330
Review article
Macrophage activation syndrome or septic arthritis: a case of mistaken identity Gemma L. Greena, Arash Aframiana, Parthiban Vinayakamb and Mark S. Cornellb We present an interesting case of macrophage activation syndrome in a 2-year-old, with no previous rheumatological diagnoses, incorrectly diagnosed with septic arthritis, to highlight the diagnostic difficulties, especially in small hospital units. We aim to present the similarities between the two conditions and to summarize the clinical, radiological and epidemiological features of macrophage activation syndrome, an underdiagnosed condition. A review of the current literature was performed, and a diagnostic algorithm was created. No current set treatment regimen exists, but current recommendations have been included. We have demonstrated the pitfalls in diagnosis and the
Introduction Septic arthritis is a common and devastating orthopaedic problem in paediatric patients [1,2], requiring prompt diagnosis, decompression, washout and appropriate antibiotic therapy [3]. Macrophage activation syndrome (MAS) is a rheumatological emergency, requiring rapid immune system modulating therapy [4,5]. This report highlights an interesting case of macrophage activation syndrome presenting as septic arthritis in a 2-yearold girl.
Background 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 [6–10]. 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. Macrophage activation syndrome is reported to occur in around 6% of sJIA cases, with no sex preference or age preference. It can occur at any disease stage, but there is usually active disease present at the time of diagnosis [11]. Macrophage activation syndrome is regarded by rheumatologists as a form of secondary haemophagocytic lymphohistiocytosis, and it has a number of ‘trigger’ factors including infections (bacterial – Enterococcus spp.; viral – Epstein Barr, Varicella spp., Coxsackie, Parvovirus spp. and hepatitis A), drugs (aspirin, non-steroidal anti-inflammatory drugs, methotrexate, etanercept) and stem cell transplantation [12,13].
importance of immediate treatment in optimizing prognosis. J Pediatr Orthop B 24:330–335 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Journal of Pediatric Orthopaedics B 2015, 24:330–335 Keywords: arthritis, infectious, juvenile, macrophage activation syndrome, pathology, therapeutics a St Georges Hospital, Tooting, London and bQueen Elizabeth the Queen Mother Hospital, Margate, Kent, UK
Correspondence to Gemma L. Green, MBChB, BSc, St Georges Hospital, Blackshaw Road, Tooting, London SW17 0QT, UK Tel: + 44 07917509028; e-mail: [email protected]
The pathophysiology of macrophage activation syndrome has not fully been understood, but it is recognized to involve uncontrolled proliferation of T cells and macrophages, which has been shown to reduce natural killer (NK) cell function. There is thought to be a genetic component, with mutations in the genes encoding for the protein perforin. This protein is used for the induction of apoptosis by cytolytic cells in virus or tumour cells. Other genes have been identified in the pathogenesis, including MUNC 13-4, which is involved in the transport of perforin; reduced transport of perforin to cells causes reduced cytolytic activity [14–17]. Clinically, macrophage activation syndrome can be difficult to identify, as often the symptoms and signs are similar to a flare in disease activity. The three most commonly seen symptoms and signs are fever, hepatosplenomegaly and lymphadenopathy, although other complications have been documented including haemorrhagic diatheses, neurological abnormalities including coma and seizures, and fixed skin rashes [11]. A diagnostic algorithm for identifying MAS is provided in Fig. 1. Radiological investigation for macrophage activation syndrome is not routinely undertaken. In some cases in which there is neurological involvement, MRI brain scans are performed and demonstrate supratentorial white matter changes, resulting in diffuse abnormal signal intensity on T2-weighted images. Radiology can, however, be useful in excluding other differential diagnoses, as well as in demonstrating effusions or abscesses in septic arthritis and osteomyelitis [18]. Treatment of macrophage activation syndrome involves a multidisciplinary approach to care and support of both the patients and their parents [19]. Immediate treatment
1060-152X Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
DOI: 10.1097/BPB.0000000000000156
Macrophage activation syndrome or septic arthritis Green et al. 331
Fig. 1
Diagnosis of paediatric rheumatological disorder − JIA, SLE, RA, Still's disease
Clinical features • Persistent fever • Splenomegaly
Cytology
Haematological investigations •
Haemoglobin concentration
Review article
Macrophage activation syndrome or septic arthritis: a case of mistaken identity Gemma L. Greena, Arash Aframiana, Parthiban Vinayakamb and Mark S. Cornellb We present an interesting case of macrophage activation syndrome in a 2-year-old, with no previous rheumatological diagnoses, incorrectly diagnosed with septic arthritis, to highlight the diagnostic difficulties, especially in small hospital units. We aim to present the similarities between the two conditions and to summarize the clinical, radiological and epidemiological features of macrophage activation syndrome, an underdiagnosed condition. A review of the current literature was performed, and a diagnostic algorithm was created. No current set treatment regimen exists, but current recommendations have been included. We have demonstrated the pitfalls in diagnosis and the
Introduction Septic arthritis is a common and devastating orthopaedic problem in paediatric patients [1,2], requiring prompt diagnosis, decompression, washout and appropriate antibiotic therapy [3]. Macrophage activation syndrome (MAS) is a rheumatological emergency, requiring rapid immune system modulating therapy [4,5]. This report highlights an interesting case of macrophage activation syndrome presenting as septic arthritis in a 2-yearold girl.
