Table 2 Description of included studies
Author, year | Study type | Participant description | No. entered/ completed study | Follow-up period | Intervention (including post-injection procedure) | Outcome measures |
|---|---|---|---|---|---|---|
Balogh et al, [30] | RCT | Fulfilment of EULAR/WHO Oslo Criteria for JCA. | 23/23 (23 knees) | 1, 3, 7 and 42 days | TH in 11/23 | Knee Joint Circumference (cm); Knee Joint Flexion (degrees). |
BM in 12/23 | ||||||
(Dose not recorded) | ||||||
Pauciarticular form of disease. | Post-injection: Not specified. | |||||
Co-interventions: Not specified | ||||||
Al-wahadneh, [31] | OBS | Failure to respond to NSAIDs with/without slow acting anti-inflammatories. | 24/24 (30 knee joints) | 3, 6, 9, 12 and 24 months. | MA 1 mg/kg/joint mixed with 1 cc 1% lidocaine without adrenaline. | Sustained Clinical Response: ‘Active Inflammation’ (joint effusion and heat and tenderness/pain with/without correction of deformity) |
Co-interventions: 10/24: MTX (10 mg/kg/wk), 24/24: Naproxen (10-20 mg/kg/day), 24/24: NSAIDs, 11/24: Prednisolone (0.25 mg/kg/day) | Post-injection: Immobilisation 24 hrs post injection before commencing physiotherapy. | |||||
Allen et al., [32] | OBS | <16 yrs of age at onset of chronic arthritis 29/40 pauciarticular onset JRA | 40/40 (53 knees) 4 patients lost to follow-up. | 3, 6, 12 and 24 months. | 20-40 mg TH with 1% xylocaine without epinephrine infiltration. | Sustained Clinical Response: ‘Active |
4/40 seronegative enthesopathy-arthropathy syndrome | Post-injection: Not specified | Inflammation’(Joint effusion and heat and tenderness, with or without complete correction of deformity) | ||||
6/40 psoriatic arthritis | ||||||
Co-interventions: 100%- acetylsalicylic acid for at least 3 months; 30%- 1 NSAID; 22.5%- 2 NSAIDs; 20%- ≥ 3 NSAIDs; 3 patients previously on oral prednisone; 1 patient on hydroxychloroquine; 4 patients prior corticosteroid injection (other than TH); all patients maintained on the same NSAIDs post-injection. | ||||||
Beukelman et al., [26] | OBS | Definitive JIA diagnosis based on criteria. | 38/38 (55 STJ injections) | 1-30 weeks (median = 6 weeks) | TH in 13/38TA in 24/38 | Sustained Clinical Response: STJ Eversion/Inversion and pain and gait abnormalities |
Decreased foot inversion or eversion on physical examination | (Medication and dose not recorded in 1/39 injection) | |||||
Co-interventions: 14/38: MTX, 3/38: TNF-alpha inhibitor, 3/38: TNF-alpha inhibitor and MTX. | TA used when TH was commercially unavailable. | |||||
Post-injection: Non-weight bearing 24 hrs post-injection. Normal activity resumed afterwards. | ||||||
Cahill et al., [25] | OBS | Clinical signs of STJ inflammation | 38/38; 24/38 | 2-3 months | 0.5-1 ml, 20 mg/ml TH | Increased STJ |
Referral for image-guided IACI. | single STJ; 4/38 bilateral STJ; 3/38 subsequent contra-lateral STJ; 7/38 at least one repeated STJ. | (active disease) 6 months (without active disease) | Post-injection: Not specified. | inversion and eversion: Normal ROM, without pain and limping | ||
Co-interventions: Not specified. | ||||||
Earley et al., [33] | OBS | Pauci-articular onset JCA. | 23/23 (86 knees) | 3, 6 and 12 months | TH 20 mg for children weighing <20 kg (63 knees) OR for children >20 mg 40 mg (20 knees) | Sustained Clinical Response: Soft tissue swelling and joint effusion and degree of flexion contracture and degree of valgus deformity. |
Painful swollen knee with poor function. | ||||||
Not respondent to at least 3 months of conventional treatment. | ||||||
Post-injection: Not specified. | ||||||
Co-interventions: All patients were on at least one NSAID and physiotherapy and splinting, 3/23 on gold, 1/23 on prednisolone | ||||||
Eberhard et al., [34] | OBS | JRA diagnosis based on ACR criteria. | 85/85 (51/99 received TH and 48/99 received TA; 14 patients received both) | 2 weeks then every 3 months for a minimum for 15 months. | TH: 40 mg (knee), 30 mg (ankle). | Sustained Clinical Response: Non-bony swelling and (if no swelling) limitation ROM pain on motion or joint tenderness. |
Co-interventions: TH group: 33/51 NSAIDs; 16/51 MTX; 9/51 sulfasalzine; 3/51 prednisone + etanercept; 14/51 no medication. | ||||||
TA: 80 mg (knee), 60 mg (ankles) | ||||||
Post injection: Minimal activity for 24 hrs post-injection. | ||||||
