5-Methoxypsoralen. A review of its effects in psoriasis and vitiligo

5-Methoxypsoralen, a naturally occurring linear furocoumarin, has been successfully used in combination with ultraviolet (UV) A irradiation [psoralen plus UV (PUVA)] to manage psoriasis and vitiligo. In patients and volunteers, PUVA 5-methoxypsoralen causes a dose-related increase in cutaneous photosensitivity. However, mean minimum phototoxic doses (MPD) were 30 to 50% greater with 5-methoxypsoralen than with 8-methoxypsoralen within individuals; this suggests lower photoactivity with 5-methoxypsoralen. In comparative clinical trials of parallel design, psoriasis clearance rates of > 90% or > 97% were observed in similar numbers of patients (60 to 77%) receiving oral PUVA 5-methoxypsoralen (typically 1.2 mg/kg) or oral PUVA 8-methoxypsoralen (0.6 mg/kg) treatment. Generally, 5-methoxypsoralen recipients required a greater total UVA exposure than 8-methoxypsoralen recipients to achieve end-point. However, study end-point was achieved sooner with oral or topical PUVA 5-methoxypsoralen in a small number of patients with psoriasis who received both treatments simultaneously and contralaterally. Up to 56% of patients with vitiligo achieved > 75% repigmentation with 5-methoxypsoralen (oral or topical) combined with UV irradiation (lamp or sun); the face and trunk were the most responsive areas. Lack of response to PUVA 5-methoxypsoralen treatment was observed in up to 16% of patients with psoriasis and, in 1 trial, in 22% of those with vitiligo. Lesion spreading during treatment of vitiligo was also observed in 7 (19%) patients in 1 study. The incidence and severity of adverse events was generally lower in PUVA 5-methoxypsoralen 1.2 mg/kg than in PUVA 8-methoxypsoralen 0.6 mg/kg recipients. Nausea and/or vomiting, pruritus and erythema were the most commonly reported adverse events in the short term; they occurred about 2 to 11 times more frequently in 8-methoxypsoralen than 5-methoxypsoralen recipients within clinical trials. Adverse hepatic events after oral administration of the drug were uncommon. Long term tolerability data for PUVA 5-methoxypsoralen are scarce; however, carcinogenicity was not reported during a 14-year observation period of 413 patients with psoriasis. CONCLUSION: Similar lesion clearance rates were observed with oral 5- or 8-methoxypsoralen plus UVA exposure in patients with vitiligo or psoriasis, although patients given 5-methoxypsoralen often required a greater total UV exposure than 8-methoxypsoralen recipients. The incidence of short term cutaneous and gastrointestinal adverse effects is markedly less with 5-methoxypsoralen than with 8-methoxypsoralen, which is an advantage, although the long term tolerability of 5-methoxypsoralen has yet to be fully established. Nevertheless, in appropriately selected patients, PUVA 5-methoxypsoralen therapy may be recommended as an alternative first-line systemic treatment option for the management of vitiligo or psoriasis.     

Simulated postaggression metabolism in healthy subjects: metabolic changes and insulin resistance

BACKGROUND: Psoriasis vulgaris can be effectively treated with trimethylpsoralen (TMP) bath PUVA therapy (psoralen plus UVA), but no data exist on the extent to which psoriatic pathology is affected by this treatment, or on its cellular mechanism of action. OBSERVATIONS: Eleven patients with recalcitrant psoriasis vulgaris were treated with TMP bath PUVA therapy and observed through clinical and histological measures. Clinical resolution of psoriasis was achieved in 10 of 11 patients. Histopathological resolution of epidermal hyperplasia (marked by keratin 16 expression) was achieved in 90% of individuals treated with TMP bath PUVA. Epidermal acanthosis was reduced by 40% at 2 weeks and 66% by the end of treatment. Epidermal improvement correlated best with reduction in intraepidermal T lymphocytes, which were reduced by 76% at 2 weeks of treatment and 93% at the end of treatment. Furthermore following TMP bath PUVA therapy, the numbers of epidermal CD1a+ Langerhans cells were markedly reduced, and CD86+ cells were eliminated. Through in vitro assays, TMP was found to be about 10,000-fold more active as a lymphotoxic agent compared with 8-methoxypsoralen (8-MOP). Additionally, at physiologic concentrations, lymphocytes were killed more readily by TMP PUVA (TMP plus UVA) than were keratinocytes. CONCLUSIONS: Treatment with TMP bath PUVA was effective in treating moderate to severe psoriasis, even in darker pigmented individuals. It is likely that this treatment ameliorates psoriasis through direct effects on activated leukocytes in lesional skin.     

