Systemic corticosteroids are frequently used in the treatment of systemic JIA [26]. However, new, effective, and safe biologic agents have been introduced to the treatment of systemic JIA in the past few years, and hopefully will change the short- and long-term course of the disease. The IL-1-blocking agents anakinra [7] and canakinumab [6] and the IL-6R antagonist tocilizumab [5] have added a completely new paradigm in the treatment of systemic JIA.

The indications for systemic corticosteroids in systemic JIA have traditionally been serositis (pleuritis, peritonitis, or pericarditis), myocarditis or evidence of MAS, in which high doses [prednisone 1–2 mg/kg per day or pulse intravenous methylprednisolone (30 mg/kg per day) for 3 days] are needed for rapid control of systemic features [27–32]. After pulse steroids, daily prednisone at 2 mg/kg per day may be initiated with gradual tapering once inactive disease is achieved. In 1996 Picco et al. published their experience with corticosteroid “minipulses” [14]. The authors used methylprednisolone 5 mg/kg per day for 3 days with an additional course of methylprednisolone 2.5 mg/kg per day for 3 days, followed by prednisone 1 mg/kg daily in 12 patients with systemic JIA. Patients had a remarkable improvement in articular, systemic, and hematologic features as compared with ten patients who received prednisone 1 mg/kg per day. Patients receiving pulse steroids may exhibit side effects (such as behavioral changes, headaches, hypertension, tachycardia, and abdominal pain) [15, 30] but they require a lower cumulative daily dosage than conventional oral corticosteroid treatment. In the 1990s, aggressive combined therapy including cyclophosphamide, methotrexate (MTX), and pulse therapy with methylprednisolone was advocated for systemic arthritis [31, 32]. With the advent of biological agents in the beginning of the following decade, these approaches were abandoned or restricted to exceptionally refractory cases. On the other hand, low-dose systemic corticosteroid therapy may be useful for minor disease features, such as anemia of inflammatory disease, persistent activity despite the use of nonsteroidal anti-inflammatory drugs (NSAIDs), and bridging to biological therapy. These indications are relative and are usually tailored for each individual by the treating physician.

Owing to the high variability in therapeutic approaches and corticosteroid usage among different groups, several efforts have been made to standardize corticosteroid therapy in systemic JIA. Recently, a group of experts defined the management of background corticosteroid therapy in clinical trials in systemic JIA that could be adopted for clinical ordinary practice [33]. These investigators identified criteria for initiating or increasing corticosteroids such as presence or development of anemia (with hemoglobin <6.5 g/dl), symptomatic myocarditis, pericarditis, pleuritis, peritonitis, pneumonitis, and either complete or incomplete MAS. The presence of fever, rash, severe fatigue, anorexia, weight loss, increasing synovitis, and low albumin did not represent criteria for initiating or increasing corticosteroids. For MAS, pericarditis, and myocarditis, they defined a corticosteroid therapy approach comprising high-dose intravenous methylprednisolone pulse (30 mg/kg/day for 1–3 days) followed by daily standard-dose corticosteroids. The rate of taper of corticosteroid dosing was defined as 10 % of the current daily dose every 2 weeks.

Another consensus meeting generated a treatment approach that offered among four treatment plans (corticosteroids alone, MTX, anakinra, or tocilizumab) a choice of either high-dose (2 mg/kg/daily) or low-dose (0.5 mg/kg/daily) oral prednisone, with methylprednisolone pulses and/or intra-articular injections as needed for patients with systemic JIA [25]. According to this consensus, the goal was to discontinue glucocorticoids by 6 months, with three defined tapering schedules (rapid, fast, and slow) to proceed as tolerated. One suggested treatment plan included corticosteroids only [prednisone 1 mg/kg per day (maximum 60 mg), with optional use of methylprednisolone pulse (30 mg/kg, max. 1 g for 3 days)]. According to the clinical status of the patient at 1–2 weeks, at 1 month and at 3 months the corticosteroid dosing could be tapered, increased to 2 mg/kg (maximum 100 mg) daily, or kept with no changes. In case of improvement, the consensus agreed that corticosteroid dosage should be tapered and total treatment with corticosteroids should not last more than 6 months. Prednisone was also included as an optional therapy in the MTX, anti-IL-1, and anti-IL-6 plans.

