Reappraisal of dermatoses of pregnancy.
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Female↗
Biomedical subjects
J D Bos
Publications and source records attributed to J D Bos.
[A questionnaire for patients with chronic urticaria; a diagnostic approach based on structured anamnesis].
In only a minority of chronic urticaria patients an underlying cause or illness can be detected. Previous studies demonstrated that detailed history taking is more important than routine laboratory investigations. To improve the process of history taking, the use of a detailed urticaria questionnaire is highly recommended. By using such a history-based diagnostic approach, the costs of laboratory investigations could be reduced from an average of 538 NLG per patient to 84 NLG per patient. The percentage of patients in whom a cause could be found increased from 29% to 53%. No severe underlying illnesses were missed by using this approach.
Clinical Laboratory Techniques↗
Serum neopterin as a marker for reactional states in leprosy.
Reactions, a relatively common phenomenon among leprosy patients in treatment, require early detection and proper management to prevent serious sequelae. It is generally accepted that reactional states are immunologically mediated and, as such, usually improve with immunomodulatory treatments such as corticosteroids or thalidomide. Neopterin, a product of gamma-interferon-activated macrophages, is a marker for cell-mediated immune activation and may be useful to detect reactional states in leprosy. Here, we compared neopterin levels in single serum samples from leprosy patients with and without reaction with untreated controls and, when available, serial samples among patients with and without reaction. Levels in the single sample measurements, conducted in 22 patients with a reversal reaction (mean 14.5 nmol l(-1), S.D. 8.7) and 13 with erythema nodosum leprosum (mean 16.9 nmol l(-1), S.D. 13.6), were significantly higher (P=0.02 and P=0.001, respectively) than levels in 26 untreated patients (mean 9.1 nmol l(-1), S.D. 7.3). Values above the upper limit of normal (10 nmol l(-1)) were found in seven of 26 untreated patients, 14 of the 22 reversal reaction patients (P=0.01) and 10 of the 13 ENL patients (P=0.003). Serial serum samples, obtained from six patients that developed reactions and 14 that remained free of reaction, indicated that reversal reaction or erythema nodosum leprosum paralleled a concomitant increase in the serum neopterin level. Neopterin levels generally declined upon corticosteroid therapy. Neopterin may be a useful marker for reactional states in leprosy by providing a laboratory parameter to assess the onset, progression, response to therapy and resolution.
Biomarkers↗
Urocanic acid isomers are good hydroxyl radical scavengers: a comparative study with structural analogues and with uric acid.
UV-exposure of the epidermis leads to the isomerisation of trans-UCA into cis-UCA as well as to the generation of hydroxyl radicals. This study shows by means of the deoxyribose degradation test that UCA isomers are more powerful hydroxyl radical scavengers than the other 4-(5-)substituted imidazole derivatives, such as histidine, though less powerful than uric acid. UCA, present in relatively high concentrations in the epidermis, may well be a major natural hydroxyl radical scavenger.
Deoxyribose↗
The development of guidelines for the treatment of vitiligo. Clinical Epidemiology Unit of the Istituto Dermopatico dell'Immacolata-Istituto di Recovero e Cura a Carattere Scientifico (IDI-IRCCS) and the Archives of Dermatology.
