Teaching Case of the Week

Dr. W. A. Ciccotelli

Sept 14, 2005

The Patient

82 y M Past Hx

Low grade B cell lymphoma Pancytopenia/transfusion dependent Interstitial lung dz HTN Ex-smoker

The Patient

Meds Amlodipine Prednisone (taperingx 4 mos)

NKDA 2-4x EtOH/wk

The Case

Referred to ID for peri-orbital cellulitis 3 day Hx of progressive

R eye swelling R frontal headache Reactive clear discharge FB sensation

No fever/chills No other ocular symptoms Vision ok On cefotaxime 36 hrs

The Case

Afebrile, VSS Peri-orbital cellulitis R eye proptosis, mild ptosis, chemosis Loss of EOM R eye CNs normal otherwise Visual acuity normal

The Case

WBC 4.9, Hgb 99, plts 54, grans 1.7 Lytes N Cr 123 TSH 1.1 Panculture neg CXR: unchanged chronic interstitial

pattern

The Case

CT scan head R pre-septal edema Minimal proptosis R eye R Maxillary & ethmoidal sinusitis R nasal septum deviation No bony lesions No retro-orbital masses

ENT consulted

The Case

Not responding on Cefotaxime Febrile New diplopia Worsening peri-orbital cellulitis

The Case

Abx changed to Clinda/Cipro MRI head

Small fluid collection lat. R eye ?abscess Maxillary & ethmoid sinusitis (L & R) Meninges inflammatory changes in R middle

cranial fossa No cavernous vein thrombosis

Nasal culture: commensal flora

The Case

Now really bad! Delirious Febrile Clonus in lower ext. R Facial droop

The Case

Urgent ethmoidectomy necrotic sinus painless procedure

LP aseptic meningitis ANCAs neg Lipo Ampho B started 5 mg/kg/day

The Case

Repeat MRI Early cerebritis R temporal operculum Ongoing inflammatory changes of all sinuses Inflammatory changes around R orbit,

masticator space, cavernous sinus

Case Resolution

Further CNS deterioration Sinus Bx

Broad ribbon like non-septate fungal filament on microscopy

ZN & PAS stains confirm non-septate hyphae Dx of Rhinocerebral zygomycosis Lipo Ampho B to 10 mg/kg/day Family withdrew care given degree of surgery

needed

Zygomycosis

Mucorales order Ubiquitous in environment Thick walled non-septate hyphae with right

angle branching Rare & mimics other invasive mould infections Inherent resistance to antifungal agents Angioinvasive disease

Zygomycosis

Multiple clinical forms Cutaneous Pulmonary Gastrointestinal Rhinocerebral Sino-orbital Disseminated

Direct inoculation, inhalation, ingestion of spores

Zygomycosis

Immunocompromised state hallmarks DM ketoacidosis Neutropenia Chemotherapy BMT patients Lymphoma/leukemia Trauma with exposure to contaminated soil

Zygomycosis

Dx is difficult & delayed Poor recovery from culture Non specific presentation Not on everyone’s DDx Mimics other invasive molds (Aspergillus) Dx generally made with invasive testing for

histopathological sampling Dx commonly made at autopsy

Yet increasingly problematic in Heme-Onc patients over 1990s

Zygomycosis

Treatment is multifaceted Immune reconstitution Aggressive surgical debridement Ampho B Prayer

Posaconazole as oral alternative Despite this still highly fatal (mortality 50-

80%)

Zygomycosis

Prognosis is poor Late Dx Not able to recover immune system Disseminated Death usually from hemorrhage

Best prognosis Limited disease Early surgery Non Heme-Onc patients

Zygomycosis

Tip offs Right patient population (esp neutropenia) Unexplained thrombosis Necrotic eschar Unexplained hemorrhage Common clinical situations

Culture neg despite real disease Not responsing to reasonable Abx