High-dose UVA1 therapy for atopic dermatitis: results of a multicenter trial.

BACKGROUND: The results of an open, single-center study suggested that phototherapy with high doses of UVA1 radiation (UVA1R; 340-400 nm) is effective for acute, severe exacerbations of atopic dermatitis (AD). OBJECTIVE: The purpose of this study was to assess the effectiveness of high-dose UVA1 phototherapy for acute, severe AD in a randomized multicenter trial in direct comparison with topical glucocorticoid therapy. METHODS: Patients were treated with high-dose UVA1R (10 days, 130 J/cm2/day; n = 20), topically with fluocortolone (10 days, 1 x daily; n = 17), or with UVA-UVB therapy (10 days, 1 x daily, minimal erythema dose-dependent; n = 16). RESULTS: With a clinical scoring system, significant differences in favor of high-dose UVA1R and fluocortolone therapy were observed (p < 0.0001), as compared with UVA-UVB therapy. At day 10, high-dose UVA1R was superior to fluocortolone (p < 0.002) therapy. Serum levels of eosinophil cationic protein and the blood eosinophil count were significantly reduced after high-dose UVA1 or fluocortolone, but not UVA-UVB therapy. CONCLUSION: This study confirms the therapeutic effectiveness of high-dose UVA1 monotherapy for treatment of severe exacerbations of AD.

Anti-CENP-B response in sera of uranium miners exposed to quartz dust and patients with possible development of systemic sclerosis (scleroderma).

OBJECTIVE: To look for anti-CENP-B antibodies and their diagnostic relevance in patients negative and positive for anticentromere antibodies (ACA) with different risk for the development of systemic sclerosis (SSc), including uranium miners exposed to quartz dust. METHODS: We studied sera of 107 patients with SSc, 121 patients with possible SSc, 202 uranium miners heavily exposed to quartz dust, 14 patients with vibration induced white fingers, and 240 control patients. Subjects were screened for ACA by indirect immunofluorescence on HEp-2 cells (IIF-ACA) and then for anti-CENP-B autoantibodies by an ELISA using eukaryotically expressed human full length recombinant CENP-B protein. RESULTS: All IIF-ACA positive sera of "idiopathic" SSc (N = 19), "idiopathic possible" SSc (N = 6) and other patients (N = 11), and 17 of 19 IIF-ACA positive sera of miners exposed to silica with (N = 13) and without (N = 6) symptoms of SSc reacted with CENP-B in this assay. Of the 622 IIF-ACA negative sera, 28 were found positive for anti-CENP-B. There was a significant increase of the prevalence of anti-CENP-B antibodies in IIF-ACA negative patients with possible SSc (11 of 109) and in miners exposed to silica (11 of 196) compared to a group of men older than 60 years with diseases or symptoms not related to SSc (1 of 138). CONCLUSION: (1) CENP-B is also the major target of the IIF-ACA response in diseases other than scleroderma and in the risk group of miners exposed to quartz dust. (2) Anti-CENP-B antibodies can be found in IIF-ACA-negative sera, particularly in those at risk for SSc. (3) The detection of anti-CENP-B antibodies in miners exposed to quartz dust may indicate a high risk group for developing SSc and reveals possibilities for the study of early pathogenetic changes as well as exogenic and endogenic factors involved in the development of this disease.

[The diagnostic value of antinuclear antibodies]. / Zur diagnostischen Bedeutung von antinukleären Antikörpern.

In this review we focus on the diagnostic importance of antinuclear antibodies (ANA), the biological function of the relevant autoantigens and on some methodological questions regarding the detection of ANA. The qualitative and quantitative evaluation of ANA has improved significantly in recent years with the introduction of several new test kits. A precondition for the rational use of those assays is knowledge of the diagnostic validity of the detected ANA with regard to the method used. ANA are autoantibodies that react with nucleic acids, protein-nucleic acid complexes and proteins of nuclei. The reasons for their in vivo production are unknown. ANA characterize several of the so-called connective tissue autoimmune diseases and their subtypes, either alone or in typical combinations. They differ significantly with regard to their prevalence and thus in their diagnostic validity. Specificity and prevalence do not correlate. ANA are not markers of disease activity except for antibodies against dsDNA. ANA levels can be interpreted correctly only in connection with clinical symptoms and other laboratory findings.

Comparison of the effects of calcipotriol, prednicarbate and clobetasol 17-propionate on normal skin assessed by ultrasound measurement of skin thickness.

