Download “The Fungus Among Us” Alyon J. Wasik, OD FAAO Gregory S. Wolfe

“The Fungus Among Us”
Alyon J. Wasik, OD FAAO
[email protected]
Southern Arizona VA Health Care System
3601 S. 6th Avenue
Tucson, AZ 85723
(520) 792-1450
Gregory S. Wolfe, OD, MPH, FAAO
[email protected]
Southern College of Optometry
1245 Madison Ave
Memphis, TN 38104
(901) 722-3375
Outline
I. Epidemiology of Invasive Fungal Pathogens
a. Significantly increased over the past 2 decades leading to excessive mortality &
morbidity
i. More people living who are at risk
1. Bone Marrow and Organ Transplants
2. Major Gastrointestinal Surgery
3. AIDS, neoplastic disease, immunosuppressive therapy
4. Premature infants, advanced age
ii. Reason for increase are multifactorial, but at least in part due to the wide
spread use of Fluconazole for prophylaxis against opportunistic fungi
iii. Most Common: Candida 42%
1. Aspergillus 29%
iv. Introduction of new extended-spectrum azole antifungal agents (e.g.
voriconazole, posaconazole) and echinocandins (e.g. micafungin,
caspofungin, anidulafungin) has increased the number of therapeutic
options for early therapy
II. Public Health Impact
a. Travel Epidemiology
i. International tourist exceeded 1 billion in 2012 & projected to increase to
~2 billion by 2030, so public health impact of travel will increase
ii. Increasing travel to areas of endemic disease (e.g. coccidiomycosis)
iii. Increasing travel to destinations in Asia (arrivals up 7% from 2011 to
2012) and Africa (arrivals up 6% from 2011 to 2012) will place more
travelers @risk for variety of travel-related conditions, including malaria,
dengue, measles, and other tropical or vaccine-preventable infections.
1. Fungi are important etiological agents of infective scleritis in
tropical regions, 38% cases of infective scleritis caused by fungi
b. Climate Change
i. Transmission of many infectious disease agents is sensitive to weather
conditions, particularly those spending part of their lifecycle outside the
human body. e.g. mold spores
ii. Increases or decreases in the geographical distribution of disease
transmission may occur, as climate-driven changes cause transmission to
become unsustainable in previously endemic areas, or sustainable in
previously non-endemic areas.
iii. Substantial body of literature on association between the El Niño cycle, a
major determinant of global weather patterns & some infectious diseases.
c. Social & Environmental Heath History
i. Given increasing exposure to multiple environments it is vital to collect a
thorough patient history, which include (1)Live (2)Work (3)Play/Travel
ii. Exposures unique to these environments may help narrow etiology
Clinical case presentations of ocular & orbital findings w/fungal etiologies
III. #1. Case History
a. Patient demographics: 83 y/o Caucasian male
b. Chief complaint: overall reduction of vision and painless red OS
c. Ocular history: unremarkable
d. Pertinent medical history: recurrent urinary tract infection s/p right ureteral stent
placement, most recent due to Candida albicans
e. Medication: fluconazole 100mg daily x 10 days
IV. Pertinent Findings
a. BCVA: OD 20/25; OS 20/70-1 PHNI
b. Anterior Segment OS: diffuse conl inj,K straie, stromal edema & haze, 3+ c/f
c. Fundus Exam OS:
i. vitreous haze, mild ONH edema, ~1DD pre-retinal yellow-white central
macular abscess
d. Laboratory studies:
i. Urine culture: previously positive for Candida albicans
ii. Blood cultures: negative for Candida albicans
e. Interdisciplinary management: Consult w/ infectious disease & retinal specialist
V. Differential Diagnosis
a. Primary: endophthalmitis
i. Sarcoidosis, Cytomegalovirus retinitis, toxoplasmosis
b. Secondary: herpes simplex, Nocardia, Aspergillus, coccidiomycosis,
Mycobacterium avium-intracellulare, Crytococcus
VI. Diagnosis and Discussion
a. Presumed Candida endogenous fungal endophthalmitis
i. Fungus is most common cause of endogenous endophthalmitis
1. Candida albicans: most frequently cultured organism
ii. Candida chorioretinitis is most common fungal infection of the retina
presenting as a ‘fluff ball’ involving the retina, choroid and if extends
into vitreous is considered Candida endophthalmitis
1. Vascular sheathing & uveitis are common
2. Rare to have positive Candida culture of vitreous
a. Diagnosis usually based on clinical observations
3. Patient had positive urine culture with distinct ocular
presentation of fungal infection leading to diagnosis
VII.
