Egon Macher

Thalidomide in the treatment of sixty cases of chronic discoid lupus erythematosus

The therapeutic effect of thalidomide in chronic discoid lupus erythematosus (CDLE) was studied in sixty patients who were followed up for 2 years. In fifty‐four patients (90%) a complete or marked regression of the disease was observed, but when the thalidomide was stopped, thirty out of forty‐one (71%) patients relapsed. Patients undergoing a second course of thalidomide treatment again responded well. Nine of the patients in whom the disease recurred after successful treatment with thalidomide and who had been unresponsive to intermittent treatment with antimalarials, showed a good response to a second or third course with thalidomide. Mild side‐effects were common and 25% of patients complained of slight to moderate polyneuritic symptoms. Since electroneurological examinations had not been performed before the thalidomide therapy, the frequency of neurological side‐effects cannot be accurately calculated but we recommend neurological examinations before and periodically during thalidomide treatment.

Topical immunotherapy changes the composition of the peribulbar infiltrate in alopecia areata

SummaryIt has previously been shown that, in patients with untreated progressive alopecia areata (AA), the peribulbar T4/T8 ratio is about 4:1. In the present study, the immunohistochemical findings obtained in untreated AA patients were compared to those obtained in patients who had received topical immunotherapy with diphencyprone. The untreated group consisted of 5 patients with progressive AA and 5 patients with inactive AA. The treated group consisted of 5 patients with a good response to diphencyprone and 5 patients with little or no hair regrowth after treatment. In untreated patients with progressive AA, the mean peribulbar T4/T8 ratio was 4:1, whereas in untreated patients with stable AA, the ratio was 2:1. In the treated patients with a good response to diphencyprone, the mean T4/T8 ratio was 1:1, while in the patients with poor or no response to treatment, the ratio was 0.7. In conclusion, topical immunotherapy considerably alters the peribulbar T4/T8 ratio in AA. The results are consistent with, but do not prove, the concept of topical immunomodulation.

Long-term adjuvant immunotherapy in stage I high risk malignant melanoma, comparing two BCG preparations versus non-treatment in a randomised multicentre study (EORTC protocol 18781)

The present study reports the results of a multicentre adjuvant trial with BCG (Bacillus Calmette-Guérin) in high risk patients (Breslow thickness > or = 1.5 mm, Clark level > or = III) with malignant melanoma, after surgical removal of their primary tumour. The trial was specifically designed in order to resolve the controversy and to provide some definite answers regarding the value of adjuvant BCG treatment in stage I malignant melanoma. Patients were randomised to either BCG RIV (108 patients) or BCG Pasteur (109 patients) for 3 years or to follow-up only (110 patients). The two vaccines used had greatly divergent properties regarding their mode of preparation, their composition and their immunomodulating activities. Of the 353 randomised patients, 23 were ineligible, 3 refused participation after randomisation and 327 were evaluable for final analysis. Median follow-up time was 6 years (range 0-10 years). The log-rank test comparison showed no statistical difference between the three arms regarding time to progression (P = 0.55) and duration of survival (P = 0.82). Treatment was generally well tolerated, with no major adverse events in either treatment arm. These findings confirm data with different BCG preparations and with stage II melanoma which also demonstrated no benefit regarding patient survival and time to relapse.

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

SummaryEighteen 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 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. These 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.

The Duhring chamber assay for corticosteroid atrophy

A new human model for the evaluation of the atrophogenicity of topical corticosteroids is proposed. Formulated corticosteroids (creams and ointments) were applied occlusively to normal forearm skin of human volunteers for 3 weeks using Duhring chambers. Visible atrophy and telangiectasia were rated under a stereomicroscope on a histologically validated five‐point scale. There was a close correlation between the parameters of atrophy and telangiectasia. Atrophogenicity varied considerably among the tested corticosteroids, ranging from none (1% hydrocortisone) via moderate (0.1% betamethasone valerate) to very severe (0.05% clobetasol propionate). A dose‐response relationship with exposure time and concentration of the corticosteroid could be demonstrated. Furthermore, the vehicle influenced the resulting atrophy and telangiectasia. Fatty ointments seem to pose less risk than oil in water creams.

