Coccidioidomycosis

Aka: Coccidioidomycosis, Coccidiomycosis, Coccidioides immitis, Coccidioides posadasii, Primary Pulmonary Coccidiomycosis, Valley Fever

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II. Epidemiology

  1. Important opportunistic infection in southwestern US
    1. Most U.S. cases occur in Arizona (two thirds) and California (one third)
    2. International regions include Mexico, Central America and South America
  2. Incidence: 42.6 cases per 100,000 in endemic U.S. regions (2011)
    1. Incidence increased 7 fold in the prior 13 years (associated with expanding territory, warming climate)

III. Pathophysiology

  1. Fungal organism: Coccidioides immitis or Coccidioides posadasii
    1. Organisms are found growing normally in soil in endemic regions
  2. Transmission: Inhalation of airborne spores (when soil is disturbed)
    1. No known person-to-person or zoonotic spread
    2. No known transplacental transmission
    3. Rarely, Solid Organ Transplant has transmitted Coccidioidomycosis
  3. Incubation: Symptom onset 3 weeks after inhalation of spores
  4. Course
    1. Subclinical and spontaneous resolution in 50% of patients
    2. Lifelong Immunity after first infection typically prevents recurrent infection with re-exposure
  5. Affected Organs
    1. Lung most commonly affected (similar to Pneumocystis)
    2. Presents as Community Acquired Pneumonia in endemic regions

IV. Risk Factors

  1. Endemic region exposure within last 2 months (all cases)
  2. Dusty outdoor activities
    1. Agriculture
    2. Construction
    3. Archaeology
    4. Outdoor recreational activities (e.g. hiking)
    5. Correctional facilities
  3. Cellular Immune Deficiency
  4. Diabetes Mellitus
  5. Older adults
  6. Black or Filipino patients
  7. Pregnancy and postpartum (disseminated disease or complicated disease)

V. Symptoms

  1. General Symptoms (onset 1-3 weeks after exposure)
    1. Prolonged Fever
    2. Prolonged Fatigue
    3. Headache
    4. Night Sweats
    5. Weight loss
    6. Arthralgias
  2. Chest symptoms
    1. Productive cough
    2. Dyspnea
    3. Hemoptysis
    4. Pleuritic Chest Pain
  3. Rash
    1. Erythema Nodosum
    2. Erythema Multiforme

VI. Signs

  1. Fever
  2. Cervical adenopathy
  3. Skin lesions
    1. Resemble Erythema Nodosum
  4. Lung
    1. Pleural Effusion
    2. Friction rub
    3. Pulmonary rales

VII. Lab

  1. Sputum KOH
    1. Positive for fungal elements
  2. Complete Blood Count
    1. Eosinophilia >5%
  3. Blood complement-fixing antibodies
    1. Positive

VIII. Imaging

  1. Chest XRay (often normal)
    1. Pulmonary Infiltrates
    2. Hilar Adenopathy
    3. Pleural Effusion
    4. Empyema

IX. Diagnosis

  1. Coccidioidomycosis Enzyme Immunoassay (EIA for IgG, IgM)
    1. Initial screening positive within 1-3 weeks of exposure
      1. IgM positive by the third week in 90% of patients
      2. Consider retesting if initially negative (esp. if Immunosuppression or early test)
      3. IgM negative after 3 months of infection
    2. High Test Sensitivity but lower Test Specificity (False Positive risk)
  2. Coccidioidomycosis Immunodiffusion
    1. Confirms positive EIA test
    2. Immunodiffusion has greater Test Specificity for Coccidioidomycosis
  3. Other tests
    1. Coccidioidomycosis PCR is not typically used

X. Differential Diagnosis

  1. See Community Acquired Pneumonia
    1. Most patients are misdiagnosed as Bacterial Pneumonia on initial presentation
  2. Fungal Lung Infection
    1. Aspergillosis
    2. Blastomycosis
    3. Histoplasmosis
    4. Paracoccidioidomycosis
    5. Sporotrichosis
  3. Pneumonia
    1. Community Acquired Pneumonia
    2. Mycoplasma pneumonia
    3. Influenza Pneumonia
  4. Lung Abscess
  5. HIV Related infections
    1. Pneumocystis jiroveci (PCP Pneumonia)
    2. Cryptococcosis
  6. Tuberculosis
  7. Parasitic Infections
    1. Loeffler Syndrome
    2. Paragonimiasis
  8. Malignancy
    1. Lung Cancer
    2. Lymphoma
  9. Autoimmune Conditions
    1. Collagen Vascular Disease
    2. Eosinophilic Pneumonia
    3. Granulomatosis with Polyangiitis (formerly Wegener's Granulomatosis)
    4. Sarcoidosis

