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Cryptococcus neoformans

Keywords (immunodeficiency): HIV, antiretroviral therapy, oropharyngeal thrush, hepatosplenomegaly, central umbilication, central necrosis, hemorrhagic crust.

  • Cryptococcus neoformans is an encapsulated yeast
  • Occurs in patients with advanced HIV (CD4<100/mm3)
  • The most common manifestation is meningoencephalitis
  • Pulmonary and/or disseminated disease may occur
  • Cutaneous cryptococcosis considered as a marker of disseminated disease
  • Rapid onset (2 weeks) of multiple widespread papular lesions with central umbilication
  • Diagnostic clue is the presence of a small area of central hemorrhage or necrosis
  • Resembles molluscum contagiosum
  • Most common areas affected are head and neck
  • Disseminated infections can affect liver, lymph nodes, peritoneum, adrenal gland, and eyes
  • Diagnosis
    • Biopsy of the lesion
    • Histopathological examination after staining (periodic acid-Schiff, Gomori methenamine silver nitrate)
    • Hyperplasia of the overlying dermis with underlying granulomas surrounding encapsulated yeasts
    • Fungal blood culture is often positive in severe disseminated cryptococcal disease but a biopsy is more sensitive and specific than blood culture (because untreated HIV patients have multiple ongoing opportunistic infections)
    • Serum antigen testing can be useful for the diagnosis
    • The most common wrong answer is skin scrapings with a microscopic evaluation which is used for the diagnosis of fungal infections as tinea or candidiasis.


  • Treatment:
    • >/= 2 weeks of IV amphotericin B plus oral flucytosine
    • Followed by a year of oral fluconazole (higher dose for 8 weeks, then maintenance)


DD:

  • Kaposi Sarcoma:
    • Primarily presents in homosexual men(men with HIV who are sexually active with other men)
    • Red or purple papules with no necrosis
  • Disseminated Mycobacterium avium complex:
    • Common opportunistic infection
    • Affects patients with advanced AIDS
    • Presents as fever, night sweats, abdominal pain, diarrhea, weight loss
    • Cutaneous lesions are uncommon and are usually nodular and ulcerating
  • Pyoderma gangrenosum:
    • Rare neutrophilic dermatitis
    • Associated with inflammatory bowel disease and inflammatory arthritides
    • Presents as a tender papule that degrades into a bluish, violaceous ulcer
  • Basal cell carcinoma
    • Single, pink, flesh-colored papules
    • Arise slowly


Tuberculosis

  • Active pulmonary tuberculosis
    • Due to reactivation of the latent disease
    • Epidemiologic risk factors
      • Substance abuse
      • Homelessness
      • Birth in a TB-endemic region
    • Clinical manifestations
      • Fever, cough >2 weeks, weight loss


Diagnosis:

  • Chest x-ray
    • signs of active disease (upper lobe cavitation 970-80%), hilar lymphadenopathy, or pleural effusion.
  • Definitive diagnosis of suspicious x-ray finding by isolation of Mycobacterium tuberculosis in body fluid or tissues (lung, pleura)
  • Sputum sampling (acid-fast bacilli smear and culture)
    • Least invasive and costly route for microbial confirmation
    • Three single sputum samples (spontaneous or induced) are submitted in 8- to 24-hour intervals with at least 1 early-morning sample
    • Sputum should be sent for acid-fast bacillus smear, mycobacterial culture, and nucleic acid amplification testing.
  • Tuberculin skin test and interferon-gamma release assay
    • both can only support the diagnosis and if positive suggest exposure
    • Can't distinguish between active and latent disease
  • Bronchoscopy with bronchoalveolar lavage
    • More invasive and expensive than sputum sampling
    • Reserved for patients who are
      • Unable to produce adequate expectorated or induced sputum
      • Have negative sputum studies with a high suspicion for active TB
      • Have possible alternate diagnosis that requires bronchoscopy for evaluation
  • Transthoracic needle aspiration
    • Invasive and associated with greater risk of complications
    • Typically reserved for patients who remain undiagnosed after less invasive tests (sputum, bronchoscopy with bronchoalveolar lavage)


Diagnosis Sensitivity Specificity BCG vaccine Cost effective Latent vs active TB TB vs non-TB mycobacteria Result
Tuberculin skin test
Interferon gamma release essay