DOUBLE DANGER!!

Dr Anakha V Ajay 
  Dr Suma Balan( Dept of Pediatric Rheumatology) Dr C Jayakumar(Dept of Pediatrics) AIMS, Kochi
Twelve year old boy presented with complaint of recurrent episode of high grade fever since 2 months associated with painful cervical swelling which was  increasing in size.and occasional joint pain.
On evaluation the swelling was found to be necrotizing in nature and diagnosed as Kikuchi disease. Patient was started on Naproxen along with Hydroxy chloroquine but fever spike didn’t abate but with pain over swelling,hence admitted for evaluation
At admission , child was febrile , sick-looking and stable vitals. Lymphadenopathy was present involving enlarged and tender right cervical(3x5cm)l and left submandibular lymph nodes(3x4cm).
PGALS showing mild tendeness in left elbow, tenderness over Left ankle and normal, mild pain in standing on left leg and no other swollen or tender joints. Systemic examination done was within normal limits.
Labs were showing Pancytopenia(WBC-2.76,Hb9.56,Plt-1.24lac)
high ferritin(4805), high LDH,(1555), high sgpt,(375), Sgot(657), high CRP(35.98), ESR(74),  
Lymphnode biopsy was done which was necrotising in nature indicative of Kikuchi disease.(Outside).
EBV IgM was done which was negative . 
Patient complaint of continued fever spike with increased swelling and pain in his lymphnodes. 
He was treated with naproxen but was refractory to the treatment.
Bone marrow aspiration was done which showed cellular marrow shows trilineage maturation with occasional hemophagocytosis.
On the basis of these finding diagnosis of Macrophage activation syndrome(MAS) secondary to Kikuchi was made and patient was pulsed with methylprednisolone @2mg/kg and patient showed good response. 
Patient became afebrile and there was improvement in total counts with resolving transaminitis.
Hence child was discharged on steroids and hydroxychloroquine and advised regular rheumatology follow up.
 
Macrophage activation syndrome (MAS) is a potentially life-threatening complication of certain rheumatic conditions. It is often considered a type of secondary hemophagocytic lymphohistiocytosis (HLH) and results from over-activation of T lymphocytes and macrophages leading to a “cytokine storm”. 
Characteristic features are persistent fever, lymphadenopathy, hepatosplenomegaly, cytopenias (anemia, leucopenia, thrombocytopenia), raised C-reactive protein, falling erythrocyte sedimentation rate, hypofibrinogenemia, transaminitis, hypertriglyceridemia and extreme hyperferritinemia often associated with multi-organ impairment. 
Key to its management is early recognition of MAS which may be difficult due to similarity to systemic sepsis or flares of the underlying rheumatic disease.
Together with appropriate supportive care, first-line treatment is high-dose intravenous corticosteroids with cyclosporin or intravenous immunoglobulin (IVIg) added if there is not initial response. Although etoposide is used hematologists in treatment of HLH, there are concerns regarding organ toxicity and bone marrow suppression which weigh against its use in initial management of MAS.The relatively rapid effectiveness of anakinra, a recombinant IL-1 receptor antagonist, has been documented.
Prognosis: Late diagnosis can lead to death as most patients don’t benefit from therapy. Now MAS is diagnosed sooner hence receives appropriate treatment and good prognosis.
Take home message: Timely diagnosis and treatment, including immunosuppressive therapy, are essential to managing this life-threatening complication.