1. Fungal sinusisit with Macrophage Activation Syndrome
Dr madan gupta
ENT & HNS
All India institute of medical sciences

2.  26/m
 c/o-
 Swelling over face and nose -40 days
 fever-40 days

3. History
 2nd june- ESS (pan sinusitis)[intra op
finding-septal perforation and sinus was
filled with purulent discharge]
 After 10th day of surgery-swelling over
nose and face
 Started on conservative management
….but no response

4. Referred to AIIMS
 Examination –
Temp-febrile pallor- mild
Icterus- no Clubbing-no
Hepatosplenomegaly+
L/E-Diffuse
midline swelling over the nose,
extending inf up to lower lip and sup up
to lower lid(B/L)

5.  Nose-septal perforation and b/l nasal
cavity filled with crust
 Neck-wnl
 Oc-wnl
 Ear-wnl
 Larynx-wnl

6. D/D
 wegener’s granulomatosis
 NK/T cell lymphoma
 fungal infection

7. Investigation
 ANCA-negative
 URINE R/M-wnl
 Nasal BX- necrotic mass with aspergillus
fungus
 Glactomannan test-positive
 TB pcr-negative
 IRCH Haemogram-RBC-normocyte ,
normochromic,
 WBC-N85 L11 M4 ,
 Reticulocyte -1% PLT-1.5 lakh
 No abnormal cell or parasite seen

8.  HIV-negative
 Viral marker-negative
 VDRL & TPHA-negative
 USG abd-enlarged spleen (14.5 cm)
 CECT PNS-B/l maxillary,ethmoid &
sphenoid sinusitis.
 CECT chest (RC discussion)-multifocal
hemorrhage??vasculitis or fungal
infection.

9.  BM aspirate-cellular reactive,all
hemopoetic element,increase in number
of histiocytes showing
hemophagocytosis
 BM Bx-prominenence of histiocytes,no
grnuloma or lymphoma

10. 28/7 6/8 12/8 16/8 17/8 18/8 19/8 20/8
HB 9.5 9.4 8.6 7.4 7.8 6.7 6.3 7.6
TLC 4700 4600 5200 2800 2500 2000 1700 2400
N 69 76 80 84
L 19 17 11 13
M 11 6 7 15
PLT 117000 103000 158000 105000 91000 71000 100000 43000
ESR 110 67 57 36
urea 28 23 28 29 32 38 40 44
creat 0.8 0.6 0.5 0.5 0.6 0.9 0.5 0.8
biliru 0.6 0.5 0.4 0.6 0.7 0.1 1.3
ALP 177 189 199 802 1773
alb 3.5 2.8 2.8 2.3 1.9
globu 3 2.6 2.9 2.1 2.9

11. POSITIVE FINDING
 Persisting fever
 Splenomegaly
 Pancytopenia
 Hemophagocytes in BM
 Triglyceride-173mg/dl
 Aspergillus fungal in culture
 Glactomannan -positive

12. 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(bon
e, spleen,bone marrow)
6. Natural killer cell
activity(low/absent)
7.Hyperferritinemia(>50
0 mcg/l)
8. Increased soluble CD
25(>2400 u/ml)

13. diagnosis
 Fungal sinusisit with Macrophage
Activation Syndrome
 IV dexa
 IVAmpho
Voriconazole
Antibiotic
 Initial improvement showed but patient
expired due to sepsis with septic shock.

14. discussion
 Macrophage Activation Syndrome or
Hemophagocytic Syndrome
 haemophagocytosis- pathologic finding
of activated macrophages engulfing
erythrocytes, leukocytes,platelets, and
their precursor cells.

15. PRIMARY
(Familial)
SECONDARY
(Acquired)
INFECTION
IMMUNODE
-FICIENCY
AUTOIMMUNE
METABOLIC
DS.
MALIGNANCY
ETIOLOGY

16. PATHOPHYSIOLOGY
TRIGGERING FACTOR
(MC INFECTION)
INAPPROPRIATE ACTIVATION &
UNCONTROLLED PROLIFERATION
OF THE MACROPHAGES
TRIGGERING OF THE
CYTOKINE CASCADE
FREE OXYGEN RADICAL
RELEASE
ACTIVATED MACROPHAGES
PHAGOCYTOSE RBCS,WBCS,PLATELETS

17. 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.

18. Work-up
 Bacterial: Bl Cx, U Cx,
 Viral pathogens: EBV, CMV, parvo, HIV
 Fungal Cx and serology
 Eval for lymphoproliferative DO – BM bx
 Recent Travel or animal exposure – eval for
Leishmaniasis, brucellosis, rickettsioses,
malaria
 HIV +: serum crypto ag,

19. Treatment
 Steroids + Etoposide + Cyclosporine A
 Other considerations
 ATG
 IVIG
 Bone Marrow Transplant
 Familial Disease
 Non-familial: only if fail immuno-/chemo- therapy

20. Prognosis
 Mortality 22-59%
 Prognostic Factors predicting death
 >30 yr
 Underlying disease process
 Hb <10
 Platelet <100 k
 Ferritin > 500 ug/l
 Bili or alk phos elevation