Clinical Spectrum and Therapeutic Management of Systemic Lupus Erythematosus-Associated Macrophage Activation Syndrome
Main Article Content
Abstract
Macrophage activation syndrome can be primary with a genetic etiology, or secondary, associated with malignancies, infections or systemic diseases. Its a severe and potentially life-threatening complication of autoimmune diseases. The incidence of MAS among patients with systemic lupus erythematosus is not well known, as most of the previous studies were limited to a small number of case series or case reports. In recent years it has been suggested that macrophage activation syndrome in systemic lupus erythemaosus may be underrecognized because it can mimic the clinical features of the underlying disease or be confused with an infectious complication. The diagnosis of macrophage activation sydrome in adults is supported by hyperferritinemia (higher than 2000 ng/ml), and/or splenomegaly, pronounced cytopenias, hypofibrinogenemia, characteristic cytokine profile and hypertriglyceridemia. In the case of systemic lupus erythematosus flare, hyerferritinemia is the strongest indicator to differentiate them from MAS. So far, no validated and universally embraced diagnostic criteria for macrophage activation syndrome in adult secondary to systemic lupus erythematosus are available. It is important to know the parameters that can guide the clinician towards the diagnosis of macrophage activation syndrome in adult with systemic lupus. Early diagnosis and intensive therapy are essential in improving clinical outcomes. Hence, we decided to write this mini- review to focus on the demographic data, on the pathophysiological mechanisms, clinical and laboratory manifestations, treatments, and outcomes of patients with systemic lupus erythematosus associated macrophage activation syndrome.
Keywords:
Lupus erythematosus systemic, Macrophage activation syndrome, Ferritin-Treatment-Prognosis
Article Details
How to Cite
W, Ammouri et al.
Clinical Spectrum and Therapeutic Management of Systemic Lupus Erythematosus-Associated Macrophage Activation Syndrome.
Medical Research Archives, [S.l.], v. 10, n. 9, sep. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2993>. Date accessed: 20 apr. 2024.
doi: https://doi.org/10.18103/mra.v10i9.2993.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Minoia F, Davi S, Horne A, Demirkaya E, Bovis F, Li C, et al. Clinical features, treatment, and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a multinational, multicenter study of 362 patients. Arthritis Rheumatol. 2014; 66(11): 3160–3169. doi: 10.1002/art.38802
2. Zhang K, Biroschak J, Glass DN, Thompson SD, Finkel T, Passo MH, et al. Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms. Arthritis Rheum. 2008; 58(9):2892–2896. doi: 10.1002/art.23734
3. Henter JI, Horne A, Arico M, et al. HLH-2004: ´ diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis’. Pediatr Blood Cancer. 2007; 48(2):124-131. doi: 10.1002/pbc.21039
4. Janka GE, Lehmberg K. Hemophagocytic syndromes--an update. Blood Rev. 2014; 28(4):135-142. doi: 10.1016/j.blre.2014.03.002
5. Ramos-Casals M, Brito-Zeron P, L ´ opez- ´ Guillermo A, Khamashta MA, Bosch X. Adult haemophagocytic syndrome. Lancet. 2014; 383(9927):1503-1516. doi: 10.1016/S0140-6736(13)61048-X
6. Stepp SE, Dufourcq-Lagelouse R, LeDeist F el al. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science. 1999; 286(5446):1957–1959.doi: 10.1126/science.286.5446.1957
7. Fukaya S, Yasuda S, Hashimoto T et al. Clinical features of haemophagocytic syndrome in patients with systemic autoimmune diseases: analysis of 30 cases. Rheumatology (Oxford). 2008; 47(11):1686–1691. doi: 10.1093/rheumatology/ken342
8. Lehmberg K, Sprekels B, Nichols KE, Woessmann W, Muller I, Suttorp M, et al. Malignancy-associated haemophagocytic lymphohistiocytosis in children and adolescents. Br J Haematol. 2015; 170(4):539–549. doi: 10.1111/bjh.13462
