[Lichen sclerosus]. / Lichen sclerosus.

Lichen sclerosus is a chronic disorder of skin and mucosa which affects patients of all age groups, particularly women, but also men. It is most commonly seen on the female genital skin, but it also occurs on extragenital areas. Most patients complain of itching and, less frequently, a burning sensation, dyspareunia, dysuria and painful defecation are reported. The cause of lichen sclerosus is largely unknown. However, it has been suggested that a genetic predisposition to inflammatory disorders, an immunological constitution, hormonal influences and local factors might play a role. Anogenital lichen sclerosus is associated with an increased incidence of malignancies, especially vulvular squamous-cell carcinomas. The life-time risk of developing this carcinoma is about 5%. Extragenital lichen sclerosus and lichen sclerosus in children do not seem to be correlated with malignancy. Potent local corticosteroids form the mainstay of treatment for lichen sclerosus. The condition is characterised by remissions and exacerbations. Long-term follow-up is required for the early diagnosis of malignant changes.

Induction of eruptive benign melanocytic naevi by immune suppressive agents, including biologicals.

BACKGROUND: Eruptive naevi have been described to potentially arise in immune compromised patients. OBJECTIVES: We describe three patients with eruptive benign melanocytic naevi during a phase of immunosuppressive therapy. METHODS/DIAGNOSIS: Two patients with Crohn disease were treated with either azathioprine monotherapy or a combination of azathioprine and infliximab, when eruptive naevi arose particularly at the palms and soles. Our third patient with plaque psoriasis developed eruptive naevi during two episodes of treatment: during a course with the biological agent alefacept and during etanercept therapy. CONCLUSIONS: We conclude that treatment with the recently available biological agents might be associated with the formation of eruptive naevi. Although positive evidence for the occurrence of malignant pigmented lesions is lacking, alertness to the development of eruptive melanocytic naevi during treatment with biological agents is indicated.

Pharmacoeconomic evaluation of calcipotriol (Daivonex/Dovonex) and UVB phototherapy in the treatment of psoriasis: a Markov model for The Netherlands.

BACKGROUND: The high prevalence and chronic nature of psoriasis leads to high costs in relation to the treatment and control of the disease. A number of clinical trials have shown that a combination therapy of calcipotriol cream (Daivonex/Dovonex), Leo Pharmaceutical Products) and ultraviolet B phototherapy (UVB) decreases the total number of UVB exposures required compared to UVB treatment alone. From a societal point of view, the addition of calcipotriol to UVB therapy could achieve cost savings due to the fewer UVB treatments needed and the reduced travelling and time off work for patients. Fewer UVB exposures may also have other beneficial effects, i.e., shortened waiting lists and less risk to patients of developing cancer or photoaging of the skin. OBJECTIVE: To compare the cost-effectiveness of treating psoriatic patients in the Netherlands with calcipotriol cream used daily combined with twice weekly UVB treatments to emollient used daily combined with UVB given 3 times weekly. METHODS: Based on the clinical results from a Canadian trial, a decision-analytical model was constructed to simulate treatment outcomes and estimate the costs of managing psoriatic patients in the Netherlands over a period of 20 weeks from initiation of therapy. Unit costs and details of standard treatment protocols were collected from Dutch dermatology centres in hospitals and the community for use in the model. Other therapies, such as topical corticosteroids, tar or dithranol were not investigated in this analysis. RESULTS: The total cost of managing psoriatic patients in the Netherlands over a 20-week period is estimated as EUR 1,175.90 for those treated with calcipotriol and UVB and EUR 1,212.14 for patients treated with emollient and UVB. Thus, the former treatment, adding calcipotriol to UVB phototherapy, provides a minor cost saving of EUR 36.24 (3%) compared to the cost of UVB treatment alone. Sensitivity analyses demonstrated that these results are sensitive to changes in the cost of UVB treatment. CONCLUSION: Calcipotriol treatment combined with UVB phototherapy is a cost-neutral alternative to UVB phototherapy used with an emollient. The patients achieve treatment success in the same time on both treatments but the former, with calcipotriol, requires less exposure to UVB radiation. The additional drug costs from using calcipotriol are offset by savings from the fewer UVB sessions required. Essential beneficial effects for patients are less inconvenience, less risk of developing photoaging of the skin and less exposure to potentially carcinogenic radiations.

Patient compliance and disease management in the treatment of psoriasis in the Netherlands.