Oral psoralen with UV-A therapy releases circulating growth factor(s) that stimulates cell proliferation

BACKGROUND: The mechanism by which oral psoralen with UV-A (PUVA) stimulates melanocyte proliferation in vitiligo is unknown. This study was conducted to examine the hypothesis that it does so by stimulating the release of growth factors that stimulate melanocyte proliferation. DESIGN: We examined the effect of serum samples obtained from patients with vitiligo before and following 2 and 4 months of PUVA therapy, and from non-PUVA-treated patients with vitiligo and normal individuals on the growth of melanocytes in vitro. SETTING: Outpatient clinic in referral center. PATIENTS: The study was conducted on serum samples obtained from 18 patients with vitiligo, 8 of whom were treated with PUVA, and from 10 normal individuals. INTERVENTION: Treatment with PUVA. MAIN OUTCOME MEASURE: Ability of serum samples to stimulate the growth of melanocytes in culture. RESULTS: Proliferation of melanocytes in serum collected after 4 months of PUVA therapy was on the average 3-fold greater than that in serum samples collected from the same patients prior to therapy with PUVA. This circulating growth factor was absent in serum samples of non-PUVA-treated patients with vitiligo and normal individuals. The effect was nonspecific, as it also stimulated the proliferation of fibroblasts. CONCLUSIONS: These findings suggest that PUVA treatment results in the release into the circulation of growth factor(s) that can stimulate a proliferation of melanocytes and of other cells. This could account for the repigmentation of vitiligo by PUVA treatment. As the growth factor(s) also stimulated the growth of other cells, it could also explain the thickening of the epidermis that occurs following exposure to UV light.     

Vitiligo. Therapeutic advances

Vitiligo often induces severe cosmetic disfigurement in patients. Both nonsurgical (medical) and surgical approaches for repigmenting vitiliginous macules are described (Table 1). Currently PUVA therapy appears to be the best method in providing reasonable hope for achieving repigmentation. Guidelines for both topical and systemic PUVA are available. Furthermore, surgical graft of autologous epidermal sheet or cultured melanocytes (often combined with keratinocyte co-culture) can be introduced to repigment the depigmented areas where PUVA is ineffective. PUVA therapy after autologous skin graft can enhance the repigmenting efficiency. Although PUVA with or without surgical procedure represents a useful tool in vitiligo treatment, we should look for other new treatment modalities based upon better understanding of basic biology of melanin pigmentation and pathophysiology of this disease. A recent development of topical pseudocatalase and calcium application combined with UVB phototherapy may be one of the typical examples in this respect. Many patients are significantly affected psychologically by the disease. Physicians should attempt to assess the degree of psychological impairment caused by vitiligo. Supportive care should always be offered if necessary in order to minimize these problems appropriately. In closing, normal skin of vitiligo patients can be totally depigmented by monobenzyl ether of hydroquinone in order to match the skin color in certain generalized vitiligo patients. There is a recent case report of extensive vitiligo with rapid repigmentation of depigmenting vitiliginous skin within a few weeks after discontinuing successful depigmentation therapy by monobenzyl ether of hydroquinone.     

Photochemotherapy in treatment of psoriatic variants

Our procedure for treating psoriatic variants--psoriasis pustulosa generalisata (PPG) and psoriasis erythrodermica (PE)--was based on the following points: (a) to quickly obtain a good tolerance level to photochemotherapy (PUVA) by applying corticosteroids and/or methotrexate (MX); (b) to discontinue the application of systemic drugs with the help of photochemotherapy, and (c) to maintain the improved condition by applying radiation in gradually prolonged intervals, thus enabling the biologic forces of the organism to participate, undisturbed by drugs, in the healing process. In some PE cases, sole PUVA therapy was sufficient, while in others small doses of MX were added to maintain the improved condition. In PPG, skin manifestations completely disappeared and general symptoms were calmed in the first application of this combined therapeutic procedure. However, in the later relapses PUVA had little share in such a combined treatment.     

