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Jennifer Pichay-Alvarado, MD, DPPS
Fever
Elevation of body temperature exceeding the normal daily variation
and occurs in conjunction with an
increase in the hypothalamic set point
(from 37C to 39C)
18 to 40 years old (mean oral temperature = 36.8C+ 0.4C)
Maximum oral temp 37.2C (6am) 37.7C (4pm)
Rectal = 0.4C higher than oral temp
Tympanic membrane = 0.8C lower than rectal temp
Axillary = 0.3-0.6C lower than oral temp
Definition:
Fever of Unknown Origin
Temperatures of >38.3C on several occasions
Duration of fever of >3 weeks
Failure to reach a diagnosis despite 1 week of in-patient investigation
Petersdorf and Beeson
1961
Classification:
better accounts for non endemic and emerging diseases, improved diagnostic technologies and adverse reactions to new therapeutic interventions
1. Classic FUO
2. Nosocomial FUO
3. Neutropenic FUO
4. FUO associated with HIV infection
Durack and Street Revised system for classification
Classic FUO
3 OPD visits 3 days in the hospital without elucidation of a
cause
1 week of intelligent and invassive ambulatory investigation
Causes : infection (bacterial, viral, protozoal or fungal)
Neoplasms
Non-Infectious inflammatory diseases
systemic rheumatologic or vasculitic disease (polymyalgia rheumatica, lupus, Stills disease)
Granulomatous diseases (Sarcoidosis, Crohns disease and granulomatous hepatitis
Multisystem diseases frequent cause in elderly patients (giant cell arteritis) 15-20% (>50 years old)
Tuberculosis most common infection causing FUO in elderly
Colon cancer most important cause of FUO with malignancy in elderly
Miscellaneous drug fever, pulmonary embolism, factitious fever, hereditary periodic syndromes (familial
mediterranean fever, hyper IgD syndrome, TNF receptor-
associated periodic fever (TRAPS or hibernian fever),
familial cold urticaria and Muckle-Wells syndrome,
Congenital lysosomal storage diseases (Gauchers and
Fabrys disease
Causes of FUO Lasting > 6 months
No fever 27%
Non identified 19%
Miscellaneous 13%
Factitious 9%
Granulomatous hepatitis 8%
Neoplasm 7%
Stills disease 6%
Infection 6%
Collagen vascular disease 4%
Familial Mediterranean fever 3%
R. Aduan et al 1978
NIH 1961-1977 (347 px)
Nosocomial FUO
Patients susceptibility
Potential complications of hospitalization
Surgical or procedural field place to begin a directed physical and laboratory exam abscesses, hematomas,
infected foreign body
50% infected
IV lines, septic phlebitis, prostheses
Focus on sites where occult infections (best approach)
sinuses intubated patients
Prostatic abscess catheterized patients
25% non infectious cause
Acalculous cholecystitis
Deep vein thrombophlebitis
Pulmonary embolism
Drug fever
Transfusion reaction
Alcohol/drug withdrawal
Adrenal insufficiency
Thyroiditis
Pancreatitis
Gout
Pseudogout
Management:
Meticulous PE
Focused diagnostic techniques
Blood, wound and fluid cultures
CT scan, ultrasound
20% no diagnosis
Change IV lines
Drugs stopped for 72 hours
Start empirical therapy
Vancomycin methicillin resistant S. aureus
Piperacillin/Tazobactam, Ticarcillin/Clavulanate, Imipenem or Meropenem broad spectrum G(-)
Neutropenic FUO
Neutropenic patients susceptible to focal bacterial and fungal infections, to bacteremic infections, to infections involving catheters (septic thrombophlebitis) and to perianal infections (candida and aspergillus)
HSV and CMV infections are common Short duration of illness Catastrophic if untreated 50% - 60% febrile neutropenics infected 20% bacteremic Severe mucositis, quinolone prophylaxis, colonization with
methicillin resistant S. aureaus, obvious catheter-related infection or hypotension use Vancomycin plus Ceftazidime, Cefepime or Carbapenem with or without aminoglycoside -provide empirical coverage (bacterial sepsis)
HIV-associated FUO
HIV ifection cause of fever
Causes
M. avium or intracellulare, NHL
Tuberculosis
Toxoplasmosis
CMV infection
Pneumocystis infection
Salmonellosis
Cryptococcosis
Histoplasmosis
Strongyloidiasis
NHL, drug fever
Diagnosis
Blood cultures
Liver, bone marrow and lymph node biopsies
Chest CT scan
