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Notes: Summary  Topical 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) is used increasingly for superficial non-melanoma skin cancer (NMSC) and dysplasia. However, the relative accumulation of the photosensitizer protoporphyrin IX (PpIX) in diseased tissue is not specific for neoplastic disease, and has been shown after the application of ALA to benign proliferative skin conditions such as viral warts and psoriasis. This review appraises the quality of evidence available for the use of topical ALA–PDT in the treatment of skin conditions other than NMSC. The diseases that have been studied in most detail are recalcitrant viral warts, acne, psoriasis and cutaneous T-cell lymphoma. Publications relating to the treatment of other diseases by topical PDT are restricted to small case series or case reports. The relevant literature will be discussed and the potential for topical PDT in the treatment of several skin diseases is highlighted, although more detailed studies are required to clarify the role of PDT beyond the treatment of NMSC.

Notes: We report the occurrence of severe symptomatic bronchoconstriction in an atopic asthmatic subject following the application of coal tar bandages. Investigations showed that this was likely to have been caused by inhalation of coal tar vapour. We suggest that coal tar preparations should be used with caution in asthmatic subjects.

Notes: Summary Indomethacin inhibits UVB erythema but is thought not to influence UVA erythema. We have examined the wavelength dependence of the effect of indomethacin on ultraviolet radiation (UVR) erythema. Duplicate sites on the back were irradiated with a series of doses at 300 and 320 nm, or single doses at 330, 340, 350 or 370 nm. Indomethacin 1% was applied to sites on one side of the back after irradiation, occluded for 2 h and erythema measured at 24h with a reflectance instrument. Indomethacin inhibited 300 and 320nm (UVB) erythema, had no effect at 330 and 340 nm (UVA2), but augmented 350 and 370 nm (UVA1) erythema. There appears to be a varied response of UVR erythema to cyclo-oxygenase inhibition at different wavelengths across the UVR spectrum. This mechanism may be deranged in certain photosensitive disorders.

Notes: An increased rate of venous ulcer healing with the use of oral enteric-coated aspirin (300mg) daily has been reported.1 Whether the effect of aspirin in this condition is related to its action on the haemostatic mechanism is unclear, and therefore this study aimed to assess the effect of aspirin on some haemostatic parameters in patients with chronic venous leg ulcers. A double-blind, randomized, placebo-controlled, parallel-group study of haemostatic activity and the effect of aspirin was implemented over a 4-month period.Twenty patients with venous leg ulcers, and 20 age- and sex-matched controls were studied. Patients received enteric-coated aspirin (300mg) or placebo (one tablet) daily for 4 months, in addition to standardized local compressive bandaging (Setopress®). Assessments made at recruitment, and at 2 and 4 months, included measurement of total ulcer surface area, haematological and biochemical screening, measurement of coagulation times, coagulation factor VIII:C (FVIII:C) and von Willebrand factor (vWF), and plasminogen activator inhibitor-1 (PAJ-1) levels. Procoagulant activity was assessed by a computer-assisted technique, to determine the rate of thrombin production in vitro.Patients with venous ulcers had increased levels of fibrinogen (P 〈 0.01), FVIII:C (P 〈 0.05), vWF (P 〈 0.05) and PAI-1 antigen (P 〈 0.01) compared with controls. Shortening of the coagulation rate, shown by a reduction of the time to generate 50% maxima! thrombin activity in seconds (T5o), was seen in patients, in comparison with control subjects (P 〈 0.05). T50 was longer in patients receiving aspirin than those receiving placebo, reflecting prolongation of coagulation rate in the aspirin-treated group. In addition, an increased rate of ulcer healing occurred in subjects receiving aspirin compared with the placebo-treated group (P 〈 0.01, P 〈 0.02 at 2 and 4 months, respectively). No significant change in fibrinogen, FVIII:C, vWF or PAI-1 levels occurred in either group during the 4-month period.

Notes: We describe two patients with painful follicular keratoses at lower limb amputation sites. Subsequent examination of 31 amputees revealed evidence of keratoses in four of 28 patients with lower limb stumps. Two of the four affected subjects experienced stump pain exacerbated by weight-bearing. This problem is not well documented. Local treatment measures may be ineffective. Painful stump follicular keratoses many be a cause of significant morbidity in lower limb amputees, and may be the result of an ill-fitting prosthesis.

Notes: Background  We recently investigated the characteristics of psoralen plus ultraviolet (UV) A erythema in skin photosensitized by topical 8-methoxypsoralen (8-MOP) in three independent studies.Objectives  In order to determine the optimal time to read the minimal phototoxic dose (MPD) after treatment with topical 8-MOP and irradiation with UVA, we assessed the overall data.Methods  One forearm of each subject was immersed in 8-MOP solution for 15 min and test sites on the flexor surface of the forearm were immediately exposed to a UVA dose series. Erythema was assessed visually and objectively using a reflectance instrument at 24-h intervals for 7 days.Results  Results were obtained from 44 subjects (predominantly Fitzpatrick skin phototype II). A broad erythemal plateau was evident beyond 72 h and the visual MPD was significantly lower at 96, 120 and 144 h than at 72 h (P 〈 0·01). Only 30% of subjects were at peak erythema at the conventional MPD assessment time of 72 h. The median time to reach maximal erythema was 96 h (range 48–144). Objectively, 85% of subjects were at peak erythema at or beyond 96 h.Conclusions  We recommend that (i) the optimal time to read the topical 8-MOP MPD is 4 days after UVA exposure as readings beyond this time may be difficult to interpret because of the development of pigmentation, and (ii) 40% of the topical 8-MOP MPD should be considered for the first treatment.

