Adult-onset Still's disease pathophysiology
Template:Adult-onset Still's disease
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Pathophysiology
Adult-onset Still's disease is an automminue inflammatory arthritis that typically affects adolescents and adults ranging from age 16-40 years. Major etiological mechanisms behind cause a dysfunction of the innate and cellular immunity (limited) leading to activation of effector cells of the disease.
Putative triggers
Although the pathogenesis of adult-onset Still's disease is largerly idiopathic. Triggers of ASOD lead to activation of toll-like receptors (TLR) and activation of immune system. The following triggers may be implicated as factors responsible for generating key pathological processes occurring in adult-onset Still's disease (ASOD):[1][2][3][4][5][6][7][8]
Pathogen-associated molecular patterns (PAMPs)
- Bacteria
- Yersinia enterocolitica
- Chlamydophila pneumoniae
- Brucella abortus
- Borrelia burgdorferi
- Viruses
- Rubella
- Echovirus 7
- Mumps
- Cytomegalovirus (CMV)
- Fungi
Danger-associated molecular patterns (DAMPs)
- Chemicals
- Toxins
- Stress
Immune dysfunction
Both innate and adaptive immunity play roles in the pathological evolution of adult-onset Still's disease with the dysfunction occurring in the innate immunity predominating the picture. The following dysfunctions are involved:
Innate immunity
- Neutrophil and macrophage activation lie at the heart of pathogenesis of ASOD due to the effects of the proinflammatory interleukin-18 (IL-18) signalling.
- CD64 a marker of neutrophil activation has been found to be upregulated in active ASOD.[9]
- Macrophage colony stimulating factor, intercellular adhesion molecule-1 (ICAM-1) and calprotectin are elevated and act as markers of active disease.[10]
Adaptive immunity
Role of interleukin-1 beta
Interleukin-i beta plays a key role in producing major characteristic features of adult-onset Still's disease. The following processes are affected by an increased production of this key interleukin:
Hypothalamic-pituitary axis influence
Liver synthesis and secretion of acute phase proteins
Osteoclasts activation and matrix metalloproteinases (MMPs) synthesis
Innate immune system cells activation
Increased gene transcription of proinflammatory molecules
Role of interleukin-18
Role of interleukin-6
Role of interleukin-17
Role of interferon gamma
Role of tumor necrosis factor-alpha (TNF-alpha)
Reactive hemophagocytic lymphohistiocytosis
Genetics
Associated Conditions
Gross Pathology
Microscopic Pathology
References
- ↑ Perez C, Artola V (March 2001). "Adult Still's disease associated with Mycoplasma pneumoniae infection". Clin. Infect. Dis. 32 (6): E105–6. doi:10.1086/319342. PMID 11247732.
- ↑ Dua J, Nandagudi A, Sutcliffe N (December 2012). "Mycoplasma pneumoniae infection associated with urticarial vasculitis mimicking adult-onset Still's disease". Rheumatol. Int. 32 (12): 4053–6. doi:10.1007/s00296-011-2107-4. PMID 21918897.
- ↑ Escudero FJ, Len O, Falcó V, de Sevilla TF, Sellas A (June 2000). "Rubella infection in adult onset Still's disease". Ann. Rheum. Dis. 59 (6): 493. PMC 1753159. PMID 10885978.
- ↑ Efthimiou P, Georgy S (December 2006). "Pathogenesis and management of adult-onset Still's disease". Semin. Arthritis Rheum. 36 (3): 144–52. doi:10.1016/j.semarthrit.2006.07.001. PMID 16949136.
- ↑ Wouters JM, van der Veen J, van de Putte LB, de Rooij DJ (September 1988). "Adult onset Still's disease and viral infections". Ann. Rheum. Dis. 47 (9): 764–7. PMC 1003594. PMID 3178317.
- ↑ Ogra PL, Chiba Y, Ogra SS, Dzierba JL, Herd JK (May 1975). "Rubella-virus infection in juvenile rheumatoid arthritis". Lancet. 1 (7917): 1157–61. PMID 48775.
- ↑ Linnemann CC, Levinson JE, Buncher CR, Schiff GM (August 1975). "Rubella antibody levels in juvenile rheumatoid arthritis". Ann. Rheum. Dis. 34 (4): 354–8. PMC 1006427. PMID 1081377.
- ↑ Blotzer JW, Myers AR (1978). "Echovirus-associated polyarthritis. Report of a case with synovial fluid and synovial histologic characterization". Arthritis Rheum. 21 (8): 978–81. PMID 737022.
- ↑ Komiya A, Matsui T, Nogi S, Iwata K, Futami H, Takaoka H, Arinuma Y, Hashimoto A, Shimada K, Ikenaka T, Nakayama H, Furukawa H, Tohma S (March 2012). "Neutrophil CD64 is upregulated in patients with active adult-onset Still's disease". Scand. J. Rheumatol. 41 (2): 156–8. doi:10.3109/03009742.2011.644325. PMID 22420333.
- ↑ Chen DY, Lan JL, Lin FJ, Hsieh TY (June 2005). "Association of intercellular adhesion molecule-1 with clinical manifestations and interleukin-18 in patients with active, untreated adult-onset Still's disease". Arthritis Rheum. 53 (3): 320–7. doi:10.1002/art.21164. PMID 15934126.