Table 1

Rates of infections, mortality and infection related mortality in major studies on primary systemic vasculitis
Study
 Type of study
 Indication
 Intervention
 Prophylaxis
 N
 Follow up (months)
 Reported infections (classified as serious)
 Type of serious infections (number of patients)a
 Total deaths (%)
 Death due to or in conjunction with infection (% of total deaths)
 Type of infection leading to death (number of patients) b
Giant cell arteritis
     Matteson et al. 1996 [4]
 CS
GC
 NI
 205
 84
 NI
 NI
 49 (24)
 3 (6)
 NI
     Chevalet et al. 2000 [5]
 RCT
Oral GC ± initial GC iv pulse
 None
 164
 12
 31 (22)
 Pneu (20), Sep (1), Abs (1)
 5 (3)
 0
 NA
     Jover et al. 2001 [6]
 RCT
GC ± MTX
 INH AA
 42
 24
 18 (4)
 Pneu (1), TB (1), PN (1), CC (1)
 0
 0
 NA
     Hoffman et al. 2002 [7]
 RCT
GC ± MTX
 None
 98
 12
 NI (3)
 Pneu (1)
 3 (3)
 1 (33)
 Pneu (1)
     Mazlumzadeh et al. 2006 [8]
 RCT
Oral GC ± initial GC iv pulse
 None
 27
 12
 18 (0)
 NA
 0
 0
 NA
     Hoffman et al. 2007 [9]
 RCT
GC ± Inflix
 TS
 44
 5.5
 NI (2)
 Histo (1), VZV (1)
 0
 0
 NA
     Martinez-Taboada et al. 2007 [10]
 RCT
GC ± Eta
 INH
 17
 12
 8 (0)
 NA
 0
 0
 NA












Takayasu arteritis
     Hoffman et al. 2004 [11]
 UCT
GC + Inflix or Eta
15
 22

0
 0
 NA












Churg-Strauss syndrome/polyarteritis nodosa
     Cohen et al. 2007 [12]
 RCT
 I
 GC + 6 pulse CY versus 12 pulse CY
 TS recommended
 48
 42
 21 (NI)
 NI
 4 (8)
 3 (75)
 CMV (1), Pneu (1) and NI
     Gayraud et al. 1997 [13]
 RCT
 I
 GC + pulse CY versus oral CY
 None
 25
 60.8
 7 (NI)
 NI
 1 (4)
 1 (100)
 Pneu (1), Sep (1), Asp (1)
     Guillevin et al. 1995 [14]
 RCT
 I
 GC + pulse CY ± PE
 TS
 62
 33
 NI (9)
 TB (3), Pneu (3), Sep (2), Sig (1)
 11 (17)
 2 (18)
 Sep (1) and NI
     Guillevin et al. 1992 [15]
 RCT
 I
 GC ± PE
 None
 78
 44
 NI
 NI
 15 (19)
 2 (13)
 Sep (1) and NI
     Guillevin et al. 1991 [16]
 CS
 I
 GC + PE ± CY
 None
 71
 69
 NI
 NI
 19 (27)
 5 (26)
 Pneu/Sep (4), TB (1)












Microscopic polyangitis
     Nachman et al. 1996 [17]
 CS
 I
 GC + CY
 NI
 107
 44
 NI
 NI
 6 (6)
 2 (33)
 Sep (2)












Wegener's granulomatosis
     Metzler et al. 2007 [18]
 RCT
 M
 GC + Lef or MTX
 None
 54
 21
 25 (0)
 NA
 0
 0
 NA
     WGET Research Group 2005 [19]
 RCT
 I, M
 GC + CY/MTX ± Eta
 TS
 174
 27
 NI
 NI
 6 (3.5)
 2 (33)
 Sep (2)
     Schmitt et al. 2004 [20]
 UCT
 I
 GC + ATG
 Optional TS, optional fungi, optional CMV
 15
 21.8
 NI (6)
 Pneu (2), Abs (1), UTI (1), CMV (1), Col (1)
 2 (13)
 1 (50)
 Pneu (1)
     Metzler et al. 2004 [21]
 UCT
 M
 GC + Lef
 None
 20
 21
 9 (1)
 Pneu (1)
 0
 0
 NA
     Bligny et al. 2004 [22]
 CS
 I, M
 Mainly GC + CY
 TS or Penta in most patients
 93
 54
 NI (54)
 PCP (12), Asp (5), VZV (3), CMV (6), Sep (8), Papo (1), TB (4), Abs (1), Toxo (2)
 25 (27)
 13 (52)
 Sep (4), PCP (5), CMV (2), Pneu (3), Asp (3), TB (1), Papo (1)
     Reinhold-Keller et al. 2002 [23]
 UCT
 M
 GC + MTX
 None
 71
 25.2
 7 (0)
 NA
 2 (3)
 0
 NA
     Mahr et al. 2001 [24]
 CS
 I
 GC + CY
 TS in most patients
 49
 23
 NI (31)
 PCP (19), Pneu (3), Asp (5), CMV (5), TB (2), VZV (2), Papo (1), Sep (2), SA (1)
 18 (37)
 7 (39)
 PCP (5), Sep (1), Pneu (3), Asp (2), Papo (1), CMV (1)
     Reinhold-Keller et al. 2000 [25]
 CS
 I, M
 Mainly GC + CY followed by MTX or TS
 TS in case of CY
 155
 84
 NI (56)
 Pneu (32), Sep (10), CMV (3), PCP (1)
 22 (14)
 5 (23)
 Sep (4), Pneu (1)
     Guillevin et al. 1997 [26]
 RCT
 I
 GC + oral CY versus GC + pulse CY
 TS in most patients after high incidence of PCP in the first patients
 50
 27
 NI (25)
 Pneu (3), Sep (3), SA (1), CMV (4), Papo (1), PCP (10)
 19 (38)
 9 (47)
 PCP (6), Pneu (1), Sep (1), Papo (1)
     de Groot et al. 1996 [27]
 RCT
 M
 MTX versus TS ± GC
 No additional
 65
 22
 NI
 NI
 0
 0
 NA
     Stegeman et al. 1996 [28]
 RCT
 M
 Placebo versus TS
 No additional
 81
 24
 NI
 NI
 1 (1.2)
 0
 NA
     Sneller et al. 1995 [29]
 UCT
 I
 GC + MTX
 None
 42
 19
 NI (4)
 PCP (4)
 3 (7)
 2 (67)
 PCP (2), Cryp (1)