Serologic tests cryptococcal antigen; 67Ga scan (Pneumocystis pulmonary infection)
>80% HIV infected patients infectious etiology
Drug fever and lymphoma important consideration
Treatment
Age and physical state elderly (trial of empirical therapy early)
Continue observation and examination
Avoid shotgun empirical therapy
Vital sign instability and neutropenia indication for empirical therapy (Fluoroquinolone plus Piperacillin)
TST + = therapeutic trial for TB up to 6 weeks, if still with fever = alternative diagnosis
Glucocorticoids = temoral arteritis, polymyalgia rheumatica and granulomatous hepatitis
Cochicine = familial mediterranean fever
*No underlying source of FUO after
>6 months = good prognosis
Debilitating symptoms = treated with NSAIDs Glucocorticoids = last resort Initiation of empirical therapy = not the end of
diagnostic work ups
Continue thorough reexamination and evaluation
Patience, compassion, equanimity, vigilance and intellectual flexibility = indispensable attributes for the clinician in dealing successfully with FUO
Fungal Infections
HISTOPLASMOSIS
Histoplasma capsulatum
Most prevalent endemic mycosis in North America
Inhalation of microconidia
Clinical Manifestation:
Asymptomatic to life threatening illness
Symptoms appear 1-4 weeks after exposure
Flu-like illness (fever, chills, sweats, headache, myalgia, anorexia, cough, dyspnea and chest pain)
Chest radiograph pneumonitis with hilar or mediastinal adenopathy
Rheumatologic symptoms of arthralgia or arthritis, associated with erythema nodosum 5%-10% cases
Pericarditis may also develop
Hilar and mediastinal lymphnodes undergo necrosis and coalesce forming large mediastinal mass
compressing great vessels, proximal airways and
esophagus
Necrotic lymphnodes may rupture and create bronchoesophageal fistula
Progressive Disseminated Histoplasmosis(PDH) immunocompromised patient 70% cases
Risk factors : AIDS, extremes of age, use of immunosuppressive medications (Prednisone,
Methotrexate, anti TNF alpha agents)
Spectrum of PDH :
Acute -rapidly fatal course (with diffuse intersttial or reticulonodular lung infiltrates causing Respiratory failure, shock, coagulopathy, Multiorgan failure
Subacute focal organ distribution (fever, weight loss, hepatosplenomegaly, meningitis, focal brain lesions, ulcerations of oral mucosa, GI ulcerations and adrenal insufficiency)
Chronic cavitary histoplasmosis
smokers with structural lung disease (productive cough, dyspnea, low grade fever, night sweats and weight loss)
CXR UL infiltrates, cavitation, pleural thickening
Slowly progressive if untreated
Fibrosing mediastinitis
serious complication but uncommon
1/3 cases fatal
Unilateral or bilateral involvement (worst prognosis)
SVC syndrome, pulmonary vessel obstruction and airway obstruction
Recurrent pneumonia, hemoptysis or respiratory failure
Broncholithiasis
in healed histoplasmosis, calcified mediastinal nodes or lung parenchyma may erode through the walls of
airway causing hemoptysis
African histoplasmosis
H. capsulatum var duboisii
Skin and bone involvement
Diagnosis:
Fungal Culture gold standard
Result up to 1 month
(-) for less severe cases
75% (+) PDH and Chronic pulmonary histoplasmosis
BAL fluid, BM aspirates and blood
Sputum or bronchial washing (+) chronic pulmonary
histoplasmosis
Fungal stains of cytopathology or biopsy materials
Histoplasma antigen in body fluids
Useful in the diagnosis of PDH
>95% sensitive (PDH)
80 % sensitive (Acute pulmonary histoplasmosis)
Serologic tests
Immunodiffusion and Compliment fixation
Useful for diagnosis of self limited histoplasmosis and chronic pulmonary histoplasmosis
1 month for antibody production
Limitations : insensitive in early infection and immunosuppressed patients, persistence of detectable antibody several years after infection
Treatment:
Acute pulmonary, moderate to severe illness with diffuse infiltrates and/or hypoxemia
Lipid Amphothericin B (3-5mg/kg/day)+glucocorticoids for 1-2 weeks; then Itraconazole(200mg BID) for 12 weeks
Mild cases recover without therapy but may give Itraconazole if no improvement
Chronic/cavitary pulmonary
