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J L Hawk

Publications and source records attributed to J L Hawk.

At least 19 recordsLinked to original sources
PubMed2001

Photodermatoses in the elderly.

Several photodermatoses specifically affect the elderly, and many others continue into old age. Photodermatoses present unique challenges in diagnosis and management when considered in the context of the multiple pathologies and problems of polypharmacy in this age group. This article examines the idiopathic photodermatoses, which include chronic actinic dermatitis, specifically a disease of the middle-aged and elderly. Endogenous (metabolic) and exogenous (drug and chemical) photodermatoses, as well as photo-exacerbated dermatoses, also are discussed.

Aged↗
PubMed2001

Familial clustering of polymorphic light eruption in relatives of patients with lupus erythematosus: evidence of a shared pathogenesis.

BACKGROUND: Abnormal photosensitivity is a common feature of many forms of lupus erythematosus (LE). OBJECTIVES: To examine the role of polymorphic light eruption (PLE) as a possible predisposing factor for cutaneous forms of LE. METHODS: Eighty-five patients with well-characterized subacute cutaneous LE (SCLE) and discoid LE (DLE) were recruited from outpatient clinics, and the prevalence of PLE determined by detailed interview and clinical examination. RESULTS: Symptoms consistent with PLE were reported in 61% and 55% of SCLE and DLE patients, respectively; this was significantly higher than the overall population prevalence of 13.6% (P < 0.001), giving a relative risk (RR) for PLE in SCLE patients of 3.37 (95% confidence interval, CI 2.46--4.28) and DLE patients of 3.11 (95% CI 2.31--3.91). PLE developed before the onset of LE in 61% of cases (median interval 12 years, range 1--40), concomitantly in 24%, and subsequently in a further 15% (median interval 3.5 years, range 1--25). To delineate the relationship between PLE and LE further, the prevalence of PLE was determined in 103 otherwise unaffected first-degree relatives of SCLE and DLE probands; we had previously demonstrated clustering of PLE in families, reflecting a strong genetic component. We found a significantly higher PLE prevalence in relatives of the LE probands than in the general population (P < 0.001), giving an RR for PLE of 2.29 (95% CI 1.55--3.03) and 2.61 (95% CI 1.32--3.89) for female and male relatives, respectively. CONCLUSIONS: The high prevalence of PLE in LE patients, together with clustering of PLE among first-degree relatives of SCLE and DLE probands, suggests that there may be a shared pathogenetic basis for PLE and cutaneous LE. We propose that predisposition to PLE may contribute to the LE phenotype in otherwise susceptible individuals.

Confidence Intervals↗
PubMed2001

A candidate gene analysis of three related photosensitivity disorders: cutaneous lupus erythematosus, polymorphic light eruption and actinic prurigo.

BACKGROUND: Polymorphic light eruption (PLE) is a common inherited photosensitivity disorder, which may predispose to several related but distinct conditions, including subacute cutaneous lupus erythematosus (SCLE), discoid lupus erythematosus (DLE) and actinic prurigo (AP). OBJECTIVES: To examine specific candidate genes for shared susceptibility alleles between these related phenotypes. METHODS: Eighty-five caucasian patients with annular SCLE or DLE were recruited, in addition to 102 first-degree relatives. The prevalence of PLE in both the patient and relative groups was determined by detailed interview and clinical examination. Eighty-five patients with pure PLE and 59 patients with AP were also recruited. Candidate genes were analysed by typing of single nucleotide polymorphisms of IL10 (-1082 G/A and -819 C/T), FCGR2A (131 R/H), SELE (128 S/R), ICAM1 (241 G/R and 469 E/K), IL1A (+ 4845 G/T), IL1B (-511 C/T and + 3954 C/T), IL1RN (+ 2018 T/C) and TNF (-308 G/A) using polymerase chain reaction (PCR) with sequence-specific primers and 5'-nuclease PCR. RESULTS: A significant association was found between SCLE and the rare TNF -308 A allele when compared with patients with DLE (P = 0.043), PLE (P = 0.001), AP (P < 0.001) and healthy controls (P < 0.001). However, there was strong linkage disequilibrium between TNF -308 A and the HLA A*01, B*08, DRB1*0301 haplotype. A negative association was also found between SCLE and the IL1B + 3954 T allele (P = 0.039), but the significance was lost on correction for multiple testing. CONCLUSIONS: We have demonstrated the association of SCLE with the rare TNF -308 A allele, which may be pathogenic or, alternatively, a marker allele for the extended HLA A*01, B*08, DRB1*0301 haplotype that is associated with a number of autoimmune conditions. Although many of the other loci that we chose failed to demonstrate an association, a candidate gene approach remains the most logical one, and the most likely to yield positive results in the future.

