P.G. Norris

A study of the role of house dust mite in atopic dermatitis

Subjects with positive skin‐prick tests to house dust mite (HDM) solution, including those with and without atopic dermatitis, participated in a double‐blind, controlled study of the role of HDM exposure in the pathogenesis of atopic dermatitis. HDM solution and diluent control were applied daily to mildly eczematous or clinically uninvolved skin of the antecubital or popliteal fossae, without prior abrasion, for 5 days. Responses were assessed by a clinical grading system and by measurement of area of dermatitis; pruritus was recorded on visual analogue scales. The clinical grading system showed that marked or moderate delayed local reactions developed in one third of patients with atopic dermatitis in response to HDM application to both mildly eczematous and clinically uninvolved skin. Relative to control sites, significant increases in area of dermatitis and degree of pruritus were also recorded in response to HDM application to mildly eczematous sites. Application of HDM solution to normal, unabraded skin of prick test positive subjects without a history of dermatitis, produced pruritus and immediate urticarial responses which were not seen at control sites, findings which demonstrate that HDM antigen may be rapidly absorbed in normal skin. Application of vehicle or antigen solution to which subjects were negative on prick testing, produced no significant local reactions. This study provides objective evidence for a role for cutaneous HDM exposure in the pathogenesis of atopic dermatitis.

Polymorphic light eruption: prevalence in Australia and England

Summary The prevalence and clinical characteristics of polymorphic light eruption were assessed by a questionnaire survey of 172, 196 and 182 subjects in Perth, Ballarat and London, respectively. The prevalence was 5·2% in Perth (latitude 32°), 3·6% in Ballarat (37·5°) and 14·8% in London (51·5°). The age distribution (mostly first three decades) and male: female ratio (1:3) was similar for affected individuals in all three areas. Development of tolerance during the summer was more common in Perth (66·7%) and Ballarat (71·4%) than in London (40·7%).

Contact and photocontact sensitization in chronic actinic dermatitis: sesquiterpene lactone mix is an important allergen

Summary Eighty‐nine patients with chronic actinic dermatitis (CAD) were retrospectively studied: 69 (78%) male and 20 (22%) female, with mean ages of 66 and 64 years, respectively; nine (10%) were dark skinned. Eight (9%) were abnormally sensitive to UVB wavelengths alone, 74 (83%) to UVB and UVA, and seven (8%) to UVB, UVA and visible radiation. Eighty‐six patients were patch tested to an extended standard European series of contact allergens, including in 80 cases a 0.1% mix of three sesquiterpene lactones, and photopatch tested to a standard photopatch series. Sixty‐four of these 86 patients (74%) had positive patch or photopatch tests; 36% (29 of 80) were sensitive to the sesquiterpene lactone mix, 21% (18 of 86) to fragrance compounds, 20% (17 of 86) to colophony, and 14% (12 of 86) to rubber chemicals. Ten (12%) had positive photopatch tests; five (6%) to musk ambrette, six (7%) to sunscreens and one to both. Fourteen of the eighty‐nine patients with CAD (16%) had preceding endogenous eczema. In 18 of 86 patients (21%), CAD occurred alone, with neither detectable contact nor photocontact allergy, nor a preceding history of endogenous eczema. This study confirms the association between Compositae (sesquiterpene lactone) dermatitis and CAD.

Polymorphic light eruption: an immunopathological study of evolving lesions

Polymorphic light eruption (PLE) papules were successfully induced on previously affected sites in 11 out of 14 patients with PLE 4–20 h after single exposures to suberythemogenic doses of solar simulated radiation. Histological examination of biopsies performed 1 h, 5 h, 24 h, 72 h and 144 h post‐irradiation revealted onset within 5 h of perivascular cellular infiltration. The infiltrate was dominated by lymphocytes in both early and established lesions, without evident epidermal pathology. Immunohistochemistry demonstrated a predominance of CD4 + cells in lesions up to 72 h post‐induction, but later biopsies were dominated by a CD8 + infiltrate. Significantly increased numbers of dermal macrophages and CD1b + cells were detected 1 h and 5 h post‐irradiation, respectively. These findings are consistent with a delayed type hypersensitivity response underlying the pathogenesis of polymorphic light eruption.

Oral psoralen photochemotherapy in severe childhood atopic eczema: an update

Over a 6‐year period, oral psoralen photochemotherapy (oral PUVA) has been used to treat 53 children (mean age 11. 2 years) with severe atopic eczema unresponsive to other therapy. Twiceweekly treatment resulted in clearance or near‐clearance of disease in 39 (74%) after a mean of 9 weeks. Thirty‐two (82%) of these 39 children were subsequently able to achieve remission of disease following gradual withdrawal of treatment: the mean duration of treatment to remission was 37 weeks; the mean cumulative UVA dose was 1118 J/cm2 and the mean number of treatments was 59. Twenty‐two remain in remission a year after discontinuing treatment. Short‐ and medium‐term adverse effects, other than occasional intolerance of treatment, have not been prominent.

