A Case of Macrophage Activation Syndrome Developing in a Patient With Chronic Granulomatous Disease-associated Colitis

Abstract

Although macrophage activation syndrome (MAS) develops in some patients with chronic granulomatous disease (CGD), all of the reported cases have been associated with pathogenic microbial infections. We report a 2-year-old boy with CGD-associated colitis who suffered from MAS without any clinical signs of a microbial infection. He was treated with 1 course of methylprednisolone pulse therapy and the clinical symptoms improved; however, the colitis was difficult to control even with immunosuppressive drugs, and he eventually required hematopoietic stem cell transplantation 1 year after the onset of MAS. It is likely that MAS develops in patients with CGD colitis independent of microbial infections.

Chronic granulomatous disease: Clinical, molecular, and therapeutic aspects

“…In most of the younger CGD patients reported (<4 years), macrophage activation developed at or before the diagnosis of CGD. In the majority of cases, the macrophage activation was associated with severe infectious events and in one child suffering from CGD-associated colitis with no clinical signs of bacterial infections (64,65). Treatment includes a wide range of MAS-directed treatment regimens, including corticosteroids alone or in combination with IVIG or cyclosporine, and generally, contrary to the familial form, MAS in CGD patients showed a good clinical outcome (64,66).…”

NADPH oxidase controls neutrophilic response to sterile inflammation in mice by regulating the IL-1α/G-CSF axis

“…A distinctive component of CGD is its association with inflammatory conditions, often unrelated to infection, including granulomatous inflammation in the gastrointestinal and genitourinary tracts, discoid lupus-like lesions, and macrophage activation syndrome. [2][3][4][5][6] Moreover, NADPH oxidase gene variants are linked to lupus, rheumatoid arthritis, and inflammatory bowel disease. [7][8][9][10] However, insights into the role of NADPH oxidase in regulating inflammatory responses to sterile endogenous ligands are lacking, an important question given the association of NADPH oxidase deficiency with noninfectious inflammatory disorders.…”

Macrophage activation syndrome or septic arthritis

“…Organisms implicated include Haemophilus influenzae and Streptococci spp. [7,8]. Another common problem during childhood is osteomyelitis, which often presents in the same manner as septic arthritis, with the inability to weight-bear and a swollen joint.…”

“…A variety of other conditions have been described in the literature to be associated with macrophage activation syndrome, including juvenile rheumatoid arthritis, chronic granulomatous colitis [7], Still's disease [13], and SLE [9,10].…”

“…Macrophage activation syndrome is a potentially lifethreatening complication of several paediatric rheumatological conditions, most commonly including systemic juvenile idiopathic arthritis (sJIA), but also systemic lupus erythmatosus (SLE) and granulomatous disease [6][7][8][9][10]. The incidence of JIA in the UK is 1/10 000, of which the literature suggest that 10-20% of cases show systemic onset (sJIA), which is recognized to be associated with worse morbidity, functional outcomes and overall prognosis.…”