BACKGROUND: Compliance behaviour and disease management are important issues in chronic skin diseases. Psoriasis patients are 'experts by experience' because of many years of treatment. Therefore, it is relevant to gather data from patients on the actual use of antipsoriatic treatments. OBJECTIVE: The following questions are addressed: (1) What is the present mode of prescription and actual use of antipsoriatic treatments, including topical treatments, photo(chemo)therapy and systemic treatments? (2) What information do patients expect from their doctor, and do they actually receive this information. METHODS: To answer these questions, a questionnaire survey was mailed to the subscribers of Psoriasis, the journal of the Dutch Psoriasis Patients' Organisation. RESULTS: (1) Major issues in the treatment of psoriasis are (a) long-term management, (b) control of mild, moderate but also extensive psoriasis and (c) control of psoriasis on difficult localisations. Patients perceive itch, scaliness and visibility as major criteria for efficacy. (2) Topical treatment is the mainstay in the management of psoriasis. Calcipotriol is the most prescribed drug. Photo(chemo)therapy has an intermediate position between topical and systemic treatments. UVB is prescribed more than twice as frequently as PUVA and 10% of the patients on photo(chemo)therapy proved to be treated with UVB at home. Only 16% of the patients were on a systemic treatment; methotrexate and acitretin were the most frequently used systemic treatments. (3) More than 70% of the patients indicated that they had taken part in the selection of a treatment. In general, the patients were satisfied about the contact with their dermatologist and general practitioner. Compliance with the duration of treatment is limited, especially with regard to topical treatment. Patient compliance with the dose of the treatment is better. Again compliance is the worst in topical treatments. (4) Patients have a strong preference for an effective treatment which is safe for long-term use. Only a minority of patients wants a fast clearing treatment. CONCLUSION: Itch, scaliness and visibility provide the most relevant information on the severity of psoriasis, as the patients perceive themselves. Treatment duration is often unrestricted, especially with regard to topical treatments, which implies that the cumulative toxicity potential of these treatments may have a serious impact on their safety profile. Patients regard it of importance to have a vote in the selection of the treatment and regard safety as more important than fast clearing.

Scalp psoriasis, clinical presentations and therapeutic management.

BACKGROUND: The scalp is a well-known predilection site for psoriasis. Many patients indicate that scalp psoriasis is both psychologically and socially distressing. OBJECTIVE: The aim of the present investigation is to provide epidemiological data on the various manifestations of scalp psoriasis, as well as on its therapeutic management. METHODS: A questionnaire, targeted on scalp psoriasis, was mailed to patient subscribers of a Dutch journal on psoriasis. In total 1,023 forms were returned and evaluated. RESULTS: Remarkably, a relatively high occurrence of facial psoriasis (25%) and nail psoriasis (40%) was recorded. The dynamics of scalp psoriasis were rather similar to psoriasis at other sites with respect to the total duration of the disease and exacerbations/remissions. In 57% of the patients, psoriasis was psychologically and socially distressing, at least occasionally. Itch and scaling proved to be the leading symptoms, in terms of frequency of occurrence as well as in terms of distress. Therefore, these parameters should be regarded as primary efficacy criteria in the treatment of scalp psoriasis. On average, most patients were seen by the dermatologist 5 times a year. The majority of prescriptions (76%) was given by the dermatologist. The application of topical corticosteroids was by far the most frequent treatment modality. To our surprise, calcipotriol was used by 28% of patients. At the time of investigation calcipotriol was only available as ointment. Tar shampoos were used by 51% of the patients, although the clinical efficacy of such a shampoo has never been demonstrated in a controlled study. A remarkable observation was the lack of instruction on the duration of treatment and the frequency of applications. In fact, 72% of the patients used topical treatments, including topical corticosteroids, for more than 8 weeks, and 42% of the patients used an intermittent schedule of a few applications per week. CONCLUSIONS: Based on the present survey, the following profile for an optimal treatment of scalp psoriasis can be constructed: (1) effective applications a few times per week; (2) either a lotion or an emulsion, and (3) safety for long-term use.

In vitro and in vivo comparison of creams containing dithranol 0.5%.

In an in vitro model, the release and penetration through a silicon membrane of different cream formulations and ointments containing 0.5% dithranol were studied. The results indicated that the method is not suitable for predicting in vivo release and penetration. Experiments with rabbits showed that the degree of skin irritation produced by a hospital-prepared product containing 0.5% dithranol was comparable to that of of a commercial product. Clinical efficacy and side-effects of these two products were investigated in a double-blind left-right comparative study in 35 patients with chronic plaque psoriasis. The two creams proved to be equally effective and showed the same incidence of side-effects.

Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris.

The therapeutic efficacy and tolerability of calcipotriol ointment and betamethasone valerate ointment in psoriasis were compared in a multicentre, prospective, randomised, double-blind, right/left trial. 345 inpatients and outpatients with psoriasis vulgaris of symmetrical distribution were treated twice daily for 6 weeks with calcipotriol ointment 50 micrograms/g and betamethasone ointment 0.1% randomly assigned to opposite sides of the body. The main outcome measures--the psoriasis area and severity index (PASI), the investigators' assessments of erythema, thickness, and scaling, and the patients' own assessments of the overall response to treatment--were sought at weeks 2, 4, and 6. Both treatments significantly reduced the PASI scores and the investigator's assessment scores, but at each visit the PASI score was significantly (p less than 0.001) lower with calcipotriol than with betamethasone. At 6 weeks the mean PASI reduction was 68.8% with calcipotriol and 61.4% with betamethasone (95% confidence interval for difference 5.1-9.8, p less than 0.001). The scores for erythema, thickness, and scaling were significantly (p less than 0.001) lower with calcipotriol than with betamethasone at the end of treatment. The patients considered that 82.1% of calcipotriol-treated sides and 69.3% of betamethasone-treated sides had improved greatly or cleared up by the end of treatment (p less than 0.001). 57 adverse events were reported by 52 patients (15.1%). The most common adverse event, lesional/perilesional skin irritation, was slightly but not significantly (p = 0.12) more common with calcipotriol treatment. 15 (4.3%) patients were withdrawn from the study, 3 because of local adverse events. There were no changes in serum calcium during the study. Thus, calcipotriol ointment was superior to betamethasone valerate ointment in psoriasis vulgaris. Though long-term results are not yet available, calcipotriol holds great promise as an antipsoriatic agent.

[The treatment of psoriasis in a day care center]. / Behandeling van psoriasis in een dagbehandelingscentrum.

We describe the treatment of 196 patients with psoriasis, in the psoriasis day care centre at Ede. Treatments involve salt water baths followed by radiation of UVB, additional radiation of the scalp and therapy-resistant parts of the skin and anthralin 'short contact therapy'. During the anthralin therapy the hairy scalp is treated with liq. carb. dexerg. 5% in soya oleum. The results were evaluated by means of the psoriasis area and severity index (PASI) and of a questionnaire which was completed by 144 patients. In an average course of 28.4 treatment sessions (range 9-51), the PASI decreased by 84.3%. Evaluation of the PASI included the hairy scalp, the axillae and the inguinal region. The answers to the questionnaire indicated a risk of rather rapid relapse however, according to many patients, only a small part of the skin surface was affected. The additional value of the treatment is attributed to the setting of the psoriasis day care centre and the relatively safe therapeutic possibilities offered there.

Fumaric acid therapy in psoriasis: a double-blind comparison between fumaric acid compound therapy and monotherapy with dimethylfumaric acid ester.

In a 4-month double-blind study the effects of dimethylfumaric acid esters (DMFAE-EC) and DMFAE plus salts of monoethylfumaric acid esters (fumaric acid combination, FAC-EC) in enteric-coated tablets were compared in 22 respectively 23 patients with psoriasis. In both groups about 50% showed a considerable improvement, i.e. the initial score was more than halved. The therapeutic effects showed no significant differences in both groups with respect to the total psoriasis score or the different parameters. In the FAC-EC group the effects were obtained more rapidly. Most frequently observed side effects in both groups were flushings, stomachache and diarrhea. Due to these complaints 3 respectively 8 patients discontinued therapy. Eosinophilia, leukopenia and lymphopenia were the most frequently observed differences in lab tests. It was concluded that FAC-EC had no significantly better effect than monotherapy with DMFAE-EC. Moreover, enteric coating of the tablets did not prevent stomach complaints. Until more information has been obtained about the pharmacokinetics, the toxicity and optimal composition of the drug, the fumaric acid therapy in psoriasis should be seen as experimental.

[2 men with active syphilis infection and HIV-I infection]. / Twee mannen met actieve luesinfectie en HIV-I-infectie.

We report the case histories of two men who were living together and who were seropositive for human immune deficiency virus (HIV) and also had positive syphilis tests. Conceivably, reactivation of an earlier syphilis infection (which had been treated) had occurred after infection with HIV. It is therefore recommended to treat such patients according to the standard of treatment of neurosyphilis.

Systemic therapy with fumaric acid derivates: new possibilities in the treatment of psoriasis.

