The Korean Journal of Internal Medicine Vol. No. 1, January, 1994 A Case of Cerebral Infarction Associated with Positive Antiphospholipid Antibody in a Systemic Lupus Patient Eun Rae Jo, M.D., Hyun Jae Shin, M.D., Jae Hong Seo, M.D., Sang Hwa Lee, M.D., Gwan Gyu Song, M.D. and Heui-Jung Pyo, M.D. Department of Internal Medicine, Guro Hospital, Coltege of Medicine, Korea University, Seoul, Korea Antiphospholipid antibody syndrome is a newly-defined clinical entity of arterial throm- bosis, venous thrombotic events, recurrent spontaneous abortion and thrombocytopenia in the presence of antiphospholipid antibodies. We have experienced a 23-year-old male SLE patient with positive anticardiolipin anti- body who presented with left hemiparesis and paresthesia. The clinical and laboratory findings were compatible with the criteria for SLE and he was found to have anticardiolipin antibody, thrombocytopenia, prolonged partial thromboplastin time and cerebral thrombo- sis. Initially, he was treated with high dose steroid and warfarin and now he is being followed up with warfarin and steroid. Key Words: Antiphospholipid antibody, SLE, Cerebral thrombosis INTRODUCTION In 1987, Harris et al?” proposed that the combi- nation of clinical features, including both venous and arterial occlusive events, recurrent spontane- ous abortions and thrombocytopenia with anti- phospholipid antibodies (aPL), should be termed the “antiphospholipid antibody syndrome” (APS). Here, we describe a case of secondary APS in a systemic lupus patient who presented with cerebral infarction in the presence of anticardiolipin anti- bodies. CASE REPORT A 23-year-old Korean man was admitted with a chief complaint of weakness and decreased sen- sation of left arm and leg for 7 days. He had suf- fered from polyarthraigia and generalized edema for 2 years, and took herbal medicine occasionally. He had a history of hair loss, but he didn't complain about allergies, photosensitivity, skin rash, oral ulcer, dry mouth, dry eye and Raynaud's phenome- non. On examination, he was normotensive (110/70 mmHg) but febrile (37.8 C). He appeared acutely ill, but showed alert mentality. There were no path- Address requests for reprints to: Gwan Gyu Song, M.D., Department of Internal Medicine, Guro Hosp., Korea Univ. Med. Ctr, #80 Guro-dong, Guro-gu, Seoul, 152-050, Korea ologic lesions in his ears, eyes, nasal or oral mucosa. The pulmonary and cardiac examinations were normal. The abdominal examination revealed shifting dullness. His joints were unremarkable, there was no cutaneous vasculitis and all peripheral puises were present with no arterial bruits. Neur- ologically, he had left-side paresthesia, hemipar- esis and a brisk, deep tendon reflex, but other abnormal neurologic signs were not noted. On admission, white blood cell count was 6.4 10°/mmié with left shift (seg.neut. 55%, band neut. 32%, lymph. 10%, mono. 3%). Hematocrit was 15%, hemoglobin 5.5gm/dl, and the reticulocyte count was 3.5%. The erythrocyte sedimentation tate was elevated at 23 mm/h (Westergren). The direct Coomb’s test was positive. Review of the peripheral blood smear showed unremarkable red cell morphology. Urinalysis showed 100 mg/dl protein, 5~7 white cells and many red cell. The urine hemosiderin and hemaglobin were negative. Renai function evaluation revealed blood urea nitrogen 26 mg/dl, creatinine 1.5 mg/dl, 24 hr urine protein 3.4 gm/day, and the creatinine clearance was 55 mi/dl. The serum electrolyte were normal, except for potassium of 3.2 mmol/I. The AST was 341U/I, ALT 421U/I, alkaline phosphatase 48 IU/I, total bilirubin 0.7 mg/di, total protein 5.8 gm/dl and albumin 2.7 gm/dl. The platelets were 22x 10°/mi, PT 10.7/100 (sec/%) and aPTT 34/28(sec, patient/ control). Rheumatoid factor was negative and ANA was positive (speckied pattern, titer 1:160). The anti-dsDNA antibody was above 100 U/ml (N; 0-25 43 E.R. JO, H.d. SHIN, J.H. SEO, S.H. LEE, G.G. SONG AND HJ. PYO IV. GURO HOSPITAL Fig. 1. Axial, T2-weighted spin echo MRI scan of brain shows area of high signai intensity in right Parieto-temporal white matter. U/ml). The anti-Sm, anti-RNP, anti-Ro and anti-La antibodies were all positive. Complement levels were decreased at C3 26.5mg/di (N; 52.6~120 mg/dl), C4 8.0 mg/dl (N; 20.5~49 mg/dl). Anticar- diolipin antibodies (aCL) were positive for both IgG and IgM (by ELISA) and VDRL was reactive, TPHA nonreactive and FTA-Abs negative. The levels of protein C, protein S and antithrombin III were within normal limits. Plain radiology of chest was normal. Abdominal ultrasonography revealed moderate amount of ascites, splenomegaly and diffusely in- creased renal parenchymal echogenicity. Magnetic resonance imaging (MRI) brain scan revealed is- chemia in right parieto-temporal white matter (Fig. 1). EKG showed sinus bradycardia and low voltage on limb leads. Echocardiography confirmed mild pericardial effusion without vegetation and throm- bus. Course: He was diagnosed as APS with cerebral thrombosis in SLE. He was given methylpred- nisolone pulse therapy and oral prednisolone. Kidney biospy showed mixed class III and V (focal and segmental proliferative glomerulonephritis and membranous lupus glomerulonephritis) lesion with activity score 4/24, and chronicity score 1/21. After the kidney biopsy, anticoagulation therapy was begun with warfarin. 