Treatment and Management
a. Fluconazole increased by infectious disease specialist to 200mg daily
b. Retinal specialist: start prednisolone acetate & atropine but vision worsened over
next 3 days so pars plana vitrectomy with biopsy done followed by amphotericin
B, vancomycin, & amikacin injection next day
c. Abscess not removed due to firm attachment to macula
d. Gram staining, vitreal & aqueous cultures: negative for any bacterial or fungal
organisms; systemic infection resolved and fellow eye not affected
VIII. Conclusion
a. Though Candida is the most common cause of fungal infection, endogenous
fungal endophthalmitis is rare. It can cause severe vision loss and be associated
with a high mortality rate.
b. The fundus findings can be the first sign of systemic candidiasis
c. The immediate initiation of oral antifungals based on clinical presentation alone
can minimize vision loss. A vitrectomy with injection of antifungal agents is
indicated in severe cases recalcitrant to systemic treatment.
IX. #2. Case History
a. Patient demographics: 16 y/o African American female
b. Chief complaint: painless gradually decreasing vision OD x 1 month
c. Ocular history: unremarkable except for mild refractive error
d. Medical history: chronic bronchitis (not actively treated)
e. Social history: no smoking/drinking/illicit drugs
f. Mediations: depot injection of medroxyprogesterone
g. Other salient information: oriented to time/place/person; however, blunted affect
noted
X. Pertinent findings
a. Clinical/Physical
i. BCVA: OD 10/600 (Feinbloom); OS 20/20
ii. Red cap desaturation: 80% deficit OD; 4+ right APD
iii. Confrontation visual fields: nasal contraction OD>OS
iv. EOMs = full and unrestricted
v. Hypertelorism: PD = 78mm and proptosis OD
vi. Anterior slit lamp exam; IOP: unremarkable OD/OS
vii. Dilated fundus exam
1. C/D ratio: 0.20 OD/OS; no edema
2. OD 4+ temporal pallor 7-10 / OS 2+ temporal pallor 3-4
viii. Goldmann Perimetry
1. OD ceco-central scotoma & generalized contracture of nasal
field / OS generalized nasal contracture
b. Laboratory studies
i. Free T4 & TSH, RPR & FTA-ABS, ACE & Serum Lysozyme, ANA,
RF, CBC, Chem-7, Mantoux test: all WNL
c. Radiological studies
i. CT and MRI: brain and orbits, with and without contrast
1. Lobulated mass extended from left sphenoid sinus into the floor
of the anterior fossa and left frontal lobe
2. Right > left ethmoid & sphenoid sinuses markedly expanded and
displaced orbits laterally
3. Compression of optic nerve @ the orbital apex right>left
4. Proptosis of both globes
5. Highly suggestive of fungal sinusitis
d. Interdisciplinary management: ENT & neurosurgery STAT consults
XI. Differential diagnosis
a. Primary/leading (tentative)
i. Orbital space occupying lesion versus thyroid ophthalmopathy versus
infiltrative optic neuropathy
b. Orbital abscess/cellulitis/mucocele, Leuitic, tuberculosis
c. Thyroid ophthalmopathy, neuro Sarcoidosis or other Infiltrative/Auto Immune,
prbital Inflammatory Pseudotumor
d. Orbital Rhabdomyosarcoma, meningioma
XII.
Diagnosis and Discussion
a. Sino-Orbital-Cerebral Aspergillosis
b. Aspergillus found throughout the world in soil & decaying vegetation
i. Most common forms contaminate of paranasal sinus & orbit
1. Commonly found in immunocompromised hosts
c. Clinical presentation can be quite varied
XIII. Treatment
XIV.
XV.
XVI.
a. Biopsy & histological examination
i. Branched septated hyphae in tangled mass w/o signs of mucosal
invasion; fungus ball of Aspergillus fumigatus
b. Immediate debridement & debulking by ENT and Neurosurgery
c. Postoperatively admitted into intensive care unit
i. Treated w/ IV infusion of fluconazole 200mg/day for 10 days
d. Discharged on 200mg Diflucan p.o. daily until told to D/C by ENT
Pre and post imaging studies reviewed with neuro ophthalmology
a. Debulking of sinuses to correct hypertelorism
b. Box-shift mobilization of the orbits
Conclusion
a. Investigate the dx of aspergillosis especially in immunosupressed patients as it
can mimic variety of orbital conditions
b. Important to gather key information from patient history, making accurate
objective observation, formulating differential diagnosis, and narrowing down
diagnosis with laboratory and imaging studies and need for coordination of
interdisciplinary patient care
#3. Case history
a. Patient demographics: 65 year old Caucasian female
b. Chief complaint: progressive OS pain, redness, blurred vision, photophobia
c. Pertinent ocular history: unremarkable
d. Pertinent medical history & medication: non contributory
e. Other salient information: originally from Ohio, last there in 2008; Arizona
resident for 20 years
XVII. Pertinent findings
a. BCVA: OD 20/25; OS 20/70-1 PHNI
b. Anterior segment and fundus exam:
i. Diffuse bulbar conjunctival injection, corneal edema OS & ant uveitis
subsequently affecting OD
ii. Mild to moderate vitritis/vitreous haze OS subsequently affecting OD
