Modifications of PUVA.

The goal of photochemotherapy in psoriasis is to attempt to lower the number of exposures and the total cumulative doses while still maintaining good control of the disease. PUVA has been modified by using better psoralen preparations and more effective light sources, and it also has been combined with other treatment modalities. The objectives in modifying PUVA and combining PUVA with other treatment modalities are to increase efficacy, to reduce short- and long-term adverse effects, and to reduce the cost of treatment. Modalities that have been combined with PUVA include topical corticosteroids, anthralin, calcipotriene ointment, methotrexate, UVB, retinoids, and cyclosporine.

Extramammary Paget's disease of the perianal and perineal regions. Evidence of apocrine derivation.

A case of perianal and perineal extramammary Paget's disease in a male is reported. The presence of gross cystic disease fluid protein--a new marker of apocrine epithelia--in Paget's cells provides additional insight into the histopathogenesis of this condition. This marker may be a valuable diagnostic adjunct in evaluating intra-epithelial malignancies at a variety of anatomic sites.

Improvement of the efficacy and safety of oral methoxsalen photochemotherapy.

To improve efficacy and safety of psoralen plus UV radiation at 320-400 nm (PUVA), investigators designed different therapeutic approaches. Our goals are to minimize the acute risks and lower the long-term hazards. Some of these therapeutic approaches focus on dosimetry and intensity of PUVA and some on combining PUVA with other therapeutic modalities. Both approaches try to minimize the total number of treatments and to decrease the amount of UVA radiation delivered to the patient and, as a result, decrease the total skin insult.

Psoralens and UV-A and UV-B twice weekly for the treatment of psoriasis.

In an effort to determine if combination phototherapy (psoralens and UV-A [PUVA]) [PUVA-UV-B]) administered twice weekly provides a substantial advantage over therapy with PUVA alone, we investigated twice-weekly PUVA-UV-B therapy for the treatment of psoriasis. In a bilateral comparison study of 11 patients, we found that seven cases of psoriasis cleared in the same number of treatments with PUVA-UV-B or PUVA, but in four cases the PUVA-UV-B treated side cleared significantly more rapidly. In a study of these 11 split cases, plus ten additional patients treated with PUVA-UV-B twice weekly, this therapy was effective in clearing psoriasis. A bilateral comparison of "aggressive" and "nonaggressive" PUVA and UV-B increments in ten patients suggested that lower doses of PUVA and UV-B may, in the majority of patients, be equally effective. Further study is necessary to define the maximally effective protocol--maximizing clearance yet minimizing UV exposure, acute side effects, and long-term toxic reactions.

Bilateral comparison of generalized lichen planus treated with psoralens and ultraviolet A.

Ten patients with generalized lichen planus were treated with oral 8-methoxypsoralen photochemotherapy (PUVA) in a bilateral comparison study. Five patients (50%) cleared completely on both sides and required no maintenance treatment after a follow-up of up to 4 years. Three other patients (30%) improved at least 50% of their previous involvement. Most of the patients experienced symptomatic improvement of the treated side by the second week of the treatment. Two patients reacted adversely and exacerbated while receiving treatment to one side of the body. While preliminary, this bilateral comparison study demonstrates that PUVA is an effective therapy for generalized, symptomatic lichen planus and suggests that maintenance therapy might not be required once complete clearance is attained. Caution should be exercised, however, since some patients might develop an exacerbation of their disease with PUVA.

Combination of psoralens and ultraviolet A and ultraviolet B in the treatment of psoriasis vulgaris: a bilateral comparison study.

Forty-two adults with psoriasis vulgaris were treated total body thrice weekly with both ultraviolet B (UVB) and psoralens and ultraviolet A (PUVA) with the use of protocols shown to be effective with either treatment alone. Patients previously difficult to manage with either UVB or PUVA and at least 25% psoriasis were selected. No other treatment was used for 2 months prior to initiation or during the study. All patients tolerated treatments well and cleared in an average of only 11.3 treatments, less than half the number of treatments usually required with either PUVA or UVB. The mean UVB dose at clearing and the mean cumulative PUVA dose were less than half that normally required with either therapy alone. The total cumulative UVB dose was only 18% of that normally required with UVB. Bilateral comparison studies comparing the PUVA-UVB combination with PUVA and UVB found that whenever there was a clear difference it was always the combination that cleared more rapidly. The marked reduction of total cumulative energy required more rapidly. The marked reduction of total cumulative energy required may be a significantly smaller insult to skin and the marked reduction in joules/cm2 of UVB and joules/cm2 of PUVA at clearing may make it possible to provide effective maintenance therapy with either treatment at a markedly lower treatment dose. Hopefully, long-term side effects may thereby be markedly diminished.

A new liquid formulation of 8-methoxypsoralen: bioactivity and effect of diet.

