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26 years’ female patient attended triage with complaints of fever of almost 1-month duration. She was diagnosed as a case of Brucellosis outside. However, her fever persisted and she was finally diagnosed to have new onset adult-onset still’s disease (AOSD) with active macrophage activation syndrome (MAS) and multi organ failure. She met the diagnostic criteria for AOSD. She had high spiky fevers, hepatosplenomegaly, Lymphadenopathy, coagulopathy, anaemia with thrombocytopenia, hemophagocytosis, markedly elevated serum ferritin, low to absent natural killer (NK) cells, and remained unresponsive to steroids, intravenous immunoglobulin (IVIG) and hemophagocytic lymphohistiocytosis (HLH) protocol treatment. Interleukin-1 (IL1) inhibitors were not available. Interleukin-6 (IL6) blockers were not considered due to greater concerns about exacerbating bacterial infections with IL-6 blockade than with IL-1 blockade and much longer half-lives of the IL-6 inhibitors. We were also reluctant in using tocilizumab or sarilumab in new-onset disease where diagnostic uncertainty remains, as is often the case. She succumbed to her disease which had rapid fulminating course with multi organ failure. Her diagnostic and therapeutic challenges are discussed.

References

  1. Magadur-Joly G, Billaud E, Barrier JH, Pennec YL, Masson C, Renou P, et al. Epidemiology of adult Still's disease: estimate of the incidence by a retrospective study in west France. Ann Rheum Dis. 1995; 54(7): 587.
     Google Scholar
  2. Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y, Kashiwagi H, et al. Preliminary criteria for classification of adult Still's disease. J Rheumatol. 1992; 19(3): 424-30.
     Google Scholar
  3. Cush JJ, Medsger TA, Jr, Christy WC, Herbert DC, Cooperstein LA. Adult‐onset Still's disease. Clinical course and outcome. Arthritis Rheum. 1987; 30(2): 186–194.
     Google Scholar
  4. Fautrel B, Zing E, Golmard JL, Le Moel G, Bissery A, Rioux C, et al Proposal for a new set of classification criteria for adult‐onset still disease. Medicine (Baltimore). 2002; 8(1): 194–200.
     Google Scholar
  5. Janka GE, Lehmberg K. Hemophagocytic lymphohistiocytosis: pathogenesis and treatment. Hematology 2013; 2013: 605-11.
     Google Scholar
  6. Crayne CB, Albeituni S, Nichols KE, Cron RQ. The Immunology of Macrophage Activation Syndrome. Front Immunol. 2019; 10: 119.
     Google Scholar
  7. Gerfaud-Valentin M, Maucort-Boulch D, Hot A, Iwaz J, Ninet J, Durieu I, et al. Adult-onset still disease: manifestations, treatment, outcome, and prognostic factors in 57 patients. Medicine (Baltimore). 2014; 93(2): 91-99.
     Google Scholar
  8. Fukaya S, Yasuda S, Hashimoto T, Oku K, Kataoka H, Horita T, et al. Clinical features of haemophagocytic syndrome in patients with systemic autoimmune diseases: analysis of 30 cases, Rheumatology. 2008; 47(11): 1686-1691.
     Google Scholar
  9. Chang-Bum B, Ju-Yang J, Hyoun-Ah K, Chang-Hee S. Reactive Hemophagocytic Syndrome in Adult-Onset Still Disease, Medicine. 2015; 94(4): e451.
     Google Scholar
  10. Maria AT, Le Quellec A, Jorgensen C, Touitou I, Rivière S, Guilpain P. Adult onset Still's disease (AOSD) in the era of biologic therapies: dichotomous view for cytokine and clinical expressions. Autoimmun Rev. 2014; 13(11): 1149-59.
     Google Scholar
  11. Al-Homood IA. Biologic treatments for adult-onset Still’s disease, Rheumatology. 2014; 53(1): 32–38.
     Google Scholar
  12. Jamilloux Y, Gerfaud-Valentin M, Henry T, Sève P. Treatment of adult-onset Still's disease: a review. Ther Clin Risk Manag. 2014; 11: 33-43.
