Skin cancer excision performance in Scottish primary and secondary care: a retrospective analysis.

BACKGROUND: In contrast with most published evidence, studies from north-east Scotland suggest that GPs may be as good at treating skin cancers in primary care as secondary care specialists. AIM: To compare the quality of skin cancer excisions of GPs and secondary care skin specialists in east and south-east Scotland. DESIGN AND SETTING: A retrospective analysis of reports from GPs in Lothian, Fife, and Tayside regions. METHOD: Skin cancer histopathology reports from GPs in Lothian, Fife, and Tayside regions in 2010 were compared with reports from skin specialists in November 2010. The histopathology reports were rated for completeness and adequacy of excision. RESULTS: A total of 944 histopathology reports were analysed. In 1 year, GPs biopsied or excised 380 skin cancers. In 1 month, dermatologists biopsied or excised 385 skin cancers, and plastic surgeons 179 skin cancers. 'High risk' basal cell carcinomas (BCC) comprised 63.0% of BCC excised by GPs. For all skin cancer types, GPs excised smaller lesions, and had a lower rate of complete excisions compared with skin specialists. A statistical difference was demonstrated for BCC excisions only. CONCLUSION: GPs in east and south-east Scotland excise a number of skin cancers including malignant melanoma (MM), squamous cell carcinoma (SCC) and high-risk BCC. Despite removing smaller lesions, less commonly on difficult surgical sites of the head and neck, GP excision rates are lower for all skin cancers, and statistically inferior for BCC, compared with secondary care, supporting the development of guidelines in Scotland similar to those in other UK regions. Poorer GP excision rates may have serious consequences for patients with high-risk lesions.

GPs have role in early detection of melanoma.

Melanoma is rare in childhood, but from the teens onwards, the incidence steadily rises with age. Exposure to ultraviolet light radiation is the main risk factor for developing melanoma. The first sign of a melanoma is usually an unusual looking freckle or mole. It may have a variety of colours including tan, dark brown, black, blue, red, light grey, or occasionally may lack pigment. Some melanomas are itchy or tender, and more advanced lesions may bleed easily or crust over. The British Association of Dermatologists suggests referring: a new mole appearing after the onset of puberty, or a long-standing mole, which is changing shape, colour or size; any mole which has three or more colours or has lost its symmetry; a mole which is itching or bleeding; or any new persistent skin lesion especially if it is growing, pigmented or vascular in appearance, and if the diagnosis is not clear. A new pigmented line in a nail, especially where there is associated damage to the nail, or a lesion growing under a nail should also be referred. Lesions which have a high index of suspicion for melanoma should not be removed in primary care. Patients should be referred urgently to secondary care with a history recording the duration of the lesion, change in size, colour, shape and symptoms.

Seasonal palmar keratoderma in erythropoietic protoporphyria indicates autosomal recessive inheritance.

Erythropoietic protoporphyria (EPP) is an inherited disorder that results from partial deficiency of ferrochelatase (FECH). It is characterized clinically by acute photosensitivity and, in 2% of patients, liver disease. Inheritance is usually autosomal dominant with low penetrance but is recessive in about 4% of families. A cross-sectional study of 223 patients with EPP in the United Kingdom identified six individuals with palmar keratoderma. We now show that these and three additional patients, from six families, have an inherited subtype of EPP which is characterized by seasonal palmar keratoderma, relatively low erythrocyte protoporphyrin concentrations, and recessive inheritance. No patient had evidence of liver dysfunction; four patients had neurological abnormalities. Patients were hetero- or homoallelic for nine different FECH mutations; four of which were previously unreported. Prokaryotic expression predicted that FECH activities were 2.7-25% (mean 10.6%) of normal. Neither mutation type nor FECH activity provided an explanation for the unusual phenotype. Our findings show that palmar keratoderma is a clinical indicator of recessive EPP, identify a phenotype that occurs in 38% of reported families with recessive EPP that to our knowledge is previously unreported, and suggest that patients with this phenotype may carry a lower risk of liver disease than other patients with recessive EPP.

C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload.

All reported mutations in ALAS2, which encodes the rate-regulating enzyme of erythroid heme biosynthesis, cause X-linked sideroblastic anemia. We describe eight families with ALAS2 deletions, either c.1706-1709 delAGTG (p.E569GfsX24) or c.1699-1700 delAT (p.M567EfsX2), resulting in frameshifts that lead to replacement or deletion of the 19-20 C-terminal residues of the enzyme. Prokaryotic expression studies show that both mutations markedly increase ALAS2 activity. These gain-of-function mutations cause a previously unrecognized form of porphyria, X-linked dominant protoporphyria, characterized biochemically by a high proportion of zinc-protoporphyrin in erythrocytes, in which a mismatch between protoporphyrin production and the heme requirement of differentiating erythroid cells leads to overproduction of protoporphyrin in amounts sufficient to cause photosensitivity and liver disease.

Erythropoiesis and iron metabolism in dominant erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) results from deficiency of ferrochelatase (FECH). Accumulation of protoporphyrin IX causes life-long acute photosensitivity. Microcytic anemia occurs in 20% to 60% of patients. We investigated 178 patients with dominant EPP confirmed by molecular analysis. Erythropoiesis was impaired in all patients; all had a downward shift in hemoglobin (Hb), and the mean decreased in males by 12 g/L (1.2 g/dL). By World Health Organization criteria, 48% of women and 33% of men were anemic. Iron stores, assessed by serum ferritin (sFn), were decreased by two-thirds, but normal serum soluble transferrin receptor-1 and iron concentrations suggested that erythropoiesis was not limited by iron supply. FECH deficiency in EPP appears to lead to a steady state in which decreased erythropoiesis is matched by reduced iron absorption and supply. This response may in part be mediated by protoporphyrin, but we found no correlation between erythrocyte protoporphyrin and Hb, sFn, total iron-binding capacity, or transferrin saturation.

Gene dosage analysis identifies large deletions of the FECH gene in 10% of families with erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is an inherited cutaneous porphyria characterized by partial deficiency of ferrochelatase (FECH), accumulation of protoporphyrin IX in erythrocytes, skin, and liver, and acute photosensitivity. Genetic counseling in EPP requires identification of FECH mutations, but current sequencing-based procedures fail to detect mutations in about one in six families. We have used gene dosage analysis by quantitative PCR to identify large deletions of the FECH gene in 19 (58%) of 33 unrelated UK patients with EPP in whom mutations could not be detected by sequencing. Seven deletions were identified, six of which were previously unreported. Breakpoints were identified for six deletions (c.1-7887-IVS1+2425insTTCA; c.1-9629-IVS1+2437; IVS2-1987-IVS4+352del; c.768-IVS7+244del; IVS7+2784-IVS9+108del; IVS6+2350-TGA+95del). Five breakpoints were in intronic repeat sequences (AluSc, AluSq, AluSx, L1MC4). The remaining deletion (Del Ex3-4) is likely to be a large insertion-deletion. Combining quantitative PCR with routine sequencing increased the sensitivity of mutation detection in 189 unrelated UK patients with EPP from 83% (95% CI: 76-87%) to 93% (CI: 88-96%) (P=0.003). Our findings show that large deletions of the FECH gene are an important cause of EPP. Gene dosage analysis should be incorporated into routine procedures for mutation detection in EPP.

Toilet seat contact dermatitis.

Allergic contact dermatitis to wooden toilet seats was a previously well-recognized pattern of regional dermatitis. We report a recent occurrence in a child that highlights a possible resurgence in this presentation, associated with the increasing popularity of wooden toilet seats.