9. Daver N, McClain K, Allen CE, et al. A consensus review on malignancy-associated hemophagocytic lymphohistiocytosis in adults. Cancer. 2017; 123(17):3229-3240. doi: 10.1002/cncr.30826
10. Rouphael NG, Talati NJ, Vaughan C, Cunningham K, Moreira R, Gould C. Infections associated with haemophagocytic syndrome. Lancet Infect Dis. 2007; 7(12): 814-822. doi: 10.1016/S1473-3099(07)70290-6
11. La Rosée P, Horne A, Hines M, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019; 133(23):2465-2477. doi: 10.1182/blood.2018894618
12. Kim JM, Kwok SK, Ju JH, Kim HY, Park SH. Reactive hemophagocytic syndrome in adult Korean patients with systemic lupus erythematosus: a case-control study and literature review. J Rheumatol. 2012; 39(1):86–93. doi: 10.3899/jrheum.110639. Epub 2011 Dec 15
13. Vilaiyuk S, Sirachainan N, Wanitkun S, Pirojsakul K, Vaewpanich J. Recurrent macrophage activation syndrome as the primary manifestation in systemic lupus erythematosus and the benefit of serial ferritin measurements: a case-based review. Clin Rheumatol. 2013 ; 3(6):899–904. doi: 10.1007/s10067-013-2227-1
14. Lambotte O, Khellaf M, Harmouche H, et al. Characteristics and long-term outcome of 15 episodes of systemic lupus erythematosus-associated hemophagocytic syndrome. Medicine (Baltimore). 2006; 85(3):169–182. doi: 10.1097/01.md.0000224708.62510.d1
15. QianJ, YangCD. Hemophagocytic syndromeasone of main manifestations in untreated systemic lupus erythematosus: two case reports and literature review. Clin Rheumatol. 2007; 26(5):807–810. doi: 10.1007/s10067-006-0245-y
16. Parodi A, Davì S, Pringe AB et al. Lupus Working Group of the Paediatric Rheumatology European Society Macrophage activation syndrome in juvenile systemic lupus erythematosus: a multinational multicenter study of thirty-eight patients. Arthritis Rheum. 2009; 60(11):3388–3399. doi: 10.1002/art.24883
17. Gavand PE, Serio I, Arnaud L, et al. Clinical spectrum and therapeutic management of systemic lupus erythematosus-associated macrophage activation syndrome: A study of 103 episodes in 89 adult patients. Autoimmun Rev. 2017; 16(7):743-749. doi: 10.1016/j.autrev.2017.05.010
18. Dall'Ara F , Cavazzana I, Frassi M, et al. Macrophage activation syndrome in adult systemic lupus erythematosus: report of seven adult cases from a single Italian rheumatology center. Reumatismo. 2018; 6; 70(2):100-105. doi: 10.4081/reumatismo.2018.1023
19. Ahn SS, Yoo BW, Jung SM, Lee SW, Park YB, Song JJ. In-hospital mortality in febrile lupus patients based on 2016 EULAR/ACR/PRINTO classification criteria for macrophage activation syndrome. Semin Arthritis Rheum. 2017; 47(2):216-221. doi: 10.1016/j.semarthrit.2017.02.002
20. Liu AC, Yang Y, Li MT, et al. Macrophage activation syndrome in systemic lupus erythematosus: a multicenter, case-control study in China. Clin Rheumatol. 2018; 37(1):93-100. doi: 10.1007/s10067-017-3625-6
21. Cohen E M, D'Silva K, Kreps D, Son MB, Costenbader K H. Arthritis and Use of Hydroxychloroquine Associated with a Decreased Risk of Macrophage Activation Syndrome among Adult Patients Hospitalized with Systemic Lupus Erythematosus. Lupus. 2018; 27(7): 1065–1071. doi: 10.1177/0961203318759428. Epub 2018 Feb 16.
22. Ammouri W, Harmouche H, Radi N, et al. Clinical spectrum and therapeutic management of systemic lupus erythematosus-associated macrophage activation syndrome: a study of 20 Moroccan adult patients. Clin Rheumatol. 2022 Jul;41(7):2021-2033. doi: 10.1007/s10067-022-06055-9.
23. Carter SJ, Tattersall RS, Ramanan AV. Macrophage activation syndrome in adults: recent advances in pathophysiology, diagnosis and treatment. Rheumatology. 2019; 58(1):5–17. doi: 10.1093/rheumatology/key006.
24. Zhang M, Behrens EM, Atkinson TP, Shakoory B, Grom AA, Cron RQ. Genetic defects in cytolysis in macrophage activation syndrome. Curr Rheumatol Rep. 2014;16:439. doi: 10.1007/s11926-014-0439-2 46.
