OT: Effective Treatment of infantile MAS/Hemophagocytic Lymphohistiocytosis w/Enbrel

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EFFECTIVE TREATMENT OF INFANTILE ONSET MACROPHAGE ACTIVATION

SYNDROME/HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (MAS/HLH) WITH ETANERCEPT

http://www.jrheum.com/subscribers/06/02/61-80.html

Objective:MAS/HLH is a rare but life threatening condition that can be

primary (familial HLH) or secondary to rheumatic diseases, infections, or

malignancies. Pro-inflammatory cytokines, such as IL-6, are thought to be

central in pathological manifestations of this disease. There is no data on

IL-6 levels in infantile MAS/HLH, nor is uniformly effective treatment

available. We describe successful treatment of infantile MAS/HLH with

anti-tumor necrosis factor agent Etanercept and provide IL-6 data.

Methods:Serum cytokine levels including pro-inflammatory IL-6 and

non-proinflammatory IL-11 and VEGF were measured by ELISA pre and days two

and six post Etanercept administration. Patient had genetic analysis for

FHLH, and measurement of T-cell function, soluble IL-2 receptor and perforin

level.

Results Obtained and Conclusion: Case: Diagnosis of MAS/HLH was made in a

3-week old female infant with fever, respiratory failure, rash,

lymphadenopathy and hepatosplenomegaly. Laboratory features included

thrombocytopenia (Plt 7), anemia (Hb 77), increased ferritin (1192),

fibrinogenemia (<0.8), increased D-dimer (>0.8), prolonged INR and PTT.

Lymph node biopsy confirmed hemophagocytosis. Infectious workup was negative

for bacterial and viral agents (EBV, Parvovirus, Toxoplasmosis, CMV,

Rubella, Mycoplasma, HSV, and HHV6).

Patient received IV Methylprednisolone, IV Cyclosporine and IV IG. On day

four of treatment she developed renal failure and deep vein thrombosis.

Cyclosporine was held, and subcutaneous Etanercept initiated with rapid

resolution of clinical and laboratory abnormalities. Pre-Etanercept serum

IL-6 level was significantly higher (959 pg/ ml) than normal (46 pg/ml).

IL-11 and VEGF levels were not elevated. IL-6 level decreased to 27 pg/ml

within two days of treatment with Etanercept. Patient remains clinically

well with normal neurologic development at 18 month follow up and continues

on SC Etanercept and q 6 week IVIG infusions. FHLH gene mutations were not

present; and NK function, perforin studies, IL-11, and soluble IL-2 receptor

levels were normal.

Brief Conclusion: 1) Etanercept with Corticosteroids and Cyclosporine

resulted in sustained remission in an infant patient with MAS/HLH. 2) IL-6

levels may aid in diagnosis and in monitoring effectiveness of treatment.

Paivi MH Miettunen, Victor , Doan Le, Aru Narendran (Division of

Pediatric Rheumatology, University of Calgary and Alberta Children's

Hospital, Division of Pediatric Oncology, University of Calgary and Alberta

Children's Hospital, Division of Pediatric Hematology, University of Calgary

and Alberta Children's Hospital)