Klaus Wolff

5-Methoxypsoralen (Bergapten) in photochemotherapy of psoriasis

5‐Methoxypsoralen (5‐MOP, Bergapten) was evaluated as a potential photosensitizing drug in oral photochemotherapy of psoriasis. Treatment results indicate that (1) 5‐MOP is as effective as, and in high doses more effective than, 8‐methoxypsoralen in clearing psoriatic lesions; (2) therapeutic doses of 5‐MOP do not lead to erythema; the acute side‐effects of 8‐MOP PUVA therapy—erythema, blistering, pruritus—are thus avoided; (3) even high doses of 5‐MOP are not followed by nausea. 5‐MOP PUVA therapy thus represents a real alternative to 8‐MOP PUVA, its advantages over 8‐MOP PUVA being greater safety and patient acceptance.

Induction of UV light tolerance by PUVA in patients with polymorphous light eruption

A tan induced by 8‐methoxypsoralen‐long wave ultraviolet light has proved an effective photo‐ protective sunscreen in 5 patients with long wave ultraviolet light‐induced polymorphic light eruption.

Long‐term photochemotherapy: histopathological and immunofluorescence observations in 243 patients

Skin biopsies of 243 patients treated with photochemotherapy (PUVA) for 1–4 years were examined histologically. Two hundred and six patients were examined retrospectively after total cumulative UV‐A doses of 579·6 ± 598·0 J/cm2 (mean ± s.d.). An eosinophilic homogenization and a reduction of elastic fibres at the dermo‐epidermal junction, and an increase of dermal macrophages were found as possible abnormalities. However, except for the increase of melanophages there was no statistically significant correlation between the incidence of these changes, the total UV‐A dose applied and the skin type of the patients. Neither were such correlations found in thirty‐seven patients biopsied twice after 394·8 ± 267·6 J/cm2 and 808·5 ± 458·9 J/cm2 (mean±s.d.), respectively. Studies with direct immunofluorescence techniques revealed no immunoglobulin deposits in PUVA treated skin in fifty‐six patients after 469·2 ± 370·2 J/cm2; antinuclear antibodies were observed in 4·6% of 129 patients after 169 J/cm2 (mean); in 11%, of fifty‐three patients reexamined after 381 J/cm2 (mean) and in 13·6% of twenty‐two patients reexamined a second time after 643 J/cm2 (mean).

Photoprotective effect of a psoralen-UVA-induced tan

SummaryTo determine whether a tan produced by 8-MOP and UVA protects from subsequent solar light irradiation, volunteers were irradiated with unfiltered Xenon arc light before and 10 days after a 1 weeks course of four 8-MOP-UVA treatments. Evaluation of the minimal erythema doses and of histological changes before and after 8-MOP-UVA treatment revealed that the 8-MOP-UVA induced tan protected against the erythemogenic and cell damaging effects of Xenon arc light. Unscheduled repair DNA synthesis, used as a measure for UVB-induced DNA damage and repair, was also investigated in skin irradiated with the Xenon arc before and after 8-MOP-UVA induced tanning. Both the number of grains per sparse labeled cell and the number of sparse labeled cells per 1000 cells, were found to be significantly lower in tanned skin; taking decreased unscheduled repair DNA synthesis as a measure for decreased DNA-damage, these findings also demonstrate a photoprotective effect of the 8-MOP-UVA induced tan.ZusammenfassungZur Klärung der Frage, ob die durch 8-Methoxypsoralen (8-MOP) und langwelliges Ultraviolett-Licht (UV-A) induzierte Hautbräunung vor Sonnenbestrahlung schützt, wurden Testpersonen mit einer ungefilterten Xenon-Lampe vor und 10 Tage nach einer einwöchigen 8-MOP/UV-A-Behandlung (4 Expositionen) bestrahlt. Die Beurteilung erfolgte klinisch durch die Bestimmung minimaler Erythemdosen, cytomorphologisch durch Beurteilung UV-inducierter Gewebs- und Zellschäden in bioptischem Material und autoradiographisch durch die »unscheduled repair«-DNS-Synthese. Ein Vergleich der cutanen Reaktion auf eine definierte, von der Xenon-UV-Quelle (sonnenähnliches Spektrum) emittierten Energiedosis vor und nach Hautpigmentierung durch 8-MOP-UVA zeigte 1) klinisch eine signifikante Anhebung der minimalen Erythemschwelle, 2) histologisch eine signifikante Abnahme UV-inducierter Zellschäden und 3) autoradiographisch eine deutliche Abnahme von Repair-Aktivität als Maß eingetretener DNS-Schädigung. Sowohl die Zahl der Zellen mit Repair-Aktivität, als auch die Summe von Silberkörnern in markierten Zellen waren signifikant erniedrigt. Da die »unscheduled repair«-DNS-Synthese ein Maß für UVB induzierte DNS-Schäden und Reparaturvorgänge darstellt, wird auch anhand dieses Parameters ein Lichtschutzeffekt durch 8-MOP-UVA-Bräunung dokumentiert.

