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Notes: J.A.M. is currently receiving a research fellowship from the Dystrophic Epidermolysis Bullosa Research Association (DEBRA).Epidermolysis bullosa, a rare genodermatosis, is characterized by increased skin fragility manifest as blistering and sometimes accompanied by scarring. The latter is particularly severe in the recessive dystrophic variant and may be complicated by the development of squamous carcinoma in up to 30% of patients. We have studied 23 such tumours in six patients with this variant, with an anti-serum to p53 protein. Twenty-six per cent of the squamous carcinomas labelled positively for mutant-type p53 protein. This low figure, however, reflects the large number of well-differentiated tumours in this series, where 14 out of 15 were negative. In the moderate to poorly differentiated examples the positivity rate was 63%. Of the three patients in the latter category, one has died from disseminated tumour and another has widespread metastases. The findings support the hypothesis that mutant p53 protein expression correlates with poorer tumour differentiation. They also suggest a possible correlation between p53 protein expression and tumour behaviour.

Notes: In this Study a variety of immunoelectron microscopic methods were used to define the precise ultrastructural binding site of epidermolysis bullosa acquisita antibodies (EBA-Ab). We used two EBA sera which immunoblotted with the same skin-extracted protein as that labelled by a monoclonal antibody (LH7.2) which is known to react with the carboxy terminus of type VII collagen. Gold-conjugated antibodies were used in two different immunoelectron microscopic procedures to compare the labelling characteristics of EBA-Ab and LH7.2 in normal human skin. Antibody incubations were performed using ultra-thin cryosections of unfixed skin and thin slices of fresh skin (en bloc technique) before conventional fixation and embedding in Epon. Both methods showed similar labelling features for both EBA-Ab and LH7.2 With ultra-thin cryosections there was labelling of the lamina densa and an undefined component of the sub-lamina densa region. With the en bloc technique, labelling of dermal ends of anchoring fibrils and of amorphous material recently defined as‘anchoring plaques’was evident. There was no labelling of the central banded portions of anchoring fibrils. We conclude that EBA-Ag is localized to the dermal ends of anchoring fibrils in addition to the lamina densa and possibly anchoring plaques, and thus has the same distribution as the carboxy terminus of type VII collagen.

Notes: The prenatal diagnosis of epidermolysis bullosa letalis was made by demonstrating a marked reduction of normal immunofluoresccnce staining with the monoclonal antibody GB3 in a fetal skin biopsy obtained at 18 weeks' gestation. The diagnosis was confirmed by conventional electron microscopy using established techniques. The affected pregnancy continued to term and a baby was delivered who rapidly developed blistering affecting the buttocks, lower limbs and mouth. This technique is simpler and quicker than electron microscopy, yet appears to retain the same degree of accuracy.

Notes: We report a patient with cholinergic urticaria in whom stroking the skin produced a band of erythema studded with the small weals characteristics of cholinergic urticaria. This respons was suppressed by pre-treatment with topical scopolamine. Light and electron microscopy of the weal showed mast cell degranulation and a moderate mononuclear cell infiltrate.

Notes: Since our first report 5 years ago (Rodeck, Eady & Gosden, 1980) the combination of fetoscopy and electron microscopy to obtain and examine fetal skin biopsy specimens has become an established method for assessing mid-trimester fetuses at risk for different genodermatoses characterized by specific ultrastructural abnormalities. Our present report concerns 39 fetuses (〈link href="#t1"〉Table).〈tabular xml:id="t1"〉TABLE〈title type="main"〉 Skin biopsy examination of 39 fetuses 〈table colsep="0" rowsep="0" frame="topbot" pgwide="1" orient="port"〉〈tgroup cols="3" align="left"〉〈colspec colnum="1" colname="col1" align="left"/〉〈colspec colnum="2" colname="col2" align="center"/〉〈colspec colnum="3" colname="col3" align="center"/〉〈thead valign="bottom"〉〈row rowsep="1"〉RiskNo. examinedNo. affected〈tbody valign="top"〉Junctional EB*†216Dystrophic EB61Bullous ichthyosis21Lamellar ichthyosis20Harlequin ichthyosis20Oculocutaneous albinism42Ectodermal dysplasia10Neu-Laxova syndrome10〈note xml:id="t1_note27" numbered="no"〉*Epidermolysis bullosa.〈note xml:id="t1_note28" numbered="no"〉†Includes one twin pregnancySkin biopsies are taken at 18–21 weeks gestation under direct vision with real-time ultrasound guidance. Usually a minimum of three samples is examined. Biopsies are taken from the limbs and trunk (for epidermolysis bullosa or ichthyosis) or from the scalp or eyebrows (for albinism). Biopsy scars are inconspicuous or very small and have never been a problem. There has been no fetal loss as a direct result of the procedure.We feel that this technique of prenatal diagnosis is now sufficiently well-tried to be offered as a service in the management of certain genetic skin diseases.

