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Table 4 Qualitative synthesis of results and overview of evidence

From: The clinical effectiveness of intra-articular corticosteroids for arthritis of the lower limb in juvenile idiopathic arthritis: a systematic review

Domain Author, year (ref.) Results Adverse effects Level of evidence (specific areas) Level of evidence (for domain)
Tenderness/pain Eich et al, [35] Knee: 0% after 1 month (no significance value given) One patient experienced focal cutaneous atrophy and a possible ruptured popliteal cyst Weak evidence for IACIs decreasing pain in the knee as 2 studies show a reduction of pain Weak evidence for IACIs decreasing pain in lower leg joints overall as 3 studies show a reduction of pain
Huppertz et al, [38] Knee: 33.3% after 7 weeks (no significance value given) Not Specified   
Laurell et al, [24] Ankle: Pain regression/partial improvement = 92.5% (no specific data included, only percentages) after 4 weeks Local subcutaneous atrophy in 3 patients at 4 injection sites Inconclusive due to lack of studies  
(No significance value given)
Swelling Eich et al, [35] Knee: 27.3% after 1 month (no significance value given) One patient experienced focal cutaneous atrophy and a possible ruptured popliteal cyst   Weak evidence for IACIs decreasing swelling in lower leg joints overall as 2 studies show a reduction in swelling
Huppertz et al, [38] Knee: 0% after 7 weeks (no significance value given) Not Specified   
Synovitis Papadopoulou et al., [40] Number of joints in remission vs. 0.9% of injected joints suffered from skin hypopigmentation or subcutaneous atrophy. Weak evidence for IACIs decreasing synovitis in the knee, ankle and STJ as 2 studies for each joint showed a reduction of synovitis. Weak evidence for IACIs decreasing synovitis in lower leg joints overall as 3 studies show reduction of synovitis
Number of joints with synovitis flare: Knee = 79.2% vs. 20.8% (p < 0.001); Ankle = 54.8% vs. 45.2% (p = 0.14) STJ = 65.5% vs. 34.5% (p < 0.0001); MTPJ = 85.7% vs. 14.2% (p = 0.008); IPJ = 90.0% vs. 10.0% (p = 0.0003).
“A few” patients developed flushing or redness of the cheeks 24-48 hrs post-injection.
Inconclusive evidence for MTPJ and IPJ due to lack of studies
Overall mean relapse time 0.5 yrs (IQR 0.3-1.3 yrs) vs. mean remission time 0.9 yrs (IQR 0.6-1.9 yrs).
Ravelli et al., [41] Knee: continued resolution at 6 months = 69% One patient suffered from subcutaneous atrophy at the injection site.   
Reoccurrence/relapse = 31%
(no significance value given)
Remedios et al., [42] Clinical synovitis vs. MRI pannus: Not Specified.   
Tibiotalar: 84.6% vs. 84.6%; STJ: 23.1% (definite) vs. 46.2% (no significance value given)
Mean duration of effect (guided vs. unguided) (weeks): 38.3 vs. 13.9 (no significance value given)
Effusion Huppertz et al, [38] Knee: 13.3% after 7 weeks (no significance value given) Not Specified   Inconclusive due to lack of studies
Hyperthermia Eich et al, [35] Knee: 18.2% after 1 month (no significance value given) One patient experienced focal cutaneous atrophy and a possible ruptured popliteal cyst   Inconclusive due to lack of studies
Sustained clinical response Al-Wahadneh, [31] Knee: 30/30 = 100% maintained resolution at 3 months (no significance value given) 1/24 (4%): short-lived pain and erythema, 2/24 (8%): subcutaneous atrophy resolved dramatically after one year, 2/24 (8%): asymptomatic periarticular calcification. Weak evidence for IACIs decreasing clinical signs and symptoms in the knee, ankle and STJ as 11, 4 and 2 studies respectively showed sustained clinical response. Weak evidence for IACIs decreasing clinical signs and symptoms in lower leg joints overall as 21 studies show sustained clinical response
Inconclusive evidence for midfoot due to lack of studies
Allen et al, [35] Knee: 18/48 = 37.5% relapse at 6 months (no significance value given) Subcutaneous fat atrophy at injection site in one patient.   
Beukelman et al, [26] Knee: 1.4 yrs of resolution before relapse (SD ± 1.0) 53%: subcutaneous atrophy or hypopigmentation at injection site.   
STJ: 1.2 yrs of resolution before relapse (TH + TA) (SD ± 0.9)
Earley et al, [33] Knee: Excellent/Good Outcome: 92.8% vs. 2/23 had areas of subcutaneous atrophy at injection site.   
