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Table 3 Consensus statements regarding the diagnosis and management of SJIA

From: Practice and consensus-based strategies in diagnosing and managing systemic juvenile idiopathic arthritis in Germany

Statements

Consensus

Levels of evidence and grades of recommendationa

Statement 1 Strategies of the PRO-KIND SJIA project group apply to the following patients with new-onset disease:

 (A) Patients with systemic juvenile idiopathic arthritis according to ILAR categorization

100%

1a, A

 (B) Patients with suspected SJIA who do not fulfill the ILAR criterion of arthritis

100%

4, D

Statement 2

 (A) The demonstration of systemic inflammation, i.e. usually elevated C-reactive protein, erythrocyte sedimentation rate, leukocytes and/or ferritin) is essential for diagnosing SJIA at disease onset

100%

1b, A

 (B) Measurement of specific autoantibodies may be useful in order to rule out other conditions.

100%

5, D

 (C) Measurement of phagocyte-specific S100 proteins may be helpful to differentiate between SJIA and other diseases associated with fever. There is insufficient data in regards to interleukin-18 and procalcitonin for the diagnosis of SJIA.

100%

2b-4, C

Statement 3

 (A) Malignancies are important differential diagnoses for SJIA. If suspected, an extended panel of diagnostic tests, including chest radiography, ultrasound of the abdomen and lymph nodes, bone marrow aspiration, and, if appropriate, biopsy of lymph nodes or other involved organs should be pursued. The indication for bone marrow aspiration should be reviewed critically prior to initiating a glucocorticoid therapy. An elevated LDH, uric acid and cytopenias represent pertinent findings.

100%

5, D

 (B) Infections are important differential diagnoses for SJIA. An adapted search for infections should be pursued (see guideline “Fever of unknown origin”).

100%

5, D

 (C) Hereditary autoinflammatory syndromes are important differential diagnoses for SJIA. Molecular genetic testing should be pursued if clinical suspicion for a known hereditary autoinflammatory syndrome exists.

91.7%b

5, D

 (D) There are no data from controlled studies regarding the utility of imaging studies in the diagnosis of SJIA. However, sonography and MRI are important modalities to assess joint and organ manifestations, to differentiate from other conditions and to monitor disease activity.

100%

5, D

 (E) Generally, in case of insufficient response to antirheumatic therapies, especially glucocorticoids, interleukin-1 or interleukin-6 blockade, the diagnosis of SJIA has to be critically reconsidered.

100%

5, D

Statement 4

 (A) The overall treatment target is achieving a clinically inactive disease, ideally without glucocorticoids, and, eventually, clinical remission. Clinically inactive disease is aimed for within six to twelve months.

100%

2A

 (B) The following interim targets are aimed for:

  a. Resolution of fever within one week of the start of treatment

  b. Improvement of CRP by at least 50% within one week of the start of treatment

  c. Marked improvement of overall disease activity within four weeks of the start of treatment, i.e. improvement of the physician global disease activity by at least 50%, reduction of actively inflamed joints (if present) by at least 50% and/or a JADAS10-Score of maximally 5.4

100%

2A

Statement 5

 (A) NSAIDs and DMARDS: Optionally, NSAIDs may be used for treating SJIA even though no data from randomized placebo-controlled clinical trials are available. The only approved DMARD for treating SJIA is methotrexate.

92%

4B

 (B) Biologics: Positive data from clinical trials are available for IL-1 blockade (anakinra and canakinumab), IL-6 blockade (tocilizumab) and, in a limited fashion, TNF-alpha blockade (etanercept).

90%

1A

 (C) Glucocorticoids: High-dose systemic glucocorticoids are an effective and proven treatment for SJIA.

100%

1A

 (D) Intraarticular glucocorticoids may be used for treating arthritis in patients with SJIA.

91%

4C

Statement 6

 (A) Initial treatment: In patients with probable SJIA, high-dose systemic glucocorticoids may be used, either as i.v. pulse therapy and/or as daily glucocorticoids with subsequent dose reduction. Alternatively, anakinra may be used, even as a monotherapy without glucocorticoids. The use of canakinumab or tocilizumab is currently discussed.

100%

2A

 (B) In case of inadequate response (interim targets not reached), i.v. pulse glucocorticoid therapy may be repeated, or an increased dose of anakinra may be considered. In case of initial exclusive glucocorticoid therapy, IL-1 blockade or IL-6 blockade may be introduced. In case of initial anakinra monotherapy, additional treatment with glucocorticoids or changing to another biologic may be considered.

100%

1A/2A

 (C) In case of persistent or recurrent signs of systemic disease activity, biologics (IL-1 blockade or IL-6 blockade) may be introduced (especially in case of previous exclusive glucocorticoid therapy or a glucocorticoid-dependent disease course). If biologics were already introduced, a dose increase or a change of the biologic can be considered.

100%

1A/2A

 (D) If arthritis should develop in patients with probably SJIA, the respective treatment strategy for patients with definitive SJIA is used.

100%

4B

Statement 7

 (A) In the case of SJIA with arthritis, high-dose systemic glucocorticoids may be used, either as i.v. pulse therapy and/or as daily glucocorticoids with subsequent dose reduction. Optionally, NSAIDs, methotrexate and intraarticular glucocorticoids may be employed.

100%

2A

 (B) Alternatively, IL-1 or IL-6 blockade may be applied, possibly in combination with glucocorticoids and/or methotrexate.

100%

1A

 (C) In case of insufficient treatment response (see treatment targets), i.v. glucocorticoid pulse therapy may be repeated, or IL-1 or IL-6 blocking agents may be increased in dose (if feasible). In case of initial glucocorticoid therapy, IL-1 or IL- blockade may be initiated. In case of initial biological monotherapy, glucocorticoids may be added (systemically or locally), the biological agent may be changed, or methotrexate may be added.

100%

1A

 (D) In case of a predominant polyarticular arthritis and in case of lack of treatment response despite the utilization of the approved biological agents, second-line agents, e.g. TNF blockers (etanercept or adalimumab) or abatacept may be applied. In addition, the use of methotrexate is reasonable and intraarticular glucocorticoids may be applied.

100%

2B

 (E) If MAS should develop in the context of SJIA, the corresponding treatment strategies are used.

100%

4C

  1. CRP C-reactive protein, DMARD Disease-modifying antirheumatic drug, IL Interleukin, ILAR International league of associations for rheumatology, MAS Macrophage activation syndrome, NSAIDs Non-steroidal anti-inflammatory drugs, SJIA Systemic juvenile idiopathic arthritis
  2. aaccording to the Oxford Centre for Evidence-based Medicine
  3. bconsensus was determined in a post-consensus meeting survey among 22 experts