25. Kaufman KM, Linghu B, Szustakowski JD, Husami A, Yang F, Zhang K, et al. Whole-exome sequencing reveals overlap between macrophage activation syndrome in systemic juvenile idiopathic arthritis and familial hemophagocytic lymphohistiocytosis. Arthritis Rheumatol. 2014; 66:3486– 95. doi: 10.1002/art.38793
26. Hayden A, Park S, Giustini D, Lee AY, Chen LY. Hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) in adults: a systematic scoping review. Blood Rev. 2016;30(6):411-420. doi:10.1016/j. blre.2016.05.00
27. Brisse E, Wouters CH, Matthys P. Advances in the pathogenesis of primary and secondary haemophagocytic lymphohistiocytosis: differences and similarities. Br J Haematol. 2016;174(2):203–217. doi:10.1111/bjh.14147
28. Shimizu M, Nakagishi Y, Inoue N, et al. Interleukin-18 for predicting the development of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Clin Immunol 2015; 160(2):277–81
29. Yang S-L, Xu X-J, Tang Y-M, et al. Associations between inflammatory cytokines and organ damage in pediatric patients with hemophagocytic lymphohistiocytosis. Cytokine 2016;85:14–7.
30. Grom AA. Natural killer cell dysfunction: A common pathway in systemic-onset juvenile rheumatoid arthritis, macrophage activation syndrome, and hemophagocytic lymphohistiocytosis? Arthritis Rheum. 2004; 50: 689-698. doi: 10.1002/art.20198 (REF34)
31. Usami M, Shimizu M, Mizuta M, Inoue N, Irabu H, Sakumura N, Nakagishi Y, Yachie A. Extensive serum biomarker analysis in patients with macrophage activation syndrome associated with systemic lupus erythematosus. Clin Immunol. 2019; 208:108255. doi: 10.1016/j.clim.2019.108255.
32. Zhang L, Zhou J, Sokol L. Hereditary and acquired hemophagocytic lymphohistiocytosis. Cancer Contr 2014; 21(4):301-12
33. Tumian NR, Wong CL. Pregnancy-related hemophagocytic lymphohistiocytosis associated with cytomegalovirus infection: a diagnostic and therapeutic challenge. Taiwan J Obstet Gynecol. 2015; 54(4):432–437. doi:10.1016/j.tjog.2014.11.023
34. Zhang Y, Liang G, Qin H, Li Y, Zeng X. Tuberculosis-associated hemophagocytic lymphohistiocytosis with initial presentation of fever of unknown origin in a general hospital: an analysis of 8 clinical cases. Medicine. 2017;96:e6575. https://doi.org/10.1097/MD.0000000000006575
35. Hashmat M, Rana RS, Mahmud TE, Rasheed A, Rehman AU, Pirzada SAR, et al. Case report of a lupus patient with a severe flare and miliary tuberculosis: need for proper guidelines for management. Oxford Med Case Rep. 2017;7:omx030. https://doi.org/10.1093/omcr/omx030
36. Brastianos PK, Swanson JW, Torbenson M, et al. Tuberculosis associated haemophagocytic syndrome. Lancet Infect Dis 2006;6:447–54.
37. Rafał Machowicz, Gritta Janka, Wieslaw Wiktor-Jedrzejczak. Similar but not the same: Differential diagnosis of HLH and sepsis. Crit Rev Oncol Hematol. 2017; 114:1-12. doi: 10.1016/j.critrevonc.2017.03.023.
38. Kumakura S, Murakawa Y. Clinical characteristics and treatment outcomes of autoimmune associated hemophagocytic syndrome in adults. Arthritis Rheumatol. 2014; 66: 2297-2307. doi: 10.1002/art.38672 ref 27
39. Eberhard OK, Haubitz M, Brunkhorst FM, Kliem V, Koch KM, Brunkhorst R. Usefulness of procalcitonin for differentiation between activity of systemic autoimmune disease (systemic lupus erythematosus/systemic antineutrophil cytoplasmic antibody-associated vasculitis) and invasive bacterial infection. Arthritis Rheum. 1997; 40(7):1250 –6. doi: 10.1002/1529-0131(199707)40:7<1250::AID-ART9>3.0.CO;2-A
40. Bador KM, Intan S, Hussin S, Gafor AHA. Serum procalcitonin has negative predictive value for bacterial infection in active systemic lupus erythematosus. Lupus. 2012; 21(11):1172 –7. doi: 10.1177/0961203312450085.
