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P M Farr

Publications and source records attributed to P M Farr.

At least 37 records · Page 2Linked to original sources
PubMed1998

Phototesting prior to narrowband (TL-01) ultraviolet B phototherapy.

A device for phototesting patients prior to narrowband phototherapy is described. One hundred and fifty patients (130 with psoriasis and 20 with eczema) of skin types I-IV were phototested on the forearm and 22 on both forearm and back. The minimal erythema dose (MED) was judged visually 24 h after irradiation, and in those patients who were tested at two body sites, objective measurement of the erythema was made using a reflectance instrument. The MED values on the arm showed a fivefold range. There was no significant association between skin type and MED. The MED values on the arm were significantly higher than those measured on the back, although the differences were small in the majority of cases. No significant difference was found between the slopes of the dose-response curves measured on the arm and on the back.

Adolescent↗
PubMed1997

Comparison of psoralen-UVB and psoralen-UVA photochemotherapy in the treatment of psoriasis.

BACKGROUND: PUVA treatment of psoriasis is usually given with broad-band fluorescent UVA lamps. Narrow-band UVB exposure after oral methoxsalen has been shown to achieve a greater therapeutic response in psoriasis than identical UVB exposure given without psoralen. OBJECTIVE: The purpose of this study was to compare conventional PUVA with psoralen-UVB therapy in psoriasis. METHODS: We studied 100 patients with plaque-type psoriasis who were randomly selected to receive either conventional psoralen-UVA or psoralen-UVB treatment. RESULTS: No significant difference was found between the two treatments in the proportion of patients whose skin cleared during treatment or in the number of exposures required for clearance of psoriasis. As expected, the cumulative UV dose for clearance was smaller in the group treated with UVB compared with those receiving UVA. Side effects and disease status at 3 months after the end of treatment were similar for the two groups. CONCLUSION: Psoralen-UVB treatment of psoriasis is as effective as conventional PUVA. The mechanism of psoralen-311 nm UVB action on psoriasis requires study to predict the long-term safety of this treatment.

Adult↗
PubMed1997

Epidermolysis bullosa acquisita associated with epidermal-binding circulating antibodies.

Epidermolysis bullosa acquisita (EBA) is a rare, immunobullous disease, characterized by circulating and tissue-bound antibodies against type VII collagen (C7) of anchoring fibrils in the cutaneous basement membrane zone. These antibodies localize to the dermal aspect of salt-split skin on indirect and direct immunofluorescence (IMF). We report two patients with clinical features of EBA, in whom circulating IgG antibodies bound to the epidermal aspect of salt-split skin. In both patients direct IMF of salt-split perilesional skin revealed dermal IgG deposits, and direct immunogold immunoelectron microscopy showed antibody deposits in the region of anchoring fibrils. Their serum failed to react with epidermal or dermal extracts on Western immunoblotting. Epidermal-binding antibodies have not been reported previously in association with EBA, and the IMF findings in these cases suggest the development of autoantibodies to additional epidermal-associated antigens. Target antigen heterogeneity has been reported in most other immunobullous diseases, and may be a hitherto unrecognized feature of EBA.

Adult↗
PubMed1996

The effect of topical indomethacin on ultraviolet-radiation-induced erythema.

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 2h and erythema measured at 24h with a reflectance instrument. Indomethacin inhibited 300 and 320 nm (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.

Adult↗
PubMed1995

Calculation of 8-methoxypsoralen dose according to body surface area in PUVA treatment.

In 41 patients about to start PUVA, the dose of 8-methoxypsoralen (8-MOP) was calculated conventionally according to body weight (0.6 mg/kg), or according to body surface area (25 mg/m2) predicted from height and weight measurements. The two different methods of dosing were used on consecutive treatment days and the plasma 8-MOP concentration was measured on each occasion 2 h after ingestion of the crystalline form of 8-MOP, given to the nearest 10 mg. Body weight calculated doses ranged from 30 to 60 mg with a significant difference in the plasma 8-MOP concentration between the dose groups, indicating a systematic variation according to the weight of the patient. When calculated according to body surface area, only two doses were used (40 or 50 mg), and there was no significant difference in plasma 8-MOP concentration between the groups. Calculation of the dose of 8-MOP using body surface area may be performed quickly and simply provided the height and weight of individual patients is known. We provide evidence that this method of dosing will improve the therapeutic effect of PUVA in psoriasis.