Alleles↗
PubMed2001

Photoallergic contact dermatitis is uncommon.

BACKGROUND: Despite the enormous increase in sunscreen use, allergic contact (AC) and photoallergic (PA) reactions to ultraviolet (UV) filters are considered rare. OBJECTIVES: To analyse the data from 2715 patients who underwent photopatch testing at St John's Institute of Dermatology during the period 1983-98. METHODS: A retrospective analysis of all positive photopatch test episodes was undertaken with the results retrieved from the environmental dermatology database and further verified with the original archived patch test documentation for each individual patient. RESULTS: In 111 patients with positive reactions (4.1%), there were 155 AC or PA reactions to allergens in the photopatch test series. Eighty PA reactions were observed in 62 (2.3%) patients (32 men and 30 women, age range 28-75 years), with UV filters accounting for 52 positive reactions (65%), drugs 16 (20%), musk ambrette 11 (14%) and the antiseptic trichlorocarbanilide one (1%). The most common UV filter photoallergen was benzophenone-3 with 14 positive results, followed by benzophenone-10 (n = 9), isopropyl dibenzoylmethane (n = 6), p-aminobenzoic acid (PABA) (n = 5), octyl dimethyl PABA (n = 5), butyl methoxydibenzoylmethane (n = 4), isoamyl methoxycinnamate (n = 2), ethyl methoxycinnamate (n = 2), octyl methoxycinnamate (n = 2), amyl dimethyl PABA (n = 2) and phenylbenzimidazole sulphonic acid (n = 1). A similar number of AC reactions to UV filters was detected in this study. Thus 49 patients (1.8%) had a total of 75 reactions: 51 due to UV filters and 24 as a result of exposure to fragrances and therapeutic agents. Benzophenone-10 accounted for 13 AC reactions and benzophenone-3 for eight reactions. Twenty-two patients had a PA reaction alone, whereas 19 patients had chronic actinic dermatitis and 15 patients polymorphic light eruption (PLE) in addition. Thus, 34 of the 62 patients (55%) had a preceding underlying photodermatosis. CONCLUSIONS: These results show a low yield of positive photopatch tests. Thus, despite the large increase in the use of UV filters over the last decade, the development of PA reactions remains rare. Furthermore, most of the common UV filter photoallergens identified in this study, including PABA, amyl dimethyl PABA and benzophenone-10, are now rarely used in sunscreen manufacture, while isopropyl dibenzoylmethane was voluntarily removed from the market in 1993. Currently, benzophenone-3 is the commonest contact photoallergen still in widespread use. In contrast, the UVB filter octyl methoxycinnamate, used in a number of sunscreens, produced only two positive PA reactions in 12 years of testing. Nevertheless, although these reactions are extremely rare, patients with photodermatoses such as PLE and chronic actinic dermatitis do represent a group of patients at increased risk of developing photoallergy. Further photopatch test series should be regularly reviewed and updated, as the relevance of individual photoallergens changes over time. Currently, there is no evidence that PA reactions represent a common clinical problem.

Adult↗
PubMed2001

Tumour necrosis factor alpha promoter polymorphism at position -308 is not associated with actinic prurigo.

Actinic prurigo (AP) has been found to be strongly associated with HLA DR4 and in particular with the DR4 subtype DRB1*0407. However, AP may occur in the absence of HLA-DR4. Furthermore, it has been shown that HLA-DR4 and DRB1*0407, even in association with polymorphic light eruption (PLE), are insufficient for the expression of the AP phenotype. It seems likely, therefore, that other genes in the HLA DR or adjacent regions may contribute to AP susceptibility. One possible predisposing factor in AP may be tumour necrosis factor (TNF)alpha as suggested by the good response of AP to the TNFalpha inhibitor thalidomide, and by the involvement of this cytokine in many immune responses. The aim of this study was to explore the relationship between AP and TNFalpha by examining the frequency of TNF2 in patients with AP, PLE and in normal controls. TNF1 and TNF2 are biallelic polymorphisms at position -308 of the TNFalpha gene promoter and are known to affect transcription of TNFalpha. TNF2 is the rarer of the two alleles and is associated with high functional levels of TNFalpha. This study confirms the positive linkage disequilibrium that has been described between HLA DR3 and TNF2, but fails to show an association between TNF2 and AP.

Case-Control Studies↗
PubMed2001

Ultraviolet therapy in lupus.