Peripheral T-cell activation in non-segmental vitiligo

Vitiligo is a hypopigmentary dermatosis of probable autoimmune origin. Previously reported aberrations in peripheral blood mononuclear cells (PBMC), especially T cells and T cell subsets, have been inconsistent. Lymphocyte subpopulations were examined using flow cytometry and monoclonal antibodies against CD4, CD8, CD20, CD25, CD45RA, and HLA-DR in 34 patients with non-segmental vitiligo. Twelve patients had not received any previous treatment and 22 had previously received at least one course of PUVA therapy that was discontinued at least four months prior to our study. Compared to matched controls, we found significant increases in CD25 and HLA-DR in vitiligo patients (p = 0.000). An inverse correlation was observed between HLA-DR and patient status with regard to treatment (p = 0.001). These results suggest a role for T cells in the pathogenesis of vitiligo and imply that previous PUVA therapy may be reflected by an alteration in circulating DR +ve cells.     

In-vitro photobactericidal activity of aminoacridines

We report four patients with severe erythrodermic, pustular psoriasis, or plaque-type psoriasis, who were treated with a combination of acitretin and bath PUVA. After 4 weeks out-patient treatment, the psoriasis in all patients had improved by > or = 90%. No patient had relapsed when reviewed at 3 months. No significant side-effects were seen with the combined retinoid/bath PUVA treatment. Acitretin and bath PUVA may be safely combined for the treatment of severe psoriasis.     

Treatment of vitiligo with UV-B radiation vs topical psoralen plus UV-A

OBJECTIVE: To compare the efficacy and safety of 2 treatment modalities, topical psoralen plus UV-A (PUVA) with unsubstituted psoralen and 311-nm UV-B radiation, in patients with vitiligo. DESIGN: This intervention study was designed as a before-and-after trial with 2 arms, in which patients were consecutively included. PATIENTS: Male (n = 99) and female (n = 182) patients, who predominantly had skin type III, with extensive, generalized vitiligo of more than 3 months' duration. INTERVENTIONS: Two patient groups were investigated. The first group of patients was treated for 4 months with either topical PUVA (n = 28) or 311-nm UV-B radiation (n = 78). The second group of patients, treated twice weekly with 311-nm UV-B radiation, was followed up for 3 (n = 60), 6 (n = 27), 9 (n = 37), or 12 months (n = 51). RESULTS: Thirteen (46%) patients in the first group treated with topical PUVA showed repigmentation after 4 months. Fifty-two patients (67%) in the 311-nm UV-B treatment group showed repigmentation after 4 months. After 3 months, 5 patients (8%) in the second group showed more than 75% repigmentation of lesional skin compared with 32 patients (63%) after 12 months. As in other treatment modalities, the face showed good repigmentation, whereas hands and feet responded poorly. No adverse effects were encountered with treatment with narrowband UV-B radiation, contrary to those seen with topical PUVA treatment. The cumulative UV-B dose was very small compared with that of the topical PUVA treatment. CONCLUSIONS: According to our results, the treatment of patients with vitiligo with 311-nm UV-B radiation is as efficient as with topical PUVA and has fewer adverse effects.     

Pharmacological enhancement of cutaneous flap survival with topical dimethyl sulphoxide and hydrogen peroxide

BACKGROUND: Epidermal autografting has been used to treat vitiligo. The pigmentation achieved at the recipient site can be variegated and incomplete compared with that of the surrounding normal skin, and sometimes remains that way for a fairly long time. OBJECTIVE: We investigated whether the clinical results from epidermal autografting are related to a change in the number of melanocytes. This was performed by counting the number of melanocytes in the epidermis obtained from biopsy and suction with and without psoralen plus UVA (PUVA) exposure of the donor sites before grafting. METHODS: The numbers of melanocytes in the epidermis were counted after staining with dopa. The epidermis from suction and biopsy was included. The biopsied specimen was treated with NaBr for dermo-epidermal separation before staining, whereas the epidermis obtained from suction was stained directly. RESULTS: The epidermis obtained from suction contained 40-60% of the number of melanocytes found in the biopsied epidermis. Melanocytes around the hair follicles seemed to be omitted. Treatment with PUVA 10-21 times caused the number of melanocytes to increase by 1.5-2 times the normal level with a promising clinical result. CONCLUSIONS: The preparation of donor sites with PUVA before the treatment of vitiligo by epidermal autografting induced an increased number of melanocytes and improved the clinical result.     