41. Quintana G, Medina YF, Rojas C, Fernandez A, Restrepo JF, Rondon F, et al. The use of procalcitonin determinations in evaluation of systemic lupus erythematosus. J Clin Rheumatol Pract Rep Rheum Musculoskelet Dis. 2008;14(3):138–42. doi: 10.1097/RHU.0b013e3181772cca.
4 Beça S, Rodríguez-Pintó I, Alba MA, Cervera R, Espinosa G. Development and validation of a risk calculator to differentiate flares from infections in systemic lupus erythematosus patients with fever. Autoimmun Rev. 2015; 14(7):586–93. doi: 10.1016/j.autrev.2015.02.005.
43. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003; 111:1805–12. doi: 10.1172/JCI18921.
44. Fardet L, Galicier L, Lambotte O, et al. Development and validation of a score for the diagnosis of reactive hemophagocytic syndrome (HScore). Arthritis Rheumatol. 2014; 66: 2613-20. doi: 10.1002/art.38690 REF
45. Batu ED, Erden A, Seyhoğlu E, et al. Assessment of the H Score for reactive haemophagocytic syndrome in patients with rheumatic diseases. Scand J Rheumatol. 2017; 46: 44-8. doi: 10.3109/03009742.2016.1167951
46. Ravelli A, Minoia F, Davi S et al. 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 68:566-76. doi: 10.1002/art.39332
47. Ravelli A, Minoia F, Davi 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. Ann Rheum Dis. 2016; 75:481-9. doi: 10.1136/annrheumdis-2015-208982
48. Melissa R Hines, Tatiana von Bahr Greenwood, Gernot Beutel et al. Consensus-Based Guidelines for the Recognition, Diagnosis, and Management of Hemophagocytic Lymphohistiocytosis in Critically Ill Children and Adults. Crit Care Med. 2021; Oct5. doi: 10.1097/CCM.0000000000005361
49. Nakagishi Y, Shimizu M, Kasai K, Miyoshi M, Yachie A. Successful therapy of macrophage activation syndrome with dexamethasone palmitate. Mod Rheumatol. 2016; 26(4):617–620. doi: 10.3109/14397595.2014.906053
50. Hines Melissa R, von Bahr Tatiana, Greenwood Gernot Beutel et al. Consensus-based guidelines for the recognition, diagnosis, and management of hemophagocytic lymphohistiocytosis in critically ill children and adults. Crit Care Med. 2021; https:// doi. org/ 10. 1097/ CCM. 00000 00000 005361
51. Wesam Gouda, Faisal Alsaqabi, Abdelhfeez Moshrif, et al. Macrophage activation syndrome triggered by systemic lupus erythematosus flare: successful treatment with a combination of dexamethasone sodium phosphate, intravenous immunoglobulin, and cyclosporine: a case report. J Med Case Rep. 2021; 7;15(1):497. doi: 10.1186/s13256-021-03072-1
52. Ueda Y, Yamashita H, Takahashi Y, Kaneko H, Kano T, Mimori A. Refractory hemophagocytic syndrome in systemic lupus erythematosus successfully treated with intermittent intravenous cyclophosphamide: three case reports and literature review. Clin Rheumatol. 2014; 33(2):281–286. doi :10.1007/s10067-013-2451-8
53. Ravelli A, Viola S, De Benedetti F, et al. Dramatic efficacy of cyclosporine A in macrophage activation syndrome. Clin Exp Rheumatol. 2001; 19:108.
