Hemophagocytic syndrome.

20
HEMOPHAGOCYTIC SYNDROME Dr. Sandip Dukare

description

HPS

Transcript of Hemophagocytic syndrome.

Page 1: Hemophagocytic syndrome.

HEMOPHAGOCYTIC SYNDROME

Dr. Sandip Dukare

Page 2: Hemophagocytic syndrome.

INTRODUCTION

• Hemophagocytic syndrome is a rare disorder of the mononuclear phagocytic system.

• It is characterized by benign proliferation of mature histiocytes and uncontrolled phagocytosis of the platelet, erythrocytes, lymphocytes and their hematopoietic precursors in the bone marrow.

• It is associated with various infections,autoimmune ds, malignancies and immunocompromised states.

• Cytopenias result in systemic manifestations.

• Prognosis is grave and mortality ranges upto 50% in absence of treatment.

Page 3: Hemophagocytic syndrome.

CASE REPORT 1: HPS associated withPlasmodium falciparum infection

• 11-month-old child presented with 20-day H/O- high fever and abdominal distention.

• G/E-lethargic, febrile.

• P/E-pallor, hepatosplenomegaly.

• Lab investigations-anemia,thrombocytopenia, leucopenia,deranged liver enzymes.

• P/S-microcytic, hypochromic picture with no e/o any haemoparasite.

Page 4: Hemophagocytic syndrome.

• Serum ferritin -2193 μg/L.

• Platelet count- 90 X109/mm3.

• Serum triglycerides- 3.2 mmol/L.

• Serum fibrinogen-(0.75 g/L).

• BMA- normal cellularity with mature monohistiocytes containing phagocytosed RBCs.

• BMS- Plasmodium falciparum gametocytes were identified.

• Treatment with i.v. Artesunate,the patient became afebrile & recovered gradually.

Page 5: Hemophagocytic syndrome.

Hemophagocyte in bone marrow smear; (Leishman, ×100)

Page 6: Hemophagocytic syndrome.

Gametocyte of Plasmodium falciparum in bone marrow smear; (Leishman, ×100)

Page 7: Hemophagocytic syndrome.

CASE REPORT 2: HPS - A cause for fatal outcome in tuberculosis.

• A 17-year-old male presented with fever,abdominal distention since 15 days.

• G/E-gross pallor,generalized lymphadenopathy.

• USG A/P-free fluid in abdomen,hepatosplenomegaly and extensive intra-abdominal lymphadenopathy.

• CXR- B/L pleural effusion.

• Lab investigations-

• Anemia,leucopenia thrombocytopenia.

• Peripheral smear—microcytic,moderately hypochromic anemia.

Page 8: Hemophagocytic syndrome.

• Serum LDH- (540 U/L).

• Serum triglycerides- (280 mg/Dl).

• Serum ferritin- (960 mcg/L),

• CRP-positive.

• Cervical lymph node biopsy-dilated sinuses containing macrophages with abundant cytoplasm stuffed with red blood cells.

• BMA-hypocellularity, focal necrotic areas. The M/E ratio was normal. Myloid and erythroid series maturation was normal.

Page 9: Hemophagocytic syndrome.

• BMS- few lymphocytes, reactive plasma cells and large histiocytes containing engulfed red blood cells, nuclear debris and platelets.

• Cervical lymph node aspiration cytology- necrotic material and acid fast bacilli on ZN staining.

• The patient was started on antitubercular therapy & dexamethasone.

• Significant response was noted and patient recovered gradually.

Page 10: Hemophagocytic syndrome.

Histopathology of cervical lymph node. H and E (×400)-Sinus histi ocytosis with prominant hemophagocytosis

Page 11: Hemophagocytic syndrome.

Leishman Stain highlighting hemophagocytic macrophage

Page 12: Hemophagocytic syndrome.

Bone marrow aspirate (×1000) . Leishman stained smearshowing hemophagocytic macrophages

Page 13: Hemophagocytic syndrome.

DISCUSSION

• Hemophagocytic syndrome/hemophagocytic lymphohistiocytosis(HLH)

• It is a rare ds.

• Characterized by benign proliferation of the mature histiocyte.

• There is uncontrolled phagocytosis of the platelet, erythrocytes, lymphocytes and their hematopoietic precursors in the BM giving rise to cytopenias.

Page 14: Hemophagocytic syndrome.

PRIMARY(Familial)

SECONDARY(Acquired)

INFECTIONIMMUNODE-

FICIENCYAUTOIMMUNE

METABOLIC DS.

MALIGNANCY

ETIOLOGY

Page 15: Hemophagocytic syndrome.

PATHOPHYSIOLOGY

Th 1 STIMULATED HYPERCYTOKINEMIA

TRIGGERING OF THE CYTOKINE CASCADE

FREE OXYGEN RADICAL RELEASE

ACTIVATED MACROPHAGES PHAGOCYTOSE RBCS,WBCS,PLATELETS

INAPPROPRIATE ACTIVATION & UNCONTROLLED PROLIFERATION OF THE MACROPHAGES

TRIGGERING FACTOR (MC INFECTION)

Page 16: Hemophagocytic syndrome.

CLINICAL FEATURES

• Onset- abrupt• Many present with fever of unknown origin.• Systemic manifestations-pallor,fever,rash,

lymphadenopathy,hepatosplenomegaly,neurological manifestations.

• It takes a fulminant course and has a fatal outcome.

Page 17: Hemophagocytic syndrome.

Histiocytic Society Protocol Criteria

1. Fever(>7days)

2. Splenomegaly

3. Cytopenias(>2 lineages)

-Anemia(hb<9.0 g/dl)

-Neutropenia(<1000)

-Thrombocytopenia(<1lk cells)

4. Hypertriglyceridemia & Hypofibrinigenemia

5. Haemophagocytosis(bone, spleen,bone marrow)

6. Natural killer cell activity(low/absent)

7. Hyperferritinemia(>500 mcg/l)

8. Increased soluble CD 25(>2400 u/ml)

Page 18: Hemophagocytic syndrome.

Differential Diagnosis

1. Griscelli syndrome.

2. X linked lymphoproliferative syndrome.

3. Autoimmune lymphoproliferative syndromes.

4. Macrophage activation syndromes.

Page 19: Hemophagocytic syndrome.

REFERENCES1. Imashuku S. Differential diagnosis of hemophagocytic

syndrome:Underlying disorders and selection of the most effective treatment.Int J Hematol 1997;66:135-51.

2. Saribeyoglu ET, Anak S, Agaoglu L, Unuvar A. Secondary hemophagocyticlymphohistiocytosis induced by malaria infection in a child with langerhans cell histiocytosis. Pediatr Hematol Oncol 2004;21:267-72.

3. Ohno T, Shirasaka A, Sugiyama T, Furukawa H. Hemophagocytic syndrome induced by plasmodium falciparum malaria infection. Int J Hematol 1996;64:263-6.

4. Aouba A, Noguera ME, Clauvel JP, Quint L. Hemophagocyticsyndrome associated with plasmodium vivax infection. Br J Haematol 2000;103:832-3.

Page 20: Hemophagocytic syndrome.

THANK YOU!....