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.

Abbreviations used are: acyclo = acyclovir, Ag = antigen, amphoB = amphotericin B, ARDS = adult respiratory distress syndrome, Aza = azathioprine, BAL = bronchoalveolar lavage, ceftaz = ceftazidime, ceftriax = ceftriaxone, cipro = ciprofloxacin, clari = clarithromycin, CPAP = continuous positive airway pressure, CT = computed tomography, coag neg = coagulase negative, cyclo = cyclophosphamide, d = day, ery = erythromycin, fluc = fluconazole, genta = gentamycin, Geq/ml = genome equivalents/ml; HHT = hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome), INH = isoniazid, Lefl = leflunomide, linez = linezolid, mero = meropenem, metro = metronidazole, moxi = moxifloxacin, MTX = methotrexate, Pred = prednisone, tazo = piperacillin/tazobactam, tobra = tobramycin, vanco = vancomycin, w = week. *testing was seasonal during winter only. **testing was at the discretion of the physician performing bronchoscopy.