OBJECTIVE: To develop and introduce evidence-based guidelines for the treatment of vitiligo in children and in adults. PATIENTS AND SETTING: Patients, residents, and dermatologists from the Department of Dermatology, Academic Medical Center, University of Amsterdam, and the Netherlands Institute for Pigmentary Disorders in Amsterdam. DESIGN: Scientific evidence obtained from 3 systematic reviews of the literature was combined with the results of 2 questionnaires and interviews of potential users of the guidelines, 3 internal expert meetings, and 1 local expert meeting, during which preliminary guidelines were presented and commented on. A final version of the guidelines was synthesized and disseminated among potential users. Six months after the introduction of these guidelines, their use was evaluated. RESULTS: Before the development of the guidelines, there was no uniformity in treatment selection, and there was a variability in estimates of treatment outcome. The metaanalysis showed class 3 corticosteroids and narrowband UV-B to be the most effective and safest therapies for localized and for generalized vitiligo, respectively. From another systematic review, it could be concluded that patients with segmental, stable, or lip-tip vitiligo could be successfully treated with most autologous transplantation methods. For vitiligo universalis, results of the systematic review showed that depigmentation using monobenzone or a Q-switched ruby laser was equally effective. The final version of the guidelines consisted of a treatment scheme together with detailed treatment protocols. Implementation of the guidelines was evaluated in 5 physicians. After the introduction of these guidelines, they were followed in most adult cases with vitiligo (71% of patients with localized vitiligo, 82% with generalized vitiligo, 100% with stable or segmental vitiligo, and 80% with universal vitiligo). In children with vitiligo, the physicians adhered to the guidelines for 52% of the cases. CONCLUSIONS: Guidelines for the treatment of vitiligo can be successfully developed and disseminated for daily clinical practice. The results of the implementation of these guidelines should be confirmed in other centers involving more clinicians.
Adrenal Cortex Hormones↗
Association of the Köbner phenomenon with disease activity and therapeutic responsiveness in vitiligo vulgaris.
OBJECTIVE: To investigate the association between the experimentally induced Kobner phenomenon (KP-e) and the Kobner phenomenon by history (KP-h), disease activity, and therapeutic responsiveness in vitiligo vulgaris. DESIGN: Cohort study. SETTING: An outpatient clinic. PATIENTS: Sixty-one consecutive patients with vitiligo vulgaris. INTERVENTION: Three months after a standardized epidermodermal injury was induced, the KP-e was evaluated. For 1 year, UV-B (311 nm) therapy or topical fluticasone propionate plus UV-A therapy was given, depending on the severity of depigmentation. MAIN OUTCOME MEASURES: The presence or absence of the KP-e and the KP-h disease activity as scored on a 6-point scale from -1 to +4 (vitiligo disease activity [VIDA] score) and therapy-induced repigmentation grade. RESULTS: Nineteen (31%) of the patients had a positive KP-h, whereas 37 (61%) showed a positive KP-e (P<.001). The VIDA score did not always predict a positive KP-e, although patients with a positive KP-e had a higher mean VIDA score (VIDA score of 1.6) than did patients with a negative KP-e (VIDA score of 0.5) (P<.001). The responsiveness to UV-B (311 nm) therapy among KP-e-positive or KP-e-negative patients was not significantly different (P=.66). However, KP-e-positive patients who were treated with fluticasone propionate plus UV-A showed a better response than did KP-e-negative patients (P=.01). Among patients responding to both therapies, VIDA scores were significantly decreased (P<.001) compared with VIDA scores before therapy. CONCLUSION: The KP-e may function well as a clinical factor to assess present disease activity and may also predict the responsiveness to fluticasone propionate plus UV-A therapy but not to UV-B (311 nm) therapy.
Administration, Topical↗
Transforming growth factor-beta isoforms regulate the surface expression of membrane cofactor protein (CD46) and CD59 on human keratinocytes [corrected].
We studied the regulation of the expression of complement regulatory proteins, membrane cofactor protein (MCP), decay accelerating factor (DAF) and CD59, on human keratinocytes by supernatant of activated mononuclear cells and by some individual cytokines present therein. Cultured keratinocytes expressed MCP, DAF and CD59. Supernatant of activated mononuclear cells and recombinant forms of transforming growth factor (TGF)-beta variants (beta1, beta2 and beta3) up-regulated MCP and CD59 but not DAF. Recombinant IL-1alpha, IL-2, IL-6, TNF-alpha and IFN-gamma had no influence. TGF-beta present in the supernatant was likely responsible for up-regulation of MCP and CD59. A monoclonal anti-TGF-beta antibody, which neutralized TGF-beta1, -beta2 and -beta3, did not inhibit the up-regulation of MCP and CD59 by the supernatant. These results indicated that TGF-beta and an additional factor(s) present in the supernatant may be responsible for up-regulating the expression of MCP and CD59 on keratinocytes; both may be acting non-synergistically.