XI. Management: General

  1. Uncomplicated cases (>50%) resolve spontaneously without Antifungal management
  2. Patient Education related to potential complications
    1. Return for persistent respiratory symptoms (Chronic Pulmonary Sequelae)
    2. Return for signs of disseminated disease findings (skin lesions, Joint Pain, atypical Headache)

XII. Management: Antifungals

  1. Indications
    1. Risk Factors for disseminated disease (see below)
    2. Clinically Significant disease
      1. Anti-coccidioides complement fixation Antibody titer >1:16
      2. Bilateral Pulmonary Infiltrates
      3. Pulmonary Infiltrates involving >1/2 of one lung
      4. Overall symptoms >2 months
      5. Fever >1 month
      6. Night Sweats >3 weeks
      7. Weight loss >10%
      8. Hospitalization
      9. Inability to work
  2. Approach
    1. Obtain initial Anti-coccidioides complement fixation Antibody titer
      1. Obtain repeat complement fixation every 1 to 3 months and continue for 2 years (from same lab)
      2. Titer >1:32 is associated with worse prognosis (including disseminated disease)
      3. Expect decreasing titer over time in response to Antifungal
    2. Obtain Chest XRay every 1 to 3 months
    3. Observe for disseminated disease and Meningitis
    4. Treatment course: 3 to 6 months up to 12 months or until complement fixation Antibody titers stabilize
  3. Children
    1. Fluconazole 6 to 12 mg/kg/day
  4. Non-Pregnant Adults
    1. Fluconazole 400-800 mg/day
    2. Itraconazole 200 mg twice daily
  5. Pregnancy
    1. Amphotericin B IV (esp. First Trimester)
    2. May consider Fluconazole instead of Amphotericin B in second and third trimesters
    3. Monitor complement fixation every 6-12 weeks
    4. Consider testing at initial Prenatal Visit in endemic regions
  6. Lactation
    1. Fluconazole 400-800 mg/day

XIII. Complications

  1. Pulmonary Granuloma
    1. May form with initial infection in immunocompetent hosts
    2. Granulomas may contain dormant, noncontagious endospores
      1. May later activate and disseminate if patient becomes immunosuppressed
  2. Chronic Pulmonary Sequelae (5-10%)
    1. Lung Nodules including cavitary Nodules
    2. Chronic fibrocavitary Pneumonia
  3. Meningitis
    1. Fatal without aggressive management
    2. Findings
      1. Frequent or atypical Headaches
      2. Altered Mental Status
      3. Meningismus
      4. Nausea or Vomiting
      5. Vision changes
    3. Management
      1. Life-long Antifungal therapy
  4. Extra-pulmonary Dissemination (1% within 2 years of initial infection)
    1. Bone, joint or soft tissue infection
    2. Risk Factors for dissemination
      1. Advanced Age
      2. Black or Filipino patient
      3. Diabetes Mellitus
      4. Pregnancy or peripartum
      5. Inflammatory rheumatic disease
      6. Immune deficiency
        1. Certain genetic mutations
        2. Hematologic Malignancy
        3. High dose Corticosteroids
        4. TNF Inhibitor
        5. Chemotherapy
        6. Lymphoma
        7. Status-post thymectomy
        8. Uncontrolled HIV Infection

XIV. Prevention

  1. Consider respirator use on construction sites in endemic regions

XV. Resources

  1. Valley Fever (CDC)
    1. https://www.cdc.gov/fungal/diseases/coccidioidomycosis/health-professionals.html

XVI. References

  1. Galgiani (2016) Clin Infect Dis 63(6): e112-46 +PMID:27470238 [PubMed]
  2. Herrick (2020) Am Fam Physician 101(4): 221-8 [PubMed]

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Related Studies

Ontology: Coccidioides immitis (C0009184)

Definition (MSH) The sole species of COCCIDIOIDES. It can cause an acute, benign respiratory infection as well as a fatal, chronic systemic disease.
Definition (CSP) mitosporic fungal species which causes coccidiodomycosis.
Concepts Fungus (T004)
MSH D003045
SnomedCT 23439005
LNC LP14437-5, MTHU009316
English Malbranchea of Coccidi immitis, immitis, Coccidioides, immitides, Coccidioides, Coccidioides immitides, coccidioides immitis, Malbranchea state of Coccidioides immitis, Coccidioides immitis (organism), Coccidioides immitis
Portuguese Coccidioides immitis
German Coccidioides immitis
French Coccidioides immitis
Czech Coccidioides immitis
Italian Coccidioides immitis
Norwegian Coccidioides immitis
Spanish Coccidioides immitis (organismo), Coccidioides immitis
Dutch Coccidioides immitis
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Coccidioidomycosis (C0009186)

Definition (MSHCZE) Druh orgánové mykózy způsobené houbou Coccidioides immitis, která je endemická v některých oblastech USA. Postihuje plíce, CNS, lymfatické uzliny aj. V těžkých případech dochází k diseminaci. Častější je u osob s oslabenou imunitou, např. u AIDS. Léčí se antimykotiky. (cit. Velký lékařský slovník online, 2012 http://lekarske.slovniky.cz/ )
Definition (MEDLINEPLUS)

Valley Fever is a disease caused by a fungus (or mold) called Coccidioides. The fungi live in the soil of dry areas like the southwestern U.S. Anyone exposed to the fungus can get the infection. The highest risk is for people whose jobs expose them to soil dust. These include construction workers, agricultural workers, and military forces doing field training. The infection cannot spread from person to person.