A new encapsulated liquid preparation of methoxsalen (8-MOP) and a commonly used crystalline preparation (Oxsoralen) were compared in 12 subjects. Each subject ingested 0.6 mg/kg body weight of each formulation on different days. Six subjects ingested a low-fat meal before ingestion of drug, and 6 subjects ingested a high-fat meal. Photosensitivity was tested from 1/2 to 6 h after ingestion of 8-MOP by exposure to 320-400 nm radiation (UVA) from a filtered xenon are lamp. A series of graduated doses of UVA were administered at each time point to determine the minimum phototoxic dose (MPD). Ingestion of 8-MOP and grading of erythema were conducted in a double-blind manner, and bilaterally symmetrical exposure sites were used to test each preparation. The phototoxic reaction was observed at 24, 48, and 72 h by two experienced observers who were unaware which formulation had been ingested. The two test days were separated by 48 h. The encapsulated liquid preparation induced greater photosensitivity than Oxsoralen (mean MPDs +/- SD: 7.1 +/- 4.7 vs 12.9 +/- 6.7 J/cm2, respectively; n = 12; p less than 0.05). The encapsulated liquid preparation also induced photosensitivity earlier than Oxsoralen (mean hours after ingestion to achieve peak photosensitivity +/- SD: 2.1 +/- 1.2 vs 3.9 +/- 1.6, respectively; n = 9; borderline significance). On a low-fat diet the encapsulated liquid peaked 2.5 h earlier than Oxsoralen, as well as showing the shortest and the most predictable period of photosensitivity. However, overall, the degree and time of peak photosensitivity induced by either preparation were unaffected by diet. Ingestion of the encapsulated liquid induced photosensitivity in all 12 subjects; Oxsoralen failed to sensitize 3 subjects. Side effects were similar after both preparations. A new encapsulated liquid preparation of 8-MOP may thus allow lower doses of UVA to achieve therapeutic results in photochemotherapy, and a shortened waiting period following ingestion of drug.

Morphologic alterations of epidermal melanocytes and melanosomes in PUVA lentigines: a comparative ultrastructural investigation of lentigines induced by PUVA and sunlight.

Ultrastructural studies were conducted in order to determine morphologic and functional differences in melanocytes and melanosomes in PUVA lentigines and solar lentigines, and light-protected buttock skin. Compared to melanocytes in solar lentigines from 7 subjects and light-protected buttock skin from 5 subjects (none of these subjects had received UV radiation therapy), melanocytes in PUVA lentigines from 6 subjects generally had longer and more numerous dendrites, and showed more active melanogenesis. Basal keratinocytes in PUVA lentigines had a significantly increased frequency of large, single melanosomes, and revealed significantly larger individual melanosomes within compound melanosomes. Other findings in some PUVA lentigines included the close apposition of Langerhans cells to melanocytes, and atypical nuclear, cytoplasmic and melanosomal alterations, including melanosomal pleomorphism and melanin macroglobules. The presence of relatively large and predominantly single melanosomes in basal keratinocytes of PUVA lentigines suggests more active melanogenesis and/or an irreversible somatic alteration. It will be important to determine the clinical course and ultrastructural findings of PUVA lentigines that persist long after PUVA is discontinued.

Ultraviolet A phototherapy in the prophylaxis of solar urticaria.

Five patients with solar urticaria were treated with ultraviolet A (UVA) radiation. Three experienced marked increases in sunlight tolerance, but two patients failed to improve. Subjective clinical improvement was documented objectively by marked increases in the minimal urtication doses obtained by provocative light testing. These results indicate that some patients with solar urticaria may respond to treatment with UVA radiation alone.

The PUVA-induced pigmented macule: a lentiginous proliferation of large, sometimes cytologically atypical, melanocytes.

Eleven PUVA-induced pigmented macules (PM) obtained from seven psoriatic adults 4 to 6 years after starting PUVA therapy were compared to eight sun-induced pigmented macules (SM) and five specimens of light-protected skin (LPS) from twelve nonpsoriatic control subjects who had not received ultraviolet radiation therapy. Unlike SM, many PM were darkly or irregularly pigmented. In a blind histologic assessment using routine and L-dihydroxyphenylalanine (dopa)-incubated tissue sections, both PM and SM were lentigines. Three of eleven PM had slight melanocytic atypism, compared to none of eight SM. When compared to SM and LPS, PM had a significantly increased proportion of hypertrophic melanocytes. These observations demonstrate that chronic PUVA induces pigmented macules characterized by a lentiginous proliferation of large melanocytes which, in some cases, may be slightly atypical. PUVA-treated individuals require continual monitoring for atypical melanocytic lesions.

Outpatient phototherapy for psoriasis.

Using a new protocol with varied exposure increments, we found that, in 18 of 20 patients with psoriasis vulgaris who were given ultraviolet (UV)-B phototherapy three times a week, the disease completely cleared. One patient's condition substantially improved, and one patient's condition failed to respond. Ten to 38 treatments were required during a three- to 13-week period. The only topical treatment agent used was white petrolatum. The results are compared with a schedule using five treatments a week and fixed UV-B--exposure increments. Infrequent (three times weekly) treatments, avoidance of hospitalization and crude coal tar treatment, and fewer episodes of UV-radiation burn may offer advantages for selected patients. Long-term effects and maintenance requirements for this treatment regimen are not known.