54. Emmenegger U, Frey U, Reimers A, Fux C, Semela D, Cottagnoud P, Spaeth PJ, Neftel KA. Hyperferritinemia as indicator for intravenous immunoglobulin treatment in reactive macrophage activation syndromes. Am J Hematol Sep. 2001;68(1):4-10. doi: 10.1002/ajh.1141
55. So MW, Koo BS, Kim YJ, et al. Successful rituximab treatment of refractory hemophagocytic lymphohistiocytosis and autoimmune hemolytic anemia associated with systemic lupus erythematosus. Mod Rheumatol. 2014;24:855–7. doi: 10.3109/14397595.2013.874740
56. Bakshi J, Hassan S, D’Cruz D, et al. Rituximab therapy in refractory macrophage activation syndrome secondary to systemic lupus erythematosus. Lupus. 2013; 22:1544–6. doi: 10.1177/0961203313504634
57. Ruscitti P, Cipriani P, Ciccia F, et al. Prognostic factors of macrophage activation syndrome, at the time of diagnosis, in adult patients affected by autoimmune disease : Analysis of 41 cases collected in 2 rheumatologic centers. Autoimmun Rev. 2017; 16(1):16-21. doi: 10.1016/j.autrev.2016.09.016
58. Yao Ke, Chengyin Lv, Wenhua Xuan, et al. Clinical analysis of macrophage activation syndrome in adult rheumatic disease: A multicenter retrospective study. International Journal of Rheumatic Diseases. 2000; 00:1–9. doi: 10.1111/1756-185X.13955
59. Machowicz R, Janka G, Wiktor-Jedrzejczak W. Similar but not the same: Differential diagnosis of HLH and sepsis. Crit Rev Oncol Hematol 114:1–12. https:// doi. org/ 10. 1016/j. critr evonc. 2017. 03. 023
2. Zhang K, Biroschak J, Glass DN, Thompson SD, Finkel T, Passo MH, et al. Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms. Arthritis Rheum. 2008; 58(9):2892–2896. doi: 10.1002/art.23734
3. Henter JI, Horne A, Arico M, et al. HLH-2004: ´ diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis’. Pediatr Blood Cancer. 2007; 48(2):124-131. doi: 10.1002/pbc.21039
4. Janka GE, Lehmberg K. Hemophagocytic syndromes--an update. Blood Rev. 2014; 28(4):135-142. doi: 10.1016/j.blre.2014.03.002
5. Ramos-Casals M, Brito-Zeron P, L ´ opez- ´ Guillermo A, Khamashta MA, Bosch X. Adult haemophagocytic syndrome. Lancet. 2014; 383(9927):1503-1516. doi: 10.1016/S0140-6736(13)61048-X
6. Stepp SE, Dufourcq-Lagelouse R, LeDeist F el al. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science. 1999; 286(5446):1957–1959.doi: 10.1126/science.286.5446.1957
7. Fukaya S, Yasuda S, Hashimoto T et al. Clinical features of haemophagocytic syndrome in patients with systemic autoimmune diseases: analysis of 30 cases. Rheumatology (Oxford). 2008; 47(11):1686–1691. doi: 10.1093/rheumatology/ken342
8. Lehmberg K, Sprekels B, Nichols KE, Woessmann W, Muller I, Suttorp M, et al. Malignancy-associated haemophagocytic lymphohistiocytosis in children and adolescents. Br J Haematol. 2015; 170(4):539–549. doi: 10.1111/bjh.13462
9. Daver N, McClain K, Allen CE, et al. A consensus review on malignancy-associated hemophagocytic lymphohistiocytosis in adults. Cancer. 2017; 123(17):3229-3240. doi: 10.1002/cncr.30826
10. Rouphael NG, Talati NJ, Vaughan C, Cunningham K, Moreira R, Gould C. Infections associated with haemophagocytic syndrome. Lancet Infect Dis. 2007; 7(12): 814-822. doi: 10.1016/S1473-3099(07)70290-6
11. La Rosée P, Horne A, Hines M, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019; 133(23):2465-2477. doi: 10.1182/blood.2018894618
12. Kim JM, Kwok SK, Ju JH, Kim HY, Park SH. Reactive hemophagocytic syndrome in adult Korean patients with systemic lupus erythematosus: a case-control study and literature review. J Rheumatol. 2012; 39(1):86–93. doi: 10.3899/jrheum.110639. Epub 2011 Dec 15
13. Vilaiyuk S, Sirachainan N, Wanitkun S, Pirojsakul K, Vaewpanich J. Recurrent macrophage activation syndrome as the primary manifestation in systemic lupus erythematosus and the benefit of serial ferritin measurements: a case-based review. Clin Rheumatol. 2013 ; 3(6):899–904. doi: 10.1007/s10067-013-2227-1