ANCA-associated vasculitis
     Pagnoux et al. 2008 [30]
 RCT
 M
 GC + MTX versus Aza
 TS or Penta
 126
 12
 46 (6)
 Sep (2)
 1 (0.8)
 1 (100)
 Sep (1)
     Walsh et al. 2008 [31]
 UCT
 I
 GC + Campath-1H
 Acyc, fungi
 71
 60
 31 (21)
 Staph (10), CMV (2), PCP (2), Asp (2), Sal (19), Pseu (1), E. coli (1), Acti (1)
 31 (44)
 12 (39)
 NI
     Jayne et al. 2007 [1]
 RCT
 I
 GC + oral CY + PE versus iv GC pulse
 TS suggested
 137
 12
 61 (37)
 NI
 35 (26)
 19 (54)
 NI
     de et al. Groot 2005 [32]
 RCT
 I
 GC + CY versus MTX
 Optional TS
 100
 18
 18 (8)
 CMV (1), SA (1), Cory (1), Pneu (2), UTI (1)
 4 (4)
 1 (25)
 CMV (1)
     Booth et al. 2004 [33]
 UCT
 I
 GC + Inflix ± CY
 TS, fungi
 32
 16.8
 NI (7)
 Pneu (3), Sep (1), Abs (1), Opht (1)
 2 (6)
 1 (50)
 Pneu (1)
     Birck et al. 2003 [34]
 UCT
 I
 GC + DSG
 NI
 20
 12
 NI
 NI
 1 (5)
 1 (100)
 PCP (1)
     Jayne et al. 2003 [35]
 RCT
 I, M
 GC + oral CY followed by GC + oral CY versus Aza
 TS recommended
 155
 18
 33 (11)
 NI
 8 (5)
 5 (63)
 Pneu (2) and NI
     Haubitz et al. 1998 [36]
 RCT
 I
 GC + oral CY versus pulse CY
 None
 47
 40
 NI (13)
 Sep (4), Pneu (5), VZV (1), CMV (1), Endo (1), SD (1)
 3 (6)
 3 (100)
 Sep (3)
     de Groot et al. 2009 [37]
 RCT
 I
 GC + oral CY versus pulse CY
 TS
 149
 18
 51 (17)
 Pneu (3), Sep (3), Div (1), PCP (1), HSV (1), Abs (1)
 14 (9.4)
 6 (43)
 Sep (6), PCP (1)

Large differences in infection-related mortality between the different indications can be observed. Mortality from infections is much less frequent in giant cell arteritis than in ANCA-associated vasculitis. In small vessel vasculitis the phase of induction of remission confers much more susceptibility to infections than the maintenance phase. Bacterial infections are the most frequently mentioned causes of death. Types of infections are given as clinical conditions or causative agents as information was available. aThe sum might be smaller than the number of serious infections due to missing information. bThe sum might be higher than the number of deaths as in some patients more than one infection was involved. Types of study are: CS, cohort study; RCT, randomized controlled trial; UCT, open label uncontrolled trial. Indications are: I, induction therapy; M, maintenance. Interventions are: ATG, anti-thymocyte globulin; Aza, azathioprine; CY, cyclophosphamide; DSG, deoxyspergualin; Eta, etanercept; GC, glucocorticoide; Inflix, infliximab; Lef, leflunomide; MTX, methotrexate; PE, plasma separation; TS, trimopthoprim/sulfomethoxazole. Prophylaxis: Acyc, acyclovir; fungi, anti-fungal prophylaxis using ether nystatin, fluconazole or amphotericin; INH, isoniazid; Penta, pentamidine; TS, trimopthoprim/sulfomethoxazole. Types of infection are: Abs, abscess; Acti, Actinomyces sp.; Asp, aspergillosis; CC, cholecystitis; CMV, cytomegalovirus; Col, colitis; Cory, Corynebacterium sp.; Cryp, cryptococccus; Div, diverticulitis; End, endocarditis; Histo, histoplasmosis; HSV, herpes simplex virus; Opht, ophtalmitis; Papo, papovavirus encephalitis; PCP, Pneumocystis jiroveci pneumonia; PN, pyelonephritis; Pneu, pneumonia; Pseu, Pseudomonas sp.; SA, septic arthritis; Sal, Salmonella sp.; SD, spondylodiscitis; Sep, septicemia; Sig, sigmoiditis; Staph, Staphylococcus sp.; TB, tuberculosis; Toxo, toxoplasmosis; UTI, urinary tract infection; VZV, varicella zoster virus. Other abbreviations: AA, as appropriate; ANCA, antineutrophil cytoplasmic antibody; iv, intravenous; NA, not applicable; NI, no information.

Moosig et al. Arthritis Research & Therapy 2009 11:253   doi:10.1186/ar2826