248.1 🎓 醫孞生版

248.1.0.1 📌 䞀頁重點

248.1.0.1.1 Paracoccidioidomycosis (PCM)
248.1.0.1.1.1 Pathogen
  • Paracoccidioides brasiliensis (+ P. lutzii Brazil)
  • Dimorphic fungus
248.1.0.1.1.2 Geography
  • Latin America endemic: Brazil, Argentina, Colombia, Venezuela
  • Soil + tropical / sub-tropical rainforest
  • Coffee + tobacco plantation regions
248.1.0.1.1.3 Demographics
  • Adult males predominantly (~ 80%; men 50-60 yr typical)
  • Latitude effect (women estrogen protective)
  • Latent infections may reactivate
248.1.0.1.1.4 Microbiology
  • Multiple budding yeast (“pilot wheel” or “Mickey Mouse” appearance — mother yeast surrounded by daughters)
  • Pathognomonic on histology
248.1.0.1.1.5 Clinical
248.1.0.1.1.6 Acute / Subacute (Juvenile)
  • Children + young adults
  • Generalized LAP + hepatosplenomegaly + bone marrow involvement
  • More aggressive than chronic
248.1.0.1.1.7 Chronic (Adult Form, More Common)
  • Months-years
  • Pulmonary involvement (~ 90%)
  • Mucocutaneous lesions (oral, nasal, perianal — painful ulcers, mulberry-like (moriform) stomatitis)
  • Skin lesions
  • Lymphadenopathy
  • Adrenal insufficiency
  • Fibrosis sequelae (lung scarring)
248.1.0.1.1.8 Diagnosis
  • Multiple budding yeast on biopsy
  • Serology (immunodiffusion, ELISA)
  • Culture (slow)
248.1.0.1.1.9 Treatment
  • Mild-Moderate: Itraconazole 200 mg PO bid × 6-12 months (preferred)
  • Severe: Amphotericin B induction → itraconazole maintenance
  • TMP-SMX alternative (very long course, 1-2 years)
  • Maintenance important due relapse
248.1.0.1.2 Talaromycosis (Penicillium marneffei)
248.1.0.1.2.1 Pathogen
  • Talaromyces marneffei (formerly Penicillium marneffei)
  • Dimorphic fungus
248.1.0.1.2.2 Geography
  • SE Asia endemic: Vietnam, Thailand, S China (Yunnan, Guangxi, Guangdong), Hong Kong, Taiwan southern, Indonesia, India NE, parts of Cambodia + Laos
  • Tropical / sub-tropical
248.1.0.1.2.3 Reservoir
  • Bamboo rats (Rhizomys, Cannomys) — natural host
  • Soil exposure
  • Inhalation primary
248.1.0.1.2.4 Demographics
  • HIV CD4 < 100 = primary clinical setting
  • Increasing in HIV-negative immunocompromise (transplant, anti-CD20, anti-IFN-γ autoantibody)
  • 3rd most common opportunistic infection in HIV in SE Asia (after TB + cryptococcosis historically)
248.1.0.1.2.5 Clinical
  • Fever + weight loss + cough + hepatosplenomegaly + LAP + pancytopenia
  • Cutaneous lesions (50-70%): umbilicated papules (mimics molluscum contagiosum) — characteristic!
  • Disseminated:
    • Marrow
    • Skin (often facial + diffuse)
    • Hepatic
    • Lymph node
    • Lung
    • GI
  • Severe / fatal without treatment
  • AIDS-defining in HIV
248.1.0.1.2.6 Diagnosis
  • Histology: yeast cells with central septum (fission) — characteristic
  • Wright + Giemsa stain shows intracellular yeast in macrophages
  • Culture: mold form produces diffusing red pigment in agar (distinctive)
  • BMR (biopsy), skin biopsy, lymph node, blood culture
  • Serology + PCR developing
248.1.0.1.2.7 Treatment
  • Liposomal Amphotericin B 3-5 mg/kg/d × 2 weeks induction
  • → Itraconazole 200 mg PO bid × 10 weeks consolidation
  • → Itraconazole 200 mg/d maintenance (until CD4 > 100 × 6 mo on ART)
  • Alternative: voriconazole, isavuconazole
248.1.0.1.2.8 Prevention
  • ART for HIV (CD4 recovery)
  • Some centers: itraconazole prophylaxis for HIV CD4 < 100 in endemic Vietnam / Thailand
248.1.0.1.2.9 Anti-IFN-γ Autoantibodies
  • Adult-onset immunodeficiency (mostly SE Asian, Filipino, Native American)
  • Anti-IFN-γ neutralizing autoantibodies
  • Predispose to disseminated talaromycosis, NTM, salmonellosis
  • Treatment: antifungal + rituximab (some cases)