Notes: Background  Fluoroquinolone antibiotics (FQs) are associated with phototoxic skin reactions following exposure to sunlight.Objectives  We aimed to compare the phototoxic potential of sitafloxacin, a novel FQ with three others: sparfloxacin, enoxacin, levofloxacin and placebo in Caucasian volunteers. In a second study, two dosage regimens of sitafloxacin were compared with placebo in Oriental subjects.Methods  Randomized, placebo-controlled, assessor-blinded clinical trial. In 40 healthy Caucasians, sitafloxacin 100 mg twice a day (n = 8), sparfloxacin 200 mg day−1 (n = 8), enoxacin 200 mg three times a day (n = 8), levofloxacin 100 mg three times a day (n = 8) and placebo (n = 8) were given in oral doses for 6 days. In the second study, sitafloxacin 50 mg and 100 mg, both twice daily, were compared with placebo in 17 healthy Oriental subjects. Using an established monochromator technique, baseline threshold erythema levels were established pre-drug and on-drug. The phototoxic index (PI) baseline, minimal erythema dose (MED) divided by on-drug MED for each medication at each wavelength was determined and related to sitafloxacin peak plasma levels. The duration of susceptibility to phototoxicity was assessed by repeat phototesting daily after stopping medication.Results  In the Caucasian study, sitafloxacin 100 mg twice a day produced mild ultraviolet (UV) A-dependent phototoxicity (median PI = 1·45) at 365 ± 30 nm (half-maximum bandwidth), maximal at 24 h with normalization by 24 h postdrug cessation. The sparfloxacin group experienced severe phototoxicity maximal at 24 h and, unusually for an FQ, extended in the visible region (430 ± 30 nm), maximal at 400 ± 30 nm (median PI = 12·35) with abnormal pigmentation at on-drug phototest sites lasting, although fading, for up to 1 year. Enoxacin showed UVA-dependent phototoxicity (335–365 ± 30 nm) median PI 3·94 (at 365 ± 30 nm) returning to normal 48 h after stopping the drug. Fading pigmentation at phototoxic sites also lasted up to 1 year. Phototoxicity was not detected in the levofloxacin or placebo groups. In the Oriental study, no clinically relevant phototoxicity was seen with either sitafloxacin or placebo groups.Conclusions  We conclude that 100 mg twice a day sitafloxacin in Caucasians is associated with a mild degree of cutaneous phototoxicity. Enoxacin 200 mg three times a day and sparfloxacin 200 mg day−1 are much more photoactive. Sparfloxacin phototoxicity is induced by UVA and visible wavelengths. Levofloxacin and placebo failed to show a phototoxic effect. In the Oriental study, sitafloxacin 50 mg twice a day and 100 mg twice a day failed to demonstrate a clinically significant phototoxic effect.

Notes: Background  St John's wort (SJW) is widely used as a treatment for depression. A phototoxic reaction, due to its content of hypericin, can occur in animals and in cell culture, and has been reported in humans. Hypericin displays absorption within the ultraviolet (UV) A1 spectrum and there may therefore be a potential for phototoxicity if taken during high-dose UVA1 therapy.Objectives  To assess the phototoxicity risk of SJW ingestion.Methods  Eleven adult volunteers of skin types I and II were exposed to a geometric dose series of UVA1 irradiation from a high-output source (Dermalight Ultra 1; Dr Hönle, Martinsreid, Germany; irradiance 70–77 mW cm−2) on the photoprotected lower back skin at eight 1·5-cm2 test areas. Irradiation was carried out at baseline and after 10 days of SJW extract 1020 mg (equivalent to 3000 µg of hypericin) daily. Four, 8, 24 and 48 h after each exposure, the minimal erythema dose (MED) and the presence or absence of pigmentation were recorded visually and erythema was assessed objectively with an erythema meter.Results  The median MED and D0·025, an objective measure of MED, were lower at all time-points after SJW ingestion. The visual erythemal peak (lowest median MED), which was seen at 8 h postirradiation, was lower after SJW (median 14 J cm−2, range 10–56) than at baseline (median 20 J cm−2, range 14–56) (P = 0·047). Similarly, the median D0·025 at 8 h postirradiation was lower after SJW (median 22·0 J cm−2, range 15·2–53·9) than at baseline (median 33·7 J cm−2, range 22·9–136·0) (P = 0·014). The MED and D0·025 were also significantly different at the 48-h and 4-h time-points, respectively. Significance was not reached at the 24-h time-point. Median intensity of postirradiation erythema increased at all time-points after ingestion of SJW. Despite these differences, the maximum slope of the dose–response curve was not increased after SJW ingestion.Conclusions  These data suggest that SJW extract has the potential to lower the erythemal threshold to UVA1 irradiation in a significant proportion of individuals and highlight the importance of ascertaining a full drug history, including herbal remedies, before initiating UVA1 phototherapy.