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Biomedical subjects

S H Ibbotson

Publications and source records attributed to S H Ibbotson.

At least 19 recordsLinked to original sources

Regulation of cutaneous drug-metabolizing enzymes and cytoprotective gene expression by topical drugs in human skin in vivo.

BACKGROUND: Individuality in the expression and regulation of hepatic drug-metabolizing enzymes (DMEs) and cytoprotective (CP) genes is an important determinant of treatment response. There is increasing evidence that many DMEs and CP genes are also expressed in human skin. Responses to topical drugs used to treat common skin diseases, such as psoriasis, are unpredictable and may potentially be rationalized, at least in part, by interindividual differences in cutaneous DME and CP gene expression. OBJECTIVES: We investigated whether three topical drugs [coal tar, all-trans retinoic acid (atRA) and clobetasol 17-propionate] used in routine clinical practice modulated the expression of a variety of DME and CP genes [cytochrome P450s, glutathione S-transferases (GSTs) and drug transporters] in healthy human skin in vivo. METHODS: Healthy adult volunteers (n = 30) were invited to participate in the study. Each subject was randomly allocated to receive two of the three study chemicals and one control site application. Crude coal tar (n = 13), atRA (n = 14) or clobetasol 17-propionate (n = 10) was applied under occlusion to photoprotected buttock skin for 96 h. A vehicle control (white soft paraffin) was also applied under the same conditions at an adjacent site in all subjects. Full-thickness punch biopsies (4-mm diameter) were then taken from treated and control sites. Total RNA was extracted and reverse transcribed into cDNA, which was used as a template in subsequent real-time polymerase chain reaction analysis, where fluorescent output was directly proportional to input cDNA concentration. Triplicate measurements of skin mRNA expression were made from each sample, and the arithmetic mean values taken. After logarithmic transformation, the paired t-test was used to compare values between treated and control skin. RESULTS: Cytochrome P450s CYP1A1, CYP1A2, CYP1B1, CYP2C18, quinone reductase (NQO-1), GSTP1, gamma-glutamyl cysteine synthetase (gamma-GCS), glutathione peroxidase-1 (GPx-1), cyclooxygenase-2 (COX-2) and haem oxygenase-1 (HO-1) were induced by coal tar; CYP26, NADPH P450 reductase (CPR), GSTP1 and HO-1 by atRA; and CYP3A5 by clobetasol 17-propionate. In contrast, CYP1A1 and CYP1A2 expression was suppressed by atRA, and gamma-GCS and MRP1 by clobetasol 17-propionate. Marked interindividual variation in gene regulation by topical drugs was seen for the majority of genes examined. CONCLUSIONS: These data demonstrate that topical drugs can modulate DME gene expression in human skin in vivo and indicate that variation in the expression and regulation of these genes may be a determinant of individuality in response to topical therapies for common skin diseases.

Administration, Cutaneous↗

Photopatch testing of 1155 patients: results of the U.K. multicentre photopatch study group.

