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Macrophage activation syndrome in systemic lupus erythematosus and systemic-onset juvenile idiopathic arthritis: a retrospective study of similarities and dissimilarities

  • Observational Research
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Abstract

Macrophage activation syndrome (MAS) is a serious complication of rheumatic diseases. Fever and hyperferritinemia are common in active systemic-onset juvenile idiopathic arthritis (sJIA) and cytopenia in active systemic lupus erythematosus (SLE), thus recognizing MAS in them is a challenge. We compared clinical and laboratory parameters, various classification criteria, and outcomes of MAS in SLE and sJIA. Clinical and laboratory data were extracted from case records of patients with clinician diagnosed cases of SLE-MAS (adult and pediatric) and sJIA-MAS, admitted (2004–2018) at a tertiary care hospital. Ravelli, International consensus, HLH-2004, and criteria proposed by Parodi et al. were applied and compared. Among 33 patients (18 females) with MAS, 19 had SLE (7, childhood-onset SLE) and 14 had sJIA. MAS was more likely to be the presenting manifestation of disease in SLE (p < 0.05). There were no differences in the clinical features among them. Patients with SLE-MAS had lower baseline total leucocyte and platelet counts (p < 0.01), whereas patients with sJIA-MAS had significantly higher median CRP (p = 0.002), fall in TLC (p = 0.012), delta ESR/CRP ratio (p = 0.02), and lower fibrinogen level (p = 0.006). Neutrophil-to-lymphocyte ratio, ferritin/CRP ratio, and the number of patients with ferritin/ESR > 80 were similar. Only 6/33(18%) fulfilled the HLH criteria. Criteria meant for sJIA-MAS or SLE-MAS performed well for both diseases and the majority of patients could be diagnosed using them. Two patients died in each group. MAS in SLE and sJIA is more similar than dissimilar in clinical features and outcome. Criteria meant for MAS in sJIA or SLE-MAS performed equally well in both diseases.

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References

  1. Lerkvaleekul B, Vilaiyuk S (2018) Macrophage activation syndrome: early diagnosis is key. Open Access Rheumatol Res Rev 10:117–128. https://doi.org/10.2147/OARRR.S151013

    Article  CAS  Google Scholar 

  2. Bennett TD, Fluchel M, Hersh AO et al (2012) Macrophage activation syndrome in children with systemic lupus erythematosus and children with juvenile idiopathic arthritis. Arthritis Rheum 64:4135–4142. https://doi.org/10.1002/art.34661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ruscitti P, Rago C, Breda L et al (2017) Macrophage activation syndrome in Still’s disease: analysis of clinical characteristics and survival in paediatric and adult patients. Clin Rheumatol 36:2839–2845. https://doi.org/10.1007/s10067-017-3830-3

    Article  PubMed  Google Scholar 

  4. Behrens EM, Beukelman T, Paessler M, Cron RQ (2007) Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis. J Rheumatol 34:1133–1138

    PubMed  Google Scholar 

  5. Kishida D, Sakaguchi N, Ueno K-I et al (2020) Macrophage activation syndrome in adult dermatomyositis: a case-based review. Rheumatol Int 40:1151–1162. https://doi.org/10.1007/s00296-020-04590-9

    Article  PubMed  Google Scholar 

  6. Poddighe D, Dauyey K (2020) Macrophage activation syndrome in juvenile dermatomyositis: a systematic review. Rheumatol Int 40:695–702. https://doi.org/10.1007/s00296-019-04442-1

    Article  PubMed  Google Scholar 

  7. Zandman-goddard G, Shoenfeld Y (2007) Ferritin in autoimmune diseases. Autoimmune Rev 6:457–463. https://doi.org/10.1016/j.autrev.2007.01.016

    Article  CAS  Google Scholar 

  8. Tripathy R, Panda AK, Das BK (2015) Serum ferritin level correlates with SLEDAI scores and renal involvement in SLE. Lupus 24:82–89. https://doi.org/10.1177/0961203314552290