Notes: An enzyme histochemical and cytochemical study of normal dermal microvasculature showed that respiratory enzymes, lipase and non-specific esterase occurred in all vascular segments. Lysosomal enzymes were also widely distributed and acid phosphatase activity was localized in lysosomes, Golgi apparatus and small portions of endoplasmic reticulum of both endothelial cells and pericytes. Alkaline phosphatase activity, however, was confined to the arterial side and tip of the capillary loop where it occurred in vesicles along the luminal surface of the endothelium and in junctions between endothelial cells. The localization of nucleoside phosphatase activity within the endothelium varied according to substrate; with adenosine triphosphate as substrate, the reaction product occurred in vesicles distributed throughout the endothelial cells; with adenosine diphosphate it was limited to vesicles along the luminal surface; and with adenosine monophosphate, activity was mostly localized to the lateral surfaces of endothelial cells.

Notes: Eight patients received PUVA for mastocytosis. Five women had typical adult-onset urticaria pigmentosa, without evidence of systemic disease. Another woman had suspected hepatic involvement while the remaining female had early-onset familial urticaria pigmentosa with morphologically atypical mast cells. The only male patient had cirrhosis with hepatic deposits of mast cells in addition to polycythaemia rubra vera. In all patients, except the man with systemic disease, there was reduced pruritus and wealing and partial to almost complete fading of the macules. The manifestations of urticaria pigmentosa recurred after treatment was discontinued. In both lesional and uninvolved skin there was no significant change in either the mean mast cell counts or mast cell ultrastructure after an average of twenty-seven PUVA exposures. In addition, PUVA did not cause a significant alteration in the histamine content of the skin.The beneficial effect of PUVA in urticaria pigmentosa therefore does not appear to be directly related to a change in mast cell numbers or morphology, or to the histamine concentration in the skin.Urticaria pigmentosa usually presents as a generalized maculo-papular rash which urticates on rubbing (Darier's sign). Many patients are troubled only by the unsightliness of the rash while some complain of pruritus, wealing or flushing. These symptoms are attributed to the release of histamine by mast cells which characteristically occur in increased numbers in the dermis.Symptomatic treatment is often unrewarding, but favourable results have been claimed for cimetidine with or without Hi blockers (Hirschowitz & Groarke, 1979; O'Laughlin & Bredfeldt, 1980) and for oral disodium cromoglycate (Soter, Austen & Wasserman, 1979; Czarnetski & Behrendt, 1981). In 1978, Christophers and colleagues reported that photochemotherapy (PUVA) produced symptomatic relief in all of ten adult patients with typical urticaria pigmentosa. Similarly encouraging results were subsequently reported from other centres (Ortonne et al., 1980; Allevato, Donatti & Cordero, 1980; Granerus, Roupe & Swanbeck, 1981; Väätäinen, Hannuksela & Karvonen, 1981).In this study we examined the effects of PUVA in eight adult patients with urticaria pigmentosa. Although PUVA produced a moderately good clinical response in seven out of these eight patients (reduced pruritus, reduced wealing and faded macules) quantitative studies failed to reveal a consistent effect of PUVA on either the mast cell population density or the histamine concentration in both lesional and clinically uninvolved skin. The findings arc discussed in relation to existing information concerning the effect of ultraviolet radiation (U VR) on mast cells and other constituents of the skin.