Adult-onset Still's disease pathophysiology

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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]

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)

Immune dysfunction

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

  1. 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.
  2. 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.
  3. 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.
  4. 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.

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