    Article  CAS  PubMed  Google Scholar 

  9. Nishiya K, Hashimoto K (1997) Elevation of serum ferritin levels as a marker for active systemic lupus erythematosus. Clin Exp Rheumatol 15:39–44

    CAS  PubMed  Google Scholar 

  10. Ravelli A, Minoia F, Davì S et al (2016) 2016 classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a European league against rheumatism/American college of rheumatology/paediatric rheumatology international trials organisation collaborative initiative. Arthritis Rheumatol 68:566–576. https://doi.org/10.1002/art.39332

    Article  PubMed  Google Scholar 

  11. Ravelli A, Davì S, Minoia F et al (2015) Macrophage activation syndrome. Hematol Oncol Clin North Am 29:927–941. https://doi.org/10.1016/j.hoc.2015.06.010

    Article  PubMed  Google Scholar 

  12. Parodi A, Davì S, Pringe AB et al (2009) Macrophage activation syndrome in juvenile systemic lupus erythematosus: a multinational multicenter study of thirty-eight patients. Arthritis Rheum 60:3388–3399. https://doi.org/10.1002/art.24883

    Article  CAS  PubMed  Google Scholar 

  13. Aytaç S, Batu ED, Ünal Ş et al (2016) Macrophage activation syndrome in children with systemic juvenile idiopathic arthritis and systemic lupus erythematosus. Rheumatol Int 36:1421–1429. https://doi.org/10.1007/s00296-016-3545-9

    Article  CAS  PubMed  Google Scholar 

  14. Henter J-I, Horne A, Aricó M et al (2007) HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 48:124–131. https://doi.org/10.1002/pbc.21039

    Article  PubMed  Google Scholar 

  15. Gavand P-E, Serio I, Arnaud L et al (2017) Clinical spectrum and therapeutic management of systemic lupus erythematosus-associated macrophage activation syndrome: a study of 103 episodes in 89 adult patients. Autoimmun Rev 16:743–749. https://doi.org/10.1016/j.autrev.2017.05.010

    Article  CAS  PubMed  Google Scholar 

  16. Borgia RE, Gerstein M, Levy DM et al (2018) Features, treatment, and outcomes of macrophage activation syndrome in childhood-onset systemic lupus erythematosus. Arthritis Rheumatol Hoboken NJ 70:616–624. https://doi.org/10.1002/art.40417

    Article  CAS  Google Scholar 

  17. Ss A, Bw Y, Sm J et al (2017) In-hospital mortality in febrile lupus patients based on 2016 EULAR/ACR/PRINTO classification criteria for macrophage activation syndrome. Semin Arthritis Rheum 47:216–221. https://doi.org/10.1016/j.semarthrit.2017.02.002

    Article  Google Scholar 

  18. Zou L-X, Zhu Y, Sun L et al (2020) Clinical and laboratory features, treatment, and outcomes of macrophage activation syndrome in 80 children: a multi-center study in China. World J Pediatr WJP 16:89–98. https://doi.org/10.1007/s12519-019-00256-0

    Article  CAS  PubMed  Google Scholar 

  19. Minoia F, Davì S, Horne A et al (2014) Clinical features, treatment, and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a multinational, multicenter study of 362 patients. Arthritis Rheumatol 66:3160–3169. https://doi.org/10.1002/art.38802

    Article  PubMed  Google Scholar 

  20. Gormezano NWS, Otsuzi CI, Barros DL et al (2016) Macrophage activation syndrome: a severe and frequent manifestation of acute pancreatitis in 362 childhood-onset compared to 1830 adult-onset systemic lupus erythematosus patients. Semin Arthritis Rheum 45:706–710. https://doi.org/10.1016/j.semarthrit.2015.10.015

    Article  CAS  PubMed  Google Scholar 

  21. García-Consuegra Molina J, Merino Muñoz R, de Inocencio AJ (2003) Grupo de estudio del síndrome de activación macrofágica y artritis idiopática juvenil de la sociedad española de reumatología pediátrica (2008) [macrophage activation syndrome and juvenile idiopathic arthritis. A multicenter study]. An Pediatr Barc Spain 68:110–116. https://doi.org/10.1157/13116224

