Autoinflammatory Syndromes

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Grupo heterogénio de doenças caracterizadas por episódios de inflamação sistémica estéril mediada pela imunidade inata, de causa hereditária ou adquirida.
 
Imunidade Cutânea
Innate
Adaptive
Lack of immunologic memory
Based on neutrophils, macrophages, eosinohils, NK cells, mast cells
Cytokines (IL1, IL6, IL18, TNF, INFs)
Complement
Antimicrobial peptides
Based on the antigen presentation (Antigen presenting cells)
Specific reaction
Enhanced with each successive antigen contact
Involves T and B lymphocytes
 
Inherited autoinflammatory disease
  • Generalidades
    • Monogenic disease related to aberrant activation of the innate immune system that are characterized by recurrent fevers and flares of multi-organ inflammation; the skin is frequently involved as are the joints, eyes and serosae
    • Cutaneous lesions reflect their pathomechanism and nosographic context
      • Aseptic neutrophilic dermatoses presenting as evanescent urticarial papules, sterile pustules, pyoderma gangrenosum and Sweet Syndrome
        • “Neutrophilic Urticarial Dermatitis” → transient urticarial papules demonstrating perivascular and interstitial infiltrates of neutrophils within the dermis
      • Acne and Hydradenitis Suppurativa
      • Cold-induced dermatoses presenting as pernio-like lesions and acral necrosis
      • Panniculitis and lipoatrophy
      • Vasculitis and livedo reticularis
      • Granulomatous dermatoses and disorders of keratinization
    • Treatment
      • IL-1/IL-1R antagonists anakinra, rilonacept, canakinumab
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Hereditary Periodic Fever Syndromes
Cryopyrin associated periodic syndromes
  • All mutations in NLRP3
  • Urticarial rash, recurrent fever attacks, arthralgia or arthritis, eye inflammation, fatigue and headaches
  • Includes:
    • Familial cold autoinflammatory syndrome (familial cold urticaria)
    • Muckle Wells syndrome (MWS)
    • Familial cold autoinflammatory syndrome (FCAS)
    • Neonatal onset multisystem inflammatory disease (NOMID)
Familial mediterranean fever
  • More erysipelas like in appearance
  • Hyperimmunoglobulinemia D with periodic fever syndrome (HIDS)
    • Partial mevalonate kinase deficiency
  • TNF receptor associated periodic fever (TRAPS)
    • Erythematous and edematous urticarial plaques can occur in addition to periorbital edema
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  • Síndrome PAPA
    Deficiency of the Interleukin (IL)-1 receptor antagonist (DIRA)
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    • Pustular psoriasis due to abnormal IL-36 signaling (DITRA)
      Interferonopathies
      Cutaneous findings in inherited autoinflammatory diseases
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      Examples of inherited autoinflammatory diseases with cutaneous manifestations (Bollognia)
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      Acquired autoinflammatory syndromes
      • Vasculite urticariana
      Schnitzler Syndrome
      Still Disease
      • Episodic angioedema with eosinophilia (Gleich syndrome)
        • Elevated IL-5
      • Systemic capillary leak syndrome (Clarkson syndrome)
        • Episodic massive plasma exudation from blood vessels leading to life-threatning hypotension analogous to anaphylaxis
        • Associated with IgG paraproteinemia
        • Medications like IL-2 can also produce a systemic capillary leak syndrome
      • SAPHO
        • Synovitis (joint inflammation), Acne, Pustulosis (sterile pustules), Hyperostosis (excessive bone growth), and Osteitis (bone inflammation)
      • PASH: Pyoderma Gangrenosum (PG), Acne, and Suppurative Hidradenitis (HS)
      • PAPASH: PAPA + Suppurative Hidradenitis
      • PsAPASH: Psoriatic Arthritis (PsA) + PASH
      • PASS: Pyoderma gangrenosum, Acne vulgaris, Hidradenitis suppurativa and Spondylarthropathy (ankylosing spondylitis)