J Rheum Dis.  2024 Jan;31(1):49-53. 10.4078/jrd.2023.0039.

Macrophage activation syndrome in neonatal lupus presenting with fever and rash

• Yu JY
• Kim TH
• Kim YJ
• Kang HM
• Yoo IH
• Rhim JW
• Lee SY
• Jeong DC

• KMID: 2549636
• DOI: http://doi.org/10.4078/jrd.2023.0039

Abstract

Neonatal lupus can occur in infants born to mother with autoimmune disorders through transplacental auto-antibodies. Clinical manifestations in neonatal lupus include cutaneous lesions and hematologic or hepatobiliary findings resembling those seen in systemic lupus erythematosus. In autoimmune state, macrophage activation syndrome (MAS) represent a critical and potentially fatal complication that can result in mortality if not immediately identified and managed with the appropriate care. Here we present a 33-day-old girl diagnosed with neonatal lupus and serious MAS. She was delivered by a primipara mother who did not exhibit any autoimmune symptoms. The patient visited the hospital due to fever and pancytopenia. Laboratory data were compatible with MAS, including pancytopenia, high level of ferritin, soluble interleukin-2, and decreased natural killer cell activity. In addition, autoimmune study showed positive results for anti-nuclear antibody (ANA), anti-Sjogren syndrome antigen A (SSA), and SSB, The autoimmune study for mother also showed positive results for ANA, anti-SSA, and SSB. The patient recovered after she received high dose steroid and supportive care. Our case indicates that neonatal lupus should be taken into consideration when fever, erythematous skin rash, and pancytopenia are observed in infants, even if their mothers have no prior history of autoimmune conditions.

Keyword

Macrophage activation syndrome; Neonatal systemic lupus erythematosus

Figure

• 

  Figure 1 Erythema marginatum like skin rash on whole body of the patient on admission.

• 

  Figure 2 Changes in ferritin and hemoglobin (Hb) of the patient after hospitalization. At the beginning of treatment, the ferritin level was decreased, which had rose again after the red blood cell transfusion. It recovered to the normal range over time. IV mPD: intravenous methylprednisolone, PO: per oral, HD: hospital day.

Reference

1. Vanoni F, Lava SAG, Fossali EF, Cavalli R, Simonetti GD, Bianchetti MG, et al. 2017; Neonatal systemic lupus erythematosus syndrome: a comprehensive review. Clin Rev Allergy Immunol. 53:469–76. DOI: 10.1007/s12016-017-8653-0. PMID: 29116459.

2. Yokogawa N, Sumitomo N, Miura M, Shibuya K, Nagai H, Goto M, et al. 2017; Neonatal lupus erythematosus. Nihon Rinsho Meneki Gakkai Kaishi. 40:124–30. Japanese. DOI: 10.2177/jsci.40.124. PMID: 28603203.

3. Zuppa AA, Riccardi R, Frezza S, Gallini F, Luciano RM, Alighieri G, et al. 2017; Neonatal lupus: follow-up in infants with anti-SSA/Ro antibodies and review of the literature. Autoimmun Rev. 16:427–32. DOI: 10.1016/j.autrev.2017.02.010. PMID: 28212920.

4. Sim SY, Choi HY, Jung MH, Lee SY, Rhim JW, Kang HM, et al. 2022; Catch-up growth of infants born to mothers with autoimmune rheumatic disorders. Pediatr Rheumatol Online J. 20:7. DOI: 10.1186/s12969-022-00667-w. PMID: 35109877. PMCID: PMC8812023. PMID: 8f050cb19a304235a34a76f3fcb0c1d1.

5. Bojan A, Parvu A, Zsoldos IA, Torok T, Farcas AD. 2021; Macrophage activation syndrome: a diagnostic challenge (Review). Exp Ther Med. 22:904. DOI: 10.3892/etm.2021.10336. PMID: 34257717. PMCID: PMC8243343.

6. Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. 2007; HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 48:124–31. DOI: 10.1002/pbc.21039. PMID: 16937360.

7. Heijstek V, Habib M, van der Palen R, van Doorn R, Muller PH. 2021; Macrophage activation syndrome in a newborn: report of a case associated with neonatal lupus erythematosus and a summary of the literature. Pediatr Rheumatol Online J. 19:13. DOI: 10.1186/s12969-021-00500-w. PMID: 33568193. PMCID: PMC7877111. PMID: 1d4b0b2ce3d44f16a643d51fa105b8c0.

8. Park JH, Kim SH, Kim HJ, Lee SJ, Jeong DC, Kim SY. 2015; Macrophage activation syndrome in a newborn infant born to a mother with autoimmune disease. J Perinatol. 35:158–60. DOI: 10.1038/jp.2014.207. PMID: 25627282.

9. Suzuki Y, Takahashi N, Yada Y, Koike Y, Matano M, Nishimura H, et al. 2013; Hemophagocytic lymphohistiocytosis in a newborn infant born to a mother with Sjögren syndrome antibodies. J Perinatol. 33:569–71. DOI: 10.1038/jp.2012.147. PMID: 23803677.

10. Parodi A, Davì S, Pringe AB, Pistorio A, Ruperto N, Magni-Manzoni S, et al. 2009; Macrophage activation syndrome in juvenile systemic lupus erythematosus: a multinational multicenter study of thirty-eight patients. Arthritis Rheum. 60:3388–99. DOI: 10.1002/art.24883. PMID: 19877067.

11. Rose E. 2021; Pediatric fever. Emerg Med Clin North Am. 39:627–39. DOI: 10.1016/j.emc.2021.04.011. PMID: 34215406.

12. Ravelli A, Minoia F, Davì S, Horne A, Bovis F, Pistorio A, 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. 68:566–76. DOI: 10.1002/art.39332. PMID: 26314788.

13. Piccinni MP, Lombardelli L, Logiodice F, Kullolli O, Parronchi P, Romagnani S. 2016; How pregnancy can affect autoimmune diseases progression? Clin Mol Allergy. 14:11. DOI: 10.1186/s12948-016-0048-x. PMID: 27651750. PMCID: PMC5025626.

14. Adams Waldorf KM, Nelson JL. 2008; Autoimmune disease during pregnancy and the microchimerism legacy of pregnancy. Immunol Invest. 37:631–44. DOI: 10.1080/08820130802205886. PMID: 18716941. PMCID: PMC2709983.

15. Wood JC. 2014; Guidelines for quantifying iron overload. Hematology Am Soc Hematol Educ Program. 2014:210–5. DOI: 10.1182/asheducation-2014.1.210. PMID: 25696857.