14. Lambotte O, Khellaf M, Harmouche H, et al. Characteristics and long-term outcome of 15 episodes of systemic lupus erythematosus-associated hemophagocytic syndrome. Medicine (Baltimore). 2006; 85(3):169–182. doi: 10.1097/01.md.0000224708.62510.d1
15. QianJ, YangCD. Hemophagocytic syndromeasone of main manifestations in untreated systemic lupus erythematosus: two case reports and literature review. Clin Rheumatol. 2007; 26(5):807–810. doi: 10.1007/s10067-006-0245-y
16. Parodi A, Davì S, Pringe AB et al. Lupus Working Group of the Paediatric Rheumatology European Society Macrophage activation syndrome in juvenile systemic lupus erythematosus: a multinational multicenter study of thirty-eight patients. Arthritis Rheum. 2009; 60(11):3388–3399. doi: 10.1002/art.24883
17. Gavand PE, Serio I, Arnaud L, et al. Clinical spectrum and therapeutic management of systemic lupus erythematosus-associated macrophage activation syndrome: A study of 103 episodes in 89 adult patients. Autoimmun Rev. 2017; 16(7):743-749. doi: 10.1016/j.autrev.2017.05.010
18. Dall'Ara F , Cavazzana I, Frassi M, et al. Macrophage activation syndrome in adult systemic lupus erythematosus: report of seven adult cases from a single Italian rheumatology center. Reumatismo. 2018; 6; 70(2):100-105. doi: 10.4081/reumatismo.2018.1023
19. Ahn SS, Yoo BW, Jung SM, Lee SW, Park YB, Song JJ. In-hospital mortality in febrile lupus patients based on 2016 EULAR/ACR/PRINTO classification criteria for macrophage activation syndrome. Semin Arthritis Rheum. 2017; 47(2):216-221. doi: 10.1016/j.semarthrit.2017.02.002
20. Liu AC, Yang Y, Li MT, et al. Macrophage activation syndrome in systemic lupus erythematosus: a multicenter, case-control study in China. Clin Rheumatol. 2018; 37(1):93-100. doi: 10.1007/s10067-017-3625-6
21. Cohen E M, D'Silva K, Kreps D, Son MB, Costenbader K H. Arthritis and Use of Hydroxychloroquine Associated with a Decreased Risk of Macrophage Activation Syndrome among Adult Patients Hospitalized with Systemic Lupus Erythematosus. Lupus. 2018; 27(7): 1065–1071. doi: 10.1177/0961203318759428. Epub 2018 Feb 16.
22. Ammouri W, Harmouche H, Radi N, et al. Clinical spectrum and therapeutic management of systemic lupus erythematosus-associated macrophage activation syndrome: a study of 20 Moroccan adult patients. Clin Rheumatol. 2022 Jul;41(7):2021-2033. doi: 10.1007/s10067-022-06055-9.
23. Carter SJ, Tattersall RS, Ramanan AV. Macrophage activation syndrome in adults: recent advances in pathophysiology, diagnosis and treatment. Rheumatology. 2019; 58(1):5–17. doi: 10.1093/rheumatology/key006.
24. Zhang M, Behrens EM, Atkinson TP, Shakoory B, Grom AA, Cron RQ. Genetic defects in cytolysis in macrophage activation syndrome. Curr Rheumatol Rep. 2014;16:439. doi: 10.1007/s11926-014-0439-2 46.
25. Kaufman KM, Linghu B, Szustakowski JD, Husami A, Yang F, Zhang K, et al. Whole-exome sequencing reveals overlap between macrophage activation syndrome in systemic juvenile idiopathic arthritis and familial hemophagocytic lymphohistiocytosis. Arthritis Rheumatol. 2014; 66:3486– 95. doi: 10.1002/art.38793
26. Hayden A, Park S, Giustini D, Lee AY, Chen LY. Hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) in adults: a systematic scoping review. Blood Rev. 2016;30(6):411-420. doi:10.1016/j. blre.2016.05.00
27. Brisse E, Wouters CH, Matthys P. Advances in the pathogenesis of primary and secondary haemophagocytic lymphohistiocytosis: differences and similarities. Br J Haematol. 2016;174(2):203–217. doi:10.1111/bjh.14147
28. Shimizu M, Nakagishi Y, Inoue N, et al. Interleukin-18 for predicting the development of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Clin Immunol 2015; 160(2):277–81
29. Yang S-L, Xu X-J, Tang Y-M, et al. Associations between inflammatory cytokines and organ damage in pediatric patients with hemophagocytic lymphohistiocytosis. Cytokine 2016;85:14–7.
