Disseminated coccidioidomycosis
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Disseminated Coccidioidomycosis. Stafford et. al., Infect Med 24 ( Suppl 8): 23-25, 2007. 31-year-old, African-American US Army Soldier Presents with fever, chills, night sweats, non-productive cough of 4 weeks Past medical history unremarkable Recently detected a painless right breast mass

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Disseminated Coccidioidomycosis

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Disseminated coccidioidomycosis

Disseminated Coccidioidomycosis

Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.

  • 31-year-old, African-American US Army Soldier

    • Presents with fever, chills, night sweats, non-productive cough of 4 weeks

    • Past medical history unremarkable

    • Recently detected a painless right breast mass

    • Stationed at Fort Irwin, CA


Disseminated coccidioidomycosis1

Disseminated Coccidioidomycosis

Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.

  • Physical exam:

    • Unremarkable

    • Firm, nontender, 3-cm subcutaneous mass over right breast

    • Multiple small nontender lymph nodes were palpable in the axillae and groin

  • Lab results:

    • WBC = 11.9/µl, 30% eosinophils

    • Elevated alkaline phosphatase


Disseminated coccidioidomycosis2

Disseminated Coccidioidomycosis

Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.

Blood cultures = negative

Cryptococcus antigen = negative

Histoplasma urine antigen = negative

HIV antibody = negative

Tuberculin test = negative

CT scan of chest revealed diffuse, 1-2 mm micronodules in all lobes and right chest wall mass.


Disseminated coccidioidomycosis3

Disseminated Coccidioidomycosis

Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.

Fine needle aspirate of the mass revealed spherules filled with endospores


Disseminated coccidioidomycosis4

Disseminated Coccidioidomycosis

Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.

Culture grew Coccidioides immitis

Serology panel for C. immitis was positive

CSF = normal

Bone scan revealed multiple region of increased osteoblastic activity


Coccidioidomycosis

Coccidioidomycosis

  • Epidemiology:

    • Endemic in arid, temperate, desert climate

      • especially Southwest United States

    • Travel history - Central-Southern CA; south NV, AZ,NM,TX

    • Fungus grows in soil and matures to form arthroconidia

    • Infection is initiated by inhalation of infectious arthroconidia

    • Filipinos, African/Native Americans & Hispanics - greatest risk of dissemination

  • Virulence factors and pathogenesis:

    • Highly infectious

    • Not highly virulent, ~99.5% of infected individuals resolve

    • Defects in CMI predispose to systemic disease


Coccidioides spp lifecycle

Coccidioides spp. Lifecycle

  • Hyphae differentiate into arthroconidia, which break loose and may be suspended in the air

  • Soil disruptions and wind facilitate spread and the probability of inhalation into lungs

  • In the human host environment, in vivo differentiation produces cleavage planes and eventually huge spherules containing endospores

  • Spherules rupture releasing endospores, which can then repeat the in vivo cycle


Coccidioidomycosis1

Coccidioidomycosis

  • Clinical Manifestations:

    • Not contagious

    • Route of infection: inhalation

    • Incubation: 10-21 days

    • Respiratory infection - 60% asymptomatic, all convert to skin test +

    • < 1% dissemination – soon after primary infection or years later

    • Often produces:

      • Meningitis

      • Lesions in viscera or cutaneousgranulomatous lesions which may form draining ulcers

    • Incidence in HIV-infected persons has increased


Disseminated coccidioidomycosis

Coccidioidomycosis - Manifestations


Coccidioidomycosis laboratory diagnosis

Coccidioidomycosis – Laboratory diagnosis

  • Coccidioides immitis:

    • Thermally dimorphic fungus

    • In tissue: Huge (20-60 μm) thick-walled, round “spherules” filled with small (2-5 μm) endospores

    • Spherules rupture

    • In 25°C culture:

      • SDA and SDA-CC positive, 2-4 weeks; SABHI positive, 1-2 weeks

      • Hyaline septate hyphae forming barrel-shaped arthroconidia

    • At 37°C: Thermal conversion requires animals, but is not done


Coccidioidomycosis laboratory diagnosis1

Coccidioidomycosis – Laboratory diagnosis

  • Coccidioidin skin test:

    • Not available in US

  • Serologic tests:

    • Combination of latex agglutination and immunodiffusion tests detects >90% early in symptomatic illness

    • Complement fixation (CF) tests for Dx

    • Serial CF titers are useful for prognosis

      • Rising titer = poor prognosis


Disseminated coccidioidomycosis

Coccidioidomycosis

Lung tissue with a large thick-walled spherule containing multiple endospores. The smaller spherule to its left has ruptured releasing endospores.


Disseminated coccidioidomycosis

Coccidioidomycosis


Disseminated coccidioidomycosis

Coccidioidomycosis


Sda sda cc

SDA + & SDA-CC +

Coccidioidomycosis

- May take ~ 2 weeks


Disseminated coccidioidomycosis

Coccidioidomycosis

Arthroconidia

Disjuncture


Disseminated coccidioidomycosis

Definitive identification of Coccidioides immitis

ExoAg

--or--

NA confirmation


Coccidioidomycosis treatment

Coccidioidomycosis - Treatment

  • Treatment:

    • Most do not require anti-fungals

    • Azoles – pneumonia & nonmeningeal dissemination

    • Amphotericin B – meningeal infection and previous treatment failures


Coccidioidomycosis2

Coccidioidomycosis

Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.

  • For our patient:

    • In spite of Amphotericin B treatment, neck pain increased and progressive enlargement of the mass was noted

    • Surgical debridement

    • Long-term antifungal therapy

  • Clues to the diagnosis of disseminated coccidioidomycosis included an infectious prodrome, peripheral eosinophilia, hilarlymphadenopathy, characteristic pattern of organ involvement (lungs, bones, soft tissues), residence in an endemic area, and African-American ethnicity.


Other endemic dimorphic mycoses

Other Endemic Dimorphic Mycoses

Histopathology:

-Yeast with multiple buds

-”Mariner’s Wheel”

  • Paracoccidioidomycosis

    • Paracoccidioidesbrasiliensis

    • Endemic to Latin American countries

    • Pulmonary infection – asymptomatic, self-limiting

    • Dissemination to mucous membranes and skin


Other endemic dimorphic mycoses1

Other Endemic Dimorphic Mycoses

  • PenicilliosisMarneffei

    • Penicilliummarneffei

    • HIV-infected individuals in Thailand and Southern China

    • Only species of Penicillium that is dimorphic

      • Intracellular yeast, with single septum

    • Infection mimics tuberculosis or histoplasmosis

    • Patient presentation:

      • Fever, cough, pulmonary infiltrates, organomegaly, anemia, leukopenia, thrombocytopenia


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