Antigens, CD↗
The pathogenesis of psoriasis: immunological facts and speculations.
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Antigen Presentation↗
Treatment of patients with systemic sclerosis with extracorporeal photochemotherapy (photopheresis).
BACKGROUND: Effective treatment modalities for systemic sclerosis, a life-threatening and disabling disease, are still lacking. Possible efficacy of photopheresis has been reported in several studies. Because of the complexity of the treatment, placebo-controlled trials are difficult to perform. OBJECTIVE: We investigated the effect of photopheresis on clinical parameters (skin score and internal organ functions), immunologic parameters, and quality of life. METHODS: Nineteen patients with progressive systemic sclerosis of less than 5 years' duration were randomized into 2 groups. One group (group A) received photopheresis for 1 year, the other group (group B) received no treatment at all. After 1 year the groups switched (crossover design). Photopheresis was performed on 2 consecutive days every 4 weeks; the psoralens were administered parenterally. The main outcome parameter was the skin score after 1 year of treatment compared with that of the control group. RESULTS: The average skin score improved with 5.4% (standard error [SE], 20. 8%) in group A and deteriorated with 4.5% (SE, 13.8%) in group B (not significant; P =.71). Before crossover, the average increase in skin score was 5.3% (means of entire group). No change was observed in other clinical parameters. Approximately 1 year after crossover, the skin score reversed to what would have been expected with an average increase of 5.3% per year. There was also no effect on immunologic parameters. Quality of life did not change during treatment. CONCLUSION: We were not able to show that photopheresis, performed as described above, is an effective treatment in systemic sclerosis. The difference in average skin score was statistically and clinically insignificant. Despite the small sample size, we concluded that the magnitude of the observed changes is too small to justify photopheresis as a regular treatment.
Adult↗
No additional effect of calcipotriol ointment on low-dose narrow-band UVB phototherapy in psoriasis.
BACKGROUND: Broad-band UVB phototherapy has appeared to be effective in clearing psoriatic lesions. After the advent of calcipotriol ointment, promising results have been obtained by combining these two therapeutic modalities. Also, an additional effect of narrow-band UVB phototherapy on treatment with calcipotriol ointment has been demonstrated. OBJECTIVE: Our purpose was to compare treatment with low-dose narrow-band UVB phototherapy both with and without calcipotriol ointment. METHODS: We included 53 patients suffering from plaque-type psoriasis. All patients underwent low-dose narrow-band UVB phototherapy. Nearly half of the patients were randomized to apply calcipotriol ointment (50 microg/g) twice daily on the affected skin. The Psoriasis Area and Severity Index (PASI) was used to evaluate psoriatic lesions. RESULTS: In this study we showed that low-dose narrow-band UVB phototherapy is effective in the treatment of psoriasis and that calcipotriol ointment does not improve treatment outcome. CONCLUSION: Calcipotriol ointment does not improve treatment with low-dose narrow-band UVB phototherapy.
Adolescent↗
Nonsurgical repigmentation therapies in vitiligo. Meta-analysis of the literature.
