|
Indian Pediatr 2014;51: 148 -149 |
|
Macrophage Activation Syndrome in Kawasaki
Disease
|
Devdeep Mukherjee, Priyankar Pal, Ritabrata Kundu and
Prabal Niyogi
From Departments of Pediatric Medicine and Pediatric
Rheumatology, Institute of Child Health,
Kolkata, West Bengal, India.
Correspondence to: Dr Devdeep Mukherjee, Flat No. 6F,
Uttara Co-operative Housing Society, 13, Broad Street,
Kolkata – 700019.
Email:
[email protected]
Received: June 21, 2013;
Initial review: July 01, 2013;
Accepted: December 27, 2013.
|
Background: Kawasaki disease is an acute febrile vasculitis of
childhood. Macrophage activation syndrome is a rare life threatening
complication. Case characteristics: 4-year-old boy with Kawasaki
Disease treated with intravenous immunoglobulins. Observation: He
developed encephalopathy, hepatosplenomegaly and pancytopenia. Blood
investigations and bone marrow aspiration suggested macrophage
activation syndrome. Outcome: Good response to pulse
methylprednisolone (30 mg/kg/d) for 5 days. Message: Macrophage
activation syndrome may complicate Kawasaki disease.
Keywords: Lymphoproliferative disorders,
Mucocutaneous lymph node syndrome.
|
M acrophage activation syndrome (MAS) occurs
secondary to many diseases, including infections, neoplasms,
hematological conditions, and rheumatic disorders. It is characterized
by persistent fever, pancytopenia, liver dysfunction, hepatosplenomegaly,
hyperferritinemia, hypofibrinogenemia, elevated serum lactate
dehydrogenase, and hypertriglyceridemia [1,2].
Case Report
A 4-year-old boy was admitted with history of high
fever for 14 days. He had a history of diffuse maculopapular truncal
rash which started on day-4 of fever and persisted for 4 days. There was
bilateral non-purulent conjunctivitis from the 3rd to 6th day of fever
along with erythema of tongue and lips. Blood counts done elsewhere on
day-12 were: hemoglobin 9.6 g/dL, total leukocyte count 18.8 × 10 9/L,
platelet count 886 × 109/L,
Erythrocyte sedimentation rate (ESR) 70 mm in 1st hour, and
C-reactive-protein (CRP) 86 mg/L. Widal and Mantoux tests were negative.
On examination, he was irritable, and had pedal edema, orange brown
chromonychia, right cervical lymphadenopathy and hepatosplenomegaly.
Investigations showed serum sodium of 130 mmol/L, Alanine
aminotransferase (ALT) of 263 U/L, serum albumin of 2.8 g/dL, and a
sterile blood culture. Urine microscopy revealed 10-12 pus cells/ high
power field; culture was sterile. Echocardiography showed perivascular
brightness with lack of tapering in left anterior descending artery and
an aneurysm measuring 5 mm. Aneurysm (4.6 mm) was also present in left
main coronary artery. A diagnosis of Kawasaki disease (KD) was made and
intravenous immunoglobulins (IVIg) were administered at 2 g/kg over 24
hours.
After being afebrile for 48 hours, fever recurred on
day-17. He became drowsy, developed gum bleeding and further increase in
size of liver and spleen. Repeat blood counts showed hemoglobin 6.8 g/dL,
total leukocyte count 4.6 × 10 9/L,
platelet count 16 × 109/L,
ESR 12 mm in 1st hour and CRP 256 mg/L. ALT increased to 468 U/L,
International normalized ratio was 1.8 and activated partial
thromboplastin time was 68 seconds. Persistent fever, encephalopathy,
hepatosplenomegaly, deteriorating liver function and pancytopenia along
with falling ESR raised the suspicion of MAS. Further blood
investigations were: ferritin 15716 ng/dL, fibrinogen 96 mg/dL,
triglyceride 463 mg/dL and lactate dehydrogenase 1775 U/L. Bone marrow
aspiration documented phagocytosis of hematopoietic cells by well
differentiated macrophages that was diagnostic of MAS.
Intravenous pulse methylprednisolone was given at 30
mg/kg/d for 5 days. Fever gradually subsided, blood counts normalized
(on day-24), and the child was discharged after 13 days on oral aspirin
5 mg/kg/d. The patient is now clinically well and on regular follow-up.
