What is the diagnosis and treatment for a young, previously healthy individual presenting with acute respiratory failure 5-7 days post upper respiratory tract infection (URTI)?

Hamman-Rich Syndrome (Acute Interstitial Pneumonia)

Definition and Clinical Presentation

Hamman-Rich syndrome, also known as acute interstitial pneumonia (AIP), is a rare fulminant form of idiopathic interstitial lung disease that presents as acute respiratory failure in previously healthy individuals, typically developing over days to weeks following a prodromal illness. 1

• AIP presents acutely (days to weeks from symptom onset) in previously healthy individuals with no pre-existing lung disease 1, 2
• The clinical syndrome mimics acute respiratory distress syndrome (ARDS) but is idiopathic in nature 1, 2
• Common presenting symptoms include fever, cough, and progressive shortness of breath 1, 3
• A flu-like prodromal illness often precedes the acute respiratory deterioration by approximately 5-7 days 2, 3
• Patients rapidly progress to moderate-to-severe hypoxemia requiring mechanical ventilation 1, 4

Diagnostic Criteria

The diagnosis of AIP requires both a clinical syndrome of idiopathic ARDS and pathological confirmation of organizing diffuse alveolar damage (DAD) on lung biopsy. 1

Radiographic Findings

• Chest radiograph shows diffuse, bilateral airspace opacification 1, 3
• CT scan demonstrates bilateral, patchy, symmetric areas of ground-glass attenuation 1, 3
• Bilateral areas of airspace consolidation may be present with a predominantly subpleural distribution 1
• These radiographic findings are indistinguishable from ARDS of other etiologies 1

Histopathologic Features

• Lung biopsy shows histologic features identical to the exudative, proliferative, and/or fibrotic phases of diffuse alveolar damage 1
• The exudative phase demonstrates edema, hyaline membranes, and interstitial acute inflammation 1
• Type 2 pneumocyte hyperplasia becomes prominent as the lesion progresses 1
• Loose organizing fibrosis is seen within alveolar septa and may be prominent within airspaces in more than one-third of cases 1
• Diffuse involvement is typical, though severity may vary among different histologic fields 1

Diagnostic Approach

• Transbronchial biopsy is a logical first diagnostic step 4
• Open lung biopsy should be performed if transbronchial biopsy is non-diagnostic 4
• AIP is a diagnosis of exclusion requiring elimination of infectious, traumatic, toxic, and metabolic causes of ARDS 3, 5
• Routine laboratory studies are nonspecific and generally not helpful 1
• Microbiological testing, including bronchoalveolar lavage, is essential to exclude infectious etiologies 3, 5

Treatment

The main treatment for AIP is supportive care, as there is no proven effective pharmacologic therapy. 1

• Mechanical ventilation is required in the majority of patients due to severe hypoxemic respiratory failure 1, 4
• The efficacy of glucocorticoid therapy remains unclear and unproven 4, 2
• Response to corticosteroids is minimal in most case series 4
• Lung transplantation may be considered in appropriate candidates who fail conventional therapy 4

Prognosis

The mortality rate from AIP is extremely high, exceeding 60%, with the majority of patients dying within 6 months of presentation. 1

• Mortality rates approach 100% in some case series, with death occurring within 5-26 days of ICU admission 4
• The disease carries a grave prognosis despite aggressive diagnostic and treatment efforts 4, 5
• If the patient survives, lungs may resolve to normal or progress to end-stage honeycomb fibrosis 1
• The fulminant nature and rapid progression distinguish AIP from other forms of idiopathic interstitial pneumonia 1

Critical Pitfalls

• Do not delay lung biopsy in patients with idiopathic ARDS, as histopathologic confirmation is required for definitive diagnosis 1, 3
• Do not assume bacterial pneumonia and initiate antibiotics without excluding AIP through appropriate diagnostic workup 2, 5
• Do not confuse AIP with other forms of idiopathic interstitial pneumonia that have better prognoses and different treatment responses 1
• Do not rely on corticosteroids as definitive therapy, as their efficacy is unproven and supportive care remains the cornerstone of management 1, 4, 2