30. Grom AA. Natural killer cell dysfunction: A common pathway in systemic-onset juvenile rheumatoid arthritis, macrophage activation syndrome, and hemophagocytic lymphohistiocytosis? Arthritis Rheum. 2004; 50: 689-698. doi: 10.1002/art.20198 (REF34)
31. Usami M, Shimizu M, Mizuta M, Inoue N, Irabu H, Sakumura N, Nakagishi Y, Yachie A. Extensive serum biomarker analysis in patients with macrophage activation syndrome associated with systemic lupus erythematosus. Clin Immunol. 2019; 208:108255. doi: 10.1016/j.clim.2019.108255.
32. Zhang L, Zhou J, Sokol L. Hereditary and acquired hemophagocytic lymphohistiocytosis. Cancer Contr 2014; 21(4):301-12
33. Tumian NR, Wong CL. Pregnancy-related hemophagocytic lymphohistiocytosis associated with cytomegalovirus infection: a diagnostic and therapeutic challenge. Taiwan J Obstet Gynecol. 2015; 54(4):432–437. doi:10.1016/j.tjog.2014.11.023
34. Zhang Y, Liang G, Qin H, Li Y, Zeng X. Tuberculosis-associated hemophagocytic lymphohistiocytosis with initial presentation of fever of unknown origin in a general hospital: an analysis of 8 clinical cases. Medicine. 2017;96:e6575. https://doi.org/10.1097/MD.0000000000006575
35. Hashmat M, Rana RS, Mahmud TE, Rasheed A, Rehman AU, Pirzada SAR, et al. Case report of a lupus patient with a severe flare and miliary tuberculosis: need for proper guidelines for management. Oxford Med Case Rep. 2017;7:omx030. https://doi.org/10.1093/omcr/omx030
36. Brastianos PK, Swanson JW, Torbenson M, et al. Tuberculosis associated haemophagocytic syndrome. Lancet Infect Dis 2006;6:447–54.
37. Rafał Machowicz, Gritta Janka, Wieslaw Wiktor-Jedrzejczak. Similar but not the same: Differential diagnosis of HLH and sepsis. Crit Rev Oncol Hematol. 2017; 114:1-12. doi: 10.1016/j.critrevonc.2017.03.023.
38. Kumakura S, Murakawa Y. Clinical characteristics and treatment outcomes of autoimmune associated hemophagocytic syndrome in adults. Arthritis Rheumatol. 2014; 66: 2297-2307. doi: 10.1002/art.38672 ref 27
39. Eberhard OK, Haubitz M, Brunkhorst FM, Kliem V, Koch KM, Brunkhorst R. Usefulness of procalcitonin for differentiation between activity of systemic autoimmune disease (systemic lupus erythematosus/systemic antineutrophil cytoplasmic antibody-associated vasculitis) and invasive bacterial infection. Arthritis Rheum. 1997; 40(7):1250 –6. doi: 10.1002/1529-0131(199707)40:7<1250::AID-ART9>3.0.CO;2-A
40. Bador KM, Intan S, Hussin S, Gafor AHA. Serum procalcitonin has negative predictive value for bacterial infection in active systemic lupus erythematosus. Lupus. 2012; 21(11):1172 –7. doi: 10.1177/0961203312450085.
41. Quintana G, Medina YF, Rojas C, Fernandez A, Restrepo JF, Rondon F, et al. The use of procalcitonin determinations in evaluation of systemic lupus erythematosus. J Clin Rheumatol Pract Rep Rheum Musculoskelet Dis. 2008;14(3):138–42. doi: 10.1097/RHU.0b013e3181772cca.
4 Beça S, Rodríguez-Pintó I, Alba MA, Cervera R, Espinosa G. Development and validation of a risk calculator to differentiate flares from infections in systemic lupus erythematosus patients with fever. Autoimmun Rev. 2015; 14(7):586–93. doi: 10.1016/j.autrev.2015.02.005.
43. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003; 111:1805–12. doi: 10.1172/JCI18921.
