B.E. Johnson

311 nm UVB phototherapy—an effective treatment for psoriasis

Fifty two psoriatic patients were treated with a new experimental fluorescent lamp (Philips TL‐01) emitting a narrow band at 311 ± 2 nm (UVB) which had the advantage of a reduction in burning and carcinogenic wavelengths when compared with conventional broad band UVB therapy. Results of the ‘311’ treated group when compared with broad band UVB therapy revealed a similar percentage of patients achieving a satisfactory response with fewer burning episodes and an increase in duration of remission.

Action spectra for the trans to cis photoisomerisation of urocanic acid in vitro and in mouse skin.

Urocanic acid (UCA) is a major UV chromophore in the upper layers of the skin where it is found predominantly as the trans isomer. UV irradiation induces photoisomerisation of trans‐UCA to cis‐UCA which has been shown to mimic some of the immunosuppressive properties of UV exposure. We examined the wavelength dependence for trans‐UCA to cis‐UCA photoisomerisation in vitro and in mouse skin in vivo over the spectral range270–340 nm. The resulting action spectra were very similar with maximal effectiveness at300–315 nm and equal activity at 270 nm and325–330 nm, demonstrating that UVA‐II radiation (320–340nm) is efficient at UCA photoisomerisation. These action spectra differed markedly from the trans‐UCA absorption spectrum in vitro and also the reported action spectrum for UV suppression of contact hypersensitivity in mice. These findings suggest that the relationship between cis‐UCA formation in skin and UV‐induced immunosuppression may be complex.

Ciprofloxacin-induced photosensitivity : in vitro and in vivo studies

Ciprofloxacin is one of the new series of broad‐spectrum antibiotic quinolones, chemically related to nalidixic acid and which may, therefore, induce photosensitization of human skin. Three in vitro tests for phototoxicity: the destruction of histidine, killing of mouse peritoneal macrophages and inhibition of PHA‐stimulated DNA synthesis in human lymphocytes have demonstrated this photosensitizing potential with UVA irradiation at an order of magnitude lower than that for nalidixic acid. The Candida albicans test and photohaemolysis were negative. Controlled irradiation monochromator phototesting of 12 subjects, before, during and after taking ciprofloxacin showed subclinical photosensitivity with significantly lowered minimal 24 h erythema doses at 335±30 nm, 365±30 nm and 400±30nm but not at 305±5 nm or above 400±30 nm.

Clinical and laboratory studies of the photosensitizing potential of norfloxacin, a 4-quinolone broad-spectrum antibiotic

Cutaneous photosensitivity reactions are a consistent although uncommon feature of the fluoroqui‐nolone group of antihiotics, which are related to nalidixic acid. Ohjective laboratory and clinical data are now routinely required by regulatory bodies for new drugs suspected of being photosensitizers. but no clear recommendations exist. A series of in vitro tests ranging in complexity revealed a UVA‐dependent phototoxic potential for the fluoroquinolone norfloxacin similar to that for ciprofloxacin. and less than that of nalidixic acid. Controlled monochromator phototesting, designed to reveal the clinical characteristics, wavelength dependence and severity of cutaneous reactions in normal subjects showed both norfloxacin and ciproHoxacin to have a weak phototoxic potential which clears within 4 weeks of stopping the drug. UVA wavelengths (335±30 nm: 365±30 nm) appear most responsible for producing an asymptomatic erythema which is maximal at 24 h.

Comparative potency of broad-band and narrow-band phototherapy sources to induce edema, sunburn cells and urocanic acid photoisomerization in hairless mouse skin.

The Philips TL01 narrow‐band (311–313 nm) fluorescent lamp provides effective phototherapy for psoriasis and atopic eczema while emitting less erythemogenic radiation than conventional broad‐band (e.g. Philips TL12; 270–350 nm) sources. We studied the potency of TL01 and TL12 radiation to induce edema and sunburn cells (SBC) and to photoisomerize naturally occumng trans‐urocanic acid (UCA) to cis‐UCA in hairless mouse skin. Cis‐UCA has immunosuppressive properties and is a putative mediator of UV‐induced suppression of immune responses. For each source, there was UV dose dependence for all three responses. Within the dose ranges used, the potency ratio of TL12: TL01 radiation to induce equivalent edema and SBC was about 6:1. However, the potency ratio to induce cis‐IJCA was less than 2.3:1. Therefore, at a given level of edema or SBC induction, TL01 was more efficient than TL12 at UCA photoisomerization. The TL01 induction of immunomodulating cis‐UCA, while causing minimal skin injury, may relate to the therapeutic efficacy of this source in skin conditions with an immunological component.

Ultraviolet Radiation Phototherapy for Psoriasis The Use of a New Narrow Band Uvb Fluorescent Lamp

Phototherapy with ultraviolet (UV) radiation, alone, or as part of a multi-faceted therapy, has been used for Psoriasis with varying degrees of success depending mainly on the radiation source, the treatment regimen used and the type of Psoriasis treated (Goeckermann, 1931; Ingram, 1953; Petrozzi et al, 1978; Levine and Parrish, 1980; Larko, 1982; Morison, 1983; Eells et al, 1984).

