PUVA治疗前后银屑病患者的免疫状态

本文对105例PUVA治疗的银屑病患者,于疗前测定其细胞免疫和体液免疫功能状态.发现:疗前LTT值较对照组低,有非常显著差异(P<0.01),血清IgG, IgM与对照组比较.前者水平明显升高.后者水平明显降低(P<0.01).此外,对其中31例银屑病患者进行了PUVA治疗前后的免疫指标变化观察,发现PUVA疗后患者血IgM及LTT值与疗前相比均有非常显著差异(P<0.01),前者较疗前明显升高,后者明显降低.可见PUVA疗法对银屑病患者的免疫功能有抑制现象,这就可能增加了癌症发生的危险性,也可能使银屑病的复发加重.     

Genital squamous-cell carcinoma after PUVA therapy.

Among our patients treated with very high doses of PUVA (more than 1,500 J/cm2) for recalcitrant disseminated psoriasis, three developed squamous-cell carcinoma of the genitalia. The tumors were located on the scrotum in all patients; one of them displayed three times running a carcinoma of the dorsal aspect of the penis. All these genital tumors arose more than 2 years after PUVA cessation, in patients with previous arsenic and tar treatment.     

Neutrophil chemotaxis in psoriasis before and after PUVA therapy

Chemokinesis and chemotaxis of neutrophil leucocytes were studied by migration under agarose in 35 patients with psoriasis and compared with 35 healthy controls. Eschericheae coli filtrate and lipopolysaccharide were used as chemo-attractants. Of these patients, 14 were tested before and after photochemotherapy. The chemotactic capacities of psoriatic serum before and after PUVA therapy were also investigated. The increase in the chemotactic activity of psoriatic polymorphonuclear leucocytes (PMNs) was not significant and remained unchanged after PUVA therapy. The activated psoriatic serum showed a slight increase in chemotactic activity when compared with normal activated serum. These results do not support an intrinsic abnormality of psoriatic PMNs, and their migration into psoriatic lesions could be chiefly due to the presence of chemotactic factors in involved epidermis.     

Activation of complement in the skin after PUVA therapy

Suction blister fluid from the abdominal skin of 14 healthy subjects was examined for the presence of split products of complement C3 (C3-split) as an indicator of complement activation before and after treatment with either UVA or PUVA. Following PUVA a significant increase in C3-split was found (p less than 0.05) in both irradiated and non-irradiated skin areas. Following UVA the increase in C3-split was less pronounced. The activation of complement may play an important role in the maintenance of the delayed erythema that appears after irradiation with long-wave ultraviolet light.     

Recovery of cutaneous immune responsiveness after PUVA therapy

We studied sensitization to dinitrochlorobenzene (DNCB) in psoriatic patients before, during and 2, 4, and 6 weeks after a course of photochemotherapy (PUVA). The inhibition of sensitivity observed during PUVA was completely reversed after 6 weeks. Thus the PUVA-mediated inhibition of cutaneous immune responsiveness is of short duration. However, whether there are long-term sequelae remains to be established.     

Keratinocyte T6 antigen expression after PUVA therapy

We report T6 antigen expression on keratinocytes in 11 cutaneous T lymphomas treated by PUVA therapy. This staining was absent before treatment. T6 reactivity was strictly limited to cell membrane. The nature of this expression is discussed, and it is suggested that it could be attributed to a passive diffusion from Langerhans's cells.     

Reappearance of epidermal Langerhans cells after PUVA therapy

Epidermal Langerhans cells (LC) disappear during photochemotherapy (PUVA) with 8-methoxypsoralen (8-MOP) and long wavelength ultraviolet (UV-A) radiation. The time course of their disappearance during treatment and their reappearance after its completion was followed. Langerhans cells lost ATPase activity before they disappeared by ultrastructural criteria: thus 90% of ATPase-stained cells had disappeared after seven treatments (2 weeks) whereas it was only after fifteen treatments (5 weeks) that they were seen to be reduced on electron microscopy. Their numbers remained low throughout the course of treatment but they had returned to normal by 3 weeks after cessation of therapy. Since PUVA lamps also emit traces of medium wavelength UV (UV-B) the separate effects of UV-A and UV-B in the presence and absence of 8-MOP were examined. Within the dose range normally used for therapy, the LC disappeared only with the combination of UV-A and 8-MOP.     

