Coccidioides Lymphadenitis



Coccidioides Lymphadenitis


Tariq Muzzafar, MBBS





Key Facts


Etiology/Pathogenesis



  • 2 species: C. immitis prevalent in California, USA; C. posadasii in other regions


Clinical Issues



  • May be seen in nonendemic areas


  • Travel history should be sought


  • 60% of infections are asymptomatic


Microscopic Pathology



  • Early acute phase: Neutrophils, histiocytes, eosinophils


  • Granulomatous phase


  • Round spherules (10-100 µm) in progressive developmental stages


  • Internal and external endospores (2-5 µm)


Ancillary Tests



  • Calcofluor white fluorescense sensitive


  • GMS and PAS stains highlight spherules


  • Recognition of endospores within spherules diagnostic


  • Culture yield variable and depends on site and phase of disease


Top Differential Diagnoses



  • Tuberculous lymphadenitis


  • Histoplasma lymphadenitis


  • Sarcoidosis


  • Kikuchi-Fujimoto lymphadenitis


Reporting Considerations



  • Classified as agents of potential bioterrorism in USA


  • Isolates should be reported to CDC within 7 days







Spherule of C. immitis with endospores is demonstrated by Calcofluor white stain. (Courtesy B.J. Harrington, MD.)






Mature spherule with endospores of C. immitis in lung is demonstrated by PAS stain. Note the dense neutrophilic infiltrate. (Courtesy L. Georg, MD, CDC Public Health Image Library, #480.)


TERMINOLOGY


Definitions



  • Inflammation of lymph nodes due to Coccidioides immitis or Coccidioides posadasii


ETIOLOGY/PATHOGENESIS


Infectious Agents



  • 2 species recognized



    • C. immitis, predominant in California, USA


    • C. posadasii, predominant in other regions


Epidemiology



  • Endemic in semi-arid to arid areas of



    • Southwest USA


    • Parts of South America


  • Organism



    • Grows in warm, sandy soil


    • Prevalent in areas having hot summers, mild winters, and < 20 inches of rainfall annually


    • Does not grow at altitudes above 3,700 feet


    • Occasional epidemics in past 30 years


    • Outbreaks can follow dust storms, earthquakes, and droughts


  • High-risk factors include



    • Occupational soil exposure



      • Agricultural workers


      • Military personnel


      • Archaeologists


    • Immunocompromised status as a result of



      • Organ transplant


      • Immunosuppressive agents


      • Acquired immune deficiency syndrome (AIDS)


      • Malignant diseases


    • Pregnancy


  • High risk of dissemination in



    • Filipinos


    • African-Americans


    • Subjects with blood group B


  • Incidence rising rapidly in USA due to



    • People settling in endemic areas


    • Growing immunocompromised population


    • New construction in uninhabited regions resulting in arthrospore dissemination


    • Increased awareness of disease entity


  • Cases seen in nonendemic areas due to increased travel



    • Travel history should be sought


    • High level of suspicion necessary


  • Incidence expected to rise in future


Pathogenesis



  • Coccidioides spp. are dimorphic


  • Mycelial phase



    • Grows in soil


    • Branching, septate hyphae


    • Can remain viable in dry desert soil for years


    • Multiplies after rainfall, forming arthroconidia


  • Arthroconidia



    • Separated by empty, thin-walled cells (disjunctors)


    • Dispersed into air and inhaled


    • Transform into multinucleated spherules within lung


  • Spherule phase



    • Spherules increase in size


    • Form thick outer wall


    • Divide to form numerous uninucleated endospores


    • Break open and release endospores, which form new spherules


    • Cycle continues


  • Spherules disseminate hematogenously to meninges, bones, skin, and soft tissue


  • Cell-mediated immunity crucial to limiting infection


  • Primary pulmonary infections asymptomatic in 60% of patients


  • Usual course of infection is healing without sequelae



  • Localized lesion (coccidioidoma) may persist


Reporting Considerations



  • C. immitis and C. posadasii classified as select agents of potential bioterrorism in USA