Adolescent↗
PubMed1994

Dissociation of erythema and p53 protein expression in human skin following UVB irradiation, and induction of p53 protein and mRNA following application of skin irritants.

The mechanisms mediating the varied effects of ultraviolet radiation (UVR) on human skin are unclear, although a relationship between erythema and DNA damage is suggested by photosensitivity in xeroderma pigmentosum. Increased p53 expression in response to UVR is thought to reflect direct DNA damage, but recent evidence indicates that UVR also activates membrane and cytosolic signal transduction pathways. In this study, we have investigated the relationship between erythema and p53 induction following UVB and whether this p53 response is specific to UVR. p53 protein expression was determined by immunocytochemistry using the monoclonal antibody DO7, and p53 mRNA expression was examined by non-isotopic in situ hybridization. Incremental doses of UVB were administered to the lower back of eight subjects. Immunostaining revealed that p53 positive nuclei were significantly increased 8 h after suberythemogenic doses of UVB (79 +/- 12), compared to normal unirradiated skin (8 +/- 6, p < 0.0005), but no change in p53 mRNA was seen. Higher UVB doses, which resulted in moderate erythema, resulted in a similar or greater induction of p53 protein. Indomethacin (1% w/v), applied immediately after UVB irradiation, significantly inhibited UVB erythema at 8 h in six subjects (p < 0.005), but did not reduce p53 immunostaining. Dithranol (1 microgram/microliter, n = 8), sodium dodecylsulphate (5%, n = 4), and retinoic acid (0.5%, n = 4), applied for 48 h, caused erythema, significantly increased p53 protein levels (p < 0.05), and also increased p53 mRNA. Our results show that in human skin, UVB-induced p53 elevation can be dissociated from erythema and skin irritants can also induce p53 protein. The induction of p53 mRNA by irritants but not UVR suggests different mechanisms of action.

Adult↗
PubMed1994

Photoprotective action of emollients in ultraviolet therapy of psoriasis.

An in vitro technique was used to measure the monochromatic protection factors of all emollients available on prescription. The action spectra for ultraviolet erythema and erythema in psoralen-sensitized skin were used to calculate, for each emollient, erythema protection factors relevant to UVB phototherapy and psoralen photochemotherapy, respectively. Of the 40 products tested, 22 (55%) had a UVB erythema protection factor > 1.2 at an application density of 2 microliters/cm2, and 31 (78%) at an application density of 4 microliters/cm2. Fewer products, 25% at 2 microliters/cm2 and 50% at 4 microliters/cm2, had a psoralen erythema protection factor > 1.2. A protection factor of 1.2 is equivalent to a reduction in ultraviolet dose of 17%, and is thus likely to be of clinical importance. These results allow a choice of emollient products which may improve response by increasing transmission of radiation through psoriasis scale without a concomitant decrease in transmission due to a sunscreening action.

Emollients↗
PubMed1994

Erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA.

In PUVA treatment of psoriasis, clinical observation suggests that uninvolved skin is more susceptible to PUVA erythema than lesions of psoriasis. If this is the case, then the efficacy of PUVA treatment might be increased by using localized high-dose UVA restricted to lesional skin. We have therefore studied the erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA and, for comparison, the erythemal response to UVB. In 14 patients, an area of psoriasis and adjacent uninvolved skin were exposed to a series of UVA doses (350 +/- 30 nm, 1-16J/cm2), using an irradiation monochromator. Six other patients were similarly phototested with a series of UVB doses (300 +/- 5 nm, 20-112 mJ/cm2) to both uninvolved and lesional skin. Erythema was judged visually at 72 h for psoralen-UVA, and at 24 h for UVB, and measured using a scanning laser-Doppler velocimeter. In 10 patients, PUVA therapy using high-dose UVA was subsequently given to lesional skin (8-16J/cm2 twice weekly) in addition to conventional whole-body PUVA. For psoralen-UVA, the minimal phototoxic dose within psoriasis was increased by a factor of 4 compared with non-lesional skin (P < 0.01, Wilcoxon signed-rank test). For UVB, the minimal erythema dose within psoriasis was higher than that for non-lesional skin (medians > 112 and 28 respectively, P < 0.05). Laser-Doppler measurements confirmed that the reduced erythemal sensitivity was not due to masking of response by pre-existing increased blood flux within psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Calcipotriol improves the response of psoriasis to PUVA.