Itraconazole(200mg BID or QID) for atleast 12 months
Continue therapy until xray show no improvement
Monitor relapse after treatment stopped
Progessive disseminated
Lipid Amphothericin B (3-5mg/kg/day) for 1-2 weeks then Itraconazole (200mg BID) for atleast 12 months
Chronic maintenance therapy necessary if degree of immunosuppression cannot be reduced
CNS
Liposomal Amphothericin B (5mg/kg/day) for 4-6 weeks then Itraconazole (200mg BID or TID) for atleast 12 months
Longer course of lipid AmB recommended due to relapse
Continue Itraconazole until CSF or CT abnormalities clear
Posaconazole, Voriconazole and Fluconazole alternative for Itraconazole
Monitor blood levels of Itraconazole 2-10ug/ml (target concentration)
Duration of treatment
APH 6-12 weeks
PDH - > 1 year
Monitor antigen levels in urine and serum during and for atleast 1 year after therapy for PDH
Stable or rising antigen level treatment failure or relapse
Maintenance therapy with Itraconazole not required
a. for patients who respond well to antiretroviral therapy
b. CD4+ T cell counts of atleast 150/uL (preferably >250/uL)
c. Completed atleast 1 year of Itraconazole therapy
d. Exhibit neither clinical evidence of active histoplasmosis
nor antigenutria level of > 4ng/ml
e. Patients receiving immunosuppressive treatment
Fibrosing mediastinitis (chronic fibrotic reaction to past mediastinal histoplasmosis rather than active infection)
does not respond to antifungal therapy
COCCIDIOIDOMYCOSIS
Valley fever
Dimorphic soil-dwelling fungi Coccidioides
C. immitis and C. posadasii
60% asymptomatic
40% pulmonary infection
Cough, fever and pleuritic chest pain
Risk of symptomatic illness increases with age
Commonly misdiagnosed as Community acquired bacterial pneumonia
Cutaneous manifestation
Toxic erythema maculopapular rash
Erythema nodosum lower extremities
Erythema multiforme necklace distribution
Arthralgia and arthritis may develop
Primary pulmonary coccidioidomycosis history of night sweats, profound fatigue, peripheral blood
eosinophilia and or hilar or mediastinal
lymphadenopathy(CXR)
10% develop pleural effusion (associated with
pulmonary infiltrate on same side, cellular content
mononuclear)
Resolves without sequela in several weeks
Pulmonary nodules residua of primary pneumonia
(single, located at the upper lobes,
Pulmonary cavities
thin walled shell which occur when nodule extrude its
contents into the bronchus
Associated with persistent cough, hemoptysis and
pleuritic chest pain
Pyopneumothorax when cavity rupture into pleural space (rare)
Acute dyspnea
Collapsed lung with pleural air fluid level
Chronic or persistent pulmonary coccidioidomycosis
Prolonged fever, cough and weight loss
Scarring, fibrosis and cavities (CXR)
< 1%
Primary diffuse coccidioidal pneumonia
Diffuse reticulonodular pulmonary process (CXR)
Associated with dyspnea and fever
Intense environmental exposure or profound suppressed cellular immunity (AIDS), unrestrained fungal growth frequently associated with fungemia
Clinical dissemination outside thoracic cavity occurs < 1%
Risk factors :mostly males, African-American or Filipino ancestry, patients with depressed cellular immunity, women on 2nd and 3rd trimester
Common sites : skin, bone, joint, soft tissue and meninges
Follow symptomatic and asymptomatic pulmonary infection, evident within first few months after primary pulmonary infection
Meningitis
fatal if untreated
Persistent headache, lethargy, confusion, (+) nuchal
rigidity
CSF exam: lymphocytic pleocytosis, profound
hypoglycorrhachia and elevated proten levels, CSF
eosinophilia
With or without appropriate therapy may develop
hydrocephalus (marked decline in mental status ften
with gait disturbances)
Diagnosis:
Serology
a. Tube Precipitin and Complement fixation assay
b. Immunodiffusion and Enzyme immunoassay detect IgG and IgM antibodies
TP and IgM antibodies found in serum soon after infection and persist for weeks (not useful for gauging disease progression and not found in CSF
CF and IgG occur later in the course of the disease and persist longer than TP and IgM antibodies
