Successful dexamethasone pulse therapy in a toxic epidermal necrolysis (TEN) patient featuring recurrent TEN to oxazepam.

A 62-year-old female patient is described who developed toxic epidermal necrolysis (TEN) after medication with phenytoin and oxazepam. Initially phenytoin was discontinued and dexamethasone pulse therapy (1.5 mg/kg on 3 consecutive days) was initiated on the tenth day of skin disease. This resulted in clinical improvement. Histologically re-epithelialization could be demonstrated below the necrotic epidermis. However, on the eighteenth day of skin disease (10 days after discontinuation of phenytoin and 8 days after the start of dexamethasone pulse therapy), a histologically verified rebound-TEN developed with a detachment of 95%. Oxazepam was stopped and a second series of dexamethasone pulse therapy was given. Re-epithelialization began within 24 h of the start of the second series of dexamethasone pulse therapy, and continued to almost complete recovery within 1 week.

Socioeconomic differences in self-assessed health in a chronically ill population: the role of different health aspects.

We investigated the role that different health aspects play in the explanation of socioeconomic differences in self-assessed health. Socioeconomic differences in self-assessed health were investigated in relation to chronic disease, functional limitations, psychosomatic symptoms, and perceived discomfort/distress. In multiple logistic regression analyses, for three cutoff points of self-assessed health, significant socioeconomic differences in self-assessed health could be observed after adjusting for age and gender. After separate adjustment for each of the four health aspects, the analyses showed that for a health assessment as less-than-good and less-than-fair, psychosomatic symptoms were the most powerful explanatory factor. Perceived discomfort/distress proved to be the most powerful factor for a poor health assessment. We found that socioeconomic differences in self-assessed health could, to a large extent (72-80%), be explained through socioeconomic differences in the prevalence of the four types of health problems included in the study. For all cutoff points, objective health aspects accounted for a relatively small part of the socioeconomic variability in self-assessed health. More subjective aspects of health accounted for more of the variability.

Inflammatory variant of epidermolysis bullosa acquisita with IgG autoantibodies against type VII collagen and laminin alpha3.

BACKGROUND: The inflammatory variant of epidermolysis bullosa acquisita (EBA) may clinically closely resemble bullous or cicatricial pemphigoid. Patients with inflammatory EBA have IgG autoantibodies against type VII collagen. Patients with anti-epiligrin cicatricial pemphigoid have IgG autoantibodies against laminin 5. OBSERVATION: We describe a patient with inflammatory EBA exhibiting nonscarring oral and vaginal involvement. Indirect immunofluorescence using skin substrate lacking an epidermal basement membrane molecule, direct immunoelectron microscopy, immunoblot, and immunoprecipitation studies revealed the simultaneous presence of circulating IgG autoantibodies against type VII collagen and laminin alpha3. A final diagnosis of EBA was based on the sublamina densa level of blister formation. CONCLUSION: This case illustrates the clinical and immunological overlap between EBA and anti-epiligrin cicatricial pemphigoid, a unique finding that may have developed as a consequence of epitope spreading.

Two type XVII collagen (BP180) mRNA transcripts in human keratinocytes: a long and a short form.

We have analysed BP180 mRNA expression in normal human keratinocytes. Here we report the presence in normal keratinocytes of two COL17A1 transcripts which differ by 0.6 kb in length. Both mRNAs hybridized on Northern blot with probes directed to sequences encoding intracellular and extracellular fragments of BP180. By BLAST homology search alignments we extended the 3' untranslated region (3'UTR) of the known BP180 mRNA sequence by 877 bases to completion. Three of 20 cDNAs identified by BLAST searches contained a 610 bp deletion in this new 3'UTR sequence. Northern blot analysis with a probe complementary to this deleted sequence showed binding only to the larger mRNA. The deletion of 610 nucleotides in the smaller mRNA was verified by reverse transcription-PCR and sequencing. Genomic PCR showed the new sequence to be an extension of exon 56 of the COL17A1 gene which suggests that the second mRNA is generated by differential splicing. In normal keratinocytes the level of the smaller transcript was 5-15% of that of the larger transcript whereas in a squamous cell carcinoma cell line this ratio was reversed, the smaller mRNA being three times more abundant than the larger mRNA. The biological significance of this newly identified transcript in protein synthesis and tissue expression or in cell differentiation, proliferation or adhesion is as yet unknown.

