Eur Respir J 1997; 10: 727–730 Copyright ERS Journals Ltd 1997 DOI: 10.1183/09031936.97.10030727 European Respiratory Journal Printed in UK - all rights reserved ISSN 0903 - 1936 CASE STUDY Diffuse microvascular pulmonary thrombosis associated with primary antiphospholipid antibody syndrome M. Maggiorini*, A. Knoblauch**, J. Schneider+, E.W. Russi* Diffuse microvascular pulmonary thrombosis associated with primary antiphospholipid Depts of *Internal Medicine, and +Pathology, antibody syndrome. M. Maggiorini, A. Knoblauch, J. Schneider, E.W. Russi. ©ERS University Hospital, Zurich, Switzerland. Journals Ltd 1997. **Pneumology Division, Kantonsspital, St. ABSTRACT: Thromboembolism is a well-known complication of the hypercoag- Gallen, Switzerland. ulable state associated with anitphospholipid (aPL) antibodies. Acute respiratory Correspondence: M. Maggiorini failure (ARF) with diffuse pulmonary infiltrates has been reported in only a few Dept of Internal Medicine patients with aPL antibodies. University Hospital We describe a 49 year old patient with spiking fever, livedo reticularis, mild Ramistrasse 100 haemoptysis and ARF. Chest radiography revealed diffuse bilateral pulmonary infil- 8091 Zurich trates, and high resolution computed tomography (CT) revealed patchy distribu- Switzerland tion of areas of ground-glass attenuations. Pulmonary emboli were excluded with angiography. Lung biopsy revealed diffuse microvascular thrombosis, without cap- Keywords: Acute respiratory failure illaritis. High serum levels of anticardiolipin (aCL) antibodies were found. The anticardiolipin antibodies patient's condition improved dramatically after intravenous infection of 1 g methyl- microvascular pulmonary thrombosis prednisolone on three consecutive days, followed by 50 mg prednisone orally. Received: July 30 1996 The rapid improvement following the administration of glucocorticosteroids sug- Accepted after revision November 20 1996 gests that anticardiolipin associated microvascular thrombosis, without inflam- β β matory lesions, may depend on an interference with 2-glycoprotein I ( 2=GPI) by anticardiolipin. Eur Respir J 1997; 10: 727–730. Shortly after the development of the anticardiolipin (aCL) Case report assay [1], it became apparent that antiphospholipid (aPL) antibodies, which include aCL antibodies and the lupus A 49 year old man was admitted to hospital because anticoagulant, were not limited to patients with lupus ery- of recurrent livedo reticularis of the fingers and toes, thematosus but could be found in persons without this fever, cough with occasional mild haemoptysis, and short- autoimmune disease. The aPL antibodies associated hyper- ness of breath at rest and at minimal exercise. For 2–3 coagulable state has been termed the "antiphospholipid yrs he had suffered from cerebral transient ischaemic thrombosis syndrome". In the aCL antibody thrombosis attacks and recurrent painful acrocyanosis of the toes syndrome, thromboses of the arteries are almost as com- and fingers. The oscillogram of the peripheral arteries mon as venous thrombotic events [2, 3]. This syndrome was normal. Capillary microscopy showed a slightly dec- occurs without underlying diseases (primary), as well as reased density of the capillaries of the toes. Five months secondary to an underlying disease such as lupus ery- prior to admission, the patient developed acute fever, dysp- thematosus or another autoimmune disorder, malignan- noea, a dry cough with occasional slightly bloody expetor- cies, infections, systemic inflammation, or ingestion of ations, and an incapacitating weakness. A chest radiogram drugs. The primary type is much more common than showed bilateral patchy infiltrates. He was treated with the secondary [2]. clarithromycin. Two months prior to admission, a deep The most common pulmonary manifestation of the aPL venous thrombosis of the left leg was detected. Lung per- syndrome are pulmonary embolism, and pulmonary hyp- fusion and ventilation scan indicated low probability for ertension secondary to recurrent pulmonary emboli [4]. pulmonary embolism. The patient received oral antico- Only a few patients with pulmonary infiltrates, spiking agulation with phenprocoumon. temperature and severe respiratory failure associated On admission, the obese patient (body mass index (BMI) with aCL antibody syndrome have been reported, and 36 kg·m-2) had a temperature of 37.4°C and a heart rate exclusively in the rheumatological literature [5–10]. We of 104 beats·min-1. His blood pressure was 115/80 mmHg, describe a patient with primary aCL antibody syndrome, and respiratory rate 18 breaths·min-1. His toes and fing- who developed an adult respiratory distress syndrome ers were cold and showed a painful livedo reticularis. (ARDS)-like clinical picture and who improved dra- Four necrotic cutaneous lesions, 5×5 mm in diameter matically after high-dose intravenous glucocorticosteroid were present on the right foot. An electrocardiogram (ECG) treatment. was normal. 