Oral psoralen and ultraviolet-A light (PUVA) treatment of psoriasis and persistent risk of nonmelanoma skin cancer. PUVA Follow-up Study

BACKGROUND/METHODS: The treatment of psoriasis with high-dose exposure to oral psoralen and ultraviolet-A light (i.e., PUVA) substantially increases the risk of cutaneous squamous cell cancer, but not of basal cell cancer, within a decade of beginning treatment. To assess the persistence of cancer risk among individuals treated with PUVA, including those who discontinued therapy long ago and those without substantial exposure to other carcinogens, we prospectively studied a cohort of 1380 patients with psoriasis who were first treated during the period from January 1, 1975, through October 1, 1976, and evaluated risk factors associated with the development of cutaneous squamous cell cancers and basal cell cancers after 1985. RESULTS: From 1975 through 1996, 237 patients developed 1422 cutaneous squamous cell cancers. From 1986 through 1996, 135 (12.5%) of 1081 patients without a prior squamous cell cancer developed 593 such tumors. From 1975 through 1997, 247 patients developed 1042 basal cell cancers; these patients included 151 individuals with a first basal cell cancer after 1985. Among those without a squamous cell or a basal cell cancer in the first decade of the prospective study, a strong dose-related increase in the risk of squamous cell cancer was observed in the subsequent decade (adjusted relative risk [> or =337 treatments versus <100 treatments] = 8.6; 95% confidence interval = 4.9-15.2). Risk of basal cell cancer was substantially increased only in those patients exposed to very high levels of PUVA (> or =337 treatments). CONCLUSIONS: High-dose exposure to PUVA is associated with a persistent, dose-related increase in the risk of squamous cell cancer, even among patients lacking substantial exposure to other carcinogens and among patients without substantial recent exposure to PUVA. Exposure to PUVA has far less effect on the risk of basal cell cancer. The use of PUVA for psoriasis should be weighed against the increased cancer risk.     

PUVA and anthraline therapy of psoriasis, a clinical, histological and autoradiographic comparison

Treatment of psoriasis with 8-Methoxypsoralen and long wave ultraviolet rays (UV-A) (PUVA) was carried out on 63 patients with severe psoriasis. 41 patients were given the medication orally, the other 22 had it applied locally. After 8.5 weeks, with an average of 25 radiations, about 54% of the patients were cleared of all symptoms or improved considerably. Histological and autoradiographical examinations were carried out to 10 of the orally treated patients. After three weeks of treatment we found a reduced H 3-thymidine-labelling-index (H 3-I) and a shortened DNA-synthesis-time (ts). The average cell cycle time (tc) was lengthened. The effect of PUVA is comparable to that of Anthralin therapy, but the clinical success and the length of treatment with the PUVA-method are inferior to those of the Anthralin-method. There we consider the Anthralin-method as used on in-patients at the Department of Dermatology at the University of Cologne, to be the more suitable method. The PUVA-method ist less complicated and its application easier for the physician as well for the patient, therefore we consider the PUVA-method more suitable for the treatment of out-patients.     

Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study

BACKGROUND: Photochemotherapy with oral methoxsalen (psoralen) and ultraviolet A radiation (PUVA) is an effective treatment for psoriasis. However, PUVA is mutagenic, increases the risk of squamous-cell skin cancer, and can cause irregular, pigmented skin lesions. We studied the occurrence of melanoma among patients treated with PUVA. METHODS: We prospectively identified cases of melanoma and documented the extent of exposure to PUVA among 1380 patients with psoriasis who were first treated with PUVA in 1975 or 1976. Using incidence data, we calculated the expected incidence of melanoma in this cohort and compared it with the observed incidence. Using regression models, we assessed the risks of melanoma associated with a long time (> or = 15 years) since the first treatment and with a large number of PUVA treatments (> or = 250). RESULTS: From 1975 through 1990, we detected four malignant melanomas, about the number expected in the overall population (relative risk, 1.1). From 1991 through 1996, we detected seven malignant melanomas (relative risk, 5.4; 95 percent confidence interval, 2.2 to 11.1). The risk of melanoma was higher in the later period than in the earlier one (incidence-rate ratio, 3.8) and higher among patients who received at least 250 PUVA treatments than among those who received fewer treatments (incidence-rate ratio, 3.1). CONCLUSIONS: About 15 years after the first treatment with PUVA, the risk of malignant melanoma increases, especially among patients who receive 250 treatments or more.     

Photochemotherapy--psoralen + UV-A (PUVA)--increased risk of cancer?