The management of moderate to severe atopic dermatitis in adults with topical fluticasone propionate. The Netherlands Adult Atopic DermatitisStudy Group.

This study was designed to investigate a long-term therapeutic strategy for the management of recurring atopic dermatitis (AD) in adults using fluticasone propionate (FP) ointment (CutivateTM) whereby FP could help to prevent a relapse of AD once symptoms were under control. Adult patients with chronic, moderate to severe AD entered this multicentre study. All patients were initially treated with FP 0.005% (g/g) ointment in two different regimens. Patients whose AD had been completely healed by these treatments then entered a long-term treatment phase applying FP or placebo ointment once daily, two times per week for 16 weeks to 'known' healed lesions. By the end of the initial treatment period, mean SCORAD values had significantly (P < 0.0005) improved from baseline. Patients who entered the maintenance phase and were treated with intermittent FP for up to 16 weeks, demonstrated its superior efficacy (P = 0.018) over placebo, maintaining the improvements achieved after the initial treatment phase, reducing risk of relapse and delaying time to relapse (P = 0.013). No significant changes were detected in either treatment group in serum cortisol levels or in skin thickness measurements. Intermittent FP applied two times per week maintained a significant level of control, and delayed relapse of AD by comparison with placebo.

The care and course of diabetes: differences according to level of education.

OBJECTIVE: The objective of this study was to describe socioeconomic differences in the utilisation of health services among persons with diabetes and to link these differences with socioeconomic differences in the course of diabetes. RESEARCH DESIGN AND METHODS: A 2-year follow-up study (1991-1993) was done with data from a population-based survey in The Netherlands (city of Eindhoven and surroundings). Those reporting diabetes who also reported treatment with a diet, oral antidiabetics or insulin and who completed questionnaires in the years 1991 and 1993 (n = 173) were included in the analysis. Main outcome measures were: (1) the odds ratios according to level of education of utilisation of 11 types of service or medical checks in 1991, relevant for diabetes; and (2) odds ratios according to level of education of the difference between 1991 and 1993 in the prevalence of symptoms of diabetic complications. RESULTS: Controlling for severity of diabetes, contact rates with the general practitioner were significantly (P < 0.05) higher among those with primary education, compared to those with an educational level of intermediate vocational training or higher. Rates of checks by a specialist, influenza vaccination and many other checks were statistically significantly lower among those with a low educational level, although the group with the lowest educational level did not always show the lowest rates. Of symptoms indicating diabetes complications, the prevalence of pain in the legs and visual impairments developed more unfavourably among those with primary education. The prevalence of all symptoms together developed more unfavourably among those with primary education. A direct contribution of uptake of checks and services to the differential course of diabetes by education could not be demonstrated. CONCLUSIONS: People with diabetes with a low level of education have lower utilisation rates of checks and services relevant for diabetes care, and a worse outcome in terms of complications.

Type XVII collagen (BP180) and LAD-1 are present as separate trimeric complexes.

This study characterized the high molecular mass BP180 complex that is observed when unheated sodium dodecyl sulfate extracts of human skin or keratinocytes are subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. In heated extracts BP180 is present as a monomer with a molecular weight of 180 kDa, in unheated extracts BP180 runs at a molecular weight position over 500 kDa. By preincubating the unheated extracts at temperatures between 31 degrees C and 40 degrees C, the high molecular weight complex could be "melted" down to monomeric BP180. Under the conditions employed the T1/2 of the dissociation process was between 35 degrees C and 36 degrees C. The temperature resistance of the high molecular weight complex was used to analyze its molecular composition by performing two-dimensional electrophoresis with a "low-temperature" first dimension step and a "high-temperature" second dimension step. Silver staining and immunoblotting of the two-dimensional gels revealed the high molecular weight complex to be composed of solely BP180, indicating that the complex is the nondissociated homotrimeric form of BP180. The 120 kDa linear IgA dermatosis antigen (LAD-1) is an collagenous anchoring filament protein with homology to the extracellular collagenous part of BP180. Two-dimensional immunoblotting showed that LAD-1, as BP180, is also present as a high molecular mass complex and does not form mixed complexes with BP180.