728 M. MAGGIORINI ET AL. a) b) Fig. 1. – High resolution computed tomography (CT) scan demon- strating bilateral perihilar and peripherally located patchy distributed areas of ground-glass attenuation. Chest radiography showed a normal sized heart and bilateral patchy infiltrates. A high resolution computed tomography (CT) scan revealed bilateral patchy areas of ground-glass attenuation (fig. 1). Pulmonary angiogra- phy revealed moderately dilated central pulmonary arter- ies but no pulmonary emboli. Forced vital capacity (FVC) was 92% predicted, and forced expiratory volume in one second (FEV1) 88% pred. Transfer factor for carbon monoxide (TL,CO) was 87% pred. Arterial blood gas values documented severe Fig. 2. – Photomicrographs of lung biopsy showing: a) Small mus- hypoxaemia: oxyhaemoglobin (HbO2) 78%; arterial oxy- cular artery (diameter 300 µm) presenting with hypertrophy of the gen tension (Pa,O2) 5.7 kPa; arterial carbon dioxide ten- media and a proliferation of the intima, in the absence of inflamma- sion (Pa,CO ) 5.2 kPa; and pH 7.38. tory cells, which narrows the arterial lumen to a considerable extent; 2 b) small arterioles (diameter 50–100 µm) presenting with prolifera- Right heart catheterization showed a pulmonary artery tion of the smooth muscle fibres. (Van Gieson-elastin stain; internal pressure of 31/18 mmHg, the mean pulmonary artery scale bar = 100 µm). occlusion pressure was 8 mmHg, and the estimated mean pulmonary capillary pressure was 12 mmHg, determined Haemoglobin value was 111 g·L-1, polymorphonuclear by analysis of the pulmonary artery occlusion pressure (PMN) leucocytes 5.5×109 cells·L-1 and the number of curve decay [11]. The cardiac index was 4.0 L·min-1·m2 thrombocytes 120×109 cells·L-1. (thermodilution). Transoesophageal echocardiography Cultures of bronchoalveolar lavage (BAL) fluid remai- showed normal left and right ventricular function, and ned sterile. A large lung biopsy was taken from the mid- a slight thickening of the aortic and mitral valves. No dle lobe by video-assisted thoracoscopy. Histology of intraventricular or atrial thrombi could be detected. the specimen revealed thickened pulmonary arteriole Duplex and pulsed-wave doppler sonography of the walls, with hypertrophy of the medial layer and an extracranial arteries and transcranial doppler sonogra- enlarged intimal layer, which presented with an increased phy of the intracranial arteries were normal. Magnetic number of fibroblasts, elastic fibres and smooth muscle resonance tomography of the brain revealed a few small cells, but without any inflammatory cells (fig. 2). The hypodensities in the left thalamus and in the basal areas internal lumen of the majority of the arterioles and of of both cerebellar hemispheres, consistent with small the capillaries was occluded by thrombi. The pulmonary cerebral and infarcts. veins were normal. The lumen of the alveoli contained Anticardiolipin- immunoglobulin G (IgG) was 0.676 pigmented macrophages, erythrocytes and PMNs. The E·L-1 (normal 0–0.01 E·L-1), aCL-immunoglobulin M interlobular septa were slightly thickened. Cultures of (IgM) 0.021 E·L-1 (normal 0–0.01 E·L-1) and aCL-immu- the biopsy specimen remained negative. noglobulin A (IgA) 0.026 E·L-1 (normal 0–0.01 E·L-1) The patient received 1 g methylprednisolone intra- Serum levels of antithrombin III, protein-S and protein- venously on three consecutive days, followed by 50 mg C were normal. Partial thromboplastin time was 63 s, prednisone p.o. daily. Heparin was given by the intra- and fibrinogen 5.8 g·L-1. Antinuclear antibodies, anti- venous route in therapeutic doses. Within days, the deoxyribonucleic acid (DNA) antibodies, antineutrophil patient's condition improved dramatically: the dyspnoea cytoplasmic antibodies, antiglomerular basal membrane decreased, the fingers and toes became warm, the live- anti-bodies and the rheumatoid factor were negative. do reticularis regressed almost completely, and the pain aCL ANTIBODIES AND MICROVASCULAR PULMONARY THROMBOSIS 729 disappeared. The pulmonary infiltrates resolved. Twelve [3]. Less frequent is the combination of both, present in days later, arterial blood gas analysis (without oxygen) 14% of the patients in the above study. The most frequ- showed: HbO2 96%; Pa,O2 11.5 kPa; and Pa,CO2 4.5 kPa. ently reported pulmonary complication of the aPL anti- The patient, while using a bicycle ergometer was able to body syndrome is pulmonary hypertension secondary to perform 25W, 50W, 100W and 125W for 3 min at each recurrent thromboembolism [4]. In the present