Rising CF titers associated with clinical progression and the presence of CF antibody in CSF (meningitis)
Antibodies disappear overtime in person whose clinical illness resolves
Coccidioidal EIA
Frequently used as screening tool
Culture
Coccidioides grows within 3-7 days at 37C artificial
media including blood agar
Sputum, other respiratory fluid and tissues
Stains
Hematoxylin Eosin
Papanicolau
Gomori methenamine silver
Test for antigenuria and antigenemia
False positive result
Treatment:
Asymptomatic 60% none
Primary pneumonia (focal) 40% - none (most cases)
Diffuse pneumonia
Duration of treatment is based on:
a. resolution of signs and symptoms of the lesion
b. Significant decline in serum CF antibody titer
Usually continued for atleast several years
Relapse 15-30% once therapy discontinued
80% relapse (meningitis) life long therapy recommended
Triazole therapy failure intrathecal or intraventricular Amphothericin B
Hydrocephalus CSF shunting plus Antifungal therapy
Prevention:
Avoid direct contact with uncultivated soil or visible dust with soil
Prophylactic antifungal therapy appropriate in patients with:
a. active or recent coccidioidomycosis
b. About to undergo allogeneic solid-organ
transplantation
Give antifungal therapy to patients with history of active coccidioidomycosis or positive coccidioidal
serology in whom therapy with TNF alpha antagonist
is being initiated
BLASTOMYCOSIS
Systemic pyogranulomatous infection involving primarily the lungs
Inhalation of conidia
Blastomyces dermatitidis
Risk factors:
a. Middle aged man
b. Outdoor occupations
Grows as microfoci in the warm, moist soil of wooded areas rich in organic debris
Exposure to soil (work or recreation)
Clinical manifestation:
Acute pulmonary infection
Diagnosed in association with point source outbreaks
abrupt onset of fever, chills, pleuritic chest pain,
arthralgias and myalgias
Non productive cough purulent
CXR alveolar infiltrates with consolidation
Chronic indolent pneumonia
fever, weight loss, productive cough and hemoptysis
CXR alveolar infiltrates with or without cavitation, mass
lesions (mimic bronchogenic ca and fibronodular
infiltrates)
Respiratory failure(ARDS) associated with miliary disease or diffuse pulmonary infiltrates more common among immunocompromised patients
Mortality rates > 50%
Deaths occur within first few days of therapy
Skin disease most common extrapulmonary manifestation
Verrucous - most common
Ulcerative
Osteomyelitis
of B.dermatitidis infection
Vertebra, pelvis, sacrum, skull,ribs or long bones
Presents with contiguous soft tissue abscesses or chronic draining sinuses
Prostate and epididymis involvement in males
CNS involvement
< 5% cases immunocompetent
40% AIDS
Presents as brain abscess
Cranial or spinal epidural abscess
Meningitis
Diagnosis:
Culture
Definitive diagnosis
Specimen: sputum, pus or biopsy material
Visualization of broad based budding yeast
Presumptive diagnosis
Serology limited due to cross reactivity
Blastomyces antigen assay detects antigen in urine and serum
Urine more sensitive
Useful in monitoring patients during therapy or for
early detection of relapse
Molecular identification techniques DNA probe
hybridization supplement traditional mtds
Treatment:
Immunocompetent/Life threatening disease
Pulmonary LipidAmB (3-5mg/kg) qd or deoxycholate AmB(0.7-1 mg/kg qd
Itraconazole 200-400mg/d (once
stabilized) alternative
Disseminated
CNS Lipid AmB or deoxycholate AmB, Fluconazole 800 mg/d intolerant with full
course AmB alternative
Non CNS Lipid AmB or deoxycholate AmB, Itraconazole 200-400mg/d (once stabilized)
Immunocompetent/Non life threatening disease
Pulmonary or disseminated (non CNS)
Itraconazole or LipidAmB or deoxycholate AmB
Fluconazole 400-800mg/d or Ketoconazole
Immunocompromised
All infections
Lipid AmB or deoxycholate AmB
Itraconazole 200-400 mg/d (non CNS once
clinically improved)
CRYPTOCOCCOSIS
Cryptococcus neoformans and C. gattii
First described in 1890s, acquired by inhalation of aerosolized infectious particle
Meningoencephalitis and pneumonia
Skin and soft tissue infection