  • Laboratories must report findings to Centers for Disease Control (CDC) within 7 calendar days


Safety Considerations



  • Laboratory workers potentially at risk of accidental exposure


  • Biosafety level 2 practices and facilities recommended


  • Manipulation of clinical material conducted in class II biological safety cabinets


CLINICAL ISSUES


Presentation



  • General comments



    • Signs and symptoms



      • Wide spectrum


      • Similar to community-acquired pneumonia


    • 60% of patients are asymptomatic


    • Most common infections self-limited and misdiagnosed


    • Disseminated disease in < 5% of symptomatic patients


  • Acute pneumonia



    • Presents 1-3 weeks after inhalation of arthroconidia


    • Profound fatigue


    • Lobar infiltrates and lymphadenopathy in patient who has traveled to endemic area are suggestive


    • Pleural effusion in 5-10% cases


    • Erythema multiforme, erythema nodosum, toxic erythema (immune mediated)


  • Diffuse pneumonia



    • Due to



      • Inhalation of large number of arthrospores


      • Hematogenous spread


      • Immunocompromised status


    • Severe illness, high fever, dyspnea, hypoxemia


    • Can progress to acute respiratory distress syndrome


  • Chronic progressive pneumonia



    • Persistent illness lasting > 3 months in small percentage of patients


    • Persistent coughing, sputum production, hemoptysis


    • Weight loss


    • Serologic testing positive


  • Pulmonary nodules and cavities



    • Can be initial presentation of primary infection


    • Can occur in immunocompetent hosts after infiltrate resolves


    • 1-2 cm nodule or cavity


    • Cavity may wax and wane


    • Usually do not cause symptoms


    • Cough, chest pain, and hemoptysis may occur


    • Rupture of cavity near pleural surface may lead to hydropneumothorax


  • Extrapulmonary noncentral nervous system disease



    • Occurs in < 5% of immunocompetent patients and in high-risk groups


    • Skin, lymph nodes, bones, and joints involved


    • Diagnosed several months after onset of pulmonary symptoms


    • Surgical excision may be necessary


  • Central nervous system disease



    • Granulomatous meningitis or coccidioidoma


    • Headache, mental status changes, neurologic deficits


    • Serologic studies essential for diagnosis


Laboratory Tests



  • Peripheral blood



    • Elevated erythrocyte sedimentation rate


    • Eosinophilia


  • Pleural fluid



    • Usually exudative


    • May show eosinophilia


  • Cerebrospinal fluid (CSF)



    • Increased white blood cells, predominantly lymphocytes


    • Increased protein, decreased glucose


  • Light microscopy




    • Round spherules (10-100 µm) in progressive developmental stages


    • Internal and external endospores (2-5 µm)


    • Recognition of endospores within spherules considered diagnostic


    • Few spherules without internal structures considered presumptive evidence


    • May be seen in giant cells, microabscesses, and in acute presentations


    • Less likely to be found in caseous, calcified, or liquefactive foci


    • Rarely seen in CSF in meningitis


    • Immature spherules in contact may simulate Blastomyces


    • Endospores without spherules (especially in CSF) may simulate Histoplasma, Cryptococcus, Candida


    • Mycelia may be identified in



      • Boundaries of old cavitary lung lesions


      • Skin lesions


      • Ventricular fluid in CNS infection


    • Mycelia without spherules not diagnostic


    • Culture isolates show slender, hyaline, and septate hyphae


    • Arthroconidia



      • Unicellular, barrel-shaped (3-4 x 3-6 µm)


      • Arise from side branches


      • Alternate with thin-walled, empty disjunctor cells


      • Released at maturity


    • Calcofluor white (CFW) fluorescence



      • Binds chitin and cellulose in fungal cell wall


      • Sensitive but may stain plant material


      • Rapid results


      • May be used on tissue, body fluids, respiratory secretions


    • KOH wet mount



      • Not as sensitive as CFW


    • Grocott methenamine silver

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Coccidioides Lymphadenitis

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