Characterization and activity of phospholipase A2 in normal human epidermis and in lesion-free epidermis of patients with psoriasis or eczema.

The kinetic properties of phospholipase A2 isolated from single large specimens of normal human epidermis and 'uninvolved' (lesion-free) psoriatic epidermis were determined. The enzymes from the two sources behaved identically with respect to changes in protein concentration, Ca2+ concentration and pH, but the enzymes responded differently to changes in substrate concentration. Furthermore, the specific activity of the enzyme derived from lesion-free psoriatic epidermis was higher than that from normal epidermis under all conditions used. Increased specific activity of the enzyme in the lesion-free epidermis was also found when biopsy specimens taken from thirty-five patients with psoriasis vulgaris at varying severity were compared with biopsies of normal epidermis from thirty-one control volunteers (P less than 0.001). Mixing experiments, in which homogenates of lesion-free psoriatic epidermis and control epidermis were combined, suggested that the relatively low activity of the enzyme in normal epidermis was due to the presence of an inhibitor. As the activity of the enzyme was not elevated in the lesion-free epidermis from twelve cases of eczema, which is also an inflammatory condition of the epidermis and superficial dermis, it is suggested that the raised phospholipase A2 activity demonstrated in the lesion-free epidermis of psoriasis may play an important role in the pathogenesis of the disease.

Utilization of epidermal phospholipase A2 inhibition to monitor topical steroid action.

The effect of several steroid creams on epidermal phospholipase A2 (PLA2) activity in symptomless psoriatic and normal epidermis was studied. The magnitude of PLA2 inhibition produced by the steroids was directly proportional to the initial level of the enzyme activity. This differential inhibition resulted in PLA2 activity approaching or attaining the normal range regardless of its initial level. Clobetasol propionate 0.05% (Dermovate) produced more enzyme inhibition than betamethasone valerate 0.1% (Betnovate) but there was no difference in inhibition between this latter steroid and clobetasone butyrate 0.05% (Eumovate). All were more inhibitory than hydrocortisone I% (Efcortelan).

Epidermal phospholipase A2 activity is raised in the uninvolved skin of psoriasis.

In uninvolved epidermis from nine psoriatic subjects, the mean phospholipase A2 activity was significantly greater (P less than 0.01) than in nine controls. The increased activity of this enzyme could lead to an increase in the concentration of free arachidonic acid which, in turn, could lead to increased concentrations of inflammatory mediators.

Assessment of liver function using fasting bile salt concentrations in psoriasis prior to and during methotrexate therapy.

To determine if fasting bile salt concentrations are an accurate indicator of pre-existing and methotrexate-induced liver disease in patients with psoriasis, the plasma concentrations of conjugated cholate, chenodeoxycholate and sulpholithocholate were measured in 18 patients being assessed for methotrexate therapy and 21 receiving long-term therapy. The results were compared with other liver function tests and liver histology. The liver function tests were a poor indicator of occult liver disease and, whilst fasting bile salts appeared more sensitive, they were still unreliable and inadequate for the clinical assessment of the hepatopathy associated with psoriasis. The reasons for these discrepancies are discussed.

Case clustering in pityriasis rosea: support for role of an infective agent.

One hundred and twenty-six cases of pityriasis rosea seen over two years in north Staffordshire were analysed for clustering in time and space. A statistically significant degree of clustering was found; this was evident among female patients considered separately but not among male patients. The incidence of the condition was higher in patients working in, or attending, educational establishments. These findings support the hypothesis that pityriasis rosea is caused by an infective agent. A search for an infective organism and a transmission mechanism now seems justifiable.

Circulating immune complexes in cutaneous and systemic vasculitis: clinicopathological correlations.

A high incidence of raised levels of circulating immune complexes has found in a group of patients with idiopathic vasculitis. Serial measurements in 8 patients with systemic vasculitis showed a good correlation between clinical status and circulating immune complex levels. Some correlation existed between the constituents of circulating and tissue-bound complexes in 6 patients so studied. However, there was no correlation between apparent organ involvement and hypocomplementaemia and the levels of size of circulating immune complexes. It is concluded that the measurement of circulating immune complexes may be clinically useful in vasculitis, but that no direct evidence is yet available that they are pathogenetically related to those which are tissue-bound.

Occupational dermatitis due to 1,2-benzisothiazolin-3-one in the pottery industry.

Three men working as mouldmakers in the pottery industry acquired a contact allergic dermatitis to a releasing oil. All three were shown to be sensitized to the biocide (1,2-benzisothiazolin-3-one) in the oil.

A case of lymphomatoid papulosis and systemic lymphoma.

A young man with a 4-year history of lymphomatoid papulosis subsequently developed a systemic lymphoma. Further doubt is therefore cast on the benign nature of this disorder.

Possible defects in triacylglycerol and phosphatidylcholine metabolism in psoriatic epidermis.

Biopsies of normal skin, psoriatic lesions and the adjacent psoriatic skin were incubated with I-14C-acetate, 32P-orthophosphate and U-14C-glycerol. Total incorporation of I-14C-acetate into psoriatic lesions (17 samples) was 50% higher than in the adjacent uninvolved epidermis (9 samples) and 120% higher than into normal epidermis (10 samples). In the psoriatic lesion a much higher proportion of the total incorporation was into the neutral lipids and was due mainly to a very high incorporation of I-14C-acetate into the triacylglycerols. The I-14C-acetate incorporated into the phospholipids and especially phosphatidylcholine was proportionally much less in the psoriatic lesion and uninvolved psoriatic epidermis than in normal epidermis even though the incorporation of 32P-orthophosphate and U-14C-glycerol, both representing de novo synthesis, into the phospholipids in the psoriatic lesions and uninvolved epidermis were higher (four-fold in lesion) than in normal epidermis. Our findings (1) are evidence for a much increased triacylglycerol synthesis in psoriatic epidermis which would account for the long-known observation of lipid droplet accumulation in psoriatic cells; (2) suggest that in psoriatic epidermis there is a defect in phospholipid metabolism mainly involving phosphatidycholine and the deacylation (phospholipase A)-reacylation (phospholipid acyltransferase) cycle for fatty acid transfer.

A comparison of nystatin cream with nystatin/triamcinolone acetonide combination cream in the treatment of candidal inflammation of the flexures.

In a multi-centre double-blind trial, 31 patients with proven bilateral candidal lesions of the flexures were treated for 14 days with nystatin cream on one side and with a combination of nystatin and triamcinolone acetonide cream on the other. Both treatments proved equally effective in terms of mycological cure and clinical improvement. There was a trend in favour of the combination preparation being preferred by both patients and physicians because of more rapid relief of symptoms.

Pyoderma gangrenosum associated with active chronic hepatitis: report of two cases.

In two patients, active chronic hepatitis was complicated by the development of pyoderma gangrenosum. The favorable response of the pyodermatous lesions to azathioprine therapy suggests that this drug may be of value in treating this disorder in patients for whom corticosteroid therapy produces no benefit or is contraindicated because of side effects. Azathioprine, too, is a potentially toxic drug and may need to be discontinued. Possible causal relationships between pyoderma gangrenosum and active chronic hepatitis are discussed.