At risk : hematologic malignancies, solid organ transplant recipient with ongoing immunosuppressive treatment, glucocorticoid therapy and with advanced HIV infection and CD4+ T lymphocyte counts 600,000 deaths annually
C. neoformans soil contaminated avian excreta, shaded and humid soil contaminated with pigeon droppings
C. gattii eucalyptus tree
Clinical manifestations:
CNS involvement chronic meningitis (headache, fever, lethargy, sensory deficits, memory deficits,
cranial nerve paresis, vision deficits and meningismus
Pulmonary cough, increased sputum production and chest pain
Crytococcomas C. gattii, granulomatous pulmonary masses
Skin lesion common in disseminated cases, papules, plaques, purpura, vesicles, tumor like lesions and
rashes
AIDS and solid organ transplant patients lesions of cutaneous crytococcosis resemble molluscum
contagiosum
Diagnosis:
CSF India Ink Examination
useful rapid diagnostic technique
(-) low fungal burden
Culture
CSF
Crytococcal antigen (CRAg) detection
CSF and blood
Based on serological detection of polysaccharide
Sensitive and specific
less useful in pulmonary disease
Treatment:
Pulmonary Fluconazole (200-400mg/d) 3-6 months
Extrapulmonary without CNS involvement same regimen, AmB .5-1mg/kg daily 4-6 weeks (severe cases)
CNS involvement without AIDS or obvious immune impairment AmB(.5-1mg/kg daily induction phase,
followed by Fluconazole (400mg/d) during
consolidation phase
Cryptococcal meningoencephalitis without concomitant immunosuppressive condition AmB plus
flucytosine (100mg.kg) daily for 6-10 weeks,
alternatively AmB plus flucytosine daily for 2 weeks
then with Fluconazole (400mg/d) atleast 10 weeks
Prognosis and Complications:
High rate of morbidity and death
Extent and duration of underlying immunologic deficits - most important prognostic factor
Curable with antifungal therapy no apparent immunologic dysfunction
Severe immunosuppression antifungal induce remission, maintained with life long suppressive
therapy
Survival period
AIDS -
CNS poor prognostic marker
(+) CSF assay for yeast cells by initial india ink exam
High CSF pressure
Low CSF glucose levels
Low CSF pleocytosis
Prevention:
No vaccine
Primary prophylaxis with Fluconazole 200mg/day
Advanced HIV infection
CD4+ T lymphocyte
CANDIDIASIS
Candida species (albicans, guilliermondii,krusei, parapsilopsis, tropicalis, kefyr, lusitaniae, dubliniensis, and glabrata)
Inhabit GIT (mouth and oropharynx), female genital tract, skin
Most common nosocomial pathogen
Predisposing factors for hematogenous spread
Antibacterial agents, respirators
Indwelling intravascular catheter, neutropenia
Hyperalimentation fluids,abdominal and thoracic surgery
Indwelling urinary catheter, cytotoxic chemotherapy
IV glucocorticoids
Immunosuppressive agents for organ transplantation
Severe burns
Low birth weight illicit IV drugs use
HIV patients
DM (mucocutaneous)
Women receiving antibacterial agent (Vaginal
candidiasis)
Clinical manifestations:
Mucocutaneous candidiasis
Thrush
white, adherent, plainless, discrete or confluent patches
in the mouth, tongue, or esophagus with fissuring at
corners of mouth
Points of contact with dentures
Vulvovaginal candidiasis
Pruritus, pain and vaginal discharge (thin , whitish
curds)
Other candidiasis
Paronychai- painful swelling at the nail-skin interface
Onychomycosis fungal nail infection
Intertrigo erythematous irritation with redness and pustules in the skin folds
Balanitis erythematous pustular infection of glans penis
Erosio interdigitalis blastomycetica infection between digit of hands or toes
Folliculitis with pustules developing most frequently in the area of beard
Perianal candidiasis pruritic erythematous pustular infection surrounding the anus
Diaper rash erythematous pustular perineal infection (infants)
Generalized disseminated cutaneous candidiasis occurs primarily in infants, widespread eruption over trunk, thorax and extremities
Chronic mucocutaneous
heterogenous infection of hair, nails, skin and mucous membranes persists despite intermittent therapy
infancy or within 1st 2 decades of life
Mild and limited to specific area of skin or nails
Candida granuloma
severely disfiguring form, exophytic outgrowths on the