Valley Fever is often mild, with no symptoms. If you have symptoms, they may include a flu-like illness, with fever, cough, headache, rash and muscle aches. Most people get better within several weeks or months. A small number of people may develop a chronic lung or widespread infection.

Valley Fever is diagnosed by testing your blood, other body fluids, or tissues. Many people with the acute infection get better without treatment. In some cases, doctors may prescribe antifungal drugs for acute infections. Severe infections require antifungal drugs.

Centers for Disease Control and Prevention
Definition (NCI) A fungal infection caused by Coccidioides immitis. Affected individuals usually have mild flu-like symptoms. However, pneumonia and systemic involvement with the formation of abscesses may develop as complications of the disease.
Definition (CSP) infection with a fungus of the genus Coccidioides, species C. immitis; primary form is an acute, benign, self limited respiratory infection due to inhalation of spores and varying in severity; secondary form is a virulent, severe, chronic, progressive granulomatous disease with systemic involvement.
Definition (MSH) Infection with a fungus of the genus COCCIDIOIDES, endemic to the SOUTHWESTERN UNITED STATES. It is sometimes called valley fever but should not be confused with RIFT VALLEY FEVER. Infection is caused by inhalation of airborne, fungal particles known as arthroconidia, a form of FUNGAL SPORES. A primary form is an acute, benign, self-limited respiratory infection. A secondary form is a virulent, severe, chronic, progressive granulomatous disease with systemic involvement. It can be detected by use of COCCIDIOIDIN.
Concepts Disease or Syndrome (T047)
MSH D003047
ICD9 114.9, 114
ICD10 B38 , B38.9
SnomedCT 442543009, 60826002, 266218008, 187035003, 187025009, 154408001, 187481007
LNC LA10444-0
English Coccidioidomycoses, Coccidioidomycosis, unspecified, Coccidioidomycosis,unspecfd, [X]Coccidioidomycosis, unspecified, [X]Coccidioidomycosis,unspecfd, San Joaquin valley fever, desert fever, coccidioidomycosis (diagnosis), coccidioidomycosis, Infection by Coccidioides immitis (disorder), Infection by Coccidioides immitis, Coccidioidomycosis NOS, Coccidioidomycosis [Disease/Finding], Coccidioides immitis Infection, Coccidioides immitis Infections, Valley Fevers, Valley Fever, Infection, Coccidioides immitis, Infections, Coccidioides immitis, San Joaquin Valley Fever, disease posada wernicke, [X]Coccidioidomycosis, unspecified (disorder), Coccidioidomycosis NOS (disorder), Coccidioides immitis infection, Valley fever, Posadas-Wernicke disease, Coccidioidomycosis (disorder), Posada-Wernicke, San Joaquin (Valley); fever (etiology), San Joaquin (Valley); fever (manifestation), Wernicke-Posada, fever; San Joaquin (Valley) (etiology), fever; San Joaquin (Valley) (manifestation), Coccidioidomycosis, NOS, Coccidioidomycosis, San Joaquin Valley fever
Dutch Coccidioides immitis-infectie, coccidioïdomycose, niet-gespecificeerd, San Joaquin Valley-koorts, San Joaquin; fever, fever; San Joaquin, Coccidioïdomycose, niet gespecificeerd, coccidioïdomycose, Coccidioïdomycose, Coccidioidomycose, Mycose, coccidioido-
French Coccidiomycose, non précisée, Infection à Coccidioides immitis, Fièvre de la Vallée de San Joaquin, Fièvre de la vallée de San Joaquin, Coccidiomycose, Coccidioïdomycose, Fièvre du désert, Fièvre de San Joaquin
German Coccidioides immitis-Infektion, Kokzidioidomykose, unspezifisch, San-Joaquin-Fieber, Kokzidioidomykose, nicht naeher bezeichnet, Coccioidesmykose, Kokzidioidomykose
Italian Coccidioidomicosi non specificata, Infezione da Coccidioides immitis, Febbre della valle di San Joaquin, Coccidioidomicosi
Portuguese Infecção por Coccidioides immitis, Coccidioidomicose NE, Febre do vale San Joaquin, Coccidioidomicose
Spanish Infección por Coccidiodes immitis, Coccidioidomicosis no especificada, Fiebre del valle de San Joaquín, infección por Coccidioides immitis, infección por Coccidioides immitis (trastorno), [X]coccidioidomicosis, no especificada (trastorno), coccidioidomicosis, SAI (trastorno), coccidioidomicosis, SAI, [X]coccidioidomicosis, no especificada, coccidioidomicosis, coccidioidomicosis (trastorno), enfermedad de Posadas - Wernicke, Coccidioidomicosis
Swedish Koccidioidomykos
Japanese ｺｸｼｼﾞｵｲﾃﾞｽｼｮｳ, ｺｸｼｼﾞｵｲﾃﾞｽｲﾐﾁｽｶﾝｾﾝ, コクシジオイデス症、詳細不明, ｺｸｼｼﾞｵｲﾃﾞｽｼｮｳｼｮｳｻｲﾌﾒｲ, サンホアキン渓谷熱, コクシジオイデス・イミチス感染, ｻﾝﾎｱｷﾝｹｲｺｸﾈﾂ, コクシジオイデス症, コクシジオイド症, 谷熱
Czech kokcidioidomykóza, Blíže neurčená kokcidioidomykóza, Kokcidioidomykóza, Infekce prvokem Coccidioides immitis, Horečka údolí San Joaquin, horečka údolí, horečka údolí San Joaquin
Finnish Koksidioidomykoosi
Russian KOKTSIDIOIDOMIKOZ, КОКЦИДИОИДОМИКОЗ
Korean 콕시디오이데스진균증, 상세불명의 콕시디오이데스진균증
Croatian KOKCIDIOIDOMIKOZA
Polish Kokcidioidomikoza, Choroba kalifornijska, Zakażenie Coccidioides, Gorączka Doliny św. Joachima, Choroba Pasady i Wernickiego, Grzybica kokcydioidowa
Hungarian coccidioidomycosis, Coccidioides immitis fertőzés, Coccidioidomycosis, nem meghatározott, San Joaquin-völgyi láz
Norwegian Koksidioidomykose
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Primary pulmonary coccidioidomycosis (C0153257)