44 DISCUSSION Lupus anticoagulant, which was described in the 1950s by Conley and Hartman”, was first as- sociated with thrombotic events by Bowie et al in 1963. In 1987, Harris et al proposed that the com- bination of clinical features, including both venous and arterial occlusive events, recurrent spontane- ous abortions and thrombocytopenia with anti- phospholipid antibodies, identified as moderate to high titers of IgG or IgM anticrdiolipin antibody or the lupus anticoagulant, should be termed as the ‘antiphospholipid syndrome’?. Minor manifesta- tions continue to be described. Cutaneous mani- festations, including livedo reticularis and leg ulcers not related to venous insufficiency, are well described*’. Our patient, who was compatible with diagnostic criteria for SLE was found to have anticardiolipin antibody, false positive VDRL, pro- longed partial thromboplastin time, throm- bocytopenia and cerebral thrombosis. Although the majority of thrombotic episodes in patients with APL are venous**), when thrombosis occurs in the arterial circulation, the brain is affected most often’®, and also can result in ocular complic- ations”, peripheral arterial disease and livedo reticularis. Cerebral ischemia is the most common neurologic symptom associated with APL!”. Venous thrombosis is often recurrent, and is fre- quently accompanied by pulmonary embolism. Hypertension has also been described in APS and attributed to renal thrombotic microangiopathy”. The average prevalence of lupus anticoagulant in SLE was reported as 34%, and anticardiolipin as 44%), Antiphospholipid antibodies (aPL) are defined by solid-phase immunoassay’ and phospholipid- dependent coagulation tests”. When detected by solid-phase immunoassay, they may be named for the specific negatively charged phospholipid, such as cardiolipin, that is used as the antigen. When detected by phospholipid-dependent coagulation tests, they are called lupus anticoagulant (LAC). A prolonged activated partial thromboplastin time (APTT) is the most useful screening test for LAC, but it is considered to be an insensitive test. In general, coagulation tests with he least amount of phospholipid in the test system are the most sensitive’. The protocols for performing solid- phase assays for aPL most commonly utilize a standard ELISA technique. However, the definition A CASE OF CEREBRAL INFARCTION ASSOCIATED WITH POSITIVE ANTIPHOSPHOLIPID ANTIBODY iN A SYSTEMIC LUPUS PATIENT of aPL positivity is far from uniform. A strong correlation exists between elevated anticardiolipin jeveis and the lupus anticoagulant’”. However, the two antibodies appear to be distinct and may be directed agains? different epitopes'®, The consen- sus of opinion is that antiphospholipid antibodies have a pathogenetic role in the vasculopathy of the antiphospholipid syndrome, but the mechanism is unknown. Any or all of the major components of the clotting system may be involved in aPL path- ogenicity, including the coagulation cascade (many of these steps are phospholipid dependent), platelet activation and aggregation, and endoth- elial cell function. Interference with each of these has been postulated as a possible mechanism?” Laboratory abnormalities that can be seen in patients with aPL include a biologically faise posi- tive VDRL test, a prolonged activated partial throm- boplastin time (APTT) and thrombocytopenia; an elevated erythrocyte sedimentation rate, positive antinuclear antibody (ANA) and elevated anti-DNA titers occur occasionally’®. In a patient with throm- bosis or fetal loss, the presence of any or all of these findings should be considered as ciues that prompt evaluation for aPL. There are no convincing data supporting the use of any specific treatment modality in patients with APS. For the treatment of patients who had throm- botic events, longterm coagulation may be preferable'*~?®. A major question is whether or how to treat patients with SLE (or others), who have never had a clinical event, with aPL. The clinical correlations of IgG and IgM aCL in patients with APS in SLE were reported that there is high correla- tion between IgG aCL titer and ITP, recurrent venous thrombosis and fetal loss, also between IgM aCL and livedo reticularis and chronic jeg ulceration. Therefore, in patients with rheum- atotogic conditions, the occurrence of ischemic events, ITP, renal abnormalities or hypertension should arouse the suspicion of APS and aPL. 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