Characterization of photosensitivity in the Smith-Lemli-Opitz syndrome: a new congenital photosensitivity syndrome

Photosensitivity has recently been reported as a feature of the Smith-Lemli-Opitz syndrome (SLO). The aim of this study was to establish the photobiological features of this disorder and to examine the hypothesis that the photosensitivity is caused by the high levels of 7-dehydrocholesterol found in SLO. All known cases of SLO in the U.K. were reviewed and clinical details of photosensitivity were recorded in detail. The action spectrum of the photosensitive eruption was defined by monochromator light testing. Thirteen of the 23 subjects (57%) had severe photosensitivity, and in 10 there was no photosensitivity. No correlation was identified between levels of 7-dehydrocholesterol and severity of photosensitivity, suggesting that the photosensitivity in SLO is not caused by a direct phototoxic effect mediated by 7-dehydrocholesterol. A novel pattern of photosensitivity was observed, with onset of a sunburn-like erythema on sun-exposed skin within minutes of sun exposure, which persisted in most cases for up to 24-48 h before fading. Monochromator light testing in three subjects showed an ultraviolet (UV) A-mediated photosensitivity eruption with greatest photosensitivity at 350 nm. Photosensitivity is a common and prominent feature of SLO and appears to be UVA-mediated. Elucidation of its biochemical basis may provide insight into normal cutaneous protective mechanisms against UVA-induced photodamage, and also sun sensitivity in general.     

Cholesterol supplementation objectively reduces photosensitivity in the Smith-Lemli-Opitz syndrome

Smith-Lemli-Opitz (SLO) affected children have multiple congenital physical and mental abnormalities; photosensitivity to ultraviolet A (UVA) has recently become a recognized feature. We present a patient with SLO and prominent photosensitivity in whom detailed phototesting has been performed at baseline and following 6 months of cholesterol supplementation. There was significant improvement in the symptoms of photosensitivity, confirmed objectively by phototesting and accompanied by partial correction of the biochemical abnormalities seen in SLO. This case report is the first to show that cholesterol supplementation in SLO can lead to an objective improvement in the associated photosensitivity.     

Photosensitivity in the Smith-Lemli-Opitz syndrome: the US experience of a new congenital photosensitivity syndrome.

Photosensitivity has been briefly mentioned in several publications on the Smith-Lemli-Opitz (SLO) syndrome, an autosomal recessive mental retardation syndrome. We conducted a questionnaire-based survey to determine the incidence and main features of photosensitivity in SLO. We confirmed a high incidence, and initial evidence suggests that SLO may be the first example of an inherited photosensitivity disorder in which sensitivity to UVA is common.     

Is accurate UVA dosimetry in photobiology and photodermatology an illusion?

Accurate UVA dosimetry is of primary importance for photobiological research as well as for UVA phototherapy and photochemotherapy. For the former, it is necessary because the success or failure of an experiment can depend on the UVA dose, and for the latter, the carcinogenic risks are dependent upon the cumulative dosage, as is the evaluation of the therapy. Experience has shown that the UVA meters used in different photodermatological and photobiological centers give divergent values when exposed to the same UVA source. One Joule/cm2 does not seem to be the same thing everywhere, and it can vary by as much as 400 p. 100.     

Evidence and conjecture about mechanisms of cutaneous disease in photodermatology

Photosensitivity disorders are caused by a variety of mechanisms. Three common themes are as follows: excess chromophore allowing visible light energy to cause photodynamic damage, reduced DNA repair capacity to UV‐induced DNA damage, and enhanced sensitivity to light‐induced allergens mediated immunologically. Although the cause of each condition may be known, the precise pathogenesis underlying the photosensitivity has taken longer to understand. By focussing on three clinical disorders under each of these themes, we have explored the following: why erythropoietic protoporphyria differs so markedly from the other cutaneous porphyrias; how a DNA repair defect was eventually revealed to be the underlying cause of the vitamin B3 deficiency disorder of pellagra; an immunological explanation for the over reactivity to photoallergens in chronic actinic dermatitis.     

Electron paramagnetic resonance in dermatologic research with particular reference to photodermatology

The study of electron paramagnetic resonance (EPR) spectra in isolated skin cells, skin biopsies and the intact skin is the most direct approach to determining the existence, role and importance of ultraviolet-mediated generation of free radicals and other reactive oxygen species in dermatopathological processes. By means of spin labeling, the physicochemical properties of skin, such as membrane fluidity and polarity, can be analyzed. Spin probes can also be employed in measuring one-electron transfer reactions, and oxygen concentration in skin. EPR imaging is an emerging new technique and can be used to investigate the spatial distribution of all these parameters. The more widespread application of the EPR method in photodermatologic research will significantly contribute to improve understanding of biologic free radical processes.     

The hairless guinea pig as an experimental animal for photodermatology.

Photobiologic reactions to various modalities of ultraviolet light (UVL) irradiation were evaluated in the recently identified hairless guinea pig, Crl: IAF(HA)BR, a mutant from the Hartley strain. The cutaneous changes were observed macro- and microscopically. The animal developed similar but somewhat stronger reactions than the Hartley guinea pig to the UVB irradiation and topical and systemic PUVA treatments. The density of the epidermal Langerhans cell of the hairless guinea pig was significantly higher than that of the hairy strain. The photoallergic contact sensitization was easily induced by tetrachlorosalicylanilide. These results indicate that the hairless guinea pig can be used as an animal model for photobiologic and photoimmunologic investigations.     

