C. J. Fleming

The genetics of allergic contact hypersensitivity to nickel

We have examined evidence for familial disposition to nickel allergic contact dermatitis (Ni ACD). 258 patients attending for routine patch testing were recruited prospectively. 39 patients were diagnosed with Ni ACD. 31 of 209 1st‐degree relatives (15%) of probands had a history of nickel hypersensitivity. 84 patients with no history of nickel hypersensitivity and negative patch tests to nickel were used as controls. 24 of 458 1st degree relatives of controls (5.2%) had a history of Ni ACD. The risk ratio for 1st degree relatives of a patient with Ni ACD is 2.83 (95% condence intervals are 2.45, 3.27). This is the 1st study to present a statistic to represent risk to relatives of developing ACD. Relatives of patients with Ni ACD have an increased risk of developing the condition, but the genetic basis for this is not yet known. With currently available techniques, this value of relative risk makes a positional cloning approach to gene identication impractical.

Reactive perforating collagenosis associated with underlying malignancy

Sir, We read with interest the recent report by Cox et al. on the association of atopic dermatitis with the beta subunit of the high-affinity IgE receptor (Fc1RI-b). The gene was originally identified as a candidate for atopy on human chromosome 11q. Fc1RI-b has been shown to be involved in the amplification of Fc1RI-mediated signalling that might be related to the pathogenesis of atopic disease. Because of the predominantly maternal transmission of atopy, it has been strongly suggested that the gene for Fc1RI-b may show a parent-of-origin effect such as genomic imprinting. One previous report consistent with this notion showed maternal transmission of the I181L allele in a British population, while another showed no parent-of-origin effect of the transmission of the E237G allele in an Australian population. The report by Cox et al. again raises this issue by demonstrating exclusive maternal transmission of Fc1RI-b alleles to offspring with atopic dermatitis. None the less, as far as we know, there has been no direct test of possible allele-specific expression of this gene. To study the possible involvement of a genomic imprinting mechanism, we have used the widely applicable mouse model system. We find, as detailed below, that the Fc1RI-b gene shows no parent-of-origin-specific expression, using F1 hybrids between a laboratory mouse strain (C57BL/6J) and wild mouse strains [either Mus musculus molossinus (MOLF/Ei) or M. spretus (SPRET/Ei)]. The parental mouse strains (C57BL/6J, MOLF/Ei, SPRET/ Ei) were purchased from Jackson Laboratory (Bar Harbor, ME, U.S.A.). Cloning, sequencing, total RNA extraction and reverse transcription±polymerase chain reaction (PCR) analysis of Fc1RI-b were done as described previously. Based on a human genomic DNA sequence (GenBank M89796) and a mouse cDNA sequence (GenBank J05019), we designed a PCR primer pair spanning exon 6, intron 6 and exon 7 of the Fc1RI-b gene, so that an intron could be included in the PCR target. This allowed us to measure the gene expression directly, without interference by possible contamination of genomic DNAs in RNA samples. Sequence polymorphisms among C57BL/6J, MOLF/Ei and SPRET/Ei were identified by sequencing PCR products from each strain (deposited in GenBank; accession numbers U90217±U90219). A 395-base pair (bp) fragment of the gene for Fc1RI-b was amplified from cDNAs with primers up6: 5 0-ATCCTGGCCTTTTGCAGTGC-3 0 and dn10: 5 0-TGTATGTGAAATTGTGACAC-3 0. To obtain enough DNA for analyses, a shorter fragment (361 bp) was reamplified from the PCR products with primers up6 and dn4: 5 0-GGAGTGAATGATATCCGCAA-3 0. Allele-specific expression in reciprocal crosses between C57BL/6J and MOLF/Ei was examined by using a Sau3AI restriction fragment length polymorphism (RFLP) in a 361-bp PCR product (Fig. 1A). For RFLP analysis, 3 mL of unpurified PCR products were digested with 5 U of Sau3AI in a 15-mL reaction mixture at 37 8C for 3 h, then electrophoresed in a 12% polyacrylamide gel. The gel was stained by ethidium bromide and photographed under ultraviolet radiation. Both paternally and maternally derived alleles were expressed in all examined tissues, i.e. embryo, placenta and yolk sac at 14 ́5 days postconception, whole body and skin at the newborn stage (Fig. 1B), and spleen, lung and colon in adults (not shown). The data clearly demonstrate the biallelic expression of the gene for Fc1RI-b. To confirm these data, interspecific hybrids between a laboratory mouse strain and M. spretus were used. In these crosses, the C57BL/6J-specific allele (296 bp) can be distinguished from the SPRET/Ei-specific allele (279 bp) by length

A controlled study of gold contact hypersensitivity

1203 patients attending for routine patch testing at 3 hospitals and 105 volunteers were tested with 0.5% and 0.05% gold sodium thiosulfate (GST). 38 patients (3.2%) and 5 volunteers (4.8%) had positive patch tests to GST. There were no significant differences between volunteers and patients with respect to age, sex, atopy or exposure to gold in dental restorations, jewellery or through occupation. There were no significant differences in prevalence of GST hypersensitivity in the 3 hospitals, or between patients and controls. This is the 1st controlled study of hypersensitivity to GST, and suggests that routine patch testing to gold is of limited clinical benefit.

Patch testing in discoid eczema

We report a retrospective study of patch testing in patients with discoid eczema. 48 patients with persistent or severe discoid eczema were patch tested. The mean age of patients was 45 years and the median duration of symptoms was 6 months. 24 patients (50%) had positive patch tests, and 16 of these (33%) were considered to be clinically relevant. The most common allergens implicated were rubber chemicals, formaldehyde, neomycin, chrome, nickel (5, 2, 2, 2, 2, 2 reactions, respectively). 13 of 16 patients were followed up by telephone in 1996, and 8/13 (61%) slated they had benefited from patch testing. This study suggests allergic contact dermatitis is relatively common in persistent discoid eczema, and allergen avoidance may be of benefit. We recommend patch testing should be considered for all patients with severe or persistent discoid eczema.

Patch testing in vulval dermatoses: how relevant is nickel?

Between 1992 and 1997, 55 women with vulval dermatoses were patch tested to the European standard series, a vulval series and other relevant allergens. The principal symptom was pruritus in 49 patients and pain or burning in 6. The mean duration of symptoms was 4.4 years (range 0.75 to 15 years) and the mean age was 50.3 years (range 14 to 78 years). Table 1 shows the clinical diagnosis prior to patch testing. Relevance of positive reactions was assessed with a follow-up questionnaire.

Survey of patch testing in Scotland.

We have surveyed Scottish dermatologists to establish the extent of patch testing, to assess the reasons for referral and to document resources and methods used by dermatologists. 104 questionnaires were sent to members of the Scottish Dermatological Society. 82 questionnaires (79%) were returned. 50% of respondents were consultants, 27% were trainees and 23% held staff grade or clinical assistant positions. The mean waiting time for a patch test appointment was 4.5 months. The most frequent reasons for patch testing were localized eczema, eczema not responding to conventional treatment, occupational eczema, history of contact sensitivity and eczema of uncertain cause. 17 of 82 respondents (21%) were the principal clinicians supervising patch testing in their hospitals. 11 of 17 read reactions at 2 and 4 days. Mean time spent on advising patients was 13 min per patients. 7 of 17 were dissatisfied with resources available for patient education and 16 of 17 felt they would benefit from a central source for patient information. Only 4 of 17 centres recorded patch test results on a database and 3 centres regularly reviewed their patch test results. In conclusion, we have identified areas of patch testing that require further improvement.