A.H. Siddiqui

Phenylalanine and UVA light for the treatment of vitiligo

SummaryThe administration of phenylalanine (Phe) combined with UVA exposure was found to be effective in vitiligo. Phe is an amino acid which constitutes part of the daily dietary protein, and when orally administered in a dose of 50 mg/kg body weight, it results in an elevated plasma level. Since peak concentrations of Phe in the blood are reached between 30 and 45 min after ingestion, UVA exposure was administered at this time. After 4 months (32 treatments) reasonable repigmentation preferentially occurred in the skin area of subcutaneous fat (adipose tissue). Apart from the repigmentation of hypopigmented macules, vitiligo patients can tolerate more sun than usual, especially at the vitiliginous lesion, and they experience no sunburn as a result of Phe-UVA therapy. Normal skin also tans very well.

Comparison of bioavailability and phototoxicity of two oral preparations of 5‐methoxypsoralen

5‐Methoxypsoralen (5‐MOP) (Psoraderm 5*) tablets obtained from France and 5‐MOP micronized in capsules (manufactured in our pharmacy department) were administered to seven psoriasis patients in a 1.2 mg/kg body weight dose schedule. Bioavailability and phototoxicity were compared. It was found that the maximum serum concentration and the area under the concentration curve were significantly higher (P < 0.01) after administration of the capsules, indicating higher bioavailability. No erythema developed in any of the patients after administration of the tablets, whereas with the capsules four of the patients developed erythema at the test site. The absence of erythema following the use of the tablets is probably due to the poor bioavailability of this preparation.

Serum levels of trimethylpsoralen after oral administration.

Serum concentrations of trimethylpsoralen were determined for up to 5 h after oral administration in four patients with vitiligo. Measureable amounts of trimethylpsoralen were found in the serum only after administration of high oral doses (100 to 400 mg TMP).

Increased anthralin irritation response in vitiliginous skin

SummaryThe irritation response to anthralin was studied using the chamber-testing technique in 17 patients with vitiligo. Anthralin concentrations of 0.1%, 0.5%, 1%, and 5% in lanette wax were applied to both vitiliginous and adjacent pigmented skin for 24 h. The extent of the erythematous reaction was evaluated on the 2nd day after application. The visual assessment of the paired anthralin patches indicated that the erythema was more intense in pigmented skin than in vitiliginous skin in 15 out of 17 patients. Chromometer readings, however, clearly indicated that the erythematous response was stronger in the vitiliginous skin than in the pigmented skin, confirming the known fact that the human eye is not accurate in the quantitative assessment of complex colors. Immunophenotypification of cellular infiltrates, using the combination of different monoclonal antibodies and the peroxidase technique, showed that inflammatory cell infiltrates caused by the anthralin exposure contained increased numbers of granulocytes and monocytes in vitiliginous skin when compared with normal skin. The percentage of T-cell subsets, Langerhans cells, and mast cells in the same infiltrates of both types of skin were similar. Our results are discussed in accordance with the view that anthralin-induced radical species of the pigmented skin can be neutralized by the scavenging properties of melanin.

Comparison of serum levels and clinical results of PUVA therapy with three different dosage forms of 8-methoxypsoralen

Various dosage forms of 8-methoxypsoralen (8-MOP) in PUVA therapy have been proposed. Previously we compared hard gelatin capsules containing micronized 8-MOP with an 8-MOP oral solution [6]. Higher and earlier maximum serum concentrations were obtained after administration of the oral solution. With this solution, however, nausea was frequently reported. Therefore, we proposed rectal administration of 8MOP in a microenema [7]. The microenema was absorbed very quickly and produced high serum concentrations. According to a preliminary report, the clinical results were reasonably good with no serious side effects [4]. Recently, H6nigsmann et al. [1] and Nitsche et al. [2] introduced a soft gelatin capsule with 8-MOP dissolved in the solution. They compared these capsules with conventional crystalline 8-MOP capsules. According to their conclusion, the soft gelatin capsule was superior to the crystalline form because of an earlier peak after ingestion and higher and more reproducible serum concentrations. In the present study, we have compared the serum concentrations after administration of three different 8-MOP dosage forms: (1) hard gelatin capsules with solid micronized 8-MOP, (2) soft gelatin capsules with dissolved 8-MOP, and (3) the microenema. The clinical results of PUVA therapy with the above mentioned dosage forms of 8-MOP were also evaluated in this study.

Serum and saliva levels of 8-methoxypsoralen after rectal administration as a micro-enema.

Serum and saliva concentrations of 8‐methoxypsoralen (8‐MOP) were determined in seven healthy human volunteers after rectal administration of a micro‐enema. High peak serum levels were reached very soon (0.7±0.3 h) after administration of 8‐MOP. Nausea was not experienced. There was a reasonably good linear correlation between 8‐MOP concentrations in saliva and serum (γ= 0.937). The saliva/serum ratio for 8‐MOP concentration was 0.08±0.02.

l-phenylalanine and UVA/sunlight for vitiligo

Professor A. Wiskemann of the University of Hamburg (Department of Dermatology, FRG) drew our attention to the publication of Ryan and Carver [3]. Since then, we have changed our dosimetric schedule of L-phenylalanine (1-phe) + UVA/sunlight exposure twice/thrice weekly [1] to daily administration of 1-phe (50 mg/kg body weight) and twice/thrice week~ UVA/sunlight exposure 30 rain after 1-phe ingestion for the treatment of vitiligo. According to Ryan and Carver [3], 1-phe inhibits antibody response to diphtheria toxoid in rats and rabbits. Their explanation is was that the excess of 1-phe causes a disturbance in the free amino acids of these animals, which results in a decrease in antibody (protein) synthesis. It is also conceivable that chronic alterations in the amino acids of the central nervous system induced by 1-phe could give rise to changes in protein synthesis. Since according to Naughton et al. [2], the majority of the vitiligo patients with active vitiligo have antibodies to melanocytes, associated antigens which were not found in patients with nonpigmentary skin diseases, administration of 1-phe would inhibit anitbody formation. UVA/sunlight exposure stimulates the migration of melanocytes from adjacent areas and activates rudimentary melanocytes present in the vitiliginous part of the skin to overcome depigmentation. However, on the basis of the abovementioned studies, the repigmentation of the vitiligo lesions as a result of 1-phe + UVA/sunlight exposure can easily be explained (see Fig. 1). Antibody against melanocytes