Tumor angiogenic activity (TAA) production in vitro and growth in the nude mouse by human malignant melanoma

The production of angiogenic activity by eleven human melanoma lines in vitro was compared with the extent of tumor growth in the nude mouse. Angiogenic activity was assayed by measuring the vascular response of the chick chorioallantoic membrane to serum-free supernatants. Growth in the nude mouse was determined after subcutaneous injection of cells 60 days later. Angiogenic activities ranged from negative to highly positive. In five lines angiogenic activity in vitro correlates with the extent of tumor growth in the nude mouse. In contrast, two lines did not show such a correlation, e.g. they produced large tumours without any detectable angiogenic activity. Histological examination of these two tumors revealed moderate degrees of vascularization and only low degrees of necrosis. It is concluded that the extent of tumor growth in the nude mouse is partly independent of the production of angiogenic activity by the tumor cells themselves.

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

SummaryA 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.

Membrane associated antigens of human malignant melanoma V: Serological typing of cell lines using antisera from nonhuman primates

SummaryAntisera against various melanoma cell lines were raised in nonhuman primates (Cercopithecus aethiop.). After exhaustive absorption with AB Rh + red blood cells and pooled platelets from about 200 donors the sera were still reactive to various degrees in the microimmune adherence test with other melanoma lines, with embryonic fibroblasts, and with non-melanoma lines. As proven by absorption experiments, the main-specificity of the antisera was not directed against components of the fetal calf serum used for cell culture or against mycoplasma grown from commercial fetal calf serum. In addition, no cross-reactivity was observed with Bacillus Calmette-Gérin, and in blocking experiments no reactivity against extracts of common bacterial antigens or mixed molds was detected. Absorption with embryonic fibroblasts or embryonic tissue showed that the reactivity of most antisera was directed against melanoma-associated antigens expressed also on fetal tissue. It was not possible to determine whether the remaining reactivity on some cell lines was melanoma-specific or directed against fetal antigens not contained in the fetal material used for absorption. Cross-absorption of antisera with other melanoma cells revealed that various cell lines express different patterns of tumor-associated antigens with no, or only partial, overlap. The cross-absorption experiments made it possible to type the cell lines according to their surface antigens and arrange the cell lines in order according to the degree of mutual antigenic relationship.

Membrane-associated antigens of human malignant melanoma IV: Changes in expression of antigens on cultured melanoma cells

SummaryEstablished melanoma cell lines were cultured for one passage (approximately 1 week) in different lots of fetal calf and new born calf sera and then tested against a panel of previously positively reacting sera from melanoma patients and polyspecific HL-A alloantisera. Using indirect immunofluorescence the cells showed varying degrees of reactivity ranging from positive to negative reactions depending on the supplementing serum in the culture medium. When standardized culture conditions were used and the cells were tested by immune adherence at several weeks intervals against panels of sera from melanoma patients, from tumor patients other than melanoma, from pregnant women, and from normal donors, most of the sera reacted identical, but some sera not only had changed quantitatively but also qualitatively from a negative to a positive reaction and vice versa indicating a shift in the spectrum of expressed antigens. When single cell clones from a cell line were isolated and tested against a panel of antisera, striking differences in reactivity were observed suggesting that the shift in the spectrum of expressed antigens was due to the outgrowth of dominating subclones with antigen patterns different from the previously dominating subclones. This conclusion was further supported by experiments in which a weakly positive reacting serum was employed to separate a cell line into positively and negatively reacting sublines. Unit gravity sedimentation and density gradient sedimentation were used in order to separate rosetted from non-rosetted tumor cells which had been prepared by immune adherence. It is concluded that cultured cell lines are in a dynamic state and that differentiation is one of the major mechanisms accounting for a change in antigen expression.

Eosinophilic Pustulosis with Pemphigus-Like Antibody

A 75-year-old male with eosinophilic pustulosis Ofuji complicated by superinfection with Pseudomonas aeruginosa and Proteus mirabilis is described. This is the first case of eosinophilic pustulosis with an antiepidermal antibody. This antibody was directed against the intercellular substance of the lower epidermis and it was detected by direct immunofluorescence in the patients normal and lesional skin. As revealed by indirect immunofluorescence the patients serum reacted with intercellular substance of human lower epidermis but not with guinea pig esophagus. Possibly the detected autoantibody is not characteristic for eosinophilic pustulosis Ofuji but rather an accompanying feature of this case similar to the antiepidermal antibodies found in patients with drug reactions and burns.