TA group: 33/51 NSAIDs; 12/51 MTX; 2/51 sulfasalazine; 4/51 etanercept; 2/51 prednisone; 2/51 leflunomide; 15/51 no medication. | ||||||
Eich et al., [35] | OBS | JCA diagnosis based on EULAR criteria. | 15/15 (11 knees) | Clinical and US assessment: 1 week and 1 month MRI: 1 month | TH: 40 mg (knee) | Pain |
Post-injection: Not specified. | ||||||
Failure of systemic therapy and physiotherapy. | Swelling | |||||
Hyperthermia | ||||||
Local growth disturbances. | ||||||
Limited ROM | ||||||
Popliteal cyst in affected knee. | ||||||
Leg-length discrepancy | ||||||
With/without complete deformity correction. | ||||||
MRI: Joint effusion | ||||||
Co-interventions: Not specified. | ||||||
Popliteal cyst | ||||||
Destruction of articular cartilage and/or bone | ||||||
Destruction of menisci | ||||||
Marrow oedema | ||||||
Avascular necrosis | ||||||
US: Joint effusion and/or pannus | ||||||
Popliteal cyst | ||||||
Hertzberger-ten Cate et al., [36] | OBS | Type 1 pauciarticular JCA. | 21/21 (27 knees) | 6 months | TA: 20 mg in children weighing >20 kg with 1 ml lignocaine. | Sustained Clinical Response: swelling and synovial fluid and no increased temperature. |
Chronic arthritis in ≥1 knee. | ||||||
No response ≥6 months of conventional treatment. | ||||||
Flexion contracture, muscle wasting and/or growth disturbances. | ||||||
Co-interventions: 81% used splints at night and 1 hr during the day, 50% received physiotherapy, 77% received NSAIDs. | Post-injection: knee passively flexed and extended several times to distribute drug. No advice regarding activity levels. | |||||
Honkanen et al., [37] | OBS | JIA diagnosis. | 79/79 (79 knees) | 6-8 weeks | MA: in 45/79 (Mean dose 1.5 mg/kg) | Sustained Clinical Response: absence/presence of ‘symptoms’ |
With/without previous IACI. | ||||||
Co-interventions: 100% on NSAID agents and regular physiotherapy, 17/79 on hydroxychloroquine, sodium aurothiomalate or auranofin (slow-acting antirheumatics), 5/79 on alternate day glucocorticoid therapy. | TH: in 34/79 (mean dose 0.7 mg/kg) | |||||
Post-injection: Non- weight bearing for 24 hrs. | ||||||
Huppertz et al., [38] | OBS | Children with chronic arthritis, not responding to NSAIDs. | 21/21(18 knees, 2 ankles) | 7, 13 weeks | Knees: 1 mg/kg TH with 20 mg min dose and 60 mg maximum dose. | Joint Swelling |
Co-interventions: Not pre-specified. After 13 weeks, 10/21 had been treated with concomitant NSAIDs and 5/21 received chloroquine. | Effusion | |||||
Ankle: “a lower dose” | ||||||
Post injection: Not specified. | Joint limitation | |||||
Joint tenderness/pain | ||||||
Laurell et al., [24] | OBS | JIA diagnosis based on ILR criteria. | 30/30 (40 ankle regions) | 4 weeks | TA 40 mg/ml | Pain |
Post-injection: Not specified. | US: Synovial hypertrophy Synovial | |||||
Active disease. | ||||||
Co-interventions: 26 patients had ongoing systemic treatment: 58% with MTX | hyperaemia | |||||
23% with MTX and biologics (3 etanercept, 2 adalimumab, 1 abatacept), 19% with systemic corticosteroids | Joint ROM | |||||
Lepore et al., [39] | OBS | JIA patients. | 37/37 (87 injections of 37 knees) | 7-65 months (average of 31.3 months) | TH: 1 mg/kg (maximum 40 mg) | Sustained Clinical Response: ‘Clinical signs of inflammation’ |
Failure to respond to 2 months NSAIDs. | ||||||
Post-injection: Advised to keep child at home for first 24 hrs and to avoid physical exertion and carrying weights. | ||||||
Relapse after full remission period. | ||||||
Co-interventions: NSAID use was discontinued in all patients at time of local treatment | ||||||
Marti et al., [19] | OBS | JIA patients who received injections and follow up as in patients. | 60/60 (108 knees; 29 ankles, 5 STJ and 3 midfoot) | Knee: 1-69 months, Ankle: 1-39 months, STJ: 13 months, Midfoot: 0-3months. Digits: 18-66 months | TH: 40 mg (knee, shoulder and hips); 20 mg (wrist, elbow, ankle and STJ); 5 mg (finger and toes) | Sustained Clinical Response: Swelling and effusion and tenderness/pain |
Co-interventions: Non-steroidal anti-rheumatic drugs, MTX, Systemic corticosteroids, Salazopyrine | ||||||
TA: 80 mg (knee, shoulder and hips); 40 mg (wrist, elbow, ankle and STJ); 10 mg (finger and toes). | ||||||
Children with a body weight 20-40 kg received 75% of these doses. Children with body weight <20 kg received 50% of these doses. | ||||||