OBJECTIVE: To assess the effectiveness and safety of nonsurgical repigmentation therapies in localized and generalized vitiligo by means of a meta-analysis. DATA SOURCES: Computerized searches of bibliographic databases, a complementary manual literature search, and contacts with researchers and pharmaceutical firms. STUDY SELECTION: Predefined selection criteria were applied to both randomized and nonrandomized controlled trials. DATA EXTRACTION: Two investigators independently assessed the articles for inclusion. When there was a disagreement, a third investigator was consulted. DATA SYNTHESIS: Sixty-three studies were found on therapies for localized vitiligo. Of these, 10 of 11 randomized controlled trials and 29 of 110 patient series were included. One hundred seventeen studies on therapies for generalized vitiligo were found. Of these, 10 of 22 randomized controlled trials and 46 of 231 patient series were included. Among randomized controlled trials on localized vitiligo, the pooled odds ratio vs placebo was significant for topical class 3 corticosteroids (14.32; 95% confidence interval [CI], 2.45-83.72). In the patient series, topical class 3 and class 4 corticosteroids carried the highest mean success rates (56% [95% CI, 50%-62%] and 55% [95% CI, 49%-61%], respectively). Side effects were reported mostly with topical psoralen and intralesional and class 4 corticosteroids. In the randomized controlled trials on generalized vitiligo, the odds ratio vs placebo was significant for oral methoxsalen plus sunlight (23.37; 95% CI, 1.33-409.93), oral psoralen plus sunlight (19.87; 95% CI, 2.37-166.32), and oral trioxsalen plus sunlight (3.75; 95% CI, 1.24-11.29). In the series, the highest mean success rates were achieved with narrowband UV-B (63%; 95% CI, 50%-76%), broadband UV-B (57%; 95% CI, 29%-82%), and oral methoxsalen plus UV-A therapy (51%; 95% CI, 46%-56%). Oral methoxsalen plus UV-A was associated with the highest rates of side effects. No side effects were reported with UV-B therapy. CONCLUSIONS: Class 3 corticosteroids and UV-B therapy are the most effective and safest therapies for localized and for generalized vitiligo, respectively.
Humans↗
A systematic review of autologous transplantation methods in vitiligo.
OBJECTIVE: A systematic review of the effectiveness, safety, and applicability of autologous transplantation methods in vitiligo. DATA SOURCES: Computerized searches of bibliographical databases, a complementary manual literature search, and contacts with researchers and pharmaceutical firms. STUDY SELECTION: Predefined selection criteria were applied to all studies found. DATA EXTRACTION: Two investigators independently assessed the articles for inclusion. When there was a disagreement, a third investigator was consulted. DATA SYNTHESIS: Sixty-three studies were found, of which 16 reported on minigrafting, 13 on split-thickness grafting, 15 on grafting of epidermal blisters, 17 on grafting of cultured melanocytes, and 2 on grafting of noncultured epidermal suspension. Of these, 39 patient series were included. The highest mean success rates (87%) were achieved with split-skin grafting (95% confidence interval, 82%-91%), and epidermal blister grafting (87%) (95% confidence interval, 83%-90%). The mean success rate of 5 culturing techniques varied from 13% to 53%. However, in 4 of the 5 culturing methods, fewer than 20 patients were studied. Minigrafting had the highest rates of adverse effects but was the easiest, fastest, and least expensive method. CONCLUSIONS: Because no controlled trials were included, treatment recommendations should be formulated with caution. Split-thickness and epidermal blister grafting can be recommended as the most effective and safest techniques. No definite conclusions can be drawn about the effectiveness of culturing techniques because only a small number of patients have been studied. The choice of method also depends on certain disease characteristics and the availability of specialized personnel and equipment.
Humans↗
The effectiveness of a history-based diagnostic approach in chronic urticaria and angioedema.
OBJECTIVE: To assess the value of extensive laboratory screening for the identification of causes in patients with chronic urticaria and/or angioedema. DESIGN: In a prospective study involving 220 patients, 2 diagnostic strategies were compared: the combination of detailed history taking and limited laboratory investigations vs detailed history taking and extensive laboratory screening. The results of the extensive screening program were initially kept secret from the patients and the physicians. Later, all results were disclosed, and an investigation was undertaken to find out whether this information changed the initial diagnosis. The patients were followed up for 1 year to evaluate the results of interventions and to detect latent causes. SETTING: The study was performed in the outpatient department of a secondary and tertiary care center with institutional practice. PATIENTS: A total of 238 consecutive new patients with chronic urticaria and/or angioedema edema were referred; 18 of them refused participation. One patient was unavailable for follow-up. MAIN OUTCOME MEASURE: The difference in the number of identified causes between both approaches and the nature of the causes that would have been missed by omitting extensive laboratory screening. RESULTS: With a questionnaire and the limited laboratory tests, a cause was found in 45.9% of the patients, compared with 52.7% with the questionnaire and the extended screening program. Except for one parasitic infection, missed diagnoses were mainly adverse reactions to drugs or food detected by standard elimination procedures, not by laboratory investigations. CONCLUSION: Routine laboratory screening did not contribute substantially to the diagnosis of chronic urticaria or to the detection of underlying disorders.