BACKGROUND: Photoallergic contact dermatitis can be difficult to diagnose if not appropriately investigated. Currently, the most common U.K. photoallergens appear to be sunscreen chemicals. The investigation of choice is photopatch testing (PPT), which is probably underused. In part, this is due to differences in methodology and results interpretation. OBJECTIVES: To conduct PPT using a group of sunscreen chemicals, defined indications and a standardized methodology including interpretation and relevance of reactions in patients attending for investigation at 17 centres across the U.K., Ireland and the Netherlands. METHODS: Patients (n = 1155) who fulfilled the inclusion criteria were investigated with PPT using sunscreen chemicals in addition to suspected topical products. Readings were taken at 24, 48 and 72 h following standardized ultraviolet A irradiation (5 J cm(-2)). The clinical relevance of any reaction was recorded. RESULTS: Of the 1155, 130 had allergic reactions (11.3%). Of these, 51 had photoallergy (PA) (4.4%), 64 had contact allergy (CA) (5.5%), and 15 patients had combined PA and CA (1.3%). Multiple PA was seen in some. The most common photoallergen was benzophenone-3 (27 reactions; 21%). Most reactions (60%) were clinically relevant. The most common indication for testing in patients found to have PA was a history of reacting to a sunscreen (41%). The other 59% had an exposed-site dermatitis/skin problem or a photodermatosis. Some centres (n = 8) performed readings after the standard 48-h reading, and an extra 32 PA and 22 CA reactions were detected, which were not evident at 48 h. A new photoallergen (octyl triazone) was detected in two patients. CONCLUSIONS: Sunscreen PA and CA are probably equally uncommon. Most reactions, of both reaction types, were relevant clinically. A large proportion of patients (59%) found to have PA was unaware of reacting to a sunscreen chemical, suggesting that PA should be considered as an explanation in any exposed-site dermatitis. Although this study focused on reactions at 48 h postirradiation, readings performed up to 96 h, while inconvenient, add value by detecting additional relevant responses. A previously unknown photoallergen was found, highlighting the need for awareness of novel photoallergens in the marketplace. A standardized PPT method not only encourages more use of this investigation, but also facilitates comparison of results between centres and so will improve our understanding of PA.

Adolescent↗

UVA1 phototherapy for treatment of necrobiosis lipoidica.

The primary cause of collagen degeneration in necrobiosis lipoidica (NL) is proposed to be immunologically mediated vascular disease. Ultraviolet (UV)A1 has been used successfully to treat scleroderma in which both vascular damage and collagen dysregulation also occur. We treated six patients with NL [(five women; mean age of 32 years (range 22-70) and mean disease duration of 2.9 years (range 6 months to 5 years)] with a high-output ultraviolet (UV)A1 2-kW filtered metal halide source (Dr Hönle; Dermalight ultrA 1) having an emission spectrum of 340-440 nm. All patients had NL on the shins, which had been unresponsive to potent topical corticosteroid therapy (n = 6) and had responded minimally or not at all to TL-01 UVB (n = 2), topical psoralen plus UVA (PUVA) soaking (n = 2) or oral PUVA (n = 1) therapy. Patients received a variable number of total exposures (15-51), given 3-5 times weekly. NL resolved completely in one patient; this patient had minimal improvement after the first course of 16 exposures, but after a further 13 exposures, resolution occurred 6 months later. Two subjects obtained moderate improvement in their overall disease severity after 15 and 24 exposures, while two had only minimal improvement after 15 and 51 exposures. The remaining patient had no improvement after 16 treatments. Patients with the shortest disease duration had the greatest response. UVA1 therapy may be of benefit for the treatment of NL as an adjuvant therapy to topical corticosteroids or as a second-line alternative to other phototherapies, and may have a superior outcome in a proportion of patients.

Adult↗

UVA1 phototherapy for genital lichen sclerosus.

BACKGROUND: Lichen sclerosus (LS) is characterized histologically by an inflammatory T-cell infiltrate, sclerosis and thickening of the dermis, and epidermal atrophy. Ultraviolet (UV) A1 therapy has been shown to be effective in the management of morphea and scleroderma, diseases that have some histological and clinical similarities with LS, and more recently in extragenital LS. AIM: To determine the effectiveness of UVA1 therapy for genital LS. METHODS: Seven women with severe genital LS uncontrolled by ultrapotent topical corticosteroids, with a median age of 62 years (range 48-78) and disease duration of 6-47 years, were treated with UVA1 therapy from a high output source. After completion of UVA1 therapy, a clinician and the patient graded the overall response of symptoms and physical signs. RESULTS: Five patients improved with therapy. Three obtained moderate improvement in overall disease severity and two had minimal improvement. Of these five, one relapsed within 3 months and another after a year. Both had a further course of UVA1 therapy, resulting in minimal improvement in one and moderate improvement in the other. In the remaining three, disease severity had improved to a point where intermittent use of topical corticosteroids resulted in acceptable control. DISCUSSION: UVA1 therapy may be of benefit in the management of vulval LS, a disease that is often poorly responsive to standard therapies. The therapy is well tolerated and could provide an acceptable therapeutic option for patients with severe disease.