44. Fardet L, Galicier L, Lambotte O, et al. Development and validation of a score for the diagnosis of reactive hemophagocytic syndrome (HScore). Arthritis Rheumatol. 2014; 66: 2613-20. doi: 10.1002/art.38690 REF
45. Batu ED, Erden A, Seyhoğlu E, et al. Assessment of the H Score for reactive haemophagocytic syndrome in patients with rheumatic diseases. Scand J Rheumatol. 2017; 46: 44-8. doi: 10.3109/03009742.2016.1167951
46. Ravelli A, Minoia F, Davi S et al. 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 68:566-76. doi: 10.1002/art.39332
47. Ravelli A, Minoia F, Davi 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. Ann Rheum Dis. 2016; 75:481-9. doi: 10.1136/annrheumdis-2015-208982
48. Melissa R Hines, Tatiana von Bahr Greenwood, Gernot Beutel et al. Consensus-Based Guidelines for the Recognition, Diagnosis, and Management of Hemophagocytic Lymphohistiocytosis in Critically Ill Children and Adults. Crit Care Med. 2021; Oct5. doi: 10.1097/CCM.0000000000005361
49. Nakagishi Y, Shimizu M, Kasai K, Miyoshi M, Yachie A. Successful therapy of macrophage activation syndrome with dexamethasone palmitate. Mod Rheumatol. 2016; 26(4):617–620. doi: 10.3109/14397595.2014.906053
50. Hines Melissa R, von Bahr Tatiana, Greenwood Gernot Beutel et al. Consensus-based guidelines for the recognition, diagnosis, and management of hemophagocytic lymphohistiocytosis in critically ill children and adults. Crit Care Med. 2021; https:// doi. org/ 10. 1097/ CCM. 00000 00000 005361
51. Wesam Gouda, Faisal Alsaqabi, Abdelhfeez Moshrif, et al. Macrophage activation syndrome triggered by systemic lupus erythematosus flare: successful treatment with a combination of dexamethasone sodium phosphate, intravenous immunoglobulin, and cyclosporine: a case report. J Med Case Rep. 2021; 7;15(1):497. doi: 10.1186/s13256-021-03072-1
52. Ueda Y, Yamashita H, Takahashi Y, Kaneko H, Kano T, Mimori A. Refractory hemophagocytic syndrome in systemic lupus erythematosus successfully treated with intermittent intravenous cyclophosphamide: three case reports and literature review. Clin Rheumatol. 2014; 33(2):281–286. doi :10.1007/s10067-013-2451-8
53. Ravelli A, Viola S, De Benedetti F, et al. Dramatic efficacy of cyclosporine A in macrophage activation syndrome. Clin Exp Rheumatol. 2001; 19:108.
54. Emmenegger U, Frey U, Reimers A, Fux C, Semela D, Cottagnoud P, Spaeth PJ, Neftel KA. Hyperferritinemia as indicator for intravenous immunoglobulin treatment in reactive macrophage activation syndromes. Am J Hematol Sep. 2001;68(1):4-10. doi: 10.1002/ajh.1141
55. So MW, Koo BS, Kim YJ, et al. Successful rituximab treatment of refractory hemophagocytic lymphohistiocytosis and autoimmune hemolytic anemia associated with systemic lupus erythematosus. Mod Rheumatol. 2014;24:855–7. doi: 10.3109/14397595.2013.874740
56. Bakshi J, Hassan S, D’Cruz D, et al. Rituximab therapy in refractory macrophage activation syndrome secondary to systemic lupus erythematosus. Lupus. 2013; 22:1544–6. doi: 10.1177/0961203313504634
57. Ruscitti P, Cipriani P, Ciccia F, et al. Prognostic factors of macrophage activation syndrome, at the time of diagnosis, in adult patients affected by autoimmune disease : Analysis of 41 cases collected in 2 rheumatologic centers. Autoimmun Rev. 2017; 16(1):16-21. doi: 10.1016/j.autrev.2016.09.016
58. Yao Ke, Chengyin Lv, Wenhua Xuan, et al. Clinical analysis of macrophage activation syndrome in adult rheumatic disease: A multicenter retrospective study. International Journal of Rheumatic Diseases. 2000; 00:1–9. doi: 10.1111/1756-185X.13955
59. Machowicz R, Janka G, Wiktor-Jedrzejczak W. Similar but not the same: Differential diagnosis of HLH and sepsis. Crit Rev Oncol Hematol 114:1–12. https:// doi. org/ 10. 1016/j. critr evonc. 2017. 03. 023