In this study, we investigated the effect of calcipotriol, prednicarbate and clobetasol 17-propionate on skin thickness over a treatment period of 6 weeks. The study was conducted as a controlled, randomized, double-blind comparison. The influence of these drugs on normal skin under occlusive conditions was assessed visually and by measuring skin thickness using 20 MHz B mode ultrasound. Both topically applied glucocorticosteroids lead to a significant decrease in skin thickness. In contrast to the glucocorticosteroid-induced atrophy, calcipotriol application on normal skin leads to an increase in skin thickness in all volunteers. The effect remains constant for the duration of treatment. The cause of this increase seems to be an irritative reaction of the skin which was histologically investigated in one volunteer. The histological features of this reaction are characteristic for a subacute dermatitis. The implications of these findings for the therapeutic mechanism of calcipotriol are discussed.

[UV-A-1 therapy of subacute cutaneous lupus erythematosus]. / UV-A-1-Therapie bei subakut-kutanem Lupus erythematodes.

Because of relative contraindications to corticosteroid or immunosuppressive treatment, a 71-year-old female patient with subacute cutaneous lupus erythematosus underwent serial whole-body irradiation with extremely long-wave ultraviolet light (UVA-1). The cumulative dosage was 186.1 J/cm2 within 9 weeks. Impressive improvement was achieved with some delay.

Studies on the effects of a high dose UVA-1 radiation therapy on surface markers and function of epidermal Langerhans cells.

Recently, high-dose UVA-1 therapy (340-400 nm) was introduced as an effective treatment of severe exacerbated atopic dermatitis. Since the target of this type of radiation in the skin is not known we investigated using the mouse model whether surface markers of the antigen-presenting function of epidermal Langerhans cells are affected by UVA-1 radiation. Even repeated high doses of UVA-1 radiation (up to 50 J/cm2) had no detectable effect on surface ATPase activity and Ia antigen expression on Langerhans cells. Also, the contact allergen oxazolone was presented normally in skin treated with UVA-1 radiation. In contrast, if the mice were injected 1 h before irradiation with 8-methoxypsoralen a dramatic reduction in ATPase activity and Ia antigen expression on Langerhans cells was observed and the induction of contact sensitivity was suppressed (PUVA effect). These results show that epidermal Langerhans cells are not impaired either in structure or function and that these cells probably do not represent the primary target of UVA-1 radiation in the skin. No side effects resulting from a diminished Langerhans cell function should result from high-dose UVA-1 therapy.

Inhibition of histamine release from human granulocytes by ions of the rare earth elements lanthanum and cerium.

The influence of the ATPase inhibitors, lanthanum or cerium, on histamine release in basophils and mast cells was studied. Both compounds inhibited IgE- or A23187-induced histamine release. To exclude a general inhibition of calcium-dependent reactions in the cell, we tested the influence of these compounds on phagocytosis and superoxide production of neutrophil granulocytes. Phagocytosis of Candida albicans was inhibited partially, superoxide generation, measured by the INT test after stimulation with zymosan or aggregated gamma globulin, was not affected. Because of the inhibitory effect of lanthanum or cerium compounds on membrane ATPase and immunological function of epidermal Langerhans cells we propose that these compounds may be used in the treatment of atopic eczema, where both histamine-releasing mast cells and IgE-bearing Langerhans cell play a pathogenetically important role.

The influence of topical dermatological treatment modalities on epidermal Langerhans cells and contact sensitization in mice.

The influence of the widely used topical dermatological treatment modalities anthralin, coal tar and pyrogallol on surface markers of epidermal Langerhans cells and contact sensitization was studied and compared with that of a PUVA treatment. A common effect of all dermatological therapies tested was inhibition of Langerhans cell ATPase, whereas an effect on MHC class II antigens was found only after PUVA or tar treatment. The induction of contact hypersensitivity was inhibited only by PUVA, and not by the other treatments. These results show that various forms of topical therapy influence surface markers and immunological function of epidermal Langerhans cells differently.

[Experiences with clofazimine therapy of Melkersson-Rosenthal syndrome]. / Erfahrungen mit der Clofazimin-Therapie des Melkersson-Rosenthal-Syndroms.

Melkersson-Rosenthal syndrome (MRS) is characterized by the triad of facial paralysis, facial oedema, and lingua plicata in association with other symptoms, such as headache and mental changes. Because the origin of this syndrome is still unknown, only symptomatic treatment is possible. In 18 patients suffering from MRS, whether with a complete or with an incomplete picture, we used the antileprosy drug clofazimine for therapy. A decrease in the frequency and intensity of oedema was achieved by this therapy in 94% of patients. However, improvement persisting throughout a follow-up period of up to 3 years was seen in only 62% of patients. We demonstrate that clofazimine is an alternative to glucocorticosteroids for the treatment of MRS.

Cis-urocanic acid as a mediator of ultraviolet-light-induced immunosuppression.