Poor/Re-injected: 7.2% at 3 months (No significance value given)
Eberhard et al, [34] Knee Median Relapse (months) Not Specified.   
TH: 11.1 +/- 0.81
TA: 7.95 +/- 0.95
(p = 0.0072)
Hertzberger-ten Cate et al, [36] Knee: resolution maintained in 70% of knees for >6 months (No significance value given) 2/21 patients suffered a small atrophic lesion at the injection site.   
1/21 patient suffered a red and painful knee the day following injection (resolved by local ice application).
Sustained clinical response (cont’d) Honkanen et al, [37] Knee: overall probability of sustained clinical response was higher for TH then MP after 6-8 weeks (p > 0.0005) Not Specified.   
Laurell et al, [24] Ankle pain Regression/Partial Improvement = 92.5% (no specific data included, only percentages) after 4 weeks (No significance value given) Local subcutaneous atrophy in 3 patients at 4 injection sites.   
Lepore et al, [39] Knee: mean remission time = 13.9 months (range = 0-54 months) (no significance value given) 10% (3 patients) subcutaneous lipolysis with spontaneous regression.   
Marti et al, [19] Mean duration of remission until flare in months (range): knee = 8.0 (0-27); ankle = 4.5 (0-13); STJ = 3.5 (0-11); midfoot = 1 (0-3) (no significance value given) Systemic effects of glucocorticoids in 7 patients (one flushed cheeks, three increased appetite, three mood changes).   
Mean follow-up time of joints with ongoing remission in months (range):knee = 27.2 (1-69); ankle = 18.2 (1-39); STJ = 13; midfoot = n/a (no significance value given) Local side effects in 12 patients (14 skin atrophies combined with hypopigmentation).
Remedios et al., [42] Clinical synovitis vs. MRI pannus: Not Specified.   
Tibiotalar: 84.6% vs. 84.6%; STJ: 23.1% (definite) vs. 46.2% (no significance value given)
Mean duration of effect (guided vs. unguided) (weeks): 38.3 vs. 13.9 (no significance value given)
Sustained clinical response (cont’d) Sornay-Soares et al., [44] Knee: continued resolution in 76.9% knees at 6 months No adverse effects were recorded.   
(no significance value given)
Zulian et al., [46] Knee and Ankle: continued resolution at 6 months 2 patients in each group developed skin atrophy at the injection site.   
TH: 81.4% 2 patients experienced reversible apnoea (<20secs duration) during the induction phase of sedation.
TA: 53.3%
(p = 0.001)
Joint ROM Balogh et al., [30] Knee: BM = 0 degree difference vs. TH = 13 degrees difference at 42 days (no significance value given) Mild skin atrophy in 1/23 who was injected with TH Weak evidence for IACIs increasing ROM in the knee as 3 studies show improvement Weak evidence for IACIs increasing ROM in lower leg joints overall as 5 studies show improvement
Eich et al, [35] Knee: 66.7% improvement after 1 month (no significance value given) One patient experienced focal cutaneous atrophy and a possible ruptured popliteal cyst   
Huppertz et al, [38] Knee: 92.9% improvement after 7 weeks (no significance value given) Not Specified   
Laurell et al, [24] Ankle: 95% improvement after 4 weeks Local subcutaneous atrophy in 3 patients at 4 injection sites Inconclusive due to lack of studies  
(No significance value given)
Cahill et al., [25] STJ: 89.5% returned to normal ROM within 13 weeks (no significance value given). Mean duration of improvement = 1.2 SD ±0.9 yrs. Subcutaneous atrophy or hypopigmentation in 53% Inconclusive due to lack of studies  
Leg length discrepancy Eich et al, [35] Improvement after 1 month: 100% (no significance value given) One patient experienced focal cutaneous atrophy and a possible ruptured popliteal cyst   Weak evidence for IACIs decreasing LLD as 3 studies show reduction
Sherry et al., [43] Mean difference in leg length for early intervention vs. control: Not Specified   
0% (±0) vs. 1.0% (±1.4) (p = 0.005)
over mean follow up of 4 months (SD ± 11 months)
  Verma et al., [45] Mean Lower Leg Difference (cm): ↓ 0.22 at 6 and 12 weeks (no significance value given). No adverse effects were recorded.   
Circumference Balogh et al., [30] Mean Knee Joint Circumference (cm): Mild skin atrophy in 1/23 who was injected with TH   Inconclusive due to lack of studies
BM = 1.0
TH = -1.7 after 1, 3, 7 and 42 days (no significance values given).
