Table 1.
Characteristics of studies included in the review.
| Author | Year | Study Design | Country | Population (n) | Age Mean ± SD/ Median (Range) |
Gender (n%) |
Risk factors |
|---|---|---|---|---|---|---|---|
| Zaja | 2003 | Clinical trial | Italy | 15;3 EMC* | 66 ± 2 | 66.6% Female | All three EMC cases experienced relapses |
| Bryce | 2006 | Retrospective | USA | 8; 6 NICV with LPD* |
65 ± 11.5 | 62.5% Male | MALT Lymphoma with Sjögrens syndrome |
| Cruz | 2006 | Case Series | Brazil | 9 | 54.44 ±17.01 | 77.7% Female | EMC cases experienced more relapses than other etiological NICV associations |
| Saadoun | 2006 | Retrospective | France | 133; 116 NICV* | 59.5 ± 16.6 | 65% Female | NICV refractory cases—Efficacy of RTX + Belimumab reported; Purpura on relapse |
| Matignon | 2009 | Retrospective | France | 20; 9 pSS, 1 BCL, 10 EMC |
59.8 ± 12.12 | 75% Female | Renal ± extra-renal relapses observed. CV relapse with purpura, concomitant BCL |
| Terrier | 2010 | Retrospective | France | 23 | 66 ± 13 | 74% Female | pSS more likely to experience relapse |
| Foessel | 2011 | Retrospective | France | 33; 13 EMC, 14 CTD 4 HM |
EMC 62.8 ± 12.2 Secondary 57.3 ± 13 |
53.8% Male 75% Female |
CS Monotherapy; RTX flare |
| De Vita | 2012 | RCT | Italy | 57; 4 NICV* | 63.27 ± 10.78 | 80.7% Female | Patients randomised to the non-RTX group failing treatment switched to RTX (RTX-switch group) |
| Terrier | 2012, 2013 | Retrospective | France | 242 | 62.6 ± 14.5 | 69% Female | Non-RTX + CS regimen |
| Terrier | 2013 | Retrospective | France | 64 | 65.4 ± 11.4 | 56% Female | Post RTX CV flare 13% |
| Terrier | 2014 | Retrospective | France | 145 | 61.2 ± 11.8 | 73% Female | Purpura; Cutaneous necrosis; Articular involvement Incomplete clinical and immunological response after treatment; CS monotherapy |
| Néel | 2014 | Retrospective | France | 227; 36 with features of MC |
63 (41–85) | 55.6% Male | With underlying LPD, demonstrated response-relapse pattern necessitating multiple treatment modalities |
| Michaud | 2015 | Retrospective | France | 29 | 57 ± 16.4 | 69% Female | Not reported |
| Retamozo | 2016 | Prospective | Spain/ Italy | 21* | 50.9 ± 13.9 | 90.4% Female | Not reported |
| Zaidan | 2016 | Retrospective | France | 230; 80 MCGN+ | 62.6 ±14.1 | 62.5% Female | Renal ± extra-renal relapses were reported. GFR <60 ml/min; non RTX + CS regimen |
| Colantuono | 2017 | Retrospective | Italy | 37; 2 EMC* | 72(35 -82) | 78% Female | The 2 EMC cases relapsed with low-dose RTX |
| Galli | 2017 | Prospective | Italy | 175; 160* | 66 (55–74) | 78% Female | Not reported |
| Sidana | 2017 | Retrospective | USA | 102; 98* | 59 (31–91) | 54% Male | Cryocrit level reported predicts symptom burden |
| Lobbes | 2018 | Case Series | France | 4 | 73 ± 9.9 | 50% Female | Non-IgM Type I CV when treated with CS monotherapy. |
| Marson | 2018 | Retrospective | Italy | 159; 42 NICV* | 68 (IQR 62–74 ) | 73.6% Female | Not reported |
| Argyropoulou | 2020 | Retrospective | Greece | 71* | 50 (21–75) | 97% Female | Reported factors influencing the risk of Lymphoma |
| Boleto | 2020 | Longitudinal study | France | 742; 266 NICV* | 55 (IQR 38–68) | 37.2% Male | Not reported |
| Desbois | 2020 | Retrospective | France | 50; 1 EMC* | 83 | 100% Male | RTX-associated flare where patients shared characteristics of type II IgM k with RF activity; renal involvement; BCL; Increased CG level and low C4 complement level |
| Lesniak | 2021 | Retrospective | Poland | 3 | 62.3 ± 4.04 | 100% Female | Refractory cases with underlying EMC |
| Fenoglio | 2022 | Prospective | Italy | 11#; 8 MC | 63.8 (54–79) | 63% Male | Type II CV with renal involvement—Proteinuria |
| Pouchelon | 2022 | Retrospective | France/Italy/Germany/Spain | 26 ^ | 56.5 (46.5–65.0) | 58% Female | Refractory to RTX -Type II Mixed CV Monoclonal IgMκ with incomplete immunological response |
| Roubertou | 2022 | Retrospective | France | 213; 142 SLE CG+ 21 CV+ |
29.2 ± 12.8 | 87% Female | Not reported |
*NICV cohort isolated from the total; ^ NICV cohort from the original study; # Inclusive of type I; BCL, B-cell lymphoma; CG, cryoglobulins; CS, corticosteroids; CV, cryoglobulinemic vasculitis; EMC, essential mixed cryoglobulinemia; GFR, glomerular filtration rate; LPD, lymphoproliferative disorders; IQR, interquartile range; MCGN, mesangio capillary glomerulonephritis; MC, mixed cryoglobulinemia; NICV, non-infectious cryoglobulinemia vasculitis; pSS, primary Sjögren's syndrome; RTX, rituximab; SLE, systemic lupus erythematosus.