Aged↗

Characteristics of 5-aminolaevulinic acid-induced protoporphyrin IX fluorescence in human skin in vivo.

BACKGROUND/PURPOSE: Topical photodynamic therapy (PDT) is increasingly being used to treat skin cancers. Knowledge of the detailed characteristics of 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence in diseased and normal skin is incomplete. Understanding the characteristics of PpIX fluorescence in normal skin may facilitate optimization of PDT regimes while minimizing side effects in the surrounding normal skin. We investigated the characteristics of ALA-induced PpIX fluorescence in normal skin. METHODS: ALA was applied to the arm, back and leg skin of 21 healthy volunteers for 1-6 h, and PpIX fluorescence was measured for up to 24 h after ALA application using a fluorescent spectrometer. The effect of tape stripping on fluorescence was also examined. RESULTS: Considerable inter-subject variation was observed in the time to reach peak PpIX fluorescence. Intra-subject variation in the time to peak fluorescence was dependent on ALA application time. Six hours after ALA application, no significant difference was observed in the degree of fluorescence achieved irrespective of ALA application times ranging between 1 and 6 h. PpIX fluorescence was reduced on the leg and increased by tape stripping. CONCLUSIONS: Marked inter- and intra-subject variation in ALA-induced PpIX fluorescence occurs in normal human skin. ALA application time, body site and the state of the stratum corneum are all determinants of PpIX fluorescence within subjects and these factors need to be taken into account in optimization of PDT regimes.

Adult↗

Carbamazepine-induced hypersensitivity syndrome occurring in a photodistributed pattern.

A 76- year- old man was commenced on carbamazepine for partial seizures. This was followed by the development of a rash in an apparently photodistributed pattern, fever, lymphadenopathy, eosinophilia, abnormal liver function tests and atypical lymphocytosis fulfilling the criteria for drug-induced hypersensitivity syndrome. Discontinuation of carbamazepine and application of topical steroid resulted in clearance of the rash, normalization of liver function tests and improvement in eosinophilia. The photodistributed pattern in this case of carbamazepine-induced hypersensitivity syndrome is of interest.

Aged↗

Photogenotoxicity of hypericin in HaCaT keratinocytes: implications for St. John's Wort supplements and high dose UVA-1 therapy.

Extract of St. John's Wort (Hypericum perforatum) is commonly used as natural remedy for treatment of mild to moderate depression. However, it contains a powerful photoactive component, hypericin, which can cause a severe photodermatitis when eaten by grazing animals (hypericism). In humans, there is evidence that supplementation with St. John's Wort can reduce the minimal erythemal dose (MED) in patients undergoing high dose UVA-1 phototherapy. This is a recent development in phototherapy where the most erythemogenic parts of the UVA spectrum are filtered out, allowing delivery of higher doses of the longer wavelengths of UVA. Although current published evidence suggests that the plasma levels of hypericin are unlikely to cause clinical phototoxicity, it has been established that photoactive compounds can cause DNA damage at sub-toxic and sub-erythemal doses, the effects of which might not be apparent for many years after the event. The present study used HaCaT keratinocytes to investigate the photoclastogenic ability of hypericin on irradiation with UVA. The results show that although the combination of hypericin and UVA light increased the genotoxic burden, when all factors are taken into account, the risk of significant photogenotoxic damage incurred by the combination of Hypericum extracts and UVA phototherapy may be low in the majority of individuals.

Anthracenes↗

The photocarcinogenic risk of narrowband UVB (TL-01) phototherapy: early follow-up data.