The use of skin substrates deficient in basement membrane molecules for the diagnosis of subepidermal autoimmune bullous disease.

A case is presented of subepidermal, autoimmune bullous disease in which the initial examinations suggested the combination of epidermolysis bullosa acquisita and bullous pemphigoid. The diagnosis of epidermolysis bullosa acquisita was made by indirect immunofluorescence microscopy: the patient's serum bound to normal skin substrate but not to type VII collagen-deficient skin substrate derived from a patient with mutilating dystrophic epidermolysis bullosa. The use of skin substrates deficient in basement membrane molecules also excluded the presence of concomitant, circulating bullous pemphigoid autoantibodies in our patient. The diagnosis of epidermolysis bullosa acquisita was confirmed by split mapping, fluorescence overlay antigen mapping and Western blot.

Low education, high GP consultation rates: the effect of psychosocial factors.

The purpose of this study was to estimate the contribution of psychosocial factors to the increased use of a general practitioner (GP) among those with a lower level of education. The use of GP services was elicited from survey data from 2867 respondents from the Dutch Longitudinal Study on Socio-Economic Differences in the Utilization of Health Services (LS-SEDUHS) using a simple "Yes/ No" format. Psychosocial variables included long-term stressful conditions, social support, external locus of control, coping styles, and tendency to consult (a measure of people's propensity to go to a doctor with health problems). People with primary education used the GP services more than people with higher vocational training or a university degree (OR 1.87, p<0.05), adjusted for health status and health insurance. Only tendency to consult partially explained this difference (OR: 1.74, p>0.05). Most psychosocial factors do not seem very important in explaining high GP utilization rates among those with a low socioeconomic status. Alternative explanations are discussed.

Course of health status among chronically ill persons: differentials according to level of education.

This article describes socioeconomic differences in the time course of several health indicators, encompassing perceived health and disabilities, among a population sample of persons reporting one or more chronic conditions. Data covering the period 1991-1993, were obtained from a Dutch follow-up study. Educational differences in the course of health status were estimated by ordinary least squares regression. The course of almost all health status measures was statistically significantly less favorable (p<0.05) for those with a low educational level compared to those with higher vocational training or a university degree, adjusting for age, sex, and marital status. After additional adjustment for health status in 1991, significant differences remained for perceived general health, long-term disabilities, and two subscales of the Nottingham Health Profile. These findings imply that socioeconomic differences in prevalence of health problems are not only attributable to differences in incidence of diseases by socioeconomic status, but also to a differential course of existing health problems. Implications for health care delivery are discussed.

Socio-economic differences in general practitioner and outpatient specialist care in The Netherlands: a matter of health insurance?

Equal treatment for equal needs, irrespective of socio-economic position, is a major issue in many countries. Although in the Netherlands differences in utilization of health care between population groups are less pronounced than in most other countries, some differences by socio-economic position do exist. Controlling for health status, individuals with a high socio-economic status have a higher probability of outpatient contacts with a specialist, but a lower probability of general practitioner contacts, compared with those with a low socioeconomic status. In this cross-sectional study, we studied whether socio-economic differences in GP and outpatient specialist care utilization that exist after health status is taken into account could be explained by different aspects of health insurance. The study population, in which people with asthma and chronic obstructive pulmonary disease (COPD), diabetes mellitus, severe back complaints, and heart diseases are overrepresented, consists of 2867 respondents. Multivariate analyses show that the socio-economic differences in outpatient specialist contacts cannot be explained by differences in health insurance, whereas differences in general practitioner contacts can partially be explained by the fact that individuals with higher socio-economic status more often have a private (instead of public) insurance. This is not owing to differences in deductible or insurance coverage between public and private insurance, but is more likely to be caused by differences in regulatory aspects between these two insurance schemes (such as the stronger gate-keeper role of the general practitioner in the public insurance scheme.