Treatment of an organism with UVB light or PUVA (8-methoxypsoralen + UVA light) not only leads to alterations in the irradiated skin but also to systemic immunomodulation, due to the release of several chemical mediators of immunosuppression like prostaglandins, acute-phase proteins, IL-1 inhibitor, alpha-melanocyte-stimulating hormone, propiomelanocorticotropin or other cytokines. A recently described mediator is urocanic acid, which is transformed by UV light in the skin from the trans- to the cis-isomer and that exerts a systemic immunomodulatory effect. In our experiments, treatment with PUVA or with cis-urocanic acid prevents the rejection of rat heart allografts in 50% and 40% of cases, respectively. Control grafts are rejected in fewer than 10 days. PUVA treatment of donor leukocytes before transfusion into the prospective recipient inhibits only their sensitizing, not their graft-protecting, effect on subsequent skin grafts in mice. PUVA treatment also prevents acute lethal GVH disease in mice after irradiation with a sublethal dose of x-rays and transfusion of semiallogeneic spleen cells. Treatment of recipient mice with cis-urocanic acid has the same effect. The humoral immune response to sheep erythrocytes is not influenced by cis-urocanic acid. These results demonstrate that PUVA treatment or its chemical mediator, cis-urocanic acid, may be used in transplantation and hematology as naturally occurring immunosuppressive agents, especially for the control and manipulation of GVH leukemia reaction.

The influence of interferon-gamma and interleukin-4 on IgE production in B lymphocytes of patients with atopic dermatitis. A possible criterion for selection of patients for interferon therapy.

The regulation of IgE production in B lymphocytes of patients with atopic dermatitis by interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) was studied. IL-4 stimulated IgE production in vitro in B-cells of healthy donors and of children with atopic dermatitis, but had only a marginal effect on the high basal level of IgE production by lymphocytes from adult patients with atopic dermatitis. The addition of IFN-gamma prevented in all cases the stimulation of IgE synthesis induced by IL-4. The production of IgG and IgM was differently influenced. These results indicate that the in vitro production of IgE by mononuclear cells from adult patients is more resistant to the regulatory effects of IL-4 and IFN-gamma than is that in B cells of children with atopic dermatitis. We propose that a previous in vitro test of the responsiveness of IgE-producing B cells to IFN-gamma may be used to select patients with atopic dermatitis for treatment with IFN-gamma.

[Effect of treatment with salt from the Dead Sea (Tomesa therapy) on epidermal Langerhans cells--a clinical study]. / Der Einfluss einer Behandlung mit Salz des Toten Meeres (Tomesa-Therapie) auf epidermale Langerhanszellen--Eine klinische Studie.

Among the therapeutical modes of psoriasis, sea-water baths with salts from the Dead Sea in combination with ultraviolet light (Tomesa therapy) play an important part. In a previous paper, we showed that treatment of isolated murine skin with Tomesa salt solutions resulted in an irreversible decrease of ATPase-positive epidermal Langerhans' cells. Our present study is concerned with the treatment of healthy persons and psoriasis patients with baths containing Tomesa salts, which lead to reduced amounts of detectable Langerhans' cells in the epidermis, as well. Baths containing sodium chloride in comparable concentrations, however, were without effect at all. Our findings demonstrate that the antipsoriatic activity of Tomesa therapy is not only due to physical effects but may also be the result of definable pharmacological actions of the salts on skin cells.

[Transitory acantholytic dermatosis (Grover) in an HIV infected patient]. / Transitorische akantholytische Dermatose (Grover) bei einem HIV-Infizierten.

We report on a patient with HIV infection and persistent generalized lymphadenopathy (stage III of HIV infection), who developed transitory acantholytic dermatosis (Grover's disease). Both the clinical picture and the histological features were typical for Grover's disease; the skin eruptions subsided within 6 months.

[The cytotoxic effect of anti-Ro- (SS-A) antibodies and UVA light on human endothelial cells in vitro]. / Zytotoxische Wirkung von Anti-Ro- (SS-A-) Antikörpern und UVA-Licht auf menschliche Endothelzellen in vitro.

There is in photosensitive lupus erythematosus a strong association of high titers of anti-Ro(SS-A) antibodies in the serum of the patient with the development of special skin reactions depending on UV-light. The aim of our experiments was to detect a cytotoxic effect of anti-Ro(SS-A) antibodies and UVA-light on human endothelial cells in vitro (standard trypan blue exclusion test, SEM). After UVA-doses of 1 to 100 J/cm2, which were tested, and influence of serum containing anti-Ro(SS-A) antibodies (62 E, ELISA) membrane destructions of endothelial cells depending on the UVA-dose can be seen, irrespective of the fact whether the antibodies are present throughout the irradiation or added afterwards. This cytotoxic reaction depends on complement. A UVA-dose of 100 J/cm2 causes lethal damage of 40% of the cells. These results were confirmed by scanning electron microscopy.