Indian Pediatr 2014;51:
Macrophage Activation Syndrome Presenting with
Hyponatremia and Renal Involvement
Shyama Choudhary, Pramod K Berwal, *Satyendra Khichar and Parasmal Baid
From Departments of Pediatrics and *Medicine, SP
Medical College, Bikaner, Rajasthan, India.
Correspondence to: Dr Shyama Choudhary, 77, PG
Hostel, PBM Hospital,
Bikaner 334001 (Rajasthan), India.
Received: June 28, 2013;
Initial review: July 08, 2013;
Accepted: March 12, 2014.
Background: Macrophage activation syndrome is a rare and life
threatening complication of childhood rheumatic disorders. Case
characteristics: 6-year-old male child with macrophage activation
syndrome complicating systemic onset juvenile idiopathic arthritis.
Observation: He developed pericardial effusion, hyponatremia and
deranged renal function. Outcome: Improvement on intravenous
cortico steroids. Message: High index of suspicion can lead to
earlier diagnosis of macrophage activation syndrome.
Keywords: Juvenile idiopathic arthritis,
Pancytopenia, Pericarditis, Hemophagocytosis.
Macrophage activation syndrome (MAS) occurs in
heterogeneous group of conditions, including infections, neoplasms,
drug-induced and rheumatic disorders. It is described most commonly with
systemic onset juvenile idiopathic arthritis (soJIA) [1-3]. We report a
rare presentation of severe MAS complicating soJIA presenting with
pericardial effusion with hyponatremia and renal involvement.
A 6-year-old boy, previously diagnosed as soJIA,
presented with a 10-day history of high grade continuous fever, cough,
pain abdomen, loose motion, breathlessness, and swelling over the feet
for past 6 days. He was symptomatic for last six months and was
diagnosed elsewhere as soJIA six month previously. He was being treated
with naproxen 250 mg twice-a-day with only partial relief of symptoms.
On admission, his weight and height were 15 kg and 107 cm, respectively.
His vitals were: temperature 103°F, pulse 154 minute, respiratory rate
54/minute, and blood pressure 102/60 mmHg.
On examination, patient had respiratory distress,
severe pallor, clubbing and pedal edema. Bilateral ankle joints were
swollen and tender without any joint deformity. Chest examination
revealed bilateral crepitations, muffled heart sounds and systolic
murmur (grade 3). Liver was 6 cm below costal margin in mid-clavicular
line and spleen was 5 cm below costal margin.
Investigations showed pancytopenia (hemoglobin 5.5
gm/dL, total leucocyte count 2800/mm3
and platelet count 1.1 106/mm3),
hyponatremia (serum sodium 126 mEq/L), deranged renal function (serum
urea 90 mg/dL serum creatinine 1.5 mg/dL) and elevated liver enzymes (alanine
aminotransferase 62 U/L, aspartate aminotransferase 52 IU/L, alkaline
phosphatase 191 IU/L). C-reactive protein, serum potassium and serum
calcium were in normal range. Antinuclear antibody and rheumatoid factor
were positive. Bacterial infection was suspected initially; blood for
culture and sensitivity was sent, and antibiotics were administered. All
bacterial cultures were negative. Urine examination showed albuminuria
(1+), peripheral smear for malarial parasite, widal test, HIV and
brucella antibody tests were negative. IgA antibodies against tissue
glutaminase (TTG) were also negative. Erythrocyte sedimentation rate
(ESR) was markedly raised (125 mm/hour). Chest radiograph showed massive
cardiomegaly with cardiothoracic ratio of 70%. Moderate pericardial
effusion was documented by transthoracic echocardiography.
Ultrasonography of the abdomen showed hepatosplenomegaly with altered
echotexture of liver, and bilateral increased renal cortical
echogenecity with maintained corticomedullary differentiation.
Over the next 2 days, patients condition worsened
with increasing respiratory distress. He was shifted to intensive care
unit and started on oxygen; antibiotic therapy was stepped up. On
further evaluation, serum ferritin was 1587.4 ng/mL serum LDH was 755.3
mg/dL and serum triglycerides were 325.5 mg/dL. Mantoux test and sputum
for acid-fast-bacilli were negative. This failure to improve, in
combination with his past history of soJIA, hepatosplenomegaly and a
very high ferritin level led to a preliminary diagnosis of macrophage
activation syndrome (MAS). Bone marrow aspiration revealed macrophages
phagocytosing hematopoeitic elements which confirmed the diagnosis of
MAS. Immunosuppressive treatment in the form of high-dose
methylprednisolone (30 mg/kg daily) was commenced. Fever and respiratory
distress improved after giving high dose steroids for three days,
cardiac size decreased on chest radiograph and repeat transthoracic
echocardiogram showed minimal pericardial effusion and trivial tricuspid
and mitral regurgitation.
MAS is a severe, potentially life-threatening
complication of soJIA characterised by the excessive activation of
well-differentiated macrophages. In less than 10% of the patients with
soJIA a pericarditis will develop, often asymptomatic, and only rarely
inducing a tamponade . The diagnostic criteria for MAS complicating
soJIA include reduced white blood cells, reduced platelet count,
elevated aspartate aminotransferase, hypofibrino-genemia, central
nervous system impairment, hemorrhages, hepatomegaly and histologic
evidence of macrophage hemo-phagocytosis in bone marrow aspirates .
Other less common findings include hypertriglyceridemia, hypoalbuminemia
and hyponatremia . Hyponatremia is one of the strongest laboratory
discriminators for MAS .
MAS is well described in the pediatric population
with soJIA, and has a median age of 5 years at presentation .
Multisystem involvement and deranged renal function may be a poor
prognostic sign . Natural killer cell activity is decreased in
patients with MAS associated with soJIA . Treatment is based on
immunosuppression; cyclosporin (with or without corticosteroids) has
been used as the first-line treatment [2,8,9].
This patient was initially given only naproxen for
soJIA at peripheral health centre by treating physician. He presented to
us with fever and prominent respiratory failure, with pericardial
effusion and deranged renal function. Non-response to antibiotics and
negative cultures should raise suspicion of MAS and prompt us to
undertake investigations for its diagnosis.
Contributors: SC and PB: were involved in
conception and preparation of manuscript; SC, SK and PB: acquired the
data and drafted the manuscript. All were involved in revising and final
approval of manuscript.
Funding: None; Competing interests: None
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