BACKGROUND: Limited information is available on the carcinogenic risk associated with narrowband TL-01 UVB phototherapy in humans. OBJECTIVES: To determine the skin cancer incidence in a population treated with TL-01 phototherapy. PATIENTS AND METHODS: All TL-01-treated patients were identified from the departmental computerized database. Patients with malignant melanoma (MM), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) were identified by record linkage with the Scottish Cancer Registry. The incidence of each was compared with the normal Scottish population matched for age and sex. RESULTS: Data were obtained from 1908 patients. The median follow-up duration was 4 years (range 0.04-13). The median cumulative number of TL-01 treatments and dose were 23 (1-199) and 13 337 (30-284 415) mJ cm(-2), respectively. No increased incidence of SCC or MM was observed. Ten patients developed BCC compared with an expected 4.7 in the Scottish population [standardized rate ratio 213 (95% confidence interval 102-391); P < 0.05]. CONCLUSIONS: A small but significant increase of BCC was detected in the TL-01 group. This could be explained by a number of factors, including ascertainment bias. To determine the true carcinogenic risk of TL-01 phototherapy, longer follow-up is essential.

Aged↗

The effect of ultraviolet (UV) A1, UVB and solar-simulated radiation on p53 activation and p21.

BACKGROUND: High-dose ultraviolet (UV) A1 therapy (doses in the order of 130 J cm(-2)) is effective for atopic dermatitis and scleroderma. UVA1 has been shown to induce a dose-dependent increase in p53 expression in keratinocytes. OBJECTIVES: To examine the effect of UVA1 on the activation of p53 by phosphorylation, which has not yet been studied. METHODS: Five adult volunteers were exposed to dose series of UVA1 (10-100 J cm(-2)) and, for comparison, narrowband UVB (TL-01) (25-550 mJ cm(-2)) and solar-simulated radiation (SSR) (5.6-30 J cm(-2)) on photoprotected buttock skin and the minimal erythema dose (MED) for each was determined at 24 h. Separate sites on the buttock were subsequently irradiated with a 3-MED dose of UVA1, TL-01 and SSR. At 24 h, punch biopsies (4 mm) were taken from each irradiated site and from an adjacent unirradiated control site, and immunohistochemical staining for p53 (Do-1), activation of p53 (assessed by phosphorylation at serine 15 and serine 392) and p21 was performed. Cell staining was expressed as the mean number of cells stained per three high-power fields (HPFs) and as a percentage of 1000 cells. Sunburn cells (SBCs) were also counted per HPF. RESULTS: UVA1 produced negligible numbers of SBCs, relatively little p53 (Do-1) staining (mean +/- SD cell count per HPF 16 +/- 10), no p53 activation and very little evidence of p21 expression (mean +/- SD cell count per HPF 5.3 +/- 7), in contrast to TL-01 (mean +/- SD cell count per HPF of 11.83 +/- 2.1 SBCs, 146.3 +/- 38 for Do-1, 26.6 +/- 15 for serine 15, 14.9 +/- 12 for serine 392 and 77.9 +/- 30 for p21) or SSR irradiation (mean +/- SD cell count per HPF of 3.5 +/- 1.2 SBCs, 147.5 +/- 62 for Do-1, 54 +/- 50 for serine 15, 38.9 +/- 18 for serine 392 and 56.7 +/- 30 for p21). CONCLUSIONS: These data indicate that there are fundamental differences in the effects of UVA1 on p53 and its activation pathways compared with TL-01 and SSR, and may in part explain the differential effects of these phototherapies.

Adult↗

A randomized controlled comparison of the efficacy of Dead Sea salt balneophototherapy vs. narrowband ultraviolet B monotherapy for chronic plaque psoriasis.

BACKGROUND: Dead Sea (DS) salt solution soaks are used in combination with narrowband ultraviolet B (NB-UVB) to treat psoriasis in many centres, particularly in continental Europe. No previously published controlled study has assessed DS salt + NB-UVB balneophototherapy. OBJECTIVES: To compare DS salt balneophototherapy with NB-UVB monotherapy for chronic plaque psoriasis. METHODS: Sixty patients with chronic plaque psoriasis participated in this paired, controlled study, with pretreatment DS salt soaks randomly allocated to each participant's right or left study limb. Psoriasis severity was assessed with a Scaling, Erythema and Induration score by a blinded observer. Assessments were weekly during the therapy course, and thereafter 8-weekly until relapse or for up to 1 year after clearance. RESULTS: The mean area under the psoriasis severity-time curves during treatment was not detectably lower with DS salt balneophototherapy than with NB-UVB monotherapy (P = 0.099). The psoriasis severity score fell slightly more from beginning to end of courses with DS salt balneophototherapy than with NB-UVB monotherapy (P = 0.019). There was no detectable difference in times to relapse. CONCLUSIONS: In this population the addition of pretreatment DS salt soaks to NB-UVB did not result in a clinically important improvement in clearance of psoriasis.