Post-injection: Advised to keep injected joint as quiet as possible for 24 hrs post-injection. | ||||||
Papadopoulou et al., [40] | OBS | Diagnosis JIA based on ILR criteria. | 220/220 (186 knees, 168 ankles, 67 STJ, 14 MTJ and 14 IPJ) | 6 months | TH: 1 mg/kg (maximum 40 mg) in knee & hips; 0.75 mg/kg (maximum 30 mg) in ankles. | Synovitis |
MA: 20-40 mg in STJ & intertarsal joints; 5-10 mg in smaller foot joints. | ||||||
Post-injection: Avoid activity or weight bearing for 24 hrs post-injection. | ||||||
Previous IACIs with minimum follow-up of 6 months. | ||||||
Co-interventions: 61.8% of patients received systemic medications including: MTX (56.8%), | ||||||
Biologic agents (9.5%), Systemic corticosteroids (11.4%) | ||||||
Ravelli et al., [41] | OBS | JIA diagnosis. | 94/94 (66/94- unilateral knee 28/94 bilateral knees) | 6 months | TH: 1 mg/kg (maximum 40 mg) with 0.5 ml lignocaine (2%). | Sustained Clinical Response: Synovitis |
Initial injection between Feb 1996 and June 1990. | ||||||
Co-interventions: 57% on NSAIDs, 24% on NSAIDs and “2nd line drugs” (no specification of second line drugs) | ||||||
Post-injection: Rest joints for 24 hrs | ||||||
Remedios et al., [42] | OBS | Children with JIA presenting as painful swollen ankles. | 11/11 (13 ankles) | >64 weeks | TH: 20 mg with 1 ml 0.5% bupivacaine. | Sustained Clinical Response: Synovitis (clinically assessed) |
Co-interventions: Not Specified | Post-injection: Not specified. | MRI: Pannus | ||||
Sherry et al., [43] | OBS | Pauciarticular JCA from ACR criteria. | 16/16 (15 knees and 6 ankles) | Mean follow-up University of Washington group: 42 months (SD +/- 11). | University of Washington Group: 20 mg TH within 2 months of diagnosis. | Leg Length Discrepancy (cm) |
<7 years at diagnosis. | ||||||
Reviewed at rheumatology centres at University of Washington or North Carolina (University of North Carolina/Duke University) | ||||||
North Carolina group: 46 months (SD +/- 15) | North Carolina Group: No IACI. | Thigh circumference discrepancy (cm) | ||||
Co-interventions: University of Washington Group: 25% on DMARD therapy, 44% with physical therapy evaluation, 31% with splints, 0% with shoe lifts North Carolina Group: 21% on DMARD therapy, 57% with physical therapy evaluation, 43% with splints, 50% with shoe lifts | Post-injection: Not specified. | |||||
Sornay-Soares et al., [44] | OBS | Children meeting the 1997 Durban criteria for JIA with knee involvement. | 8/8 (13 knees) | 6 months, 12 months | Joint lavage using 2 needles and 0.5-1.51 ml saline. Followed by one vial of TH, except in 2 knees (one patient) BM was used. | Sustained Clinical Response: Pain and joint effusion |
Co-interventions: 6/8 on NSAIDs, 5/8 on MTX, 1/8 on Azathioprine, 2/8 on Cyclosporine | ||||||
Post-injection: Knees were taped and advised to rest for 24 hrs, keeping in extension with walking crutches. Ice packs could be used for pain relief. | ||||||
Verma et al., [45] | OBS | Diagnosis of unresponsive oligoarticular/polyarticular JIA. | 13/13 (13 knees and 3 ankles) 3 patients were lost to follow-up at 6 months due to uncontrolled arthritis. | 6, 12 weeks. | TA (0.5-1 ml, 20-40 mg). | Mid-leg circumference (cm) |
Joint swelling/effusion, limitation of ROM, tenderness, pain, warmth. | 4 children were lost to follow-up at 12 months. | Post-injection: Reduced movement for 24 hrs. | ||||
12 weeks daily oral naproxen and/or weekly MTX. | ||||||
Co-interventions: All patients were on NSAIDs. | ||||||
Zulian et al., [46] | OBS | Diagnosis persistent or extended oligoarticular JIA | 85/85 (115 knees and 15 ankles) | 1, 3, 6, 9, 12, 18 and 24 months | TH: 42 patients treated; 1 mg/kg (>40 mg) | Sustained Clinical Response: Swelling and limited ROM and pain and warmth. |
Patients managed at University of Padua paediatric rheumatology unit | TA:43 patients treated; 1 mg/kg (>40 mg) (Availability issues of TH meant TA was used as an alternative in some cases). | |||||
Received IACIs from Jan 1996 and Dec 2000. | ||||||
Unsatisfactory response to NSAIDs. | ||||||
Persistent isolated joint involvement. | Post-injection: Non-weight bearing for | |||||
Co-interventions: TH: 64.3% on NSAIDs, 11.4% on MTX | at last 72 hrs post-injection. | |||||
TA:51.7% on NSAIDs, 5% on MTX |