50 First and successful selective treatment of hemophagocytic syndrome secondary to tuberculosus with interleukin-1 blockage
Meerten, T. van, Zhang, D., Rutgers, A.
Locatie(s): Zaal 2.1
Categorie(ën): Parallelsessie
Introduction: Hemophagocytic syndrome or macrophage activation syndrome (MAS) is a rare and often fatal complication of autoimmune disorders, severe infections or malignant diseases, especially in the immune compromised host. It is characterized by uncontrolled activation of macrophages and T lymphocytes. Sometimes, patients deteriorate fast due to the vicious cycle of insufficient effect of the treatment with non-selective immune suppressive drugs that also cause a boost of opportunistic infections.
Case: A 25-year old girl was diagnosed with systemic lupus erythematosus based on chilblain vasculitis, polyarthritis, seropositive ANA and anti-dsDNA and treated with prednisolone and hydroxochloroquine. After several weeks she was admitted with a spiking high-grade fever and progressive dyspnea with a non-productive cough. Positive blood cultures and CT angiography showed a Streptococcus pneumoniae pneumonia together with pulmonary embolism. Despite two weeks of antibiotics and LMWH, fever persisted and dyspnea steadily worsened. In addition, she developed anemia (Hb 5.5 mmol/l), lymphopenia (0.09109/l) and elevated transaminases (ASAT 303 mmol/l, ALAT 201 mmol/l). Ultrasound of the liver was normal. Additional blood, urine and sputum cultures remained negative for bacteria, viruses and funghi.
An autoimmune-related HFS/MAS was suspected. It was confirmed by a very high ferritin (10283 ug/l), increased triglycerides (4.37 mmol/l), and a bone marrow aspiration demonstrating hemophagocytosis. Methylprednisolone and cyclophosphamide were started intravenously, with good result. However, dyspnea worsened by the development of pulmonary interstitial abnormalities. Bronchoscopy with lavage showed acid-fast bacilli, revealing disseminated tuberculosis as a second cause of HFS/MAS. Tuberculostatics were started. However, the increasing ferritin to 24705 ug/l was indicative of refractory HFS/MAS. Additional methylprednisolone and IVIG were not sufficient and immunosuppresion with etoposide was considered contraindicated by the active tuberculosis, therefore we decided to selectively target the interleukine-1 (IL-1) pathway with an IL-1 receptor antagonist (anakinra). Autoimmune diseases as well as mycobacteria are known to induce IL-1, which is crucial in the activation of macrophages.
Within two days, there was an impressive decrease of the ferritin level towards 800 ug/l with a continuous decline over several weeks. She clinically improved with gradual disappearance of the fever and dyspnea. At this time she is at home in a good condition and receives medication for the tuberculosis and the SLE as an outpatient.
Conclusion: For the first time, we treated an adult HFS/MAS-secondary to TB patient with the interleukin-1 receptor antagonist anakinra, with a spectacular response. We think, interleukin-1 antagonism could be part of a promising and selective method to target the hemophagocytic syndrome.