|LETTER TO EDITOR
|Ahead of print publication
Macrophage activation syndrome as the presenting manifestation of systemic lupus erythematosus
Digvijay Gajanan Ekbote, Kriti Kishor, Rasmi Ranjan Sahoo, Anupam Wakhlu
Department of Clinical Immunology and Rheumatology, King George's Medical University, Lucknow, Uttar Pradesh, India
|Date of Submission||29-Aug-2020|
|Date of Acceptance||06-Oct-2020|
Department of Clinical Immunology and Rheumatology, King George's Medical University, Lucknow - 226 003, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
A 48-year-old male patient with no known co-morbidities presented with 6-week history of high-grade fever with chills and multiple joint pain. There was no history of rash, oral ulcer, photosensitivity or recent travel. On examination, he was febrile (101°F) with tender metacarpophalangeal (MCP) joints and the presence of oral candidiasis. Systemic examination was unremarkable except for mild nontender hepatomegaly. Investigations revealed leukopenia, thrombocytopenia, and raised inflammatory markers [Table 1]. He had transaminitis with normal serum bilirubin. An acute presentation with fever, arthritis, and bicytopenia necessitated screening for viral illness including parvo, chikungunya, dengue, hepatitis B surface antigen, hepatitis C virus and HIV, which were negative. Tests for malaria and typhoid were negative. Blood and urine cultures were sterile. Chest X-ray was normal, and ultrasonography of the abdomen showed mild hepatomegaly. Worsening cytopenias prompted suspicion of hemophagocytosis. Serum ferritin and lactate dehydrogenase (LDH) were done, which were markedly elevated. A diagnosis of probable hemophagocytic lymphohistiocytosis (HLH) was made, and prednisolone 0.5 mg/kg/day was started. Bone marrow examination revealed the presence of hemophagocytosis [Figure 1]a and [Figure 1]b. Possible viral triggers such as cytomegalovirus and Epstein–Barr virus were ruled out by polymerase chain reaction. The fasting serum triglyceride was normal, and fibrinogen was mildly elevated. The presence of proteinuria prompted tests for antinuclear antibody (ANA), ANA profile and anti-double-stranded DNA (dsDNA) [Table 1], which suggested a diagnosis of systemic lupus erythematosus (SLE). Hydroxychloroquine 5 mg/kg weight was started along with oral cyclosporin (3 mg/kg weight), and prednisolone was increased to 1 mg/kg. The patient gradually became apyrexic and the cytopenias normalized.
|Figure 1: Leishman stain of bone marrow aspirate showing (a) haemophagocytosis (arrow, ×200) and (b) histiocyte engulfing neutrophil (arrowhead), lymphocyte (blue arrow), and platelets (white arrow) (×1000)|
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Macrophage activation syndrome (MAS) is an accepted terminology for acquired HLH in the context of autoimmune disorders including systemic-onset juvenile idiopathic arthritis (sJIA), SLE, Kawasaki disease, adult-onset Still's disease and rheumatoid arthritis. MAS accompanying SLE has been reported and is associated with clinic-serological active disease., Our patient had pancytopenia and MCP arthritis along with high anti-dsDNA and low complement levels. The etiology of pancytopenia in SLE is multifactorial and at times difficult to ascertain. Besides disease activity, infections, drugs like azathioprine, MAS and secondary myelofibrosis are the important considerations. Nutritional deficiencies like folate and B12 should also be ruled out. The diagnosis of MAS in SLE is challenging, as it often mimics disease flare or an infection. Elevated ferritin and LDH levels alongwith bone marrow biopsy usually help in differentiating disease activity from MAS. The diagnosis of MAS is made by modified criteria suggested by Kumakura et al., as HLH-2004 criteria are less sensitive in these patients. The simultaneous diagnosis of MAS has also been reported in pediatric SLE, sJIA and Kawasaki disease. High-dose steroid including pulse methyl prednisolone, cyclosporine, and intravenous immunoglobulin are used to control MAS, with the aggressive HLH protocol reserved for refractory disease.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
We are thankful to Dr Namrata Awasthi, Professor, Department of Pathology, RML Institute of Medical Sciences, Lucknow, for providing the images of the bone marrow aspirate.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dall'ara F, Cavazzana I, Frassi M, Taraborelli M, Fredi M, Franceschini F, et al
. Six cases of macrophage activation syndrome as presenting manifestation of systemic lupus erythematosus. Ann Rheum Dis 2017;76:1225.
Carvalheiras G, Anjo D, Mendonça T, Vasconcelos C, Farinha F. Hemophagocytic syndrome as one of the main primary manifestations in acute systemic lupus erythematosus-case report and literature review. Lupus 2010;19:756-61.
Diaz P, Vieira MA, Carneiro A, Fernandes N. A case of pancytopenia with many possible causes: How do you tell which is the right one? Eur J Case Rep Intern Med 2019;6:001012.
Kumakura S, Ishikura H, Kondo M, Murakawa Y, Masuda J, Kobayashi S. Autoimmune-associated hemophagocytic syndrome. Mod Rheumatol 2004;14:205-15.
Avcin T, Tse SM, Schneider R, Ngan B, Silverman ED. Macrophage activation syndrome as the presenting manifestation of rheumatic diseases in childhood. J Pediatr 2006;148:683-6.