    Article  Google Scholar 

  22. Yao HH, Wang YN, Zhang X et al (2019) Clinical characteristics and treatment outcomes of macrophage activation syndrome in adults: a case series of 67 patients. Beijing Da Xue Xue Bao 51:996–1002. https://doi.org/10.19723/j.issn.1671-167X.2019.06.003

    Article  CAS  PubMed  Google Scholar 

  23. Ruscitti P, Ciccia F, Cipriani P et al (2016) The CD68(+)/H-ferritin(+) cells colonize the lymph nodes of the patients with adult onset Still’s disease and are associated with increased extracellular level of H-ferritin in the same tissue: correlation with disease severity and implication for pathogenesis. Clin Exp Immunol 183:397–404. https://doi.org/10.1111/cei.12738

    Article  CAS  PubMed  Google Scholar 

  24. Lehmberg K, Pink I, Eulenburg C et al (2013) Differentiating macrophage activation syndrome in systemic juvenile idiopathic arthritis from other forms of hemophagocytic lymphohistiocytosis. J Pediatr 162:1245–1251. https://doi.org/10.1016/j.jpeds.2012.11.081

    Article  CAS  PubMed  Google Scholar 

  25. Liu A-C, Yang Y, Li M-T et al (2018) Macrophage activation syndrome in systemic lupus erythematosus: a multicenter, case-control study in China. Clin Rheumatol 37:93–100. https://doi.org/10.1007/s10067-017-3625-6

    Article  PubMed  Google Scholar 

  26. Maruyama J, Inokuma S (2010) Cytokine Profiles of Macrophage Activation Syndrome Associated with Rheumatic Diseases. J Rheumatol. https://doi.org/10.3899/jrheum.090662

    Article  PubMed  Google Scholar 

  27. Sato S, Uejima Y, Arakawa Y et al (2019) Clinical features of macrophage activation syndrome as the onset manifestation of juvenile systemic lupus erythematosus. Rheumatol Adv Pract 3:rkz013. https://doi.org/10.1093/rap/rkz013

    Article  PubMed  PubMed Central  Google Scholar 

  28. Nishino A, Katsumata Y, Kawasumi H et al (2019) Usefulness of soluble CD163 as a biomarker for macrophage activation syndrome associated with systemic lupus erythematosus. Lupus 28:986–994. https://doi.org/10.1177/0961203319860201

    Article  CAS  PubMed  Google Scholar 

  29. Hs Z, Xy X, Yd W et al (2008) Macrophage activation syndrome in 13 children with systemic-onset juvenile idiopathic arthritis. World J Pediatr WJP 4:97–101. https://doi.org/10.1007/s12519-008-0018-6

    Article  Google Scholar 

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Acknowledgements

Department of Pathology and Hematology, Sanjay Gandhi Postgraduate Institute of Medical Sciences.

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Authors and Affiliations

  1. Department of Clinical Immunology and Rheumatology, SGPGIMS, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raibareli Road, Lucknow, 226014, India

    R. Naveen, Avinash Jain, Hafis Muhammed, Latika Gupta, Durga P. Misra, Able Lawrence, Vikas Agarwal, Ramnath Misra & Amita Aggarwal

  2. Department of Rheumatology, SMS Medical College and Hospital, Jaipur, India

    Avinash Jain

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Contributions

All authors contributed to the data. NR extracted the data from records. NR and AJ performed the search for articles and wrote the draft manuscript. AA was involved with conception and critical revision of the manuscript. All authors approved the final version of the manuscript, take responsibility for the content of the entire manuscript, and affirm that any queries related to any aspect of the same are appropriately managed.

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Correspondence to Amita Aggarwal.

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Naveen, R., Jain, A., Muhammed, H. et al. Macrophage activation syndrome in systemic lupus erythematosus and systemic-onset juvenile idiopathic arthritis: a retrospective study of similarities and dissimilarities. Rheumatol Int 41, 625–631 (2021). https://doi.org/10.1007/s00296-020-04763-6

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