Combining PUVA with other therapeutic agents which reduce the UVA dose required for clearance of psoriasis may be of benefit by reducing the long-term risk of cutaneous malignancy and by increasing the efficacy of treatment. We have therefore studied the effect of calcipotriol in 13 patients with plaque-type psoriasis who were about to start twice weekly PUVA. In each patient, from the start of PUVA treatment, two plaques on symmetrical body sites were selected for assessment. Calcipotriol ointment was applied to one twice daily, and placebo to the other. Response was assessed weekly for 6 weeks: an investigator, unaware of treatment allocation, compared psoriasis severity within each of the plaques, and blood flux was measured using a scanning laser-Doppler velocimeter. Of the 11 patients who completed the study, in nine the calcipotriol-treated plaque either cleared before the placebo-treated plaque (n = 7), or was consistently judged to be better (n = 2). From the third week of the trial, mean blood flux was significantly lower in the calcipotriol-treated plaques than in those treated with placebo. In the seven patients whose psoriasis was clear in at least one plaque at the end of the study period, there was a median reduction in UVA dose of 26.5% for calcipotriol compared with placebo. With the exception of one patient, the improved response was not associated with earlier relapse.

Adult↗
PubMed1994

Skin cancers or premalignant lesions occur in half of high-dose PUVA patients.

Although treatment of psoriasis with psoralen and ultraviolet A (PUVA) is associated with a long-term risk of development of cutaneous squamous cell carcinoma (SCC), the role of PUVA alone is not established, as many patients in reported series had also received treatment with other carcinogens, such as superficial X-rays or arsenic. We have recalled and examined 54 of the 63 patients still alive who have had PUVA treatment in our department, and who have been exposed to a cumulative UVA dose greater than 2000J/cm2. None of the patients had been treated with superficial X-rays or arsenicals. Ten patients (19%) had developed SCC, and 25 (46%) had histologically atypical squamous keratoses arising at body sites similar to the carcinomas. The patients with SCC were significantly older at the start of PUVA treatment than those with keratoses alone. None of the 13% of patients without PUVA lentigines had keratoses or SCCs. These results show that high-dose PUVA treatment in the U.K., even when given alone, can frequently result in the development of SCC. Further malignancies are to be expected with continued follow-up of the patients with squamous keratoses. Absence of PUVA lentigines may be a useful indicator of a lower risk of PUVA malignancy.

Adult↗
PubMed1994

Improved prediction of the minimal phototoxic dose in PUVA therapy.

In an attempt to improve the prediction of PUVA erythemal sensitivity, we have examined, in 251 patients, the relationship between the minimal phototoxic dose (MPD) and a number of variables, including skin type, ingested dose of 8-methoxypsoralen (8-MOP) and history of previous PUVA treatment. The MPD was determined by phototesting 2 h after ingestion of crystalline 8-MOP, given at a standard dose of 0.6 mg/kg (calculated to the nearest 10 mg). No reaction to the highest dose of UVA used for phototesting occurred in 16% of cases; the dose of 8-MOP was significantly associated with non-response. In the patients in whom an erythemal response was obtained, a significant association was found between the MPD and the variables of skin type, ingested dose of 8-MOP, and history of previous PUVA treatment. Thus, by taking these factors into account, a more accurate prediction can be made of an individual patient's erythemal sensitivity to PUVA than relying on skin type alone. That erythemal sensitivity is affected by the ingested dose of 8-MOP (even when all patients received 0.6 mg/kg) suggests that conventional psoralen dosing according to body weight is not ideal.

Adolescent↗