Photochemotherapy with psoralens + ultraviolet (UV)-A light (PUVA) has been used for about 16 years to treat psoriasis. Some reports have indicated a higher frequency of cutaneous squamous cell carcinoma among treated patients. The results are not consistent, however, and are not generally conceded. Our material from Ullev?l Hospital comprises 585 patients who have been treated with PUVA from 1977 until 1991. Three patients developed cutaneous squamous cell carcinoma, but in one of them the tumour developed before start of PUVA treatment. The two others had received only very small doses. One of them had an intraepithelial cancer of the penis. In addition we registered various internal cancers in 25 patients. The Norwegian Cancer Registry compared our patient materiel with a matched control group as regards sex, age and age-specific incidence rate. There was no statistically significant difference in incidence between the patient and the control group.     

Two distinct levels of gap junction assembly in vitro

Ultraviolet radiation (UVR) is known to suppress some cell-mediated immune responses to antigens encountered during or soon after exposure. Phototherapy is widely used in psoriasis, and this study was undertaken to monitor changes in a range of immunological parameters during standard courses of treatment, with the aim of ascertaining whether such modulations contribute to the effectiveness of therapy. The responses of 17 patients with psoriasis undergoing UVB therapy, and four receiving PUVA therapy, were compared with 15 patients receiving coal tar treatment and four normal subjects undergoing UVB irradiation. In each case, samples were taken before starting therapy, after 4 weeks of therapy, and 4 weeks after completion of treatment. Serum immunoglobulin isotypes and complement components were within normal ranges in most of the psoriasis patients, and remained unchanged throughout therapy. Similarly, percentages of subsets of peripheral blood mononuclear cells (PBMC) were normal, and were unaltered by treatment. Patients who were already infected with herpes simplex virus (HSV), as demonstrated by a positive lymphoproliferation test in vitro, were monitored for asymptomatic HSV shedding and HSV recrudescences during therapy. There was little evidence that phototherapy caused reactivation of the virus. No significant alteration in lymphoproliferative response to HSV and to the mitogen concanavalin A was observed during therapy. Epidermal cells and blood adherent cells were used to present HSV to PBMC, depleted of adherent cells and enriched for T cells, in a lymphoproliferative assay. The functional antigen-presenting ability of adherent cells remained unchanged throughout therapy, whereas that of epidermal cells was suppressed during UVB irradiation and recovered, in most instances, after UVB therapy had been completed. The epidermis of patients with psoriasis contained about three times the quantity of urocanic acid (UCA) of normal subjects, whereas the UCA concentration in suction blister fluid did not differ between the two groups. During UVB irradiation, the percentage of cis-UCA rose in both the epidermis and suction blister fluid of all subjects, and it remained elevated in the blister fluid after therapy had finished. Tumour necrosis factor-alpha was measured in suction blister fluid, and its concentration did not alter consistently as a result of therapy. Whether any of the immunological parameters measured, and the changes noted, contribute to the effectiveness of phototherapy in the treatment of psoriasis remains uncertain.     

Diagnosis of Lyme neuroborreliosis

PUVA and UVB phototherapies are used in the treatment of psoriasis and other inflammatory skin diseases. Ultraviolet radiation causes inflammation and modulates cell kinetics in the skin. PUVA also has an inhibitory effect on skin DNA synthesis. In this study, the effects of PUVA and UVB treatments on epidermal would healing were examined using the suction blister wound model. The healing of the wound was studied indirectly by measuring water evaporation and blood flow in the wound area. On the fourth day, water evaporation was more abundant in PUVA-treated patients (42 +/- 5 g/m2h) than in UVB treated (36 +/- 4 g/m2h) or control patients (27 +/- 3 g/m2h) (analysis of variance, the least significant difference test at a level of 0.05). The P value for the difference of means between the PUVA and control groups was 0.014. Blood flow was also more abundant during the fourth (PUVA 162 +/- 11 arbitrary units, UVB 122 +/- 10, controls 115 +/- 15) and sixth (PUVA 108 +/- 18, UVB 73 +/- 17, controls 57 +/- 13) day in PUVA treated patients (analysis of variance, the least significant difference test at a level of 0.05). The results suggest that PUVA treatment decreases the restoration of the epidermal barrier function. The PUVA-treated patients also showed a more intense and prolonged vascular response that may be due to PUVA-related inflammation.     

Photochemotherapy: identification of a metabolite of 4, 5', 8-trimethylpsoralen

A compound, 4, 8-dimethyl, 5'-carboxypsoralen (DMeCP), has been identified in mouse urine as a major metabolite of the photoactive drug, 4, 5', 8-trimethylpsoralen (TMeP). This drug is widely used in the treatment of vitiligo and psoriasis. DMeCP is fluorescent, and nonphotosensitizing when tested on guinea pig skin. DMeCP also occurs in the urine of human patients receiving TMeP orally.     

