing. In October 1996, a working group of the European Society of Contact Dermatitis (ESCD) called the "European Surveillance System on Contact Allergies (ESSCA)" was established with a similar aim of communal data collection and analysis.