iii. Mild sheathing of veins leading to severe occlusive vasculitis and iris
rubeosis, marked arteriolar attenuation & intraretinal hemorrhages OS
iv. Subsequent vascular fibrosis & arteriolar attenuation OD
c. Laboratory studies:
i. Coccidioidomycosis IDCF: positive & titer detectable \
ii. RPR/FTA-ABS, Lyme titer, PPD, Bartonella henselae, toxoplasmosis,
HIV, RF, C- & P-ANCA, CBC, Blood Chemistry 7: negative/non
reactive
iii. Cytomegalovirus DNA: not detected & CD-4 count: WNL
iv. ANA titer: 1:320 but subsequent autoantibody testing negative
v. HLA B-27/B-44: detected; sensitive C-RP, ESR: elevated
d. Radiology studies
i. PET scan: PET-negative pulmonary nodule, which was determined to
likely represent Coccidioidomycosis
ii. MRI/MRA brain: unremarkable
e. IVFA: periarteritis & periphlebitis w/ mild occlusion OS; periphlebitis OD
f. Interdisciplinary management
i. Rheumatology: rule out underlying systemic autoiummune diseases and
assist with management of immunosuppressive treatment
ii. Infectious disease: manage and treat Coccidioidomycosis
XVIII. Differential diagnosis
a. Primary
i. Disseminated Coccidioidomycosis
ii. Sarcoidosis, Syphilis, CMV retinitis, systemic lupus erythematosus
b. Secondary
i. Other viral (herpes, HIV) retinitis, fungal endophthalmitis, toxoplasmosis
ii. Ocular histoplasmosis, Tuberculosis, Lyme disease
iii. Wegener’s granulomatosis, Behçet’s disease
XIX. Diagnosis and Discussion
a. Rapidly progressive severe non-granulomatous bilateral panuveitis with
severe occlusive vasculitis OS>OD
i. Subsequent finding of disseminated Coccidioidomycosis, a dimorphic
fungus endemic to regions in Arizona, through extensive testing
ii. Disseminated Coccidioidomycosis to liver, brain, heart, and other organs
is rare affecting less than 1% with primary Coccidioidomycosis
iii. Systemic antifungal treatment depends on the type & severity of
infection
b. Ocular sequelae infrequently reported though true prevalence is unknown
i. Anterior segment may include phlyctenular conjunctivitis, iridocyclitis
ii. Posterior segment may include chorioretinal lesions retinal
hemorrhages, serous retinal detachment, vitreous haze, vascular
sheathing
XX.
Treatment and Management
a. Topical Medications: Pred Forte and Cyclogel
b. Systemic Medications: Prednisone, Valgancyclovir, Fluconazole & Azathioprine
c. Avastin, repeated PRP for occlusive disease, subtenon Kenalog injection
d. Continued care with infectious disease, pulmonary, and rheumatology clinics
XXI. Conclusion
a. Coccidioidomycosis is subclinical in most individuals, with ocular involvement
being regarded as rare and usually associated with disseminated disease.
b. Incidence of Coccidioimycosis increasing in the US & should be considered as a
differential diagnosis in patients who have been traveling or living in highly
endemic areas and present with ocular findings consistent with previously
reported ocular sequelae, as well as panuveitis and occlusive vasculitis not
attributable to other conditions.
XXII. Public Health Application to Disease Presentation
a. 3 Ways to think about “health.”
i. Medical Tradition
1. Focused on the individual
ii. Environmental
1. External factors affecting health
iii. Social
1. Nature of interactions between individuals and their environment
b. Environmental and Socio-Economic factors played a large role in these cases
i. Review of Case #1, #2, #3 highlighting: Medical/Environmental/Social
factors that led to the fungal pathogen disease process.
c. Importance of taking a detailed social & environmental history
i. Otherwise could not have explained etiology of condition
XXIII. References
a. Haines A, Kovats RS, Campbell-Lendrum D, Corvalan C. Climate change and
human health: Impacts, vulnerability and public health. Public Health (2006)
120, 585–596.
b. Klotz S, Penn C, Negvesky G, Butrus S. Fungal and Parasitic Infections of the
Eye. Clinical Microbiology Reviews, October 2000, 662-685.
c. P Garg. Fungal, Mycobacterial, and Nocardia infections and the eye: an update.
Eye (2012) 26, 245–251; doi:10.1038/eye.2011.332; published online 16
December 2011.
d. Holland G. Endogenous fungal infection of the retina and choroid. In: Ryan SJ,
editor. Retina, 4th ed. St Louis: Mosby; 2005. p.1683-98.
e. Levin LA., Avery R., Shore JW., et al: The spectrum of orbital aspergillosis: A
clinicopathological review. Serv Ophthalmol 41:142-154, 1996.
f.
Sivak-Callcott JA.,Livensley N., Nugent RA., et at: Localised invasive
sino-orbital asperfillosis: characteristic features. Br J Ophthalmol 88:681-687,
2004.
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Galgiani JN. Coccidioidomycosis. West J Med. 1993; 159:153-171.
h.
Rodenbiker HT, Ganley JP. Ocular Coccidioidomycosis. Surv of Ophthal.
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wwwnc.cdc.gov/travel/yellowbook/2016/introduction/travelepidemiology