Concepts Disease or Syndrome (T047)
ICD9 114.0
SnomedCT 187026005, 88036000, 417018008
English Prim pulmon coccidioidomycosis, COCCIDIOIDOMYCOSIS PRIMARY PULMONARY, Primary coccidioidomycosis (pulmonary), primary coccidioidomycosis (diagnosis), primary pulmonary coccidioidomycosis (diagnosis), primary pulmonary coccidioidomycosis, primary coccidioidomycosis, Primary coccidioidomycos, Primary pulmonary coccidioidomycosis, desert rheumatism, fever joaquin san valley, san joaquin fever, san joaquin valley fever, fever valley, pulmonary coccidioidomycosis, valley fever, desert fever, Pulmonary coccidioidomycosis (diagnosis), coccidioidomycosis pulmonary, San Joaquin Valley fever, Coccidioidal pneumonitis, Coccidioidomycotic pneumonitis, Desert rheumatism, Primary pulmonary coccidioidomycosis (disorder), Primary coccidioidomycosis, Pulmonary coccidioidomycosis, Pulmonary coccidioidomycosis (disorder)
Dutch primaire coccidioidomycosis (pulmonaal)
French Coccidiomycose primitive (pulmonaire)
German primaere Kokzidioidomykose (pulmonal)
Italian Coccidioidomicosi primitiva (polmonare)
Portuguese Coccidioidomicose (pulmonar) primária
Spanish Coccidioidomicosis (pulmonar) primaria, coccidiomicosis pulmonar, coccidioidomicosis pulmonar, coccidioidomicosis pulmonar (trastorno), coccidiomicosis pulmonar (trastorno), coccidioidomicosis pulmonar primaria (trastorno), coccidioidomicosis pulmonar primaria, fiebre de San Joaquín, fiebre del Valle de San Joaquín, neumonitis coccidioidomicótica, reumatismo del desierto, neumonitis coccidioidal
Japanese ｹﾞﾝﾊﾟﾂｾｲｺｸｼｼﾞｵｲﾃﾞｽｼｮｳﾊｲｶﾞﾀ, 原発性コクシジオイデス症（肺型）
Czech Primární kokcidioidomykóza (plicní)
Hungarian Primaer coccidioidomycosis (pulmonalis)
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: coccidiomycosis (C0262426)

Concepts Disease or Syndrome (T047)
English coccidiomycosis
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Coccidioides posadasii (C1219666)

Concepts Fungus (T004)
SnomedCT 406645005
English Coccidioides posadasii, Coccidioides posadasii (organism), Non-CA Coccidioides immitis, Non-California Coccidioides immitis
Spanish Coccidioides posadasii (organismo), Coccidioides posadasii
Derived from the NIH UMLS (Unified Medical Language System)

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