Sister chromatid exchange and chromosome aberration rates in a group of psoriatics before and after a course of PUVA treatment

Blood was cultured and chromosome preparations were examined for sister chromatid exchanges and chromosome aberrations in eighteen patients receiving photochemotherapy with 8-MOP and UV-A for the treatment of psoriasis, both before starting treatment and again 6 months later. The UV-A was administered both by means of low output (irradiance: 1.1–2.25 mW/cm²) and high output (irradiance: 6.1–7.6 mW/cm²) UV-A radiation cubicles. Irrespective of the intensity of irradiation or the total dose of UV-A administered there was no evidence of chromosome damage in lymphocytes following treatment.     

Squamous cell carcinoma in vitiligo lesion after long-term PUVA therapy

Photochemotherapy using psoralen and ultraviolet (UV)A irradiation (PUVA) is a useful treatment method for vitiligo. However, long-term PUVA therapy may cause several adverse effects including skin cancer, especially squamous cell carcinoma (SCC). We describe a case of SCC in vitiligo lesion after long-term PUVA therapy.     

Skin vessel leakage of plasma proteins after PUVA therapy

In eight healthy volunteers the effect of PUVA therapy on skin vessel leakiness was examined (a quadrant on one side of the abdominal skin was shielded during the UVA irradiation). The relative concentration of intravenously injected labeled albumin in suction blister fluid from irradiated skin was only slightly elevated 2 days after PUVA treatment, whereas a significant elevation (P less than 0.01) was observed on non-irradiated skin. No significant changes were observed in the concentrations of four endogenous plasma proteins in serum and blister fluid. It is concluded that PUVA therapy can induce an increased vascular leakage of albumin from the skin vessels due to humoral factors. In exposed--in contrast to non-exposed--skin, the findings are influenced by an interstitial oedema.     

Melanin granula distribution and phagocytosis in psoriasis vulgaris after PUVA therapy

Summary Melanin-containing basal cells of the epidermis, melanin-containing macrophages, mast cells, eosinophilic granulocytes and plasma cells were quantitatively investigated with the purpose of gaining an understanding of the quantitative changes in these cell systems under PUVA therapy. This patients have been exposed to solar radiation some weeks ore months before the begin of the PUVA-treatment. Different dying-processes were used to investigate biopsy samples of psoriatically healthy and psoriatically affected skin, from 28 patients before, and 39 patients after PUVA therapy, using a 2 d m with a field of view of 0.1 mm². Altogether more than 9,000 fields of view have been analysed. The average radiation amount was 12 irradiations with an average total energy of 21.5 J/cm². It was found that the count of granula-containing basal layer cells decreases in the psoriatic healthy region due to pigment incontinence and increase in the psoriatically affected region. The subepidermal melanincontaining phagocytes increase in both regions to a similar extent. In the case of the mast cells there was no trend to degranulation. The count of eosinophilic granulocytes and plasma cells was unchanged.     

Carcinogenic risk of bath PUVA in comparison to oral PUVA therapy

The potential carcinogenic risk of bath PUVA therapy was compared to that of systemic (oral) PUVA. An analysis of the epidemiological data on cancer risk following bath PUVA with trimethylpsoralen does not support the conclusion that bath PUVA per se is less carcinogenic than systemic PUVA with 8-methoxypsoralen (8-MOP). Pharmacokinetic studies indicate that both the concentration of 8-MOP in the target organ for PUVA carcinogenicity (skin) at the relevant time point (time point of UVA irradiation) and the extents of biological effects in the skin are comparable following bathwater or systemic 8-MOP administration. Furthermore, the therapeutic effects of PUVA arise from the same photochemical reaction mechanisms as do the carcinogenic effects. Theoretically, the ratio of (desired) cytotoxic versus (undesired) mutagenic effects could increase with increasing efficiency of the PUVA therapy itself. On the basis of the available evidence, it is concluded that all forms of PUVA therapy, independently of the route of 8-MOP administration, contribute to a small but dose-dependent increase in nonmelanoma skin cancer risk.     

