Complications of complications: diagnosis and treatment of recurrent macrophage activation syndrome in a patient with well-controlled systemic juvenile idiopathic arthritis

Abstract

Macrophage activation syndrome (MAS) is a subtype of haemophagocytic lymphohistiocytosis (HLH), and a well-described complication of systemic juvenile idiopathic arthritis (SJIA), triggered by disease onset or flare, infection, or some medications. Here, we report a 20-year-old man with previously well-controlled SJIA, who developed first time MAS after acute Epstein-Barr virus (EBV) infection, with MAS recurrence due to a drug reaction, ‘3-week sulfasalazine syndrome’, secondary to prophylactic trimethoprim/sulfamethoxazole. Both episodes of MAS were minimally responsive to pulse corticosteroids. Initial EBV-driven MAS was treated with multiple doses of emapalumab prior to resolution, while MAS secondary to sulfasalazine-induced 3-week syndrome required the initiation of ruxolitinib. This case exhibits two rare but life-threatening causes of MAS/secondary HLH in a single patient and the difficulties in their diagnosis and management.

Juvenile idiopathic arthritis: a limiting disease

“…Hay pruebas de que los glucocorticoides interfieren con la producción o la acción de la hormona del crecimiento y sus mediadores a diferentes niveles del eje I del factor de crecimiento similar a la insulina-GH. (11) La inflamación se caracteriza por la activación de diferentes células inmunitarias con la producción de citoquinas, quimioquinas, interleucinas (ILs) e interferones (IFN), activando la reabsorción ósea e inhibiendo la formación ósea a nivel sistémico y local. La GH y los IGF son los reguladores más importantes del crecimiento lineal.…”

“…La prevalencia de talla baja varía desde el 10,4 % en niños con enfermedad poliarticular hasta el 41 % de los pacientes con la forma sistémica. (10,11) La oligoartritis se asocia principalmente con un crecimiento óseo excesivo localizado en la extremidad afectada, con fusión prematura de las epífisis que conduce a un acortamiento de la extremidad en el niño; el tratamiento precoz con glucocorticoides intraarticulares (GC) ayuda a prevenir la aparición de disimetrías en las extremidades. (12) Los datos del Estudio Prospectivo de Artritis Infantil (CAPS) mostraron que una cohorte de niños con AIJ experimentó una restricción del crecimiento durante los primeros 3 años de la enfermedad.…”

Immunopathology of and potential therapeutics for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome: a translational perspective

“…EBV, the most common pathogen triggering sHLH/MAS, typically infects B cells via CD21 and replicates within these cells; it can also infect NK and T cells. Acute EBV infection causes fulminant life-threatening sHLH/MAS, and persistent infection can result in transformation into malignancy 61 , 62 . Owing to the proliferation of EBV-activated CTLs, acute EBV-sHLH/MAS evokes fever, hepatosplenomegaly, lymphadenopathy, atypical lymphocytosis, and pharyngitis, a constellation of symptoms clinically defined as infectious mononucleosis 63 .…”

JAK Inhibition in Juvenile Idiopathic Arthritis (JIA): Better Understanding of a Promising Therapy for Refractory Cases

“…Moreover, pharmacokinetics differs in young patients and may need specific future studies. Several case reports and case series paved the way for randomised trials on pJIA and SoJIA, with JAKis used in off-label indications [31][32][33][34][35][36][37][38][39][40][41]. To date, 45 patients have been reported to be at least partially efficiently treated with tofacitinib, 4 pJIA patients with baricitinib and 1 sJIA patient with ruxolitinib (Table A1) [31][32][33][34][35][36][37][38][39][40][41].…”

“…Several case reports and case series paved the way for randomised trials on pJIA and SoJIA, with JAKis used in off-label indications [31][32][33][34][35][36][37][38][39][40][41]. To date, 45 patients have been reported to be at least partially efficiently treated with tofacitinib, 4 pJIA patients with baricitinib and 1 sJIA patient with ruxolitinib (Table A1) [31][32][33][34][35][36][37][38][39][40][41]. Among them, two patients with JIA were efficiently treated during adulthood, respectively, with tofacitinib for microscopic colitis (and arthritis) and with ruxolitinib for EBV-related MAS in previously controlled sJIA [37,41].…”