Ultraviolet A1 phototherapy: a British Photodermatology Group workshop report.

Whole-body ultraviolet (UV)A1 (340-400 nm) phototherapy was first introduced 30 years ago, but is currently available in the UK in only three dermatology departments. A workshop to discuss UVA1 was held by the British Photodermatology Group in May 2009, the aim of which was to provide an overview of UVA1 phototherapy and its role in practice, and to identify areas in which further studies are required. The conclusions were that UVA1 phototherapy is an effective treatment in several inflammatory skin diseases, including localized scleroderma and atopic eczema (AE); however, deficiencies and limitations exist in the published evidence base. For most diseases, such as AE, other treatments also exist, which are generally more effective than UVA1. However, for some diseases, particularly morphoea, the evidence of efficacy is stronger for UVA1 than for other treatments. Acute adverse effects of UVA1 are minimal. The risk of long-term adverse effects, particularly skin cancer, is unknown. Medium to high doses of UVA1 are needed for efficacy in most situations, but the equipment to deliver such doses is large, expensive and difficult to install. UVA1 is currently underprovided, and the recommendation of the workshop is that more tertiary centres should have access to UVA1 phototherapy in the UK.

Cutaneous manifestations of tuberculosis.

Cutaneous involvement is a rare manifestation of tuberculosis (TB). The correct diagnosis is often significantly delayed because cutaneous TB is not routinely considered in the differential diagnosis or because investigations fail to reveal the presence of Mycobacterium tuberculosis. The clinical features of cutaneous TB are diverse, and result from exogenous and endogenous spread of M. tuberculosis and from immune-mediated mechanisms. The recognition of cutaneous TB is important, as the diagnosis is frequently overlooked resulting in delayed treatment.

Persistent severe amiodarone-induced photosensitivity.

Amiodarone, a benzofuran derivative, has been used therapeutically as an antiarrhythmic and coronary vasodilator in Europe since 1964. One of its commoner side effects is cutaneous photosensitivity; more rarely, after ingestion of the drug for around 12 months, a slate-grey or violaceous discoloration of sun-exposed sites may gradually develop. Both of these side effects usually resolve within 2 years of discontinuation of the drug. We now present a woman who developed both photosensitivity and a slate-grey discoloration whilst taking amiodarone; on discontinuation of the drug, the dyspigmentation gradually resolved, but the photosensitivity has persisted and the patient remains symptomatic more than 17 years later.

Fish odour syndrome with features of both primary and secondary trimethylaminuria.

We report a patient with the fish odour syndrome who has both primary and secondary trimethylaminuria. The diagnosis was made using biochemical and genetic analysis in the apparent absence of any characteristic smell. Differentiation of primary and secondary trimethylaminuria is usually made on urinary analysis of trimethylamine and its metabolite trimethylamine N-oxide, with different, characteristic patterns of both compounds in primary and secondary trimethylaminuria. Our patient had biochemical analysis consistent with a diagnosis of secondary trimethylaminuria, while analysis of the flavin-containing mono-oxygenase 3 gene, the causative gene in primary trimethylaminuria, demonstrated three sequence polymorphisms, two of which are known to reduce enzyme activity. The patient showed temporary clinical and biochemical response to treatment with metronidazole and neomycin. It is important to be aware of this diagnosis in patients without obvious clinical signs, and of the subjective benefits of treatment.

Guidelines for dosimetry and calibration in ultraviolet radiation therapy: a report of a British Photodermatology Group workshop.

This report examines the dosimetry of ultraviolet (UV) radiation applied to dermatological treatments, and considers the definition of the radiation quantities and their measurement. Guidelines are offered for preferred measurement techniques and standard methods of dosimetry. The recommendations have been graded according to the American Joint Committee on Cancer classification of strength of recommendation and quality of evidence (summarized in Appendix 5).

Sequence variations in the flavin-containing mono-oxygenase 3 gene (FMO3) in fish odour syndrome.