UVA sunbeds: tanning, photoprotection, acute adverse effects and immunological changes

The effects on 31 normal subjects following exposure to sunbeds containing UVA lamps with minimal UVB emission have been compared in a double‐blind study with the effects on nine control subjects of a similar exposure course three times weekly for 4 weeks to sunbeds emitting visible light. On previously untanned areas, all those subjects on active treatment developed a mild tan; in tanned areas they all developed a moderate tan, while all control subjects developed a minimal to mild tan. The mean protection factor against later UVB‐induced erythema was 3.2±0.3 after the active course and 1.6±0.2 among the controls. Significantlsy more frequent adverse cutaneous effects for active subjects were pruritus, erythema, freckling, burning sensation, dryness and polymorphic light eruption. Cutaneous Langerhans cell numbers, and blood CD3+ (pan T‐cell) and CD4+ (helper T‐cell) lymphocyte subsets were reduced in both active and control groups. CD8+ (cytotoxic/suppressor T‐cell) counts were significantly reduced in both groups. The changes found in both groups seem attributable to small amounts of UVB emission from both active and control lamps.

Measurement of mRNA for E-selectin, VCAM-1 and ICAM-1 by reverse transcription and the polymerase chain reaction

Stimulation of cultured human umbilical vein endothelial cells by cytokines such as interleukin-1 and tumour necrosis factor induces de novo synthesis and expression of the adhesion molecules E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). In general, alterations in cell surface expression of these molecules are known to be related to increased gene transcription and altered levels of mRNA. The extension of these observations to the study of inflammatory processes in different human organs necessitates the development of techniques for the quantification of mRNA in small tissue samples. Here we present a method for the quantification of mRNA for E-selectin, VCAM-1 and ICAM-1 using reverse transcription and the polymerase chain reaction (RT-PCR). For each molecule of interest a mutant RNA was synthesised consisting of the wild-type sequence deleted of 15-20 bases. The mutant and wild-type RNA sequences are recognised by the same primers, and can therefore be amplified competitively in the same tube by RT-PCR. As the mutant and wild-type RNAs compete for the primers, the amount of wild-type RNA can be determined by the size of the dominant product that results after addition of known quantities of mutant RNA. Using this detection and quantification method we have examined the dose dependency and time course of mRNA accumulation following TNF-alpha stimulation of HUVEC. Similar time-courses of E-selectin, ICAM-1 and VCAM-1 mRNA accumulation were observed by competitive RT-PCR as by laser densitometry of Northern blots. Finally we were able to show that the technique could measure changes in levels of mRNA for these three molecules in human skin biopsies taken at different times during the development of a delayed hypersensitivity response to tuberculin purified protein derivative. This technique should be useful for the study of adhesion molecule mRNA in small tissue culture samples and in biopsies.

Low-dose ultraviolet-B irradiation depletes human epidermal Langerhans cells

We have examined the effects of low‐dose monochromatic UVB irradiation (295±5 nm), biologically equivalent to that generally incident on the skin during a 12‐session sun‐bed course, on the expression of the CDla epidermal Langerhans cell surface marker in human skin in vivo. In five subjects, 1.5 minimal erythema doses (MEDs) at 295 nm depleted its expression by 50%. In five further subjects, a single 1.5 MED dose, 1.5 MEDs in 10 equal fractions on alternate days, and a single 1.5 MED dose at one‐tenth the previously used irradiance, delivered to separate sites, also led to variable but significant depletion of CD la expression of around‐30–50%. Thus, low‐dose UVB irradiation, whether received rapidly or slowly, appears significantly and approximately equally to deplete human epidermal Langerhans cell numbers as measured by CDla expression.

The efficacy of psoralen photochemotherapy in the treatment of aquagenic pruritus

Summary Psoralen photochemotherapy (PUVA) was effective in the treatment of five patients with aquagenic pruritus, associated in one with polycythaemia rubra vera and in another with the myelodysplastic syndrome. Relapse occurred within 2–24 weeks when treatment was discontinued. Maintenance therapy or a further course of PUVA was necessary to maintain remission. This requirement may limit the value of the therapy.

LONG-TERM SURVIVAL AND PRESERVATION OF NATURAL-KILLER-CELL ACTIVITY IN A XERODERMA-PIGMENTOSUM PATIENT WITH SPONTANEOUS REGRESSION AND MULTIPLE DEPOSITS OF MALIGNANT-MELANOMA

Summary A 67‐year‐old man with xeroderma pigmentosum (XP) originally presented with malignant melanoma at the age of 28 years. This recurred 22 years later and subsequently numerous primary and secondary melanomas developed on the skin, several of which underwent spontaneous regression. Despite a marked lymphopenia, the proportion of natural killer cells was elevated and it is proposed that this led to the regression of the melanomas. Skin‐derived fibroblasts from the patient were more sensitive to UVC (D10ε3 J/m–2) than those from normal individuals (D10– 15 J/m–2).The fibroblast culture was shown to be defective in excision repair with <10% of residual activity compared with controls. No assignment to a complementation group has yet been made. There was an elevated frequency of mutants resistant to 6‐thioguanine in the circulating T lymphocytes.