An Overview of the Amyloidosis in Children with Rheumatic Disease

Abstract

Amyloidosis is a disease resulting from extra cellular accumulation of insoluble proteins in different organs and blood vessels. The term systemic amyloidosis is used to define applied to a variety of disease entities with a wide morphological and clinical spectrum (1). All amyloid proteins have biophysically comparable features (congo red binding, green color in polarized light, fibrillar appearance on electron microscopy) (2). Depending on the organ involvement type and amount, amyloid may cause progressive and life threatening organ dysfunction (3). There are numerous distractive types of amyloid fibrils are now known (4-7). The main protein types leading to amyloidosis are shown in Table 1. In children, the most common form of amyloidosis is reactive AA amyloidosis due to hereditary periodic fever (HPF) syndromes. The genetics causes of these syndromes derive from defects of the innate immunity and have been well defined at the clinical and genetically level are. Familial Mediterranean Fever (FMF), Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS), tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) and the cryopyrin-associated periodic syndrome (CAPS), which encompasses MuckleWells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), and chronic infantile neurological cutaneous and articular syndrome (CINCA). Juvenile idiopathic arthritis (JIA) is one of the more common chronic diseases of childhood, with a prevalence of approximately 1 per 1,000 (8). The most dramatic systemic inflammation is seen in patients with systemic JIA. This disorder is somewhat different from the other forms of JIA. A role for T cell and antigen –specific responses and many of the manifestations seem to be caused by the overproduction of IL-6 (figure 1). The prevalence of secondary amyloidosis in JIA varies between 1% and 10% (9-11). Risk for amyloidosis in systemic JIA patients is associated with a long-lasting inflammation (12). Although its frequency is dramatically decreasing, probably in relation with a more active DMARD treatment policy (13) Cantarini et al (14) suggest that MEFV may represent a triggering factor for the development of inflammatory state in systemic JIA, that may be an autoinflammatory disorder in itself rather than a subtype of JIA. Amyloid A precursor, serum amyloid A (SAA), is a major acute phase reactant, therefore being raised in chronic inflammatory diseases (15,16).