Systemic juvenile idiopathic arthritis and macrophage activation syndrome: SAQ

This girl has the classic presentation of systemic JIA and the subsequent development of the macrophage activation syndrome under the tocilizumab, which is the scenario that tests the candidate on the ILAR criteria, the 2016 MAS classification, the interleukin-one and interleukin-six pathway, and the management of the paradoxical MAS. [1]

Question 1 (10 marks)

Outline the ILAR classification criteria for the systemic subtype of juvenile idiopathic arthritis, and then describe the 2016 EULAR ACR PRINTO classification criteria for macrophage activation syndrome complicating systemic JIA, applying them to this girl's presentation. [1]

A full-mark answer reproduces the ILAR criteria, the 2016 MAS criteria and their application. [2]

The ILAR criteria for systemic JIA (4 marks). The child must have arthritis in one or more joints, with or preceded by a quotidian fever for at least two weeks documented for at least three days of each week, plus at least one of four extra-articular features: an evanescent non-fixed erythematous rash, a generalised lymphadenopathy, a hepatomegaly or splenomegaly, and a serositis. The onset must be before sixteen years and the duration at least six weeks. The exclusions include a personal or a first-degree family history of psoriasis or HLA-B27, and a first-degree family history of systemic JIA. [2]

The 2016 MAS criteria (4 marks). A febrile patient with known or suspected sJIA is classified as having MAS if the ferritin is over six hundred and eighty-four nanograms per millilitre and any two or more of the following are present: a platelet count under one hundred and eighty-one times ten to the nine per litre, an AST over forty-eight units per litre, triglycerides over one hundred and fifty-six milligrams per decilitre, and a fibrinogen under three hundred and sixty milligrams per decilitre. These criteria have a sensitivity of around seventy-three percent and a specificity of around ninety-nine percent. [1]

Application to this girl (2 marks). This girl meets the ILAR criteria with her quotidian fever, her evanescent rash and her arthritis. She meets the 2016 MAS criteria with her ferritin at four thousand two hundred and her platelets at one hundred and sixty under the one hundred and eighty-one threshold, which gives the ferritin criterion plus at least one additional criterion. The full picture with the AST, the triglycerides and the fibrinogen would be needed to confirm the two additional criteria, but the clinical picture is strongly suggestive of the MAS. [1]

Question 2 (10 marks)

Discuss the stepwise management of the macrophage activation syndrome in this child, including the specific consideration of the paradoxical MAS under the tocilizumab and the escalation pathway for the refractory case. [10]

A full-mark answer reproduces the resuscitation, the first-line therapy, the paradoxical MAS mechanism and the escalation pathway. [3]

Resuscitation and the first-line therapy (4 marks). The child is transferred to the paediatric intensive care unit early. The first-line therapy bundle includes the intravenous methylprednisolone pulse at ten to thirty milligrams per kilogram per day for three to five days, the ciclosporin at two to seven milligrams per kilogram per day, and the anakinra at two to four milligrams per kilogram per day subcutaneously. The broad-spectrum antibiotics are given empirically for the presumed sepsis until the cultures are negative. [10]

The paradoxical MAS under the tocilizumab (3 marks). The interleukin-six blockade with the tocilizumab suppresses the CRP and the fever, which are the usual warning signs of the MAS, so the syndrome develops silently. The mechanism is that the tocilizumab blocks the interleukin-six but not the interferon-gamma, so the underlying interferon-gamma storm continues beneath the masked exterior. The management is to reduce or to stop the tocilizumab and to add the anakinra and the glucocorticoid. This is the paradoxical MAS under the interleukin-six blockade, and it is the reason the ferritin and the platelet trend must be monitored regularly for the child on the tocilizumab. [5][10]

The refractory escalation (3 marks). If the MAS does not respond to the glucocorticoids, the ciclosporin and the anakinra, the anakinra is escalated to four to eight milligrams per kilogram per day, and the etoposide at one hundred and fifty milligrams per square metre on the HLH-2004 protocol and or the emapalumab, the monoclonal antibody against the interferon-gamma, are considered. The haematopoietic stem cell transplantation is reserved for the refractory case with the sJIA lung disease. [3][10]