Adolescent↗
The development of practice guidelines for the treatment of severe plaque form psoriasis.
OBJECTIVE: To develop and introduce evidence-based guidelines for the selection of 5 commonly used treatment modalities--UV-B, photochemotherapy, methotrexate, acitretin, and cyclosporine--for adult patients with severe plaque form psoriasis. PATIENTS AND SETTING: Patients, residents, and dermatologists from the Department of Dermatology of the Academic Medical Center of the University of Amsterdam, Amsterdam, the Netherlands, were involved in this process. DESIGN: The development process started with a questionnaire to evaluate how patients with severe psoriasis were treated. A systematic literature review was set up to provide evidence-based estimates of effectiveness, adverse effects, and dropout rates. In 2 meetings, the opinion leaders and intended users discussed the results of the questionnaire and systematic review as well as the clinical considerations in the treatment choices. Guidelines were then made regarding the sequence of selection of 5 modalities in the concept of rotational therapy. These guidelines were introduced. Their use was analyzed for 6 months. RESULTS: Before the guidelines, there was no uniform approach. In the systematic review, 665 studies concerning the treatments were found. Exclusion rates were high. No studies of methotrexate therapy could be included. Photochemotherapy showed the highest average proportion of patients with clearance (70% [6947/9925]) and good response (83% [8238/9925]), followed by UV-B (67.9% [620/913]) and cyclosporine (64% [1030/1609]) therapy. In the second internal meeting, the following sequence for the treatments was defined: UV-B, photochemotherapy, methotrexate, acitretin, and cyclosporine. In 78% (69/88) of patients treated after the introduction, the guidelines were followed to determine the treatment choice. CONCLUSIONS: Guidelines for treating severe plaque form psoriasis can be successfully developed, introduced, and implemented and were considered to improve clinical care.
Evidence-Based Medicine↗
Effectiveness of the ascomycin macrolactam SDZ ASM 981 in the topical treatment of atopic dermatitis.
OBJECTIVE: To compare the safety and efficacy of 1% SDZ ASM 981 cream and a matching placebo cream in the treatment of patients with moderate atopic dermatitis. DESIGN: A randomized, double-blind, placebo-controlled, right-and-left comparison study. SETTING: Academic referral center. PATIENTS: Thirty-four adult patients with moderate atopic dermatitis. INTERVENTION: Topical 1% SDZ ASM 981 cream was applied twice daily (n=16) or once daily (n=18) and compared with a corresponding placebo cream base. MAIN OUTCOME MEASURES: Efficacy was measured using a 4-point (0-3) scale for erythema, pruritus, exudation, excoriation, and lichenification (Atopic Dermatitis Severity Index [ADSI]). The ADSI score was defined as the sum of these 5 ratings (range, 0-15) and was determined on the pretreatment day (1 to 14 days before day 0) and on days 0, 2, 4, 7, 9, 11, 14, 16, 18, and 21. The percentage change from baseline (day 0) in the ADSI score was calculated on each of these days. Safety was evaluated by monitoring of adverse events, physical examination, hematologic examination, clinical chemistry studies, urinalysis, and measurement of blood levels of SDZ ASM 981. RESULTS: Of the 38 patients recruited, 34 started and 28 completed treatment according to the protocol. Sixteen patients used the cream twice daily, with significant improvement after 2 days of treatment. Within 3 weeks of topical therapy with 1% SDZ ASM 981 cream twice daily, a mean reduction of 71.9% in the ADSI score was observed at the actively treated test sites compared with a mean reduction of 10.3% at the placebo-treated test sites (P<.001). Efficacy was significantly less in the group treated once daily (n=18), with mean reductions of 37.7% and 6.2%, respectively. The efficacy was especially apparent for pruritus and excoriation. There were no clinically relevant drug-related adverse effects. CONCLUSIONS: Treatment with 1% SDZ ASM 981 cream was well tolerated. Twice-daily application of 1% SDZ ASM 981 cream was significantly more effective than use of the corresponding placebo and more effective than once-daily treatment. The new macrolactam ascomycin derivative SDZ ASM 981 is a promising agent for the treatment of patients with atopic dermatitis. More elaborate phase 2 and 3 trials are under way to fully investigate the potential of this medication.