Evidence that certain phototoxic drugs photosensitize urocanic acid isomerization

Abstract Trans to cis photoisomerization of epidermal urocanic acid (UCA) has been proposed as a primary event in UV-induced immunosuppression. 8-Methoxypsoralen (8-MOP) in combination with UVA radiation (PUVA) is used for photochemotherapy of several immunologicaly based skin disorders, and PUVA is known to cause immunosuppression. We examined the photointeraction of 8-MOP and other skin photosensitizing drugs (amiodarone, ciprofloxacin, doxycycline and ketoprofen) with trans-UCA in vitro. In oxic condition 8-MOP did not enhance the ability of radiation from standard PUVA fluorescent sources (0.2% radiation below 320 nm) to produce cis-UCA. When oxygen was removed, some 8-MOP photosensitization could be detected. 8-MOP, ciprofloxacin and ketoprofen also enhanced inefficient UCA photoisomerization by radiation from a filtered tungsten halogen source (0.2% radiation below 320 nm). 8-MOP photosensitization is essential for radiation from PUVA tubes to have a therapeutic or immunosuppressive effect. We have shown in vitro that 8-MOP does not enhance cis-UCA production by this source. Extrapolation of our data to the in vivo situation suggests that UCA may not be involved in either the therapeutic or the immunosuppressive effect of PUVA.

Photochemotherapy. A study of its efficacy in fifty patients sufFering from psoriasis and other dermatoses

Three patients, aged 22, 47 and 60 years, with painful cyanosis of several fingers have been studied. Investigations for primary systemic disease were negative. All the patients smoked 20 or more cigarettes a day but none had been on any drugs. The peripheral pulses were present. Arteriography revealed vascular anomalies of the palmar arch. In the patient with ischaemia of the thumb and index fingers the palmar arch was almost exclusively supplied by the ulnar artery; in the patient with ischaemia ofthe ring and fifth finger, the arch was supplied by the radial artery; in the third patient with ischaemia of all fingers except the thumb, there was poor blood supply from both the radial and ulnar arteries. Bilateral arteriography in one patient showed the changes to be similar in both hands. Evidence from other patients suggests that similar vascular anomalies occur in the feet. It is proposed that arteriography is indicated in all patients presenting with persistent ischaemia of the fingers and toes when the peripheral pulses are present and systemic disease has been excluded.

(12) Thiazide‐induced photosensitivity, the use of bumetanide as alternative therapy: in vitro and in vivo studies

Thiazide diuretic-induced photosensitivity can be a management problem. Stopping drug therapy may not be possible on medical grounds and sunlight avoidance and broad-spectrum sunscreen use is unsatisfactory for some patients, Bumetanide, a structurally different, potent loop diuretic, is a possible alternative. With four model systems, photohaemolysis, the photosensitized destruction of histidine, killing of mouse peritoneal macrophages and inhibition of DNA synthesis in PHA stimulated lymphocytes, the phototoxic potential of bumetanide was less than that of thiazides. For example, with an exposure of i 75 J/cm^ of UVA, a 50% reduction in lymphocyte DNA synthesis was obtained with i-io /̂ g/ml hydrochlorthiazide, 05-5 /̂ g/ml bendrofiuazide but > 50 /ig/ml bumetanide. Standard monochromator phototesting of seven patients with the clinical features of thiazideinduced photosensitivity revealed significantly abnormal minimal erythema doses (MEDs) with the ultraviolet/visible wavebands (30515-430130 nm). One to 3 months after changing therapy to bumetanide there was no evidence of clinical abnormality and a significant reduction in photosensitivity on phototesting (Table i shows the data with a representative waveband where P = o 0008),

(14) A comparison of the efficacy and relapse rates of 311 nm phototherapy with etretinate 311 therapy (re‐311) and etretinate PUVA (re‐PUVA) in psoriasis therapy

in two (5 %)—one with a hypertrophic scar and one with marginal hyperpigmentation. No effect was observed in four patients. These results are extremely promising as both groups responded poorly to Argon laser therapy. Pallor is slow to develop and improved responses with longer follow-up are expected. Six-month follow-up after carbon dioxide laser therapy in 31 patients with tattoos is available. Treatment was with 5-10 W in defocussed mode and then 5-10 W with spot size of 0-2 mm and pulse duration of 0-05 s (energy fluence 6-12 J/cm̂ ) to residual pigment. Three patients failed to attend follow-up. The remaining 28 patients were pleased with the result and wanted further therapy for other tattoos. Objectively, all patients developed a scar, which was hypertrophic in two. Two patients had residual pigmentation, one post-inflammatory hyperpigmentation, and three required antibiotics for wound infections. Other lesions treated have included plantar warts (5), keloids (4), facial telangiectases (4), lymphangioma circumscriptum (3), verrucous haemangiomas (2), and trichoepitheliomata (2), all with satisfactory results. In conclusion, the carbon dioxide laser is the most versatile laser for the treatment of a wide variety of dermatological conditions and appears particularly useful in pink port wine stains, if used cautiously, and in the treatment of tattoos where patients will accept scarring.