TAFRO syndrome requiring combined IL 6 and IL 1 inhibition: a case report

Ahmad Wael Sultan^1,2,3,4,5*Eva Grießhammer^2,3,4,5,6Carl Hinrichs^2,3,4,5,6Lars Trenkmann^2,3,4,5,6Ilske Oschlies^7,8Leif Gunnar Hanitsch^2,3,4,5,9Haibel Hildrun^1,2,3,4,5Thomas Schneider^1,2,3,4,5Rasmus Leistner^1,2,3,4,5

• ¹Department of Gastroenterology, Infectious Diseases and Rheumatology, Berlin, Germany
• ²Charite - Universitatsmedizin Berlin, Berlin, Germany
• ³Freie Universitat Berlin, Berlin, Germany
• ⁴Humboldt-Universitat zu Berlin, Berlin, Germany
• ⁵Berlin Institute of Health at Charite Center for Regenerative Therapies, Berlin, Germany
• ⁶Department of Nephrology and Intensive Care Medicine, Berlin, Germany
• ⁷Department of Hematopathology and Lymph Node Registry (Division of Pathology), Kiel, Germany
• ⁸Christian-Albrechts-Universitat zu Kiel Medizinische Fakultat, Kiel, Germany
• ⁹Institute of Medical Immunology, Berlin, Germany

Abstract Introduction: TAFRO syndrome is a rare and severe variant of idiopathic multicentric Castleman disease (iMCD). The name giving presentation is a combination of Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis/ Renal dysfunction and Organomegaly. The disease's complex but unspecific presentation shows overlapping features with hyperinflammation syndromes of infectious, malignant or autoimmune origin. Here, we present a case of a young patient with iMCD TAFRO refractory to targeted IL-6 inhibition. Case description: A 21-year-old previously healthy male developed progressive systemic inflammation with fever, persistent generalized lymphadenopathy, bicytopenia, polyserositis and renal failure. Infectious diseases, oncological and immunological workup within the first 6 months after symptom onset yielded an unclear hyperinflammatory syndrome. Subsequently the patient was treated with IL-1 inhibition resulting in partial symptom relief. However, after a flare the repeated lymph node histopathology showed immunohistochemical features of iMCD and the diagnosis iMCD TAFRO was establishes. The patient was then additionally treated with IL-6 inhibition. An attempt to switch to monotherapy with IL-6 inhibition resulted in another flare-up of the disease. This demonstrated the need for continued combined IL-6 and IL-1 inhibition. Under this combination therapy, the patient showed complete and stable remission, which persisted even after 12 months of follow-up. Conclusion: This case highlights the diagnostic and therapeutic challenges posed by iMCD TAFRO. In cases with refractory disease despite targeted IL-6 inhibition, additional IL-1 inhibition might pose a further treatment option.