For the past two decades fumaric acid (FA) therapy has become an increasingly popular treatment in Western Europe for psoriasis. FA therapy originally was developed by Schweckendiek and subsequently standardized by Schäfer. Schäfer's fumaric acid compound therapy (FACT) consists of the oral intake of dimethylfumaric acid ester (DMFAE) and several salts of monoethylfumaric acid ester (MEFAE) in combination with topical fumaric acid therapy (1% to 3% MEFAE in an ointment or FA in bathing oils) and a diet. Schäfer claimed excellent results in a large number of patients. Preliminary studies by German dermatologists, however, revealed contradictory therapeutic results and serious side effects, and FA treatment was soon abandoned by dermatologists. To assess the value of FA therapy we conducted an open pilot study of 36 patients in which FACT therapy appeared to be rather effective. Thereafter, several controlled studies with MEFAE sodium in two different dosages versus placebo, and DMFAE versus placebo, were done. The results indicated that MEFAE sodium in dosages up to 240 mg daily was ineffective, whereas daily dosages of 720 mg resulted in a significant decrease in scaling and itching but did not affect extension of the eruption. DMFAE, 240 mg daily, produced a significant amelioration and prevented extension. Side effects of FA treatment were nausea, diarrhea, general malaise, and severe stomachache. Mild disturbances of liver and kidney function during treatment were observed with the 720 mg dosage of MEFAE and with the 240 mg dosage of DMFAE. Moreover, a relative lymphopenia with a selective decrease of suppressor T lymphocytes occurred in about 50% of the patients treated with DMFAE.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative study of treatment of uncomplicated gonorrhea with thiamphenicol and cefotaxime.

Results of treatment of uncomplicated urogenital gonorrhea caused by penicillinase- and non-penicillinase-producing Neisseria gonorrhoeae were compared. In The Hague treatment consisted of thiamphenicol (2.5 g given orally), whereas the treatment in Rotterdam was cefotaxime (1 g given im). All isolates were tested for production of penicillinase and sensitivity to cefotaxime and thiamphenicol. Special attention was given to possible hematological effects of treatments with thiamphenicol. Of 55 patients treated with thiamphenicol, 87.3% were cured; however, all of 55 patients treated with cefotaxime were cured. The frequency of postgonococcal urethritis among male patients was 34.1% after thiamphenicol and 39.5% after cefotaxime treatment. The only adverse effect seen after cefotaxime treatment was a rash (2%). After treatment with thiamphenicol, 10.9% of patients had diarrhea. No significant changes in hematologic tests were seen after treatment with thiamphenicol. There was a remarkable and significant difference in sensitivity to thiamphenicol between the two treatment groups; this fact could point to the importance of specific local factors in comparison of different treatments for gonorrhea.

Hepatitis B antigen and antibody in the blood of prostitutes visiting an outpatient venereology department in Rotterdam.

We took blood samples from 128 prostitutes visiting the outpatient venereology department of the University Hospital, Rotterdam-Dijkzigt to test for the presence of hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface antigen (anti-HBs). The prevalence of anti-HBs was found to be significantly higher in the group of prostitutes than in "normal populations", and we concluded that more of the former had been in contact with the hepatitis B virus (HBV). We recommend that the advice on vaccination of the hepatitis B committee of the Health Council of The Netherlands should be followed by screening prostitutes for the presence of HBsAg and anti-HBs in the blood, and vaccinating those who have no anti-HBs.

Detection of Neisseria gonorrhoeae antigen by a solid-phase enzyme immunoassay.

The Gonozyme test (Abbott Laboratories) is a new enzyme immunoassay for detecting Neisseria gonorrhoeae antigens in specimens from the urethra in men and the endocervix in women. To evaluate the usefulness of the assay 249 patients were investigated. The results obtained with the immunoassay were compared with those of culture and microscopy of Gram-stained smears. The sensitivity and specificity of the test were high in men with urethritis and acceptable in different groups of women. As the sensitivity of the Gonozyme test was much higher than that of microscopy for endocervical specimens it might be useful as a rapid screening test for the detection of gonorrhoea in women.

Infections with non-penicillinase-producing Neisseria gonorrhoeae treated with cefuroxime: treatment failures.

Two men who acquired acute gonococcal urethritis in The Netherlands and who were treated with cefuroxime (1.5 g given intramuscularly) failed to respond to this therapy. Pre- and post-treatment isolates of Neisseria gonorrhoeae from these patients had MICs of 0.5 and 1.0 microgram of cefuroxime/ml.