Imaging      Weak evidence for IACIs decreasing imaging findings in lower leg joints overall as 3 studies show improvement
MR imaging      Weak evidence for IACIs decreasing MRI detectable clinical signs and symptoms as 3 studies show detectable improvement
Effusion Eich et al., [35] Knee: 36.4% detected by MRI at 1 week and 1 month (no significance value given) One patient experienced focal cutaneous atrophy and a possible ruptured popliteal cyst Weak evidence for IACIs decreasing MRI detectable effusion as 2 studies show detectable improvement.  
Huppertz et al, [38] Knee and Ankle: 40.0% at 7 and 13 weeks (no significance value given) Not Specified.   
Pannus Eich et al., [35] Knee: 63.6% detected by MRI at 1 week and 1 month (no significance value given) One patient experienced focal cutaneous atrophy and a possible ruptured popliteal cyst Weak evidence for IACIs decreasing MRI detectable pannus as 3 studies show detectable improvement.  
Huppertz et al, [38] Knee and Ankle: 10.0% at 7 and 13 weeks (no significance value given) Not Specified.   
Remedios et al., [42] Clinical synovitis vs. MRI pannus: Not Specified.   
Tibiotalar: 84.6% vs. 84.6%; STJ: 23.1% (definite) vs. 46.2% (no significance value given)
Mean duration of effect (guided vs. unguided) (weeks): 38.3 vs. 13.9 (no significance value given)
Popliteal cyst Eich et al., [35] Knee: 33.3% detectable at 1 week and 1 month (no significance value given) One patient experienced focal cutaneous atrophy and a possible ruptured popliteal cyst Inconclusive due to lack of studies  
Destruction of articular cartilage/bone Eich et al., [35] Missing outcome data at 1 week and 1 month (no significance value given) One patient experienced focal cutaneous atrophy and a possible ruptured popliteal cyst Inconclusive due to lack of studies  
Destruction of meniscus Eich et al., [35] 100% (no ligament destruction reported) at 1 week and 1 month (no significance value given) One patient experienced focal cutaneous atrophy and a possible ruptured popliteal cyst Inconclusive due to lack of studies  
Bone marrow oedema Eich et al., [35] None reported at 1 week and 1 month (no significance value given) One patient experienced focal cutaneous atrophy and a possible ruptured popliteal cyst Inconclusive due to lack of studies  
Avascular necrosis Eich et al., [35] None reported at 1 week and 1 month (no significance value given) One patient experienced focal cutaneous atrophy and a possible ruptured popliteal cyst Inconclusive due to lack of studies  
Uptake of contrast medium Huppertz et al, [38] Knee and Ankle: 20.0% detectable at 7 and 13 weeks (no significance value given) Not Specified. Inconclusive due to lack of studies  
US imaging      Weak evidence for IACIs decreasing US detectable clinical signs and symptoms as 2 studies show detectable improvement
Joint effusion and/or pannus Eich et al., [35] Knee: 100% detectable after 1 week and 1 month (no significance value given) One patient experienced focal cutaneous atrophy and a possible ruptured popliteal cyst Inconclusive due to lack of studies  
Popliteal cyst Eich et al., [35] Knee: 0% detectable after 1 week and 1 month (no significance value given) One patient experienced focal cutaneous atrophy and a possible ruptured popliteal cyst Inconclusive due to lack of studies  
Synovial hypertrophy Laurell et al., [24] Talocrural joint = 87% regression vs. 13% no effect Local subcutaneous atrophy in 3 patients at 4 injection sites. Inconclusive due to lack of studies  
Posterior-STJ = 95% regression vs. 5% no effect
Midfoot joints = 91% regression vs. 9% no effect (no significance value given).
Mean synovial thickness: statistically significant difference at 4 weeks (p < 0.001)
Synovial hyperaemia Laurell et al., [24] Talocrural Joint = 86% normalisation vs. 14% no normalisation Local subcutaneous atrophy in 3 patients at 4 injection sites. Inconclusive due to lack of studies  
Posterior-STJ = 95% normalisation vs. 5% no normalisation
   Midfoot Joints = 80% normalisation vs. 20% no normalisation (no significance value given) after 4 weeks.    
  1. Abbreviations: STJ subtalar joint, SD standard deviation, IACI(s) intra-articular corticosteroid injection(s), TH triamcinolone hexacetonide, TA triamcinolone acetonide, MP methylprednisolone acetate, BM betamethasone, MRI magnetic resonance imaging US ultrasound, IQR inter-quartile range, ROM range of motion, LLD leg length discrepancy, MTPJ metatarsophalangeal joint, IPJ interphalangeal joint.