PUVA therapy in lichen aureus.

Lichen aureus is one of the subtypes of a rare group of diseases, pigmented purpuric dermatoses. The natural course of the disease is slow evolution and slow resolution. Treatment is generally limited. We report a case of lichen aureus that responded dramatically to photochemotherapy (PUVA).     

Dose measurement in PUVA therapy.

The dose emitted by the fluorescent tubes used in PUVA therapy is not constant: it varies in function of time, age of the lamps, and several other factors. Exact knowledge of the dose given to the patient requires continuous measurement and integration of the UV-A output.     

Lymphocyte proliferation during PUVA therapy

Summary The lymphocyte proliferation of 15 psoriatic patients was studied after stimulation with tuberculin, trichophytin, varidase, concanavalin A (Con A), and pokeweed mitogen (PMW) during the first and the eighth PUVA treatment, 2 h after oral intake of 8-methoxypsoralen (8-MOP), immediately after UVA-irradiation, and 24h later.There was a significant decrease of the lymphocyte proliferation, after stimulation with Con A (P<0.05), trichophytin (P<0.01) and varidase (P<0.05), not with PWM and tuberculin, during the first PUVA treatment, by 8-MOP alone. This decrease was not significantly changed by the following UVA irradiation and could not be demonstrated after 24 h. No dark effect of 8-MOP on the lymphocyte proliferation could be seen during the eighth treatment.8-MOP seems to influence lymphocyte proliferation in the dark by interfering with the cell surface, not with the nucleus. The disappearence of this effect during PUVA therapy could be explained by a modification on the surface structure of lymphocytes.     

In vivo autoradiography and planimetry of epidermis in psoriatics under PUVA-therapy

Summary The effects of oral 8-methoxypsoralen-photochemotherapy (PUVA-therapy) on involved epidermis of nine psoriatics and on normal skin of four control subjects was investigated by means of in vivo autoradiography and planimetry. Under PUVA-therapy there is a significant decrease of 3H-TdR labeled cells per epidermal cross-sectional surface, per length of basal membrane and per length of epidermal surface. There is also a significant decrease of epidermal thickness. In the initial phase of PUVA-therapy the decrease of 3H-TdR labeled cells is most pronounced. The reduction of epidermal thickness is less than the decrease of 3H-TdR labeled cells.By grants of the Deutsche Forschungsgemeinschaft Br 147/47 T1     

Bcl‐2 expression in mycosis fungoides before and after PUVA therapy

PUVA is the first therapeutic choice in early stages of mycosis fungoides (MF). In this study the effect of PUVA on bcl‐2 expression in MF was assessed in 15 patients (three stage Ia and 12 stage Ib) and 10 controls. Two biopsies were taken from each patient before and after 24 sessions of PUVA therapy. Histopathological assessment and immunohistochemical staining for bcl‐2 was performed and showed positive bcl‐2 staining of lymphocytes in 53% of MF cases (8/15) before PUVA, with no statistically significant difference in the bcl‐2 level before and after PUVA therapy (P value 0.3). A statistically significant difference was found in the bcl‐2 level between control samples and MF patients' biopsies before (P value 0.02) and after PUVA therapy (P value 0.011). In conclusion, a lack of decline in the bcl‐2 level and the absence of clinical or histopathological correlation with the bcl‐2 level before and after PUVA therapy in MF patients suggest that PUVA‐induced apoptosis in MF cases may occur through pathways other than bcl‐2 inhibition.