skin, associated with immunologic dysfunction
APECED syndrome
autoimmune polyendocrinopathy-candidiasis-
ectodermal dystrophy
due to mutation in autoimmune regulator gene
most prevalent among Finns, Iranian, Jews, Sardinians,
northern Italians and Swedes
Hypoparathyroidism, Graves disease
Adrenal insufficiency, autoimmune thyroiditis
Chronic active hepatitis, alopecia, juvenile onset
pernicious anemia, malabsorption, primary
hypogonadism
Dental enamel dysplasia
Vitiligo
Pitted nail dystrophy
Calcification of tympanic membranes
Deeply invasive candidiasis
Result of hematogenous seeding of various organs as a complication of candidemia
Brain, chorioretina, heart and kidneys (most common)
Liver and spleen (less common)
Endocrine gland, pancreas, heart valves (native or prosthetic), skeletal muscle, joints, bone and meninges
Skin (macronodular lesion)
Diagnosis:
KOH pseudohyphae or hyphae
Grams stain, PAS or methenamine silver stain - inflammation
Presence of ocular or macronodular skin lesion highly suggestive of widespread infection of multiple deep
organs.
Prophylaxis:
Prophylactic Fluconazole ( 400mg/d) allogeneic stem cell transplants and high risk liver transplant recipients
Neutropenic patients Fluconazole (200-400mg/d); Lipid AmB (1-2mg/d); Caspofungin(50mg/d); Itraconazole(200mg/d); Posaconazole(200mg tid)
Surgical patients not always given prophylaxis
a. Low incidence of disseminated candidiasis
b. Suboptimal cost-benefit ratio
c. Increased resistance
Prophylaxis for oropharyngeal or esophageal candidiasis in HIV infected patients not recommended unless with frequent recurrences
ASPERGILLOSIS
All disease entities caused by any one of 35% pathogenic and allergenic species of Aspergillus
A. fumigatus most cases of invasive aspergillosis (chronic aspergillosis and most allergic syndromes
A. flavus prevalent in hospitals and cases of sinus and cutaneous infections and keratitis
A. niger invasive infection but more commonly colonizes respiratory tract and otitis externa
A. terreus invasive disease with poor prognosis
A. nidulans ninvasive infection, primarily with chronic granulomatous disease
Most commonly growing in decomposing plant materials and in bedding.
Found in indoor and outdoor air, on surfaces, and in water from surface reservoir
Incubation period : 2 90 days
Risk factors:
a. Profound neutropenia
b. Glucocorticoid use
c. Advanced HIV infection
d. Relapsed leukemia
Clinical Manifestations
Invasive pulmonary aspergillosis
Acute - < 1 month
Subacute 1-3 months
80% lung involvement
Fever, cough, chest discomfort, hemoptysis, shortness of
breath
Key to early diagnosis in at-risk patients:
a. High index of suspicion
b. Screening for circulating antigen (leukemia)
c. Urgent CT of the thorax
Invasive sinusitis
5-10% of cases
Leukemia and recipients of hematopoieticstem cell transplant
Fever, nasal or facial discomfort, blocked nose and bloody nasal discharge
Endoscopic exam of nosepale, dusky or necrotic looking tissue
CT or MRI of sinuses essential but does not distinguish invasive aspergillus sinusitis from
preexisting allergic or bacterial sinusitis early in the
disease process
Tracheobronchitis
Only airways are infected
Acute or chronic bronchitis to ulcerative or pseudomembranous tracheobronchitis
Common among lung transplant recipients
Obstruction with mucous plugs occurs in normal individual, persons with ABPS and
immunocompromised
Disseminated aspergillosis
Severely immunocompromised
Lungs to multiple organs brain (most often), skin, thyroid, bone, kidney, liver, git, eye, heart valves
Cutaneous lesions
Gradual clinincal deterioration over 1-3 days, low grade fever, mild sepsis and non specific abnormalities in lab test
Blood cultures almost always negative
Cerebral Aspergillosis
Devastating complication
Single or multiple lesions develop
Acute disease hemorrhagic infarction and abscess
Rare meningitis,mycotic aneurysm and cerebral granuloma
Mood changes, focal signs, seizures, decline in mental status
MRI most useful
Endocarditis
Prosthetic valve infections resulting from contamination during surgery
Native valve
