Table 2 Synopsis of patient data on all cases with a positive HSV-1 result on PCR of bronchoalveolar lavage
Clinical data | Case 1 | Case 2 | Case 3 | Case 4 | Case 5 | Case 6 |
|---|---|---|---|---|---|---|
Age at presentation (yrs), gender | 74, f | 74, m | 60, m | 67, m | 72, m | 65, f |
Rheumatological diagnosis (duration in years) | Rheumatoid arthritis, seronegative 8 | pulmonary microscopic Polyangiitis 3 | Wegener's Granulomatosis 2 | Rheumatoid arthritis, seropositive 10 | Wegener's Granulomatosis 8 | Systemic lupus erythematosus 4 |
Co-Morbidities | allergic asthma | renal insufficiency | diabetes, septic arthritis | HHT, renal insufficiency | ||
Immunosuppression (severity score) | Pred 20 mg/d + MTX 15 mg/w + Lefl 20 mg/d (3) | Pred 50 mg/d + Cyclo 150 mg/d p.o. (4) | Pred 20 mg/d +Cyclo 150 mg/d (4) | Pred 20 mg/d + MTX 7.5 mg/w + Anakinra 100 mg/d (3) | Pred 40 mg/d + Cyclo 500 mg/m i.v. (4) | Pred 20 mg/d + Aza 150 mg/d, pancytopenia (3) |
clinical presentation in the outpatient setting prior to admission | 21 days of cough, fever | 3 days of bloody cough, dysphagia | 3 days of dyspnea, syncope | 7 days of dyspnea, cough | 5 days of dyspnea, cough, weakness | 1 day of dyspnea, non-productive cough |
Notable findings | HSV-1 positive oral lesion | none | HSV-1 positive oral lesion | none | HSV-1 positive nasal lesion | none |
Ventilatory support required | CPAP | no | intubation | intubation | no | no |
Radiological findings | ||||||
Chest-XR | diffuse bilateral ground-glass opacities | interstitial pattern | interstitial pattern | bilateral bronchopneumonic infiltrates with pleural effusions | bilateral bronchopneumonic infiltrates | unilateral infiltrate |
High-resolution CT-scan | diffuse bilateral ground-glass opacities | right-sided diffuse pleural effusions | diffuse bilateral ground-glass opacities (no granulomas) | extensive bilateral bronchopneumonic infiltrates with pleural effusions, atelectasis, hilar lymphadenopathy | diffuse bilateral granulomas | unilateral bronchopneumonic infiltrate |
Bronchoscopy/pathology | ||||||
performed on hospital day | 2 | 2 | 2 | 2 | 2 | 4 |
Macroscopic mucosal aspect | Vulnerable, inflammamation | normal | inflammation | acute bronchitis | vulnerable, acute bronchitis | vulnerable |
BAL cytology: inclusion bodies | Positive | positive | positive | n.a. | n.a. | n.a. |
Lung biopsy | Non-specific (chronic) bronchitis | n.p. | non-specific fibroelastosis | n.p. | n.p. | n.p. |
HSV-1 immunohistology of BAL cytology or of lung biopsy | n.p. | positive | n.p. | n.p. | n.p. | n.p. |
Relevant identified infectious agents of pneumonia/pneumonitis (from BAL) | HSV-1 as sole agent | HSV-1 as sole agent | Aspergillus, K. pneumoniae, HSV-1 | MRSA, P. aeruginosa, K. pneumoniae, HSV-1 | S. aureus, P. aeruginosa, Influenza A, HSV-1 | S. aureus (coag neg), P. aeruginosa, Enterococci, HSV-1, M. kansasii |
Treatment | - day 1: ceftriax+ery (for 7 days; overlap with acyclo 5 days) - day 2: acyclo | - day 1: moxi (for 2 days) - day 2: swap to acyclo monotherapy | - day 1: mero + ery + fluc - day 2: add acyclo + amphoB for fluc - later: add cipro+ tobra + vanco for mero | sequential: - ceftr+moxi - genta+tazo+fluc - mero - vanc+linez from day 2: acyclo | sequential: - metro+clari +ceftriax - day 3 ceftaz for ceftriax | sequential: - clari+cipro+ceftaz - fluc (for 14 days) from day 14: INH+ rifampicin+ethambutol |
Outcome | recovery after 7 days | recovery after 11 days | lethal after 28 days (ARDS) | lethal after 33 days (ARDS) | Initial recovery after 28 days, but lethal after 110 days (ARDS) with persistant high HSV-1 viral load on BAL | recovery after 38 days |
Our Diagnosis/comment | most likely isolated HSV-1 pneumonitis | most likely isolated HSV-1 pneumonitis | Bacterial, fungal and HSV-1 pneumonia/pneumonits | Bacterial bronchopneumonia with HSV-1 reactivation | Bacterial pneumonia with untreated HSV-1 reactivation. A second BAL PCR showed an increasing viral load | Mycobacteriosis due to M. kansasii (responsive to treatment). HSV-1 reactivation without radiographic signs of pneumonitis that was not treated antivirally. |
Complete microbiological work-up | ||||||
Blood cultures | negative | negative | negative | negative | negative | negative |
Mycobacteria culture/PCR BAL | negative | negative | negative | negative | negative | positive (M. kansasii) |
Aspergillus | negative | negative | positive (serum Ag & culture) | negative | n.p. | negative (serum AG) |
P. jirovecii BAL | negative | negative | negative | negative | negative | negative |
MRSA culture Sputum | negative | negative | negative | positive | negative | negative |
P. aeruginosa culture BAL | negative | negative | negative | positive | positive | positive |
K. pneumoniae culture BAL | negative | negative | positive | positive | negative | negative |
M. pneumoniae | negative (PCR BAL) | negative (serology) | negative (serology) | negative (PCR BAL) | negative (PCR BAL) | n.p. |
C. trachomatis/pneumoniae | negative (serology) | n.p. | negative (PCR BAL) | negative (PCR BAL) | negative (PCR BAL) | negative (PCR BAL) |
Legionella-Ag (Urine) | negative | negative | negative | negative | negative | n.p. |
Complete virological work-up | ||||||
HSV-1 PCR BAL, Geq/ml | 9.750.000 | 284.000 | 700.000 | 850.000 | 10.250.000 | 310.000 |
CMV-PCR BAL | negative | Negative | negative | negative | negative | negative |
Influenza A PCR BAL* (season of presentation) | n.p. (May) | n.p. (April) | negative (January) | n.p. (September) | positive (February) | n.p. (June) |
Adenovirus PCR BAL** | Negative | negative | negative | n.p. | n.p. | n.p. |
HIV-1/2-Ag ELISA | n.p. | n.p. | negative | n.p. | Negative | n.p. |