Therapeutic plasma exchange in catastrophic antiphospholipid syndrome: a rare case with concomitant systemic lupus erythematosus and infection

A 49-year-old woman with a 16-year history of systemic lupus erythematosus (SLE), previously without signs of renal involvement (antinuclear antibodies titer 1: >20 480 identified with the immunoblot method as antihistones, antinucleosomes, anti-SSB, and anti-RNP) in remission for over 6 months, was admitted to the Immunology Department at the University Hospital in Kraków. She had been receiving chronic but irregular (due to poor compliance) treatment with systemic steroids. At the time of admission, the patient was receiving treatment with 10 mg of prednisone daily. The admission was prompted by the presence of fever, digital ulcers, and erythematous-blistering lesions with painful skin necrosis on the abdomen and lower chest (Figure 1A and 1B). Further examination revealed hypotension not requiring the use of pressor agents, and decreased vesicular murmur at the lung bases. Laboratory workup revealed anemia (hemoglobin, 7.8 g/dl; reference range [RR], 11.2–15.7 g/dl), thrombocytopenia (38 000/µl; RR, 180 000–370 000/µl), prolonged prothrombin time (18.5 s; RR, 9.8–12.1 s) and activated partial thromboplastin time (118.7 s; RR, 25–33.5 s), decreased estimated glomerular filtration rate (eGFR; 31 ml/min/1.73 m²; RR >90 ml/min/1.73 m²), elevated C-reactive protein (CRP; 465.2 mg/l; RR, 0–10 mg/l), procalcitonin (37.03 ng/ml; RR <⁠0.25 ng/ml), fibrinogen (6.3 g/l; RR, 1.8–3.5 g/l), D-dimers (7692.6 ng/ml; RR <⁠500 ng/ml), and factor VIII (542.2%; RR, 50%–150%). Changes in the laboratory test results during treatment are presented in Supplementary material, Table S1. During hospitalization, the patient developed severe acute respiratory distress and exacerbated chronic kidney disease, without a need for kidney replacement therapy. A computed tomography (CT) scan showed diffused alveolar hemorrhage (Figure 1C). No thromboembolic signs were detected on deep-vein ultrasound of the lower extremities, as well as on chest and abdominal CT scans. Based on the clinical findings, positive lupus anticoagulant and immunoglobulin G anticardiolipin antibodies, catastrophic antiphospholipid syndrome (CAPS) was diagnosed. The patient was transferred to an intensive care unit, where invasive mechanical ventilation (IMV) was initiated. Five sessions of plasmapheresis were performed, and pulses of methylprednisolone (500 mg) and rituximab (500 mg) were given. For the next 4 weeks, methylprednisolone at a dose of 1 mg/kg body weight was administered, and then gradually tapered off. Broad-spectrum antibiotic therapy (meropenem, linezolid) was also initiated at that time; as diffused alveolar hemorrhage was stopped, anticoagulation was continued. The patient’s condition transiently improved, but later she required reinitiation of IMV, along with introduction of noradrenaline. She also suffered from sudden cardiac arrest, and was successfully resuscitated. Bronchoscopy was performed, along with microbiologic examination of urine and swabs from a secretion of the necrotic skin area. Candida albicans and Acinetobacter baumannii were isolated, and targeted treatment with colistin and fluconazole was initiated. Following the treatment, the patient’s condition improved, and she underwent multiple surgical interventions, including removal of the necrotic skin area (Figure 1D and 1E). Toward the end of the hospitalization, signs of bone marrow suppression (white blood cell count, 2440/µl; RR, 4000–10 000/µl; red blood cell count, 2.71 million/µl; RR, 3.9–5.2 million/µl, platelet count, 142 000/µl) were observed, further confirmed on bone marrow biopsy. However, eGFR, CRP, and procalcitonin were within normal range (176 ml/min/1.73 m², 5.9 mg/l, and 0.14 ng/ml, respectively; Supplementary material, Table S1). Consequently, methylprednisolone was increased to 1 mg/kg body weight, and a single intravenous dose of immunoglobulins (IVIGs, 1 g/kg) was administered, resulting in a favorable clinical response. Despite the critical condition associated with CAPS likely triggered by an infection, and the absence of anticoagulation despite previously detected antiphospholipid antibodies and SLE, the patient condition stabilized following collective efforts of the medical team and the broad-spectrum treatment applied, which included antibiotics, anticoagulant medication, immunosuppressive drugs, and plasmapheresis. The patient was discharged home in a stable condition and was scheduled for regular monthly follow-ups at an outpatient clinic. Unfortunately, she passed away 5 months after the hospital discharge due to complications of anorexia nervosa.

CAPS is a life-threatening condition characterized by rapid development of severe thrombotic episodes. It affects approximately 1% of patients with antiphospholipid syndrome.¹ In terms of clinical manifestations, the kidneys are the most frequently affected organ system (about 74%), followed by the lungs (about 60%), brain (about 56%), heart (about 53%), and skin (about 45%).^2,3 Trigger factors for CAPS are found in approximately two-thirds of patients, and include infections, surgery, malignancies, ineffective anticoagulation, and SLE flares.⁴ Treatment includes anticoagulation and immunosuppressive drugs (ie, systemic steroids, cyclophosphamide, rituximab, IVIGs).^1,2 The mortality rate of CAPS is around 50%; however, concomitant SLE is associated with a higher mortality rate.⁵