Effect of Biologic Therapy on Clinical and Laboratory Features of Macrophage Activation Syndrome Associated With Systemic Juvenile Idiopathic Arthritis

Schulert, Grant S.; Minoia, Francesca; Bohnsack, John F.; Cron, Randy Q.; Hashad, Soah; Koné‐Paut, Isabelle; Kostik, Mikhail M.; Lovell, Daniel J.; Maritsi, Despoina; Nigrović, Peter A.; Pal, Priyankar; Ravelli, Angelo; Shimizu, Masaki; Staņēvicha, Valda; Vastert, Sebastiaan J.; Woerner, Andreas; Benedetti, Fabrizio; Grom, Alexei A.

doi:10.1002/acr.23277

Cited by 114 publications

(88 citation statements)

References 49 publications

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“…This may be explained by the pathophysiology in MAS, which is related to the production of many cytokines. Inhibition of IL-1 or IL-6 might not be able to prevent MAS because other cytokines, for instance, IL-18, might play a major role in developing MAS 57. A summary of the MAS treatment is shown in Table 2.…”

Section: Managementmentioning

confidence: 99%

Macrophage activation syndrome: early diagnosis is key

Lerkvaleekul¹,

Vilaiyuk²

2018

OARRR

114

103

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Macrophage activation syndrome (MAS) is a life-threatening condition, and it is a subset of hemophagocytic lymphohistiocytosis (HLH). The clinical features include a persistent high-grade fever, hepatosplenomegaly, lymphadenopathy, hemorrhagic manifestations, and a sepsis-like condition. From the clinical features, it is usually difficult to differentiate between a true sepsis, disease flare-ups, or MAS. Although the laboratory abnormalities are similar to those of a disseminated intravascular coagulation, which shows pancytopenia, coagulopathy, hypofibrinogenemia, and an elevated d-dimer test, it can also be a late stage of MAS. Currently, MAS is still underrecognized and usually results in delayed in diagnosis, which leads to high morbidity and mortality. This literature review was conducted in the context of the clinical manifestations and the laboratory abnormalities in MAS, which might provide some clues for an early diagnosis. The best ways for an early recognition and a satisfactory diagnosis were based on the relative changes in the overall parameters from the baseline, together with a thorough and continuous physical examination for these kinds of patients. At present, diagnostic criteria have been proposed for HLH, MAS-associated systemic juvenile idiopathic arthritis, and an MAS-associated systemic lupus erythematosus. Therefore, selecting the proper diagnostic criteria for use is essential because not all of the criteria are suitable for every autoimmune disease.

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Section: Managementmentioning

confidence: 99%

Macrophage activation syndrome: early diagnosis is key

Lerkvaleekul¹,

Vilaiyuk²

2018

OARRR

114

103

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“…Several criteria have been developed for children, but these still need validation in adult patients (see Statement 3). 42,[106][107][108][109] Notably, symptoms of MAS-HLH may be different in patients treated with biologic agents 110.…”

mentioning

confidence: 99%

Recommendations for the management of hemophagocytic lymphohistiocytosis in adults

Rosée

Horne

Hines

et al. 2019

Blood

690

713

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Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome induced by aberrantly activated macrophages and cytotoxic T cells. The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity and immune regulation, is most common in children, whereas the secondary (acquired) form is most frequent in adults. Secondary HLH is commonly triggered by infections or malignancies but may also be induced by autoinflammatory/autoimmune disorders, in which case it is called macrophage activation syndrome (MAS; or MAS-HLH). Most information on the diagnosis and treatment of HLH comes from the pediatric literature. Although helpful in some adult cases, this raises several challenges. For example, the HLH-2004 diagnostic criteria developed for children are commonly applied but are not validated for adults. Another challenge in HLH diagnosis is that patients may present with a phenotype indistinguishable from sepsis or multiple organ dysfunction syndrome. Treatment algorithms targeting hyperinflammation are frequently based on pediatric protocols, such as HLH-94 and HLH-2004, which may result in overtreatment and unnecessary toxicity in adults. Therefore, dose reductions, individualized tailoring of treatment duration, and an age-dependent modified diagnostic approach are to be considered. Here, we present expert opinions derived from an interdisciplinary working group on adult HLH, sponsored by the Histiocyte Society, to facilitate knowledge transfer between physicians caring for pediatric and adult patients with HLH, with the aim to improve the outcome for adult patients affected by HLH.

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“…Soluble IL-2 receptor and soluble CD163 are also elevated in active MAS [7]. The low CRP of the patient at admission in the setting of a MAS was attributed to the recent Tocilizumab administration [8], rise in CRP being IL6 mediated.…”

Section: Discussionmentioning

confidence: 96%

Experience with Cidofovir as an adjunctive therapy in a patient of adenovirus-induced macrophage activation syndrome in systemic arthritis

et al. 2020

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A 5-year-old female child, with known systemic juvenile idiopathic arthritis diagnosed at 18 months of age (on low dose Prednisolone + Methotrexate + Leflunomide + Tocilizumab), presented with fever for 1 day, vomiting, drowsiness followed by seizures. On admission to PICU, she was drowsy, tachycardic, tachypneic, with rashes, and hepatosplenomegaly. Lab findings showed thrombocytopenia, leucopenia, low ESR, normal CRP, elevated liver enzymes, high ferritin, LDH, and triglycerides suggestive of macrophage activation syndrome (MAS). Chest X-ray showed left basal pneumonia and DNA PCR of throat swab revealed adenovirus. She was diagnosed as adenovirus-triggered MAS and was initiated on pulse methylprednisolone (6 mg/kg). Because of suboptimal response after 2 doses, manifested by increasing drowsiness, further fall in platelets and rising ferritin, methylprednisolone dosage was increased to 30 mg/kg/day with the addition of oral cyclosporine (4 mg/kg/day). In view of worsening of the chest X-ray and increasing oxygen requirement, Cidofovir infusion (1 mg/kg thrice weekly) was also started simultaneously considering increased activity of the adenoviral infection concurrent to immunosuppression. Within 48 h, the child showed signs of recovery with improved consciousness, lower oxygen requirements, and improving lab parameters. She was discharged after 3 weeks of IV Cidofovir, on oral prednisolone and cyclosporine. To the best of our knowledge, this is the first reported use of Cidofovir in adenovirus-induced MAS.

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Effect of Biologic Therapy on Clinical and Laboratory Features of Macrophage Activation Syndrome Associated With Systemic Juvenile Idiopathic Arthritis

Abstract: These findings show substantial alterations in MAS features that may limit utility of defined criteria for diagnosis of systemic JIA patients treated with biologic agents.

Cited by 114 publications

References 49 publications

Macrophage activation syndrome: early diagnosis is key

Macrophage activation syndrome: early diagnosis is key

Recommendations for the management of hemophagocytic lymphohistiocytosis in adults

Experience with Cidofovir as an adjunctive therapy in a patient of adenovirus-induced macrophage activation syndrome in systemic arthritis

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