Administration, Topical↗
Topical tacrolimus is not effective in chronic plaque psoriasis. A pilot study.
BACKGROUND: Cyclosporine for the treatment of psoriasis constitutes a new approach. Alternative systemic cyclosporine derivatives have been studied to find an immunosuppressive drug with fewer adverse effects. Tacrolimus is one of these new immunosuppressive drugs. Systematically, it has been proven effective in treating psoriasis. A topical formulation of tacrolimus is attractive because it has fewer adverse effects and is useful for a large group of patients. We report for the first time on the efficacy of nonocclusive topical tacrolimus in the treatment of psoriasis. OBSERVATIONS: After a washout phase of 2 weeks, patients were randomized to receive 0.005% calcipotriol ointment twice daily, placebo ointment once daily, or 0.3% tacrolimus ointment once daily. One psoriatic plaque was treated with a surface area of 40 to 200 cm2. Efficacy was estimated using the local psoriasis severity index. The reduction in the local psoriasis severity index score after 6 weeks was 62.5% in the calcipotriol group, 33.3% in the tacrolimus group, and 42.9% in the placebo group. CONCLUSIONS: There was no statistically significant difference between the efficacy of tacrolimus and placebo ointment (P = .77). Calcipotriol ointment, applied twice daily, had a better effect than tacrolimus ointment and placebo ointment once daily.
Administration, Cutaneous↗
Relative contributions of decay accelerating factor (DAF), membrane cofactor protein (MCP) and CD59 in the protection of melanocytes from homologous complement.
Complement regulatory molecules, membrane cofactor protein (MCP), decay accelerating factor (DAF) and CD59, protect body cells from autologous complement. They have wide tissue distribution but nothing is known about the expression of these molecules on human melanocytes. Since melanocytes are lysed in the lesional skin of patients with a depigmentary disorder vitiligo, it is important to compare the protection offered by complement regulatory molecules to melanocytes present in normal and vitiligo epidermis, against autologous complement. From this point of view, we investigated the differential expression of MCP, DAF and CD59 on normal cultured human melanocytes and assessed their individual contribution in the protection of these cells against complement-mediated damage. Flow cytometric analysis showed that MCP and DAF but not CD59 were expressed on cultured melanocytes. When heat inactivated sera of patients with vitiligo were used as a source of anti-melanocyte antibody to sensitize melanocytes, and guinea pig serum (GpS) or normal human serum (NHS) as a source of complement, GpS was found to be more effective in causing the lysis of melanocytes than NHS. When melanocytes were sensitized with autoantibody as well as F(ab')2 fragment of either anti-MCP or anti-DAF and subsequently incubated with NHS or GpS, both antibody fragments increased the killing of melanocytes by NHS as well as by GpS. F(ab')2 fragment of anti-DAF was much more effective in causing enhancement of lysis than that of anti-MCP. Thus, cultured normal human melanocytes express functionally active MCP and DAF but not CD59. Contribution of DAF in protecting melanocytes against complement attack was much more than that of MCP.
CD55 Antigens↗
Immunological aspects of psoriasis.
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Humans↗