Illicit IV drug use
Culture negative endocarditis with large vegetation most common presentation
Cutaneous aspergillosis
Erythematous or purplish nontender area that progresses to necrotic eschar
Direct invasion in neutropenic patients at IV catheter insertion site and burn patients
Chronic pulmonary aspergillosis
1 or more pulmonary cavities expanding over months or years in association with pulmonary symptoms and systemic manifestations
Fatigue, weight loss
Insidious onset
Systemic features more prominent than pulmonary
Cavities may have fluid level or a well formed fungal ball
Pericavitary infiltrates and multiple cavities are typical
Chronic fibrosing pulmonary aspergillosis unilateral or upper lobe fibrosis, end stage entity if CPA untreated
Aspergilloma
Fungal ball
20% residual pulmonary cavities > 2.5cm. Diameter
Cough, hemoptysis, wheezing and mild fatigue
Caused by A. fumigatus
A. niger in diabetics oxalosis with renal dysfunction
Life threatening hemoptysis complication
Fungal ball resolve spontaneously
Cavity may still be infected
Chronic sinusitis
Sinus aspergilloma
Maxillary sinus
Sinus cavity filled with fungal ball
Associated with upper-jaw root canal work and chronic bacterial sinusitis
90% CT scan focal hyperattenuation related to concretions
Removal of fungal ball curative
Chronic invasive sinusitis
Slowly destructive process
Ethmoid and sphenoid sinuses, any sinus
Imaging of cranial sinus opacification of sinus, local bone destruction and invasion of local structures
Chronic nasal discharge, blockage, loss of smell, persistent headache
Orbital apex syndrome blindness and proptosis
Facial swelling, Cavernous sinus thrombosis,
Carotid artery occlusion, pituitary fossa and brain and
skull base invasion
Chronic granulomatous sinusitis
Most commonly seen in the Middle East and India
Often cause by A. flavus
Presents late, with facial swelling and unilateral proptosis
Tissue necrosis with low grade mixed cell infiltrate typical
Allergic bronchopulmonary aspergillosis (ABPA)
Hypersensitivity to A. fumigatus
Occurs in 1% asthma patients
25% adults with cystic fibrosis
Bronchial obstruction with mucous plugs
Breathlessness
Coughing up thick sputum casts, usually brown or clear
Eosinophilia
Cardinal diagnostic test elevated serum level of total IgE (>1000IU/ml), (+) skin prick test to A. fumigatus
extract or detection of aspergillus specific IgE and
IgG(precipitating) antibodies
Central bronchiectasis characteristic
Severe asthma with fungal sensitization
Many adults do not fulfill the criteria for ABPA and yet allergic to fungi
A. fumigatus as a common allergen, numerous other fungi are implicated by skin prick testing and/ or specific IgE
radioallergosorbent testing
Allergic sinusitis
Chronic sinusitis
Nasal polypscongested nasal mucosa
Sinuses full of mucoid material
Local eosinophilia and charcot leyden crystal hallmark
Removal of mucous and polyp with glucocorticoid resolution
Ethmoidectomy persistent or recurrent symptoms
Superficial aspergillosis
Keratitis and otitis externa
Local surgical debridement
Systemic and topical antifungal therapy
Otitis externa resolves with debridement and local application of antifungal agents
Diagnosis:
Culture 10-30%(+)
Molecular diagnosis faster, more sensitive
Antigen detection detection of galactomannan release from aspergillus during growth, sensitivity reduced by antifungal prophylaxis
histopathology
Definitive confirmation of diagnosis require
a. Positive culture of a sample taken directly from an
ordinarily sterile site
b. Positive results of both histologic testing and culture of
a sample taken from affected organ
Halo signs present 7 days early in neutropenic patients and good prognosis
Outcome:
Invasive aspergillosis
curable if immune reconstitution occurs
50% mortality if treated
100% mortality if diagnosis is missed
Allergic and chronic forms not curable
Cerebral, endocarditis, bilateral extensive invasive pulmonary aspergillosis very poor outcomes
Invasive infection late stage AIDS or relapsed uncontrolled leukemia and recipients of allogeneic
hematopoietic stem cell transplants poor outcome