Table 1.

Rheumatic diseases

Author, date	Study design	Study population	Intervention	Outcomes	Complications
Gizińska et al., 2015 [12]	Randomized	RA (women) N = 25 WBC + rehab N = 19 control (rehab)	WBC at − 110 °C for 3 min 1 × a day, 2 weeks	Pain reduction: WBC and control groups had decreased mean pain VAS by 1.08 cm and 1.11 cm, respectively (no significant difference b/w groups) Inflammation: WBC decreased IL-6 and TNF-α	None reported
Schlesinger et al., 2002 [36]	Randomized	Gouty arthritis N = 10 LC N = 9 control	LC (ice pack) for 20 min 4 × a day, 1 week	Pain reduction: WBC decreased mean pain VAS by 7.75 cm compared to 4.42 cm in the control group (significant difference b/w groups)	None reported
Straub et al., 2009 [16]	Randomized	RA N = 10 LC w/o GC N = 5 WBC − 60 °C w/o GC N = 9 WBC − 110 °C w/o GC N = 10 LC w/GC N = 12 WBC − 60 °C w/ GC N = 9 WBC − 110 °C w/ GC	WBC at − 110 °C or − 60 °C for 2 min 2–3 × a day, 1 week LC b/w − 20 and − 30 °C for 10–30 min 2–3 × a day, 1 week	Pain reduction: WBC at − 110 °C decreased pain VAS in groups w/ and w/o GC Inflammation: WBC at − 110 °C in group w/o GC had IL-6 increase and swollen joint count decrease	None reported
Hirvonen et al., 2006 [34]	Randomized, single-blinded	RA N = 20 WBC − 110 °C + rehab N = 17 WBC − 60 °C + rehab N = 17 LC + rehab	WBC at − 110 °C or − 60 °C 2–3 × a day, 1 week LC (cold pack, cold air at − 30 °C) 2–3 × a day, 1 week	Pain reduction: LC and WBC at − 110 °C significantly decreased VAS pain by 1.1 cm and 2.4 cm, respectively; WBC at − 110 °C significantly decreased more than the LC and WBC at − 60 °C groups Disease activity: decrease in DAS in all groups	LC: respiratory infection (2), frost bite (1), joint or muscle pain (1) − 60 °C WBC: headache (1), hypertension (1), dizziness (1), malaise (2), joint or muscle pain (1), nervousness (1) − 110 °C WBC: respiratory infection (1), hypertension (1), urticaria (1), long lasting freezing (2), malaise (1)
Jastrzabek et al., 2013 [13]	Randomized	RA N = 20 LC − 160 °C N = 20 LC − 30 °C	LC at − 160 °C with liquid nitrogen flow or − 30 °C with cold air flow for 30 min 2 × a day, 10 days	Pain reduction: − 160 °C and − 30 °C LC decreased pain VAS by 3.34 cm and 2.69 cm, respectively Disease activity: Increased ROM and improvements in 50-m walk test in both groups Inflammation: both LC groups decreased TNF-α, no change found in IL-6	None reported
Sadura-Sieklucka et al., 2019 [29]	Randomized	RA N = 25 WBC + rehab N = 25 control (rehab)	WBC at − 120 °C to − 140 °C for 2 min 1 × a day, 20 days	Pain reduction: WBC and control groups decreased VAS morning pain (1.2 cm, 1.9 cm), VAS activities of daily living pain (1.6 cm, 1.8 cm), VAS night pain (1.2 cm, 2.1 cm) (no significant difference b/w groups) Inflammation: no changes in IL-6, IL-10, and TNF-α	None reported
Stanek et al., 2015 [28]	Randomized	AS N = 32 WBC + rehab N = 16 control (rehab)	WBC at − 120 °C for 3 min 1 × a day, 10 days	Pain reduction: WBC and the control decreased VAS pain by 2.48 cm and 0.91 cm, respectively (significant difference b/w groups)	Slight aggravation of symptoms in the beginning days of treatment
Hinkka et al., 2017 [35]	Randomized, crossover	Inflammatory arthritis (RA, AS, Psoriatic arthritis) N = 121 WBC	WBC for 2 min 2 × a day, 1 week	Pain reduction: WBC group had a significantly greater reduction in VAS pain compared to control group at the end of the treatment week	None reported
Straburzynska-Lupa et al., 2018 [33]	Randomized	AS N = 23 WBC − 110 °C + rehab N = 21 WBC − 60 °C + rehab N = 21 control (rehab)	WBC at − 110 °C or − 60 °C for 3 min 1 × a day, 6 days	Disease activity (including pain): BASDAI decreased in − 110 °C (1.62), − 60 °C (1.78) and control (1.23) groups; significant difference in BASDAI b/w − 110 °C and control groups; no significant difference b/w WBC at − 110 °C and − 60 °C after therapy Inflammation: IL-8 decrease in all groups, no changes in IL-17 Oxidative stress: No change in TAS	None reported
Stanek et al., 2018 [32]	Randomized	AS (male) N = 16 WBC + rehab N = 16 control (rehab)	WBC at − 120 °C for 3 min 1 × a day, 8 days	Disease activity (including pain): BASDAI decreased in both groups, WBC group had significantly greater decrease in BASDAI than control (2.14 and 0.74, respectively) Inflammation: no change in IL-6	None reported
Stanek et al., 2018 [24]	Randomized	AS (male) N = 16 WBC + rehab N = 16 control (rehab)	WBC at − 120 °C for 3 min 1 × a day, 8 days	Disease activity (including pain): BASDAI decreased in both groups, WBC group had significantly greater decrease in BASDAI than control (2.16 and 0.74, respectively) Oxidative stress: decrease in TOS and OSI	None reported
Stanek et al., 2011 [31]	Randomized	AS (male) N = 16 WBC + rehab N = 16 control (rehab)	WBC at − 120 °C for 3 min 1 × a day, 10 sessions in 2 weeks	Pain reduction: WBC and control groups had a decrease in VAS pain (2.41 cm and 0.91 cm), but the WBC group had a significantly greater reduction in pain than the control	None reported

RA rheumatoid arthritis; WBC whole-body cryotherapy; VAS Visual Analogue Scale; LC local cryotherapy; b/w between; w/ with; w/o without; GC glucocorticoids; DAS Disease Activity Score; ROM range of motion; AS ankylosing spondylitis; BASDAI Bath Ankylosing Spondylitis Disease Activity Index; TOS Total Oxidative Status; TAS Total Antioxidant Status; OSI, Oxidative Stress Index