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.     

Analysis of photodermatoses seen in a predominantly Asian population at a photodermatology clinic in Singapore

BACKGROUND: The idiopathic photodermatoses have been reported to be rarer in tropical Singapore than in countries of higher latitude, with photoaggravated dermatoses and systemic phototoxicity making up most of the photodermatoses seen here. This study aims to reassess the spectrum of photodermatoses seen at the National Skin Centre, Singapore, compared with almost a decade ago, and analyse the clinical and photobiological characteristics, as compared with other countries. MATERIALS AND METHODS: We reviewed the clinical data of 141 patients phototested from January 2000 to December 2001, and analysed the epidemiological, clinical and photobiological features. RESULTS: Photosensitive dermatoses were diagnosed in 88% (124/141) of patients phototested. In those diagnosed with photodermatoses, polymorphic light eruption (PMLE) (28%) was the most common diagnosis, followed by photoaggravated dermatoses (26%), chronic actinic dermatitis (CAD) (15%), systemic phototoxicity (15%), solar urticaria (SU) (7%), actinic prurigo (AP) (5%) and photoallergic contact dermatitis (4%). Ethnic Indians appeared to be more predisposed to PMLE; AP was diagnosed only in ethnic Chinese. The other photodermatoses occurred proportionally in all racial groups. AP differed from that found in Caucasians, being of adult onset and persistent. Abnormal phototest results were obtained in all patients with CAD, SU and AP, but only in 56% and 49% of systemic phototoxicity and PMLE, respectively. CONCLUSION: Idiopathic photodermatoses are more commonly diagnosed in Singapore than a decade ago, while the incidence of systemic phototoxicity has remained stable. The spectrum of photodermatoses in our Asian population now approximates that seen in Caucasian cohorts.     

Analysis of patients with suspected photosensitivity referred for investigation to an Australian photodermatology clinic

BACKGROUND: Australia's first dedicated photodermatology clinic was established at St Vincent's Hospital Melbourne in 1993. OBJECTIVE: We sought to review clinical diagnoses and results of investigations performed on patients seen at this institution. METHODS: A database was created to enable a retrospective and prospective analysis of all patients attending for evaluation of suspected photosensitivity from April 1993 to October 2000. RESULTS: A total of 513 patients were seen, 289 (56.3%) female and 224 (43.7%) male, with a mean age of 45.2 years (range: 2.6-85.9). A photosensitive disorder was diagnosed in 397 patients (77.4%), with the acquired idiopathic photodermatoses accounting for diagnoses in 215 (41.9%) of all patients seen. The most common diagnosis was polymorphous light eruption. Reduced minimal erythema doses were seen in 25.3% of all patients light tested. In those photopatch tested, 23.3% had at least 1 photocontact reaction. Allergic contact dermatitis in a photosensitive distribution was diagnosed in 7.4% of the clinic population. CONCLUSION: A large proportion of referrals to a photodermatology clinic comprise people with acquired idiopathic photodermatoses, with other common diagnoses that may mimic photosensitivity including allergic contact dermatitis, atopic dermatitis, and rosacea.     

Photosensitive Smith-Lemli-Opitz syndrome is not caused by a single gene mutation: analysis of the gene encoding 7-dehydrocholesterol reductase in five U.K. families

BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive malformation syndrome characterized by a disorder in cholesterol metabolism. SLOS is caused by mutations in the DHCR7 gene which encodes 7-dehydrocholesterol reductase, an enzyme that catalyses the final step in cholesterol biosynthesis. We have previously established the clinical and photobiological features of the photosensitivity that is frequently a feature of SLOS. OBJECTIVES: In this study, we have performed mutational analysis of the DHCR7 gene in individuals from five families with SLOS. In each family, one member was affected by severe photosensitivity as a manifestation of SLOS. METHODS: Fifteen samples (including family controls) were screened using polymerase chain reaction amplification and direct automated sequencing. RESULTS: Six different DHCR7 mutations were identified of which five were single point mutations that caused missense amino acid substitutions (P51H, T93M, L99P, E448K and R450L). The other was a splice site mutation (G-->C in splice acceptor site) affecting the intron 8-exon 9 splice junction (IVS8-1 G-->C). This splice site mutation and four of the five missense mutations have been previously published as causal in SLOS but the P51H is a novel mutation which has not previously been reported. CONCLUSIONS: This is the first study in which DHCR7 gene mutational analysis has been performed on SLOS subjects with severe photosensitivity and indicates that no single mutation is responsible for the photosensitivity which characterizes this disorder.     

Tinea Capitis in Birmingham: Survey of Elementary School Students

Abstract: Trichophyton tonsurans is currently the leading cause of tinea capitis, but was only introduced into the United States less than six decades ago. In this study, we found a prevalence of 11% in Birmingham, Alabama, which is similar to earlier reports from other geographic regions. Despite previous reports concerning escalation, the prevalence appears to be stable over the past decade.     

Trichothiodystrophy: PIBIDS syndrome

Trichothiodystrophy comprises a heterogeneous group of autosomal recessive entities. This fact gives rise to different interrelated neuroectodermal disorders. From a structural point of view these features are the result of the low tissue sulfur content. We report a case of trichothiodystrophy initially classified as Tay syndrome that based on clinical features, complementary exams as well as on the disease evolution was labelled as PIBIDS syndrome.