Photochemotherapy for pustular psoriasis (von Zumbusch).

Photochemotherapy (PUVA) with oral methoxsalen and UV‐A was instituted in 8 patients with generalized pustular psoriasis (von Zumbusch). Complete clearing of skin lesions and of systemic symptoms was achieved in all patients. Patients who had been on systemic treatment prior to PUVA had to be treated with considerably more UV‐A energy than patients who had received topical therapy alone. Seven patients were kept in complete remission by maintenance therapy for an observation period of up to 1½ years. Side effects of systemic pre‐PUVA treatment resolved during several months of maintenance therapy.

Hereditary angio-oedema: treatment with danazol. Report of a case.

An 8‐year‐old boy with hereditary angio‐oedema was treated with danazol under close endocrinological supervision. The boys C1 esterase inhibitor (Clinh) and C4 levels increased rapidly to near normal values under a daily doses of 400 mg and were maintained at about 50% of the normal by maintenance doses of 200 mg danazol every other day. Throughout the entire treatment period (11 months) the boy has been maintained free from attacks of angio‐oedema. No hormonal imbalance was detected in the follow‐up period. Our results indicate that danazol should be suitable for the treatment of HAE not only in adults but also in prepubescent children.

Diffuse melanosis in metastatic melanoma: Further evidence for disseminated single cell metastases in the skin

Electron microscopy (EM) and electron microscopic cytochemistry have shown that diffuse melanosis in advanced metastatic melanoma is the result of an unlimited spread of single melanoma cells throughout the dermis; these cells retain their melanogenic capacity and continue to produce melanized melanosomes which eventually are deposited within dermal macrophages and thus impart to the skin a diffuse slate-blue color. These findings are in accordance with previous observations in a similar patient and thus support the concept that single cell metastasis represents a common pathogenic event in these patients.

Reticulate urticarial erythema in hereditary angio‐oedema

SIR, In his recent article on reticulate erythema as a prodrome in hereditary angio-oedema (HAE), Williamson (1979) describes a peculiar skin eruption occurring in several members of a large family affected with HAE. We would like to relate our own observation of a similar case. Full details of the diagnosis, the clinical course and the treatment of this patient have been published (Hintner et aL, 1979). In our patient there were attacks of a peculiar reticulate urticarial erytbema that had been recurring at 3-week intervals almost since birth; after 1-3 days the skin eruption was followed by abdominal pain and vomiting. The erytbema always subsided within 1-2 days together witb tbe gastrointestinal symptoms. Attacks of typical angio-oedema occurred independently. The skin eruption did not appear in his mother who has HAE, nor is it reported to have been present in his sister, who had died from laryngeal oedema some years previously. Clinically, tbe skin eruption of our patient is characterized by a bizarre, polycyclic configuration involving most of the skin surface. It looks like regressing urticaria; its configuration changes within fractions of an hour and the skin between tbe linear weal-like lesions appears clinically normal (Fig. i). Upon treatment witb Danazol, as detailed (Hintner et a/., 1979), the attacks of angio-oedema, the skin lesions and the gastrointestinal attacks subside. The features of our patients skin eruption are reminiscent of tbe reticulate erythema described by Williamson (1979), whicb, even tbougb occurring independently from angio-oedema of the skin, was also a prodrome to abdominal symptoms. However, there are also differences: although tbe family is small (only three members are known to have or have had HAE) and thus not very informative, tbere is no evidence for a familial occurrence of this peculiar eruption and perbaps more importantly, Williamson describes the lesions as annular and reticulate erytbema, whereas in our patient tbey were urticarial in character.

Dermatitis herpetiformis: immune complex detection with CIq and monoclonal rheumatoid factor

To determine the significance of circulating immune complexes in dermatitis herpetiformis, serum samples from thirty patients with active disease were tested by a CIq binding radioassay, while serum samples from twenty‐one of these patients were tested by a monoclonal rheumatoid factor (mRF) inhibition radioassay. By direct immunofluorescence, all patients demonstrated typical IgA deposition in dermal papillae. Using the Ci q binding assay, only seven of forty‐two serum samples had elevated Ci q binding activity, while by the mRF inhibition assay, thirteen of twenty‐five samples had elevated immune complex levels. Nine of these latter thirteen positive serum samples, however, were minimally elevated. Thus, IgG and/or IgM containing immune complexes are infrequently present, or at very low levels, in sera of patients with active dermatitis herpetiformis.

Skin : Structure, Natural and Therapeutical Targets of Ultraviolet Radiation

Absorption of radiant energy by the skin initiates photochemical reactions which involve alterations of cellular metabolism, structure and function, changes of cellular kinetics, blood flow and pigmenta tion. Though most of these effects are due to the 290–320 nm (UV-B) or so-called sunburn spectrum there is now growing awareness that UV-A (320–400 nm) is also effective in inducing structural and functional changes in the skin.