Adult↗

Differential effects of 5-aminolaevulinic acid photodynamic therapy and psoralen + ultraviolet A therapy on p53 phosphorylation in normal human skin in vivo.

BACKGROUND: Phosphorylation of the tumour suppressor p53 by the CK2/FACT pathway plays a central role in suppressing ultraviolet (UV)-induced skin cancer in animal models. Although p53 protein stabilization is induced after solar-simulated irradiation of human skin in vivo, p53 phosphorylation has not been defined. OBJECTIVES: To investigate the effects of clinically effective treatments for skin diseases including psoralen + UVA (PUVA) and photodynamic therapy (PDT) on p53 phosphorylation to determine whether the tumour-suppressing p53 kinase pathways are activated upon use of these therapies. METHODS: We used antibodies to the ATM/ATR and CK2/FACT phosphorylation sites on p53. RESULTS: We found that p53 activation was induced selectively by PUVA treatment, while 8-oxo-7,8-dihydroguanine DNA damage was induced selectively by 5-aminolaevulinic acid (ALA)-PDT treatment. Importantly, PUVA treatment resulted in p53 kinase activation, as defined by p53 modification at AT (serine-15) and CK2/FACT (serine-392) sites within the proliferative compartment. CONCLUSIONS: These data demonstrate that PUVA provokes accumulation and phosphorylation of p53 by AT and CK2/FACT within critical proliferative focal points (as determined by p63 colocalization studies) where DNA damage may lead to tumorigenesis. PDT is mechanistically distinct in that there is a lower level of induction of p53 expression with no evidence of AT- or CK2/FACT-mediated phosphorylation. This suggests that the type of DNA damage created by the reactive oxygen species generated by ALA-PDT does not induce the p53 pathway classically required for the repair of DNA photoadducts induced by UV.

Aminolevulinic Acid↗

Can St John's wort (hypericin) ingestion enhance the erythemal response during high-dose ultraviolet A1 therapy?

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-cm(2) test areas. Irradiation was carried out at baseline and after 10 days of SJW extract 1020 mg (equivalent to 3000 microg 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 D(0.025), 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 D(0.025) 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 D(0.025) 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.

Adult↗

Does narrow-band ultraviolet B phototherapy work in atopic dermatitis through a local or a systemic effect?

The likely mechanisms of action of narrow-band ultraviolet B (NB-UVB) in atopic dermatitis are several. We attempted, in a 12 patient prospective intraindividually controlled study, to determine whether the effect of NB-UVB in atopic dermatitis is primarily through systemic or local effects. Change in observer-assessed severity of patches of dermatitis covered during each whole-body NB-UVB treatment was compared with change in uncovered neighbouring patches. We found great variation between patients in responses. Only in two (of 12) patients was there a large difference between directly exposed and covered patch dermatitis severity. We suspect that the balance of local and systemic effects important in determining response to NB-UVB in atopic dermatitis varies from patient to patient. This study did not conclusively answer our original question, but did show that in some patients localized effects of NB-UVB are important.

Case-Control Studies↗

Treatment of superficial cutaneous vascular lesions: experience with the KTP 532 nm laser.

