Clinical Analysis: 50-Year-Old Man with Hemoptysis and Previous TB

Most Likely Diagnosis: Pulmonary Aspergilloma (Mycetoma)

• Prior treated TB leaves residual parenchymal cavities
• Hemoptysis is the hallmark symptom
• Right upper lobe involvement - the typical site (TB preferentially destroys apices/upper lobes)
• Dullness to percussion + decreased breath sounds = consolidation or cavity with surrounding fibrosis

Pathophysiology

• 11-17% of patients with post-TB cavities develop aspergilloma
• 20% of patients who recover from cavitary TB develop aspergilloma within 3 years
• In developing countries, TB is the predisposing factor in >90% of aspergilloma cases

Differential Diagnosis

Radiographic Features

• Globules of gas within the hyphal mass
• CT angiography may identify hypertrophic bronchial arteries supplying the cavity wall - important for planning bronchial artery embolization (BAE) in hemoptysis

Diagnostic Workup

Management

General Approach

Step-by-Step:

• Massive hemoptysis (>200-600 mL/24h) is life-threatening
• Bronchial artery embolization (BAE) is first-line for acute hemoptysis control - controls bleeding in 75-90% of patients, allows stabilization before definitive surgery
• Position patient with bleeding lung side DOWN to protect contralateral lung
• If airway compromised: intubate + emergency bronchoscopy

• Lobectomy or segmental resection is the gold standard for fit patients with single large aspergilloma and recurrent/massive hemoptysis
• Pre- and peri-operative antifungal therapy reduces relapse
• Significant morbidity/mortality risk, especially with underlying TB-damaged lung

• Itraconazole 200-400 mg/day orally for 6-18 months: radiographic + symptomatic improvement in ~two-thirds of patients; recurrence common on stopping
• Voriconazole: used for itraconazole-resistant Aspergillus fumigatus cases; secondary resistance can develop with long-term use
• Jawetz Medical Microbiology: Aspergilloma treated with itraconazole or amphotericin B + surgery

• CT-guided percutaneous instillation of amphotericin B deoxycholate (AMB-D)
• Shown effective in cases of massive hemoptysis with resolution within 5 days
• Also: endobronchial instillation of ketoconazole via fiberoptic bronchoscopy
• Indicated when patient is unfit for surgery with severe pulmonary dysfunction

• Performed under local anesthesia
• Associated with significant mortality and mediocre outcomes

• Careful follow-up with periodic chest X-rays without intervention is often appropriate

Poor Prognostic Predictors

• Progressive increase in aspergilloma size or number
• Severe underlying lung disease (poor reserve from prior TB)
• Immunosuppressive therapy or AIDS
• Rising Aspergillus-specific IgG titer
• Repetitive severe hemoptysis episodes

Summary Algorithm

Post-TB hemoptysis + upper lobe cavity
           ↓
Chest CT → Air crescent sign?
           ↓ Yes
Aspergillus precipitins (IgG) → likely >95% positive
           ↓
Assess fitness for surgery + hemoptysis severity
           ↓
Massive hemoptysis → BAE first → then lobectomy
Mild/moderate + operable → surgical resection
Inoperable → itraconazole ± intracavitary AmB
Asymptomatic → watchful waiting

Updated Diagnosis: Invasive Pulmonary Aspergillosis (IPA) in AIDS

How the New Data Changes Everything

Pathogenesis of IPA in HIV/AIDS

1. Intravascular thrombosis
2. Local hypoxia
3. Coagulative necrosis (angioinvasive form)

Microscopy: Narrow Septate Hyphae

CT: The Halo Sign

• Early: Halo sign (nodule + ground-glass)
• Late: Cavitation → Air crescent sign (as immune reconstitution begins or fungus retracts)

Complete Diagnostic Workup

Treatment

First-Line: Voriconazole (IDSA Guideline)

Additional Management in This HIV Patient

• CD4 of 43 means ART is urgently needed
• ART initiation timing: generally after 2 weeks of antifungal therapy to avoid IRIS (Immune Reconstitution Inflammatory Syndrome)
• Drug interactions: voriconazole is a CYP2C19/3A4 substrate - significant interactions with ritonavir-boosted regimens; efavirenz induces CYP and reduces voriconazole levels markedly

• CD4 <200: start trimethoprim-sulfamethoxazole (TMP-SMX)
• CD4 <50: also add azithromycin for MAC prophylaxis
• CD4 <100: consider fluconazole for cryptococcal prophylaxis (especially in high-prevalence settings)

• When ART is started, immune reconstitution may cause paradoxical worsening of IPA
• Characterized by fever, respiratory deterioration, expanding CT lesions despite antifungal therapy

• Minimum 6-12 weeks; continue until:
  • Lesions resolve/stabilize on CT
  • CD4 count recovers on ART
  • Clinical improvement

Prognosis

• Untreated: near 100% mortality
• With prompt voriconazole + ART: mortality remains ~30-50%
• Poor prognostic factors: profound immunosuppression (CD4 <50), delayed diagnosis, dissemination to CNS or other sites, azole-resistant Aspergillus, inability to start ART

Summary: Diagnostic Framework

HIV+ (CD4 = 43) + Post-TB cavity
        ↓
Hemoptysis + narrow septate hyphae + CT halo sign
        ↓
INVASIVE PULMONARY ASPERGILLOSIS
        ↓
Confirm: serum/BAL galactomannan + beta-glucan + BAL culture + Aspergillus PCR
        ↓
Start VORICONAZOLE immediately (don't wait for culture confirmation)
        ↓
Check susceptibility (azole resistance)
Start ART (after 2 weeks, avoid IRIS)
Prophylax: TMP-SMX + Azithromycin
        ↓
Monitor: TDM voriconazole, CT at 4-6 weeks, CD4 recovery

White Patches on the Lateral Tongue - 40-Year-Old Man

Most Likely Diagnosis: Oral Hairy Leukoplakia (OHL)

The Appearance

• Early: Subtle smooth/macular white streaks
• Intermediate: Vertical white keratotic ridges (the "corrugated" pattern)
• Advanced: Thick, shaggy, irregular white surface alterations

Histopathology

• Hyperkeratosis with irregular surface projections
• Ballooning degeneration of subsurface keratinocytes
• Nuclear "beading" - chromatin displacement to inner nuclear membrane by viral replication
• Confirmed by in situ hybridization or PCR demonstrating EBV

Differential Diagnosis of White Tongue Patches

The Single Most Important Bedside Test:

• Yes (leaves raw/bleeding base) = Candidiasis (thrush)
• No = OHL, leukoplakia, lichen planus, or carcinoma

How to Confirm OHL

Clinical Significance of OHL

• Caused by EBV (not Candida, not a premalignant lesion - no malignant potential)
• It is asymptomatic - patients usually notice the white patches incidentally
• It is not painful (contrast with candidiasis which may burn, or erosive lichen planus which ulcerates)
• It is strongly associated with CD4 <200 - the lower the CD4, the more extensive the lesion
• In HIV patients, it is a clinical marker that immunosuppression is significant and ART is needed
• Less commonly seen in: organ transplant recipients, hematologic malignancy, other causes of immunosuppression (can occur even in HIV-negative immunosuppressed individuals)

Management

Summary in Context

• The white lateral tongue patches are almost certainly Oral Hairy Leukoplakia (EBV-driven)
• Co-existing oral candidiasis is also highly likely at CD4 = 43 (the two often co-exist)
• Both resolve with ART initiation and CD4 recovery
• The lesion carries no malignant risk but is a powerful marker of immune failure