The American College of Rheumatology (ACR) elaborated and recently revised the recommendations for the treatment of JIA [34, 35]. In the original recommendations [34], two categories were considered for systemic JIA: patients with systemic features and patients with active arthritis. Introduction of systemic corticosteroids was recommended after the unsuccessful use of NSAIDs for 2 weeks, or earlier for patients with persistent fever or higher disease activity (MD global ≥7). The 2013 revision of these guidelines provided an expanded recommendation on the use of corticosteroids and other agents in the treatment of systemic JIA [35]. For patients with active systemic features and varying degrees of synovitis, systemic corticosteroid monotherapy (either oral or intravenous) was recommended for a maximum period of 2 weeks, with an evidence level 3. Continuing corticosteroids as monotherapy for more than 1 month for patients with continued disease activity was considered inappropriate (level 4). For this same group of patients, anakinra was recommended as an initial therapeutic option. For systemic JIA without active systemic features and active synovitis, corticosteroids were recommended only as intra-articular therapy at any time. However, the utility of repeating intra-articular injection as the only intervention was considered uncertain. Since the efficacy of intra-articular corticosteroid therapy in systemic JIA is usually shorter than the one observed in other forms of JIA [36–40], this approach should probably be limited to special situations (quick relief of pain or dysfunction) [41]. Additional recommendations were made for patients with systemic JIA and features suggestive of MAS. These recommendations are described in the next sections.

A summary of the different studies on the use of systemic corticosteroids in systemic JIA is given in Table 2.

Systemic corticosteroids are not the mainstay of therapy in polyarticular JIA (rheumatoid factor-positive or -negative). However, systemic corticosteroids are frequently used as bridging therapy in low doses (0.1–0.2 mg/kg per day) and short periods to help ameliorate the inflammatory features until the background medications (MTX or biologics) are effective. This strategy is useful for reaching an earlier resolution of synovitis as well as improvement in functional capacity and quality of life [29].

An “aggressive” approach to the initial therapy of polyarticular JIA was recently published by Wallace et al. [42]. It included prednisolone, MTX, and etanercept as the components of a combined therapeutic set of drugs. Prednisolone was given at 0.5 mg/kg/day (maximum 60 mg) tapered to 0 by 17 weeks. This 6-month trial conducted with 85 children could not show any statistically significant advantage of the combined therapy over MTX monotherapy in achieving clinically inactive disease at 6 months (primary endpoint) or clinical remission at 12 months (secondary endpoint). However, the proportion of responders was higher in the combined-therapy arm.

Finally, single or multiple articular corticosteroid injections may be useful for controlling joint inflammation, inducing disease remission, or as a bridge procedure until systemic immunomodulatory therapy (MTX or biologics) becomes effective [37, 38, 43, 44]. Alternatively, intra-articular corticosteroid therapy may be used to treat arthritis flares in children already receiving such agents [45].

Oligoarthritis is the JIA category where intra-articular steroids are the mainstay of treatment. In patients with oligoarticular JIA refractory to NSAIDs, intra-articular corticosteroid therapy is the treatment of choice. However, some pediatric rheumatologists actually use the intra-articular therapy at disease onset to reduce disability and avoid systemic treatment [39, 45]. Intra-articular corticosteroids have been used particularly in children with arthritis that proves refractory to NSAIDs, but they may be used early in the disease to resolve synovitis and to facilitate physiotherapy, the prevention of leg-length discrepancy, and a quicker correction of joints contractures [46, 47].

However, some of these patients will eventually need concomitant MTX therapy if remission is not achieved [45]. Four randomized controlled trials comparing different types of steroids showed the higher beneficial effect of triamcinolone hexacetonide over other agents (such as triamcinolone acetonide, methylprednisolone acetate, or betamethasone) [43, 44, 48, 49]. Other observational retrospective studies reported the effectiveness of intra-articular triamcinolone both as hexacetonide or acetonide in patients with oligoarthritis [37, 38, 49, 50].

The only indication for systemic corticosteroid therapy in this group is refractory JIA-related uveitis (see section “Corticosteroids in JIA-related uveitis”).

For patients with psoriatic arthritis refractory to NSAIDs, intra-articular corticosteroid therapy may be beneficial [38, 39]. The only indication for systemic corticosteroid therapy in this group is refractory JIA-related uveitis (see section “Corticosteroids in JIA-related uveitis”).

Patients with ERA are usually treated with NSAIDs and biologics. Additionally, some patients may benefit from intra-articular corticosteroid therapy [38, 39, 51]. Subtalar arthritis, a common inflammation site in ERA, may also be responsive to such treatment [52]. The only indication for systemic corticosteroid therapy in this group is refractory JIA-related uveitis. However, there are some reports in the literature of the successful use of pulse steroid therapy in patients with juvenile spondyloarthropathy [53].