Bullous pemphigoid and linear IgA dermatosis sera recognize a similar 120-kDa keratinocyte collagenous glycoprotein with antigenic cross-reactivity to BP180.

Circulating IgG from a large subset of bullous pemphigoid (BP) patients reacted on immunoblot with a 120-kDa protein in conditioned keratinocyte culture medium and in keratinocyte cell extracts. A protein with a similar molecular weight was recognized by circulating IgA from a subset of patients with linear IgA dermatosis (LAD). Both affinity-purified 120-kDa-specific BP IgG and 120-kDa-specific LAD IgA bound to the roof of salt-split skin. Both proteins recognized are collagenous glycoproteins. Deglycosylation with N-glycosidase F resulted in an identical reduction in molecular weight for both the BP-IgG-recognized protein and the LAD-IgA-recognized protein. Both proteins were equally susceptible to digestion with type VII collagenase. Furthermore, both proteins were absent from conditioned culture medium of keratinocytes from patients with BP180-deficient general atrophic benign epidermolysis bullosa (GABEB). Immunodepletion studies showed that the 120-kDa LAD antigen could be removed from conditioned culture medium by anti-120-kDa BP IgG. Thus these results indicate that these proteins are either highly related or, most probably, identical. A strong antigenic relationship between the 120-kDa protein and the 180-kDa bullous pemphigoid antigen (BP180) was detected by cross-reaction of affinity-purified anti-120-kDa BP patient antibodies to BP180 and cross-reaction of monoclonal anti-180-kDa antibodies to the 120-kDa protein. Notwithstanding this cross-reactivity, the 120-kDa protein also exhibits unique epitopes demonstrated by the nonreactivity of individual anti-120-kDa BP and LAD patient serum with the 180-kDa antigen.

Socioeconomic differences in the utilization of health services in a Dutch population: the contribution of health status.

The main question addressed here is to what extent socioeconomic differences in the utilization of health services in the Netherlands can be explained by health status. Our aim is to assess whether the health services has achieved equal assess for equal needs, and which health status measures best control for need. Cross-sectional survey data from 2867 respondents with respect to utilization of six different types of health services are used for analysis. Socioeconomic differences in utilization were present for all services after we controlled for age, sex and marital status. By controlling for health status, differences changed markedly for all health services analyzed. Differences in general practitioner contacts diminished but did not disappear (adjusted odds ratio primary education/university 2.22). The pattern of excess contacts with specialist physicians reverses (adjusted odds ratio 0.74). This is also true for the physiotherapist. The pattern of hospitalizations is unclear. Use of over-the-counter medicines is little affected by control for health status. Adjusted differences in use of prescription medicines become small. Control for health status is best achieved with a set of health measures covering several dimensions of health. Whether low relative utilization among those with low education reflects limited access, or whether higher use of other services is compensatory is hard to decide on the basis of the study. Monitoring access to health care is important for all sorts of systems, including those which are believed to be equitable.

Differences in the misreporting of chronic conditions, by level of education: the effect on inequalities in prevalence rates.

OBJECTIVES: Many studies of socio-economic inequalities in the prevalence of chronic conditions rely on self-reports. For chronic nonspecific lung disease, heart disease, and diabetes mellitus, we studied the effects of misreporting on variations in prevalence rates by respondents' level of education. METHODS: In 1991, a health interview survey was conducted in the southeastern Netherlands with 2867 respondents. Respondents' answers were compared with validated diagnostic questionnaires in the same survey and the diagnoses given by the respondents' general practitioners. RESULTS: Misreporting of chronic lung disease, heart disease, and diabetes may be extensive. Depending on the condition and the reference data used, the confirmation fractions ranged between .61 and .96 and the detection fractions between .13 and .93. Misreporting varied by level of education, and although various patterns were observed, the dominant pattern was that of more underreporting among less educated persons. The effects on prevalence rates were to underestimate differences by level of education to a sometimes considerable degree. CONCLUSIONS: Misreporting of chronic conditions differs by respondents' level of education. Health interview survey data underestimate socioeconomic inequalities in the prevalence of chronic conditions.