Echocardiography after 6 weeks showed regression of aneurysms.
Discussion
Kawasaki disease is an acute multi system vasculitis
of the small and medium-sized arteries with a predilection for
coronaries. Our patient had all the clinical features of KD [3-5]. Our
patient had a recurrence of fever despite intravenous administration of
IVIg, and he deteriorated rapidly after 48 hours. Refractory fever
occurs in 10% of patients with KD despite treatment with IVIg; the
suggested treatment is intravenous pulse therapy with methylprednisolone
or infliximab [6]. Persistent fever following IVIg administration,
falling blood counts and ESR, hepatosplenomegaly, and alteration of
mental status prompted us to investigate him for MAS.
MAS patients have profoundly depressed natural-killer
(NK) cell function. NK cells and cytotoxic T-lymphocytes fail to kill
infected cells and thus remove the source of antigenic stimulation
leading to persistent antigen-driven activation and proliferation of
T-cells associated with persistent production of cytokines, that
stimulate macrophages. Cytotoxic dysfunction leads to persistent
expansion of T cells and macrophages, and escalating production of
proinflammatory cytokines [7-9].
There have been few reported cases of MAS in KD
[10-12]. Latino, et al. [11] reported that 10 out of the 12
patients with KD in their series met at least 5 of the 8 criteria
necessary for diagnosis of MAS. Treatment beyond the standard KD
protocol (aspirin + IVIg) was necessary in all but 1 patient. Eight of
these patients were also given multiple doses of IVIg. We administered
methylprednisolone pulse therapy after single dose of IVIg with dramatic
response.
We conclude that MAS may rarely complicate the course
of KD; prompt treatment with pulse methylprednisolone may result in
favourable outcome .
Acknowledgement: Dr Prabhas Prasun Giri and Dr Md
Fekarul Islam.
Contributors: All authors were involved in case
management. DM drafted the manuscript that was approved by all authors.
Funding: None; Competing interests: None
stated.
References
1. Sawhney S, Woo P, Murray KJ. Macrophage activation
syndrome: a potentially fatal complication of rheumatic disorders. Arch
Dis Child. 2001;85:421-6.
2. Mashuku S, Hibi S, Todo S. Hemophagocytic
lymphohistiocytosis in infancy and childhood. J Pediatr.1997;130:352-7.
3. Kawasaki T, Kosaki F, Okawa S, Shigematsu I,
Yanagawa H. A new infantile acute febrile mucocutaneous lymph node
syndrome (MLNS) prevailing in Japan. Pediatrics. 1974;54:271-6.
4. Dajani AS, Taubert KA, Gerber MA, Shulman ST,
Ferrieri P, Freed M. Diagnosis and therapy of Kawasaki disease in
children. Circulation. 1993;87:1776-80.
5. Pal P, Giri PP. Orange-brown chromonychia, a novel
finding in Kawasaki disease. Rheumatol Int. 2013;33: 1207-9.
6. Wright, DA, Newburger JW, Baker A, Sundel RP.
Treatment of immune globulin-resistant Kawasaki disease with pulse doses
of corticosteroids. J Pediatr. 1996;128:146-9.
7. Kuzmanova SI. The macrophage activation syndrome:
a new entity, a potentially fatal complication of rheumatic disorders.
Folia Med (Plovdiv). 2005;47:21-5.
8. Ramanan AV, Schneider R. Macrophage activation
syndrome – what’s in a name! J Rheumatol. 2003;30:2513-6.
9. Sawhney S, Woo P, Murray KJ. Macrophage activation
syndrome: a potentially fatal complication of rheumatic disorders. Arch
Dis Child. 2001;85:421-6.
10. Muise A, Tallett SE, Silverman ED. Are children
with kawasaki disease and prolonged fever at risk for macrophage
activation syndrome? Pediatrics. 2003;6: e495-6.
11. Latino GA, Manlhiot C, Yeung RS, Chahal N,
McCrindle BW. Macrophage activation syndrome in the acute phase of
Kawasaki disease. J Pediatr Hematol Oncol. 2010;32:527-31.
12. Servel AC, Vincenti M, Darras JP, Lalande M, Rodière M, Filleron
A. Intravenous immunoglobulin-resistant Kawasaki disease with
hemophagocytosis. Arch Pediatr. 2012;19:741-4.
|
|
|
|