Background 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 [6–10]. 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. Macrophage activation syndrome is reported to occur in around 6% of sJIA cases, with no sex preference or age preference. It can occur at any disease stage, but there is usually active disease present at the time of diagnosis [11]. Macrophage activation syndrome is regarded by rheumatologists as a form of secondary haemophagocytic lymphohistiocytosis, and it has a number of ‘trigger’ factors including infections (bacterial – Enterococcus spp.; viral – Epstein Barr, Varicella spp., Coxsackie, Parvovirus spp. and hepatitis A), drugs (aspirin, non-steroidal anti-inflammatory drugs, methotrexate, etanercept) and stem cell transplantation [12,13].
importance of immediate treatment in optimizing prognosis. J Pediatr Orthop B 24:330–335 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Journal of Pediatric Orthopaedics B 2015, 24:330–335 Keywords: arthritis, infectious, juvenile, macrophage activation syndrome, pathology, therapeutics a St Georges Hospital, Tooting, London and bQueen Elizabeth the Queen Mother Hospital, Margate, Kent, UK
Correspondence to Gemma L. Green, MBChB, BSc, St Georges Hospital, Blackshaw Road, Tooting, London SW17 0QT, UK Tel: + 44 07917509028; e-mail: [email protected]
The pathophysiology of macrophage activation syndrome has not fully been understood, but it is recognized to involve uncontrolled proliferation of T cells and macrophages, which has been shown to reduce natural killer (NK) cell function. There is thought to be a genetic component, with mutations in the genes encoding for the protein perforin. This protein is used for the induction of apoptosis by cytolytic cells in virus or tumour cells. Other genes have been identified in the pathogenesis, including MUNC 13-4, which is involved in the transport of perforin; reduced transport of perforin to cells causes reduced cytolytic activity [14–17]. Clinically, macrophage activation syndrome can be difficult to identify, as often the symptoms and signs are similar to a flare in disease activity. The three most commonly seen symptoms and signs are fever, hepatosplenomegaly and lymphadenopathy, although other complications have been documented including haemorrhagic diatheses, neurological abnormalities including coma and seizures, and fixed skin rashes [11]. A diagnostic algorithm for identifying MAS is provided in Fig. 1. Radiological investigation for macrophage activation syndrome is not routinely undertaken. In some cases in which there is neurological involvement, MRI brain scans are performed and demonstrate supratentorial white matter changes, resulting in diffuse abnormal signal intensity on T2-weighted images. Radiology can, however, be useful in excluding other differential diagnoses, as well as in demonstrating effusions or abscesses in septic arthritis and osteomyelitis [18]. Treatment of macrophage activation syndrome involves a multidisciplinary approach to care and support of both the patients and their parents [19]. Immediate treatment
1060-152X Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
DOI: 10.1097/BPB.0000000000000156
Macrophage activation syndrome or septic arthritis Green et al. 331
Fig. 1
Diagnosis of paediatric rheumatological disorder − JIA, SLE, RA, Still's disease
Clinical features • Persistent fever • Splenomegaly
Cytology
Haematological investigations •
Haemoglobin concentration
