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We have examined the urinary excretion of stable immunoreactive eicosanoids in 23 female patients with systemic lupus erythematosus (SLE), 16 patients with chronic glomerular disease (CGD), and 20 healthy women. SLE patients had significantly higher urinary thromboxane B2 (TXB2) and prostaglandin (PG) E2 excretion and significantly lower 6-keto-PGFI. than did healthy women. In contrast, CGD patients only differed from controls for having reduced 6-keto-PGF1I excretion. The group of SLE patients with active renal lesions differed significantly from the group with inactive lesions for having a lower creatinine clearance and urinary 6-keto-PGFI. and higher urinary TXB2.Higher urinary TXB2 excretion was associated with comparable platelet TXB2 production in whole blood, undetectable TXB2 in peripheral venous blood, and unchanged urinary excretion of 2,3-dinor-TXB2. A significant inverse correlation was found between urinary TXB2 and creatinine clearance rate (Cc,). In contrast, the urinary excretion of 6-keto-PGFI. showed a significant linear correlation with both Cc, and para-aminohippurate clearance rate (CPAH). In four SLE and seven CGD patients, inhibition of renal cyclooxygenase activity by ibuprofen was associated with a significant reduction in urinary 6-keto-PGFIe, and TXB2 and in both Ccr and CPAH. However, the average decrease in both clearances was 50% lower in SLE patients than in CGD patients, when fractionated by the reduction in urinary 6-keto-PGFi, or PGE2 excretion.We conclude that the intrarenal synthesis of PGI2 and TXA2 is specifically altered in SLE. Such biochemical alterations are

1 The present study was undertaken to characterize the spectrum of arachidonic acid metabolites present in synovial effusions of patients with rheumatoid or psoriatic arthritis, and to compare changes in their concentration following a short-term treatment with 6a-methyl-prednisolone (6-MeP: 4-8mg/day) or indoprofen (1.2g/day), a nonsteroidal anti-inflammatory agent with proven synovial prostaglandin inhibitory effect.2 Measurements of prostaglandin E2 (PGE2), thromboxane (TX) B2, 6-keto-PGF1a and PGF2c, were performed by radioimmunoassay techniques in synovial effusions obtained from 23 patients, and validated by thin-layer chromatographic analysis of the extracted immunoreactivity. 3 PGE2 and TXB2 accounted for more than 60% of the total immunoreactivity in untreated patients. The absence of any constant ratio between the different arachidonic acid metabolites detected in synovial fluid is consistent with a heterogeneous cellular origin of these compounds. 4 Indoprofen treatment was associated with a consistent reduction of synovial prostaglandin and thromboxane concentrations, ranging from 36% in the case of 6-keto-PGF1, to 90% in the case of PGE2. 5 In contrast, 6-MeP caused opposite changes on different metabolites originating via the cyclo-oxygenase pathway. Thus, 6-keto-PGF,a concentrations were reduced by 35%, PGF2", concentrations were increased by 30%, while PGE2 and TXB2 were unchanged following 6-MeP. 6 Although the mechanism(s) underlying the failure of 6-MeP to reduce synovial PGE2 and TXB2 levels are uncertain, the results of the present study clearly indicate that therapeutic doses of steroidal and nonsteroidal anti-inflammatory drugs cause quite distinct changes in arachidonic acid metabolism, which might be relevant to their specific therapeutic actions and side-effects.

SummaryErythema nodosum recurred in a woman during each of her four pregnancies and every time she was started on oral contraceptives. The lesions always disappeared in the fifth month of gestation or when contraceptives were withdrawn. Erythema nodosum is mediated by immune mechanisms, and both pregnancy and oral contraceptive use can interfere with the immune system. The concentrations of oestrogen and progesterone or the ratio between them may be critical to the development of erythema nodosum. The observation that the lesions spontaneously resolved in the fifth month of pregnancy supports this hypothesis. IntroductionErythema nodosum is a rare complication of oral contraceptive use'; in other women it is sometimes associated with pregnancy.' We describe here a young woman in whom repeated pregnancies and oral contraceptive use were regularly complicated by erythema nodosum.

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