CASE REPORT Rube´ n Queiro ® Ana Weruaga ® Jose´ L. Riestra C4 deficiency state in antiphospholipid antibody-related recurrent preeclampsia evolving into systemic lupus erythematosus Received: 17 December 2001 /Accepted: 28 April 2002 / Published online: 8 June 2002 Ó Springer-Verlag 2002 Abstract The case of an apparent healthy woman who developed recurrent preeclampsia with antiphospholipid antibodies and evolved towards systemic lupus erythe- matosus during her last pregnancy is presented. The diagnostic dilemma between lupus renal flare and tox- emia is discussed. The potential role of immunological alterations, such as complement genetic deficiencies, in women with primary antiphospholipid syndrome who develop systemic lupus erythematosus is also discussed. Keywords Preeclampsia ® Antiphospholipid syndrome ® C4 null alleles ® Lupus Introduction In normal healthy women, the recurrence rate of pree- clampsia is generally low (<10%). However, some ex- periences suggest that aPL are found in a substantial proportion of recurrent cases of early-onset severe preeclampsia. In addition, women with preeclampsia and aPL may be at significant risk for serious peripar- tum morbidity (i.e., thromboembolic events), and some authors argue that women with primary antiphospholi- pid syndrome (APS) who develop amaurosis fugax and transient ischemic attacks (TIA) may be prone to sys- temic lupus erythematosus (SLE) development [1, 2]. Antiphospholipid syndrome was first recognized in association with SLE, in which the frequency of aPL is about 10–30%. However, the notion of a primary APS has led to the relation between the two conditions being questioned [3]. Some works have suggested that there is a different genetic background for the two groups of patients with APS, and this has led to renewed interest in the concept that the primary APS could switch to full- blown SLE [4]. We present the case of a young healthy woman who developed recurrent preeclampsia followed by a full- blown SLE during her fourth pregnancy. This is an unusual event that poses some diagnostic and thera- peutic challenges, and therefore it is important to be cautious about this possibility. Case report A 27-year-old Caucasian woman was transferred to our rheuma- tology clinic on the 10th week of her last gestation with acute arthritis, malar rash, and malaise. Her obstetric history included preeclampsia with intrauterine growth retardation (IGR) and fetal intrauterine deaths at 28, 30, and 27 weeks’ gestation over a 3-year period. Intergestational periods had been remarkably normal from the serological and clinical perspectives, and the patient denied a history of hypertension, thromboembolic events, or data suggesting active lupus. Necropsy of her third gestation showed a placenta with multiple infarcted areas. Prior investigations of the last two gestations – including cariotype, antinuclear antibodies (ANA), anti-DNA antibodies, anti-Ro, anti-La, rheumatoid factor, full blood count, and complement – revealed positive tests on only two occasions for anticardiolipin antibodies (aCL) and low C4 levels, and therefore a diagnosis of primary APS was made. At age 27, she became pregnant again and was prescribed aspirin 125 mg daily with subcutaneous heparin (15,000 IU daily). In the 10th week, she developed a butterfly rash, Raynaud’s syn- drome, vasculitic digital lesions, metacarpophalangeal joint arthritis, and severe malaise and was referred to a rheumatology clinic. Complementary data showed hemoglobin 11.5 g/dl, normal white cell count, platelet count 100,000 per ll, erythrocyte sedi- mentation rate (ESR) 45 mm/h, ANA 1/2560 (indirect immuno- fluorescence with homogeneous pattern), positive anti-DNA antibodies (Crithidia), positive anti-Ro (CIE), C3 68 mg/dl (normal 100–185 mg/dl), C4 8 mg/dl (normal 20–47 mg/dl), negative lupus anticoagulant (Russell viper venom test), aCL (enzyme-linked immunosorbent assay, or ELISA) IgG 80 GPL/ml (normal 0–13 GPL/ml), and IgM 120 MPL/ml (normal 0–11 MPL/ml). Tissue typing by serological testing showed HLA A1, A3, B7, B8, Cw5, Cw7, DR3, DR7, and DQ2. Her total hemolytic complement Rheumatol Int (2002) 22: 126–128 DOI 10.1007/s00296-002-0210-2 R. Queiro (&) Hospital San Agustı´n, Camino de Heros 4, 33400 Avile´s-Asturias, Spain E-mail: ruquei@mixmail.com A. Weruaga ® J.L. Riestra Hospital Central de Asturias, Celestino Villamil s/n, 33600 Oviedo-Asturias, Spain R. Queiro C/Marcelino Ferna´ndez 7, 30B, 33010 Oviedo-Asturias, Spain