This review examines the use of ultraviolet (UV) therapy in lupus erythematosus (LE), a disorder usually associated with abnormally increased photosensitivity. In addition to the abnormal cutaneous response to ultraviolet radiation (UVR) exposure, photo-aggravation of systemic disease activity in systemic LE (SLE) may also occur. However, courses of UVR exposure may also be used in the treatment or prophylaxis of various photodermatoses, and LE now appears to be included in that group. Thus, several studies have reported apparent benefits of phototherapy in both cutaneous and systemic LE, although the underlying mechanisms remain obscure and final confirmation of such efficacy is still awaited in continuing studies.

Humans↗
PubMed2001

Polymorphic light eruption and the HLA DRB1*0301 extended haplotype are independent risk factors for cutaneous lupus erythematosus.

Recent evidence suggests that polymorphic light eruption (PLE) is an inherited photosensitivity disorder which may predispose to cutaneous lupus erythematosus (LE). In this study we examine the relative risk (RR) attributable to the presence of PLE, together with the effect of the major histocompatibility complex (MHC) in the development of cutaneous LE. Eighty-five Caucasian patients with annular subacute cutaneous LE (SCLE) and discoid LE (DLE) were recruited, together with 102 first degree relatives and 200 healthy local Caucasian controls. Symptoms suggestive of PLE were elicited in patients and relatives, and human leukocyte antigen (HLA) typing determined by PCR-SSP. Standard association analysis and family transmission disequilibrium testing (TDT) were then used to compare the HLA frequencies between groups. We found a significant (P < 0.05) association of the HL4 A*01, B*08, DRB1*0301 extended haplotype with both SCLE and DLE and also significant association of DLE with the HLA A*03, B*07, DRB1*15 haplotype, with a possible protective effect in SCLE for HLA B*44 and DRB1*04 (P=0.002 and 0.001 respectively). Association was observed between PLE and cutaneous LE (P < 0.001), but not between PLE and any HLA allele. From these figures we estimate, for the general population, that the RR of developing SCLE given the presence of (a) PLE, (b) DRB1*0301 and (c) both PLE and DRB1*0301 is 3.37, 5.45 and 12.03, respectively. For DLE, equivalent RRs are 3.11, 2.15 and 6.94. In conclusion, these data imply the involvement of both PLE and HLA DRB1*0301 in the development of SCLE and DLE. They form a basis for examining the genetic architecture of photosensitivity, some aspects of which may be common to both cutaneous LE and PLE.

Alleles↗
PubMed2000

Guidelines for topical PUVA: a report of a workshop of the British photodermatology group.

Psoralen photochemotherapy [psoralen ultraviolet A (PUVA)] plays an important part in dermatological therapeutics, being an effective and generally safe treatment for psoriasis and other dermatoses. In order to maintain optimal efficacy and safety, guidelines concerning best practice should be available to operators and supervisors. The British Photodermatology Group (BPG) have previously published recommendations on PUVA, including UVA dosimetry and calibration, patient pretreatment assessment, indications and contraindications, and the management of adverse reactions.1 While most current knowledge relates to oral PUVA, the use of topical PUVA regimens is also popular and presents a number of questions peculiar to this modality, including the choice of psoralen, formulation, method of application, optimal timing of treatment, UVA regimens and relative benefits or risks as compared with oral PUVA. Bath PUVA, i.e. generalized immersion, is the most frequently used modality of topical treatment, practised by about 100 centres in the U.K., while other topical preparations tend to be used for localized diseases such as those affecting the hands and feet. This paper is the product of a recent workshop of the BPG and includes guidelines for bath, local immersion and other topical PUVA. These recommendations are based, where possible, on the results of controlled studies, or otherwise on the consensus view on current practice.

Administration, Oral↗
PubMed2000

Efficacy of short-course oral prednisolone in polymorphic light eruption: a randomized controlled trial.

BACKGROUND: Polymorphic light eruption (PLE) is the most common so-called idiopathic photosensitivity disorder and affects up to 15% of the population in the U.K.; brief courses of systemic steroids have been tried and anecdotally have apparently been dramatically effective in the treatment of acute attacks. OBJECTIVES: To assess the efficacy and safety of a short course of moderate-dose oral prednisolone used from the earliest onset of the eruption in the treatment of PLE. METHODS: The study was double-blind placebo-controlled, all patients being given both prednisolone and placebo, but randomized to take either one or the other from the earliest sign of onset of rash; if within 48 h there was no improvement, they transferred to the other medication. Each participant also applied a broad-spectrum, highly protective sunscreen 2-hourly during sun exposure, continued his or her usual degree of exposure after any development of PLE, and kept a diary noting details of the eruption, amount of exposure, weather conditions and any adverse events. Statistical analysis was performed by means of the non-parametric log rank test based on Kaplan-Meier plots and bootstrapped confidence intervals (CIs) for the means, using the time in days for the itch and rash to clear as the end-points. RESULTS: Twenty-one patients entered the study but only 10 required medication. Eight who took prednisolone first and remained on it or transferred to it from placebo all improved, with the itch settling fully within a mean 2.8 days of starting the prednisolone and the rash clearing by 4.2. In the two who took placebo first and remained on it, the itch took a mean 5.4 days to settle and the rash a mean 7.8. No patient who started with prednisolone changed to placebo. Thus, the prednisolone as randomized was better than placebo at settling both the itch (mean 2. 6 days less, CI 0.7-4.0, P = 0.015) and rash (mean 3.6 days less, CI 0.6-6.1, P = 0.036); only one patient experienced mild adverse effects of transient gastrointestinal upset and depressed mood. CONCLUSIONS: The acute eruption of PLE is likely to respond rapidly to short courses of prednisolone therapy given from the earliest onset of the condition, and the treatment is safe.

