Sarcoidosis

name: Sarcoidosis
creation_date: '2026-01-13T07:11:10Z'
updated_date: '2026-02-27T21:53:03Z'
category: Immune
description: >
  Sarcoidosis is a multisystem inflammatory disease of unknown etiology characterized
  by the formation of non-caseating granulomas, most commonly affecting the lungs
  and lymph nodes. It predominantly affects adults aged 20-40 years, with higher
  incidence in African Americans and Northern Europeans. Clinical presentation
  ranges from asymptomatic to severe organ dysfunction. While many cases resolve
  spontaneously, chronic progressive disease occurs in a significant subset.
disease_term:
  preferred_term: sarcoidosis
  term:
    id: MONDO:0019338
    label: sarcoidosis
parents:
- Granulomatous Disease
- Immune-Mediated Disease
has_subtypes:
- name: Pulmonary Sarcoidosis
  description: Most common form, affecting lungs and hilar lymph nodes; staged by chest radiograph findings.
- name: Cardiac Sarcoidosis
  description: Myocardial granulomas causing conduction abnormalities, heart failure, or sudden death.
- name: Neurosarcoidosis
  description: CNS involvement causing cranial neuropathies, meningitis, or mass lesions.
- name: Cutaneous Sarcoidosis
  description: Skin manifestations including erythema nodosum, lupus pernio, and papular lesions.
pathophysiology:
- name: Granuloma Formation
  description: >
    Non-caseating granulomas consist of organized collections of activated
    macrophages (epithelioid cells), multinucleated giant cells, and CD4+ T cells.
    Th1/Th17 immune responses drive granuloma development in response to
    unidentified antigens.
  evidence:
  - reference: PMID:35011621
    supports: PARTIAL
    snippet: "Sarcoidosis is a chameleon disease of unknown etiology, characterized by the growth of non-necrotizing and non-caseating granulomas"
    explanation: "This review confirms the characteristic non-caseating granuloma formation in sarcoidosis."
  cell_types:
  - preferred_term: epithelioid macrophage
    term:
      id: CL:0002150
      label: epithelioid macrophage
  - preferred_term: CD4-positive helper T cell
    term:
      id: CL:0000492
      label: CD4-positive helper T cell
  biological_processes:
  - preferred_term: granuloma formation
    term:
      id: GO:0002432
      label: granuloma formation
- name: Dysregulated Immune Response
  description: >
    Exaggerated CD4+ T helper cell response with Th1 polarization leads to
    interferon-gamma and TNF-alpha production. Regulatory T cell dysfunction
    contributes to persistent inflammation. Paradoxical peripheral anergy
    coexists with organ-specific hyperactivity.
  evidence:
  - reference: PMID:35011621
    supports: PARTIAL
    snippet: "Lungs and intrathoracic lymph nodes are the sites that are most often involved, but virtually no organ is spared from this disease."
    explanation: "Review describes the multisystem inflammatory nature of sarcoidosis affecting multiple organs."
  cell_types:
  - preferred_term: CD4-positive helper T cell
    term:
      id: CL:0000492
      label: CD4-positive helper T cell
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
- name: Fibrosis
  description: >
    Chronic granulomatous inflammation can progress to fibrosis, particularly
    in the lungs. Fibroblast activation and excessive collagen deposition
    lead to irreversible organ damage and functional impairment.
phenotypes:
- name: Mediastinal Lymphadenopathy
  category: Pulmonary
  frequency: VERY_FREQUENT
  description: Symmetric enlargement of hilar and mediastinal lymph nodes, often the presenting finding on chest radiograph.
  phenotype_term:
    preferred_term: Mediastinal lymphadenopathy
    term:
      id: HP:0100721
      label: Mediastinal lymphadenopathy
- name: Dyspnea
  category: Pulmonary
  frequency: FREQUENT
  description: Shortness of breath due to pulmonary involvement and reduced lung function.
  phenotype_term:
    preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
- name: Nonproductive Cough
  category: Pulmonary
  frequency: FREQUENT
  description: Dry, non-productive cough from airway and parenchymal inflammation.
  phenotype_term:
    preferred_term: Nonproductive cough
    term:
      id: HP:0031246
      label: Nonproductive cough
- name: Fatigue
  category: Constitutional
  frequency: VERY_FREQUENT
  description: Chronic fatigue is one of the most debilitating symptoms, often persisting after disease resolution.
  phenotype_term:
    preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
- name: Erythema Nodosum
  category: Dermatologic
  frequency: OCCASIONAL
  description: Painful red nodules on the shins, often associated with acute sarcoidosis (Lofgren syndrome).
  phenotype_term:
    preferred_term: Erythema nodosum
    term:
      id: HP:0012219
      label: Erythema nodosum
- name: Uveitis
  category: Ophthalmologic
  frequency: OCCASIONAL
  description: Eye inflammation that can lead to vision impairment if untreated. May be anterior, posterior, or panuveitis.
  phenotype_term:
    preferred_term: Uveitis
    term:
      id: HP:0000554
      label: Uveitis
biochemical:
- name: Elevated ACE
  presence: Elevated
  context: Serum angiotensin-converting enzyme often elevated but not specific for diagnosis
- name: Hypercalcemia
  presence: Elevated
  context: Due to ectopic 1,25-dihydroxyvitamin D (calcitriol) production by granuloma macrophages
- name: Elevated Inflammatory Markers
  presence: Elevated
  context: ESR and CRP may be elevated during active disease
genetic:
- name: HLA-DRB1 Variants
  association: Susceptibility
  notes: HLA-DRB1*03 associated with acute, self-limited disease; HLA-DRB1*15 with chronic disease
- name: BTNL2 Variants
  association: Susceptibility
  notes: Butyrophilin-like 2 gene variants increase sarcoidosis risk
environmental:
- name: Occupational Exposures
  notes: Increased risk with exposure to insecticides, mold, and certain industrial dusts
- name: Infectious Triggers
  notes: Mycobacterial and propionibacterial antigens have been implicated as potential triggers
treatments:
- name: Corticosteroid Therapy
  description: >
    First-line treatment for symptomatic sarcoidosis. Prednisone typically
    initiated at 20-40mg daily with gradual taper over months. Effective
    for most organ manifestations.
  treatment_term:
    preferred_term: corticosteroid agent therapy
    term:
      id: MAXO:0000640
      label: corticosteroid agent therapy
- name: Methotrexate
  description: >
    Most commonly used steroid-sparing agent for chronic sarcoidosis.
    Allows reduction of corticosteroid dose while maintaining disease control.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    therapeutic_agent:
    - preferred_term: methotrexate
      term:
        id: CHEBI:44185
        label: methotrexate
- name: Anti-TNF Therapy
  description: >
    Infliximab or adalimumab for refractory disease, particularly effective
    in neurosarcoidosis, lupus pernio, and cardiac sarcoidosis.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
datasets: