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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
Smear microscopy
Sputum culture