Acute Disease↗
PubMed2000

An unusual case of purpuric erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is the most common of the erythropoietic porphyrias. Recent advances in diagnostic laboratory tests have led to the discovery of a number of previously undiagnosed cases. We describe a case of EPP presenting late with a purpuric eruption and discuss the pathogenesis and significance of purpura in EPP.

Child↗
PubMed2000

Genetic modeling of abnormal photosensitivity in families with polymorphic light eruption and actinic prurigo.

Actinic prurigo and polymorphic light eruption are two of the so-called idiopathic photodermatoses, resulting from abnormal cutaneous responses to ultraviolet radiation (photosensitivity). Whereas they are clinically distinct in most cases, there are sufficient similarities between them to suggest they may be related conditions. To take this further, we examined the prevalence of polymorphic light eruption in families ascertained through actinic prurigo probands, as evidence of a shared pathogenesis. We then determined the heritability of photosensitivity in 420 individuals from families ascertained through polymorphic light eruption and actinic prurigo probands using segregation analysis. Across 58 pedigrees the prevalence of photosensitivity in first-degree relatives was 20.9% compared with a population prevalence of 13.6%, giving a relative risk of 1.5 (confidence interval 1.15-2.0) and providing evidence of clustering within families. The prevalence of photosensitivity (predominantly polymorphic light eruption) in relatives of actinic prurigo probands was 23.7%, with a relative risk of 1.74 (confidence interval 1.24-2.36). Modeling for polymorphic light eruption across all pedigrees revealed a strong genetic component with polymorphic light eruption showing a dominant mixed mode of inheritance. The model parameters estimate that 72% of the U.K. population carry a low penetrance polymorphic light eruption susceptibility allele, but that among this highly prevalent genotype only 24% of susceptible females and 13% of susceptible males will have polymorphic light eruption. Expression of polymorphic light eruption in genetically susceptible individuals (intergenotype variance) is determined in large part by a polygenic component, with an important additional environmental component. In summary, this study provides clear evidence that polymorphic light eruption is an inherited condition. It also suggests that polymorphic light eruption and actinic prurigo share a common genetic background, supporting the view that actinic prurigo may represent a human leukocyte antigen-restricted subset of polymorphic light eruption.

Family Health↗
PubMed2000

Photosensitivity in lupus.

A wide variety of skin conditions may present in patients with lupus erythematosus (LE). These can be broadly divided into three main groups: cutaneous forms of LE ('LE-specific skin disease'), non-specific cutaneous manifestations of SLE ('LE non-specific skin disease') and cutaneous complications of drug treatments for LE. This review examines clinical photosensitivity in LE, a trait most commonly associated with cutaneous forms of LE but which may also manifest in SLE. All humans are photosensitive, developing reddening of the skin if exposed to sufficient ultraviolet radiation (UVR). Therefore we define photosensitivity in clinical practice as an abnormal cutaneous response to UVR. Abnormal photosensitivity in LE may manifest in a number of different forms. The lesions of LE-specific skin disease may be induced or exacerbated by UVR. Patients with LE who are prescribed photosensitizing medications such as thiazide diuretics, neuroleptics and tetracyclines may also develop phototoxic reactions which usually present as easy sunburn. Photosensitivity may also, rarely, manifest as fragile skin and blistering in patients with both LE and porphyria cutanea tarda. Several other photosensitive disorders have been reported in association with LE, including solar urticaria and erythropoetic protoporphyria (EPP), but these appear to be chance associations. Assessment of patients with LE and photosensitivity requires a careful history and examination. Phototesting and photoprovocation tests may be used to demonstrate photosensitivity in some cases, but these are rarely required for diagnosis. Photosensitive patients should be advised about sun avoidance, photoprotection and sunscreen use as a first line treatment.

Humans↗