Whilst most facial telangiectasias respond well to short-pulse-duration pulsed dye laser therapy, studies have shown that for the treatment of larger vessels these short-duration pulses are sub-optimal. Long-pulse frequency-doubled neodymium:YAG lasers have been introduced with pulse durations ranging from 1-50 ms and treatment beam diameters of up to 4 mm. We report the results of KTP/532 nm laser treatment for superficial vascular skin lesions. The aim was to determine the efficacy of the KTP/532 nm laser in the treatment of superficial cutaneous vascular lesions at a regional dermatology centre in a 2 year retrospective analysis. Patients were referred from general dermatology clinics to a purpose-built laser facility. A test dose was performed at the initial consultation and thereafter patients were reviewed and treated at 6 week intervals. Outcome was graded into five classifications by the patient and operator independently based on photographic records: clear, marked improvement, partial response, poor response, and no change or worsening. Over the 2 year period, 204 patients with 246 diagnoses were treated [156 female; median age 41 (range 1-74) years; Fitzpatrick skin types I-III]. Equal numbers of spider angioma (102) and facial telangiectasia (102) were treated. Of those patients who completed treatment and follow up, 57/58 (98%) of spider angiomas and 44/49 (90%) of facial telangiectasia markedly improved or cleared. Satisfactory treatment outcomes, with one clearance and two partial responses, occurred in three of five patients with port-wine stain. Few patients experienced adverse effects: two declined further treatment due to pain, and a small area of minimal superficial scarring developed in one case. Two patients developed mild persistent post-inflammatory hyperpigmentation, and one subject experienced an episode of acute facial erythema, swelling and blistering after one treatment. The KTP/532 nm frequency-doubled neodymium:YAG laser is a safe and effective treatment for common superficial cutaneous vascular lesions in patients with Fitzpatrick skin types I-III.

Adolescent↗

A randomized, double-blind, placebo-controlled study of the efficacy of tetracaine gel (Ametop) for pain relief during topical photodynamic therapy.

BACKGROUND: Many patients find topical 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) painful. Local anaesthetics are not routinely used and their effect on PDT pain has not been examined. OBJECTIVES: To evaluate the efficacy of tetracaine gel (Ametop) for pain relief during and after PDT. METHODS: A prospective, double-blind, placebo-controlled study of 42 patients with lesions (< or =2 cm diameter) of superficial nonmelanoma skin cancer or dysplasia. Patients were randomized to either tetracaine (4% w/w) (n=22) or vehicle (n=20) gel under occlusion for 1 h pre-irradiation. Pain was assessed during and after irradiation using a visual analogue scale (VAS) and faces pain scale. RESULTS: Patients who received tetracaine gel experienced only slightly less pain during PDT (median VAS 4) compared with those who received placebo (median VAS 4.5) (95% confidence interval for difference 0-3, P=0.08). No significant difference in pain was experienced between the treatment groups immediately after irradiation or later. CONCLUSIONS: When compared with placebo, tetracaine gel did not significantly reduce pain during or after PDT for small lesions of superficial basal cell carcinoma, Bowen's disease or actinic keratosis.

Administration, Topical↗

A pilot study of treatment of lentigo maligna with 5% imiquimod cream.

BACKGROUND: Lentigo maligna (LM) is an in situ form of malignant melanoma, and surgical excision is often unsatisfactory. Imiquimod cream is an immune response modifier and induces a predominantly T-helper 1 type response. OBJECTIVES: Assessment of histological and clinical response of surgically resectable LM after treatment with 5% imiquimod cream. METHODS: Six patients with LM were treated with 5% imiquimod cream daily for 6 weeks. The whole site of the original lesion was then excised. Clinical and histological and appearances were measured using clinical response and histological grading scores. RESULTS: Complete or almost complete clearance of pigmentation with minimal residual histological evidence of LM was observed in four patients, one patient showed no clinical or histological improvement, and the remaining patient had almost no residual pigmentation clinically after treatment yet histopathological changes remained as severe as before treatment. CONCLUSIONS: Topical imiquimod cream merits further investigation as a new therapy for LM.

Administration, Topical↗

The optimal time to determine the minimal phototoxic dose in skin photosensitized by topical 8 methoxypsoralen.

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.

Adult↗