Induction of atopic dermatitis by inhalation of house dust mite.

BACKGROUND: The pathogenetic role of house dust mite in atopic dermatitis remains controversial. Recent studies have shown that intensive epicutaneous contact of house dust mite allergen with premanipulated skin may induce dermatitis. It is, however, uncertain whether such conditions are met during natural contact with house dust mite. In the past, allergen inhalation has been suggested to induce exacerbation of atopic dermatitis. The aim of this study was to investigate whether dermatitis could be induced in patients with atopic dermatitis by inhalation of house dust mite. METHODS: Twenty patients with atopic dermatitis underwent bronchial provocations with house dust mite. Challenge tests were performed with four concentrations of a standardized house dust mite extract in a double-blind, randomized, placebo-controlled fashion. Spirometry was performed, and FEV1 was measured before and after each challenge dose. Changes in severity or localization of itching or erythema were recorded. RESULTS: In nine of 20 patients with atopic dermatitis bronchial challenge with house dust mite induced unequivocal skin symptoms after 1.5 to 17 hours. Pruritic erythematous lesions on noninvolved sites together with exacerbations of existing lesions were seen in three patients. Three patients had an exacerbation only, and three other patients had new lesions only. In eight of nine patients with house dust mite inhalation-induced dermatitis, skin symptoms were preceded by an early bronchial reaction. All patients with house dust mite-induced dermatitis had a history of asthma, and as a group they had a higher mean blood total IgE level compared with the "negative skin responders." One patient had pruritic erythema on the placebo challenge day, without a preceding bronchoconstrictive reaction. The number of patients who had a skin response on the house dust mite challenge day was significantly higher than the number of patients who had a skin response on the placebo day (p = 0.011 [Prescott's test]). CONCLUSIONS: The respiratory route may be relevant in the induction and exacerbation of dermatitis in a subset of patients with atopic dermatitis who have early bronchial reactions after house dust mite inhalation, a history of asthma, and an elevated blood total IgE level. Furthermore, these findings suggest a possible causal relationship between bronchial reactions and skin reactions.

Bullous pemphigoid and epidermolysis bullosa acquisita. Differentiation by fluorescence overlay antigen mapping.

BACKGROUND AND DESIGN: From previous studies, we concluded that the fluorescence overlay antigen mapping (FOAM) technique could be of value to the differential diagnosis of the acquired subepidermal bullous skin disorders, bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA). In these diseases, ultrastructural identification of the site of skin-bound IgG deposits at the epidermal basement membrane zone (EBMZ) may be essential to the correct diagnosis. Since ultrastructural studies are more expensive, time-consuming, and less widely available than immunofluorescence, we addressed the question of whether the FOAM technique can reliably identify the site of IgG deposits at the EBMZ, and distinguish BP from EBA. For this purpose, the technique was applied to perilesional skin from seven patients with BP and six with EBA, using computer-aided imaging of red-stained type VII collagen and green-stained IgG, according to previous findings. RESULTS: Digitized multicolor FOAM images of perilesional skin from patients with BP showed nonoverlap band patterns of green-stained lamina lucida IgG deposits (ultrastructurally proven) and red-stained type VII collagen. By contrast, FOAM images of EBA skin typically showed overlap patterns of green-stained sublamina densa IgG deposits and red-stained type VII collagen. These findings were observed also in skin tissue stored in Michel's transport medium or stored frozen for 15 years. CONCLUSIONS: The computer-aided FOAM technique may have great potential in distinguishing between IgG deposits above (BP) and just below (EBA) the lamina densa of the EBMZ in skin tissue. The technique is not as simple as saline-split skin methodology but offers more flexibility, and it certainly is quicker and less expensive than electron microscopy. Furthermore, the use of digitized fluorescence images offers improved possibilities for evaluating the various "linear" patterns of immune reactant deposition at the EBMZ in subepidermal bullous autoimmune skin diseases.