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vol. 52
Case report

Does early treatment of macrophage activation syndrome prevent fatal outcome in patients with severe systemic juvenile idiopathic arthritis?

Marzena Janczewska
Teresa Kołcun-Penkowska

Reumatologia 2014; 52, 1: 82–85
Online publish date: 2014/03/23
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Macrophage activation syndrome (MAS) belongs to a large heterogenic group of diseases. These conditions are characterized by excessive activity and proliferation of T lymphocytes and macrophages. Macrophage activation syndrome occurs in children with rheumatic diseases: systemic-onset juvenile idiopathic arthritis (sJIA), systemic lupus erythematosus (SLE), dermatomyositis, scleroderma, polyarteritis nodosa (PAN), Kawasaki disease [1].

We report the case of MAS diagnosed in a 7-year-old boy hospitalized in February and March 2010 due to new incidents of severe generalized sJIA. Owing to deterioration of general condition of a patient we decided to introduce treatment with cyclosporine, despite the fact that not all MAS criteria were met. In our opinion this treatment prevented a fatal outcome.

Case report

In February 2010, a boy aged 7 7/12 was admitted to our department because of recurring spiking fever up to 39ºC lasting 8 days, resistant to ibuprofen, concomitant with lower limb pain (the patient was unable to walk), purpuric rash, swollen face and crus, as well as hand, shoulder, knee and foot joints movement limitation and swelling. Two days prior to admission he had a fit. On account of his delayed psychomotor development (he began to sit and walk at the age of 2 and 3, respectively), discrete left-sided hemiparesis, seizures (over last 2 years no medication administered) and suspected Asperger syndrome, he was regularly reviewed by a neurologist and a psychologist.

The patient was admitted in critical condition, suffering from hyperaesthesia and fatigue. Physical examination revealed skin paleness, significant muscle weakness in the upper and lower limbs (he could not walk or lift up his arms), knee joint effusion as well as attenuation of vesicular sound in left lung. Laboratory tests showed increased erythrocyte sedimentation rate (ESR) 83 mm/h, C-reactive protein (CRP) 15.6 mg/dl, white blood cells (WBC) 21.3 × 109/l, blood platelets (PLT) 493 × 109/l, dysproteinemia with hypoalbuminemia (Albumin 39.2%), increased lactate dehydrogenase (LDH 709 U/l) and aspartate transaminase (AST 87 U/l) as well as positive immunoglobulin (Ig) A antibodies against Mycoplasma pneumoniae (17.49 VE; positive result > 9). Ultrasound scan revealed fluid in both knee joints and spleen enlargement.

Despite intensive antibiotics therapy (Biofuroksym 3 × 600 mg i.v., Fromilid 2 × 250 mg p.o.) and NSAIDs (Naproxen 2 × 200 mg p.o.) general condition of the patient worsened in the second week after admission (spiking fever, peritoneal effusion, dyspnoea and subcutaneous tissue swelling increased). In spite of switching to Tarcefoksym 4 × 0.5 γ i.v. and Amikin 2 × 150 mg i.v., then to Meronem 400 mg TID, introducing Metypred 16 mg daily, Flebogamma IV 2 × 20 γ and Albumin 20% 100 ml intravenous administration, the patient’s clinical state was still deteriorating. Weight loss, weakness, significant hyperaesthesia, fatigue and central nervous system symptoms (apathy, hand tremor, high-pitched cry) were noted. Lower limb and abdominal pain were rated at 10 according to VAS scale. Additional laboratory tests showed anemia (ESR 3.0 × 109/l, Hb 8.4 g/dl, Ht 24.7%), decreased serum iron (Fe 15 µg/dl), elevated serum fibrynogen 6.04 g/l, triglycerides 171 mg/dl, D-dimers 6379.8 ng/ml, ferritin > 1000.0 ng/ml, platelets 848 × 109/l, reticulocytes 39‰ as well as hyponatremia 127 mmol/l. Ultrasound scan revealed synovial hyperplasia in both knee joints. Bone marrow biopsy (Fig. 1) revealed the presence of well – differentiated actively phagocytising macrophages. Since patient’s general condition was worsening we decided to administer cyclosporine 30 mg BD (up to 40 mg BD on day 9) which led to clinical stabilization and improvement of laboratory tests results. The boy was discharged in clinical remission after 6 weeks of treatment.

Due to a new exacerbations, the patient was admitted to the Institute of Rheumatology in Warsaw. In the 6th week of cyclosporine treatment an increase in drug level and serum creatinine were noted leading to strong suspicion of acute renal failure. Equoral was discontinued and kidney function tests returned to normal. However, in a view of patient’s worsening clinical condition, Methotrexat a 2.5 mg 5 tabl weekly (MTX) was started. The boy was on IV immunoglobulins for 6 months. Later the patient was sent to a local rheumatology out-patient clinic.


Among rheumatic diseases, MAS occurs most frequently in sJIA [2]. We report a paediatric case of severe sJIA complicated by MAS which due to the risk of death was treated with cyclosporine before all results of laboratory tests were available. Constellation of symptoms like high fever lasting 4 weeks, evanescent rash, knee and ankle arthritis, splenomegaly, serositis, increased ESR, CRP, WBC and PLT, as well as RF 5 IU/ml and 9 IU/ml made us suspect sJIA. This set of symptoms is wildly described in the literature [3, 4]. Additionally, decreased number of NK cells and reduced NK cell catalytic activity are features that distinguish sJIA from other forms of JIA [5, 6]. During process of diagnosis we considered an overlap syndrome with dermatomyositis since following symptoms were present: lower limb pain, significant muscle weakness in the upper and lower limbs, hyperaesthesia and fatigue, dyspnoea, lung involvement.

As presented in Table I our patient fulfilled the criteria of MAS acc. to Ravelli et al. that were in use at that time [7]. These preliminary diagnostic guidelines for MAS in sJIA include: high fever, rash, splenomegaly, oliguria, hypertriglyceridemia, hyperferritinemia, anemia, hypoalbuminemia, low serum sodium, elevated serum LDH, abnormal clotting tests, serositis as well as presence of macrophages in bone marrow biopsy [7, 8]. According to newly developed diagnostic criteria for MAS the presence of two or more of laboratory or clinical criteria is required [9–11]. As shown in Table II our patient met 4 out of 8 of these.

Lack of cytopenia in a described patient could have been masked by leucocytosis and thrombocytosis that occur in sJIA. Moreover, cytopenia and hypofibrynogenemia are more characteristic for hemophagocytic lymphohistiocytosis.

Management of MAS involves elimination of triggering factors, usually viral infection, and treatment with high-dose corticosteroids, cyclosporine A, intravenous immunoglobulins and etoposide.

In our opinion, the factor that had presumably triggered the disease was one of the following: M. pneumoniae, Parvovirus B19, Cytomegalovirus or EBV infection.


Diagnosing MAS is difficult, especially at the early stage. Considering the severe course of MAS, diagnosis should be established as soon as possible. Early introduction of the suitable therapy and cyclosporine A may prevent further complications.

Authors declare no conflict of interest.


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Copyright: © 2014 Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

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