     Google Scholar
  13. Lenert A, Yao Q. Macrophage activation syndrome complicating adult onset Still's disease: A single center case series and comparison with literature. Semin Arthritis Rheum. 2016; 45(6): 711-6.
     Google Scholar
  14. Schulert GS, Grom AA. Pathogenesis of macrophage activation syndrome and potential for cytokine- directed therapies. Annu Rev Med. 2015; 66: 145-59.
     Google Scholar
  15. Gianella S, Schaer DJ, Schwarz U, Kurrer M, Heppner FL, Fehr J, et al. Retinal microangiopathy and rapidly fatal cerebral edema in a patient with adult-onset Still's disease and concurrent macrophage activation syndrome. Am J Hematol. 2008; 83(5): 424-7.
     Google Scholar
  16. Kaneko K, Kaburaki M, Muraoka S, Tanaka N, Yamamoto T, Kusunoki Y, et al. Exacerbation of adult-onset Still's disease, possibly related to elevation of serum tumor necrosis factor-alpha after etanercept administration. Int J Rheum Dis. 2010; 13(4): e67-9.
     Google Scholar
  17. Kobayashi M, Takahashi Y, Yamashita H, Kaneko H, Mimori A. Benefit and a possible risk of tocilizumab therapy for adult-onset Still's disease accompanied by macrophage-activation syndrome. Mod Rheumatol. 2011; 21(1): 92-6.
     Google Scholar
  18. Banse C, Vittecoq O, Benhamou Y, Gauthier-Prieur M, Lequerré T, Lévesque H. Reactive macrophage activation syndrome possibly triggered by canakinumab in a patient with adult-onset Still's disease. Joint Bone Spine. 2013; 80(6): 653-5.
     Google Scholar
  19. Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007; 48(2): 124-31
     Google Scholar
  20. Opoka-Winiarska V, Grywalska E, Roliński J. Could hemophagocytic lymphohistiocytosis be the core issue of severe COVID-19 cases? BMC Med. 2020; 18(1): 214
     Google Scholar
  21. Agarwal A, Agarwal M, Khandelwal V, Mathur P. Adult-onset Still's disease masquerading as multiple organ failure: Neither benign nor so rare. Journal of clinical rheumatology. 2018; 24(6): 342-346
     Google Scholar
  22. Agarwal A, Agarwal A. Adult onset stills disease: Advocating for new markers to overcome the diagnostic challenge. Asian Journal of Medicine and Health.2018; 10(4): 1-8.
     Google Scholar
  23. Agarwal A, Agarwal A, Khan A. A case of Adult Onset Stills Disease: Not so Uncommon Cause of Fever of Unknown Origin. Asian Journal of Medicine and Health. 2018; 11(3): 1-7
     Google Scholar
  24. Agarwal A, Gondaliya D N. Adult-onset Still's disease: A case report J Acute Dis.2020; 9(4): 179-182.
     Google Scholar
  25. Agarwal A, Agarwal A. Infection Associated Secondary Hemophagocytic Lymphohistiocytosis in Sepsis Syndromes - A Tip of an Iceberg. J Assoc Physicians India. 2016; 64(10): 44-50.
     Google Scholar
  26. Carter SJ, Tattersall RS, Ramanan AV. Macrophage activation syndrome in adults: recent advances in pathophysiology, diagnosis and treatment. Rheumatology (Oxford). 2019; 58(1): 5-17.
     Google Scholar
  27. Fukaya S, Yasuda S, Hashimoto T, Oku K, Kataoka H, Horita T, et al. Clinical features of haemophagocytic syndrome in patients with systemic autoimmune diseases: analysis of 30 cases. Rheumatology (Oxford). 2008; 47(11): 1686-91.
     Google Scholar