Trimethylaminuria is inherited recessively as a defect in hepatic N-oxidation of dietary derived trimethylamine (TMA) which causes excess excretion of TMA so that affected individuals have a body odour resembling rotten fish. Flavin-containing mono-oxygenase 3 (FMO3) catalyses TMA oxidation and mutations in the FMO3 gene have recently been shown to underlie trimethylaminuria/fish odour syndrome. We searched for FMO3 mutations in a previously unreported individual with this disorder using polymerase chain reaction of genomic DNA, heteroduplex analysis and direct sequencing of heteroduplex band shifts. We identified a heterozygous missense Pro153-->Leu153 mutation in exon 4. Leu153 has been reported previously as a homozygous mutation in two unrelated siblings with trimethylaminuria and has been shown to result in total loss of FMO3 enzyme activity. In our patient, two further missense mutations were identified on the other FMO3 allele, Val143-->Glu143 and Glu158-->Lys158. Lys158 is known to be a common polymorphism, but has functional significance in reducing enzyme activity by 10%. Glu143 has not been documented previously, but was shown to be a rare polymorphism and may be of further relevance in reducing FMO3 activity. Mutagenesis studies and enzyme assays will be necessary to confirm or refute the potential pathogenic significance of Glu143 in this patient, but the mutation Pro153-->Leu153 appears to be a recurrent cause of this distressing metabolic disorder.

Sesquiterpene lactone mix contact sensitivity and its relationship to chronic actinic dermatitis: a follow-up study.

In a retrospective case note analysis over a 4-year period, 0.9% of all patients tested with a standard patch test series (65 of 7600) were demonstrated to have clinically relevant responses to a sesquiterpene lactone (SQL) mix. Of these patients, 11 (17%) also had a diagnosis of chronic actinic dermatitis. This group made up 25% of all patients diagnosed as suffering from CAD in this 4-year period. These figures differ somewhat from those reported by our group in an initial 4-year period immediately following the introduction of the mix into our standard patch test series, when 1.5% of all patients tested had a clinically relevant response to the SQL mix, including 36% of all patients with a diagnosis of CAD. It is not uncommon for the prevalence of sensitivity to an allergen to be overestimated immediately following its introduction into routine testing. Possible reasons for our findings are discussed.

Endobronchial involvement in a patient presenting with cutaneous sarcoid.

Half of all patients with cutaneous sarcoidosis will develop pulmonary disease. We report a case of cutaneous and endobronchial sarcoidosis and describe a scheme for identifying pulmonary involvement in patients with cutaneous sarcoid.

A study of the kinetics and pattern of E-selectin, VCAM-1 and ICAM-1 expression in chronic actinic dermatitis.

It has been postulated that chronic actinic dermatitis (CAD), an eczematous photodermatosis, is a type IV hypersensitivity reaction. Expression of adhesion molecules on dermal blood vessels is critical to the recruitment of inflammatory cells into the skin; the pattern and kinetics of upregulation of these molecules in the skin differ following ultraviolet irradiation and delayed hypersensitivity reactions. We therefore investigated the kinetics of expression of endothelial leucocyte adhesion molecules (E-selectin) vascular-cell adhesion molecules 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) in CAD lesions induced by suberythemal solar-stimulated radiation, by immunohistochemical staining of biopsies taken at 1-168 h after irradiation. In control, unirradiated skin from CAD patients, baseline vessel-associated and interstitial ICAM-1, and vessel-associated VCAM-1 were noted; focal keratinocyte ICAM-1 expression was observed in two of the five patients. Endothelial E-selectin, and vessel-associated and interstitial VCAM-1 expression, were upregulated in induced lesions by 1-5 h in all patients, and remained elevated at 120-168 h. Vessel associated, dermal interstitial, and keratinocyte ICAM-1 expression was upregulated in all patients at 24 h, and remained increased at 120-168 h. These findings differ from those observed following ultraviolet irradiation of normal skin, and resemble those seen in normal skin during a delayed-type hypersensitivity reaction, supporting the hypothesis that CAD involves a type IV response to an as yet unidentified photo-induced antigen.

The action spectrum for induction of chronic actinic dermatitis is similar to that for sunburn inflammation.

The action spectrum for induction of the abnormal cutaneous response at 24 h in the photosensitivity disorder chronic actinic dermatitis (CAD) was determined in 15 patients and found to be the same in shape as that for normal sunburn in fair-skinned individuals at 24 h, as determined for 47 control volunteers, although displaced in magnitude. This suggests that an endogenous chromophore(s), the same as or similar to that/those responsible for human sunburn, may be responsible for initiation of the abnormal reaction to irradiation in CAD, and that the putative antigen associated with the CAD reaction may be derived from that/those or associated molecules.