Helix-coil transitions in DNA using a pH variation method: case of a melting paradox as a function of ionic strength

We describe a 31-year-old Japanese woman with generalized pustular psoriasis treated with PUVA who subsequently developed a bullous disease. Throughout the disease course, there was no phase of psoriasis vulgaris. Although several reports describe coexistence of psoriasis vulgaris and bullous disease such as bullous periphigoid, coexistence of generalized pustular psoriasis without any phase of psoriasis vulgaris and bullous disease is rare. As for the bullous disease, direct immunofluorescence study showed IgG and C3 deposition along the basement membrane zone. Indirect immunofluorescence disclosed IgG antibasement membrane zone antibodies. Indirect immunofluorescence on 1 mol/l sodium chloride-split skin demonstrated linear IgG staining almost exclusively on the dermal side of the split. Western immunoblot analysis revealed that the antibody was directed to neither epidermolysis bullosa acquisita antigen nor bullous pemphigoid antigens. Considering the unusual clinical course, we suspect the possibility of a novel autoimmune blistering disease.     

Hepatitis C virus diagnostics: technology, clinical applications and impacts

To determine the basis of the therapeutic efficacy of Psoralens and UVA (PUVA) in inflammatory skin diseases, the effect of PUVA on the expression of cell adhesion molecules of keratinocytes was investigated in vitro. The addition of IFN-gamma and TNF-alpha to human keratinocytes in culture up-regulated the expression of ICAM-1 and HLA-DR on the cell surface. The cultured human keratinocytes were exposed to UVA light in the presence of 8-methoxypsoralen (PUVA). The ICAM-1 and HLA-DR surface molecules were stained by monoclonal antibodies, and the intensity of the resultant fluorescence was analyzed by FACS-can. PUVA treatment suppressed the expression of these cell surface molecules, with increasing UVA fluence. Moreover, PHA-blasts failed to adhere to PUVA treated keratinocytes. When keratinocytes were treated with PUVA prior to the addition of IFN-gamma and TNF-alpha, ICAM-1 and HLA-DR expression was suppressed. These results suggest that one of the therapeutic mechanisms of PUVA in inflammatory skin diseases is by inhibition of the adhesion of activated lymphocytes to keratinocytes due to suppression of cell surface molecules. It also suggests that PUVA may be useful as maintenance therapy for inflammatory skin diseases.     

Histopathology and histochemistry of psoriasis under photochemotherapy (author''s transl)

Fifty-two biopsies from involved and clinically normal looking skin of patients with psoriasis vulgaris and from normal control subjects, all being treated with 8-MOP-UVA (PUVA) were obtained between days 2 and 300. The following parameters were investigated: 1. initial PUVA effects; 2. initial regression of psoriasis under PUVA-therapy; 3. late effects of PUVA-therapy on regression of psoriatic lesions; 4. EFFects on melanocytes and pigmentation; and 5. long-term effects of PUVA-therapy. Paraffin embedded and cryostat sections were prepared with routine stains for light microscopy and enzyme histochemical special stains. The regression of psoriatic lesions following PUVA-therapy was separately assessed for epidermal and dermal components. The sequence of events was as follows: re-establishment of a continous stratum granulosum, re-establishment of a continuous normal appearing stratum corneum, regression of acanthosis and papillomatosis, and regression of inflammatory infiltration. During the initial phase of PUVA-therapy there is a sharp increase of melanocytes which leads to a foamy appearance of the basal cell area. Long term studies did not reveal actinic damage of the skin, neither in the epidermis (absence of actinic keratoses or squamous cell carcinomas) nor in the dermis (absence of actinic "solar" elastosis).     

Satisfactory remission achieved by PUVA therapy in a case of crisis-type adult T-cell leukaemia/lymphoma with generalized cutaneous leukaemic cell infiltration

We used PUVA therapy in a patient with crisis-type adult T-cell leukaemia/lymphoma and generalized cutaneous leukaemic cell infiltration. PUVA proved very effective in reducing leukaemic cells and in clearing the eruption. To understand the way in which PUVA produced a reduction in the number of leukaemic cells, we examined peripheral blood cells by light and electron microscopy. Light microscopy was of little help, but electron microscopy revealed that PUVA induced apoptosis-like changes in circulating leukaemic cells. This suggests that apoptosis-like changes in leukaemic cells might be the reason for the success of this treatment.