Sarcoidosis

 

• Multisystem granulomatous disease
• Commonly affects young adults
• Presents with bilateral hilar lymphadenopathy, pulmonary infiltration with skin or eye lesions
• Characterised by non caseating granulomas
• Beryllium poisoning can produce a similar clinical and histological picture
• Prevalence higher in women than in men
• More common in black than whites

 

Aetiology/pathogenesis

 

• Due to disordered immune regulation in genetically susceptible individuals exposed to certain environmental stimuli
• Immunological factors
  • Process driven by CD4+ T cells
  • Intra-alveolar and interstitial accumulation of CD4+ T cells and oligo-expansion of certain subsets suggesting antigen driven proliferation
  • Increased levels of Th1 cytokines, IFNg and IL-12
  • Increased levels of inflammatory cytokines in the environment, IL-1, TNFa and MIP-1a. TNF level in the bronchoalveolar fluid is a marker or disease severity
  • Systemic immunological abnormalities;
  • Anergy to common skin test antigens e.g. candida or purified protein derivative
  • Polyclonal hypergammaglobulinemia
• Genetic factors
  • Familial and racial clustering
  • Association with certain Class I HLA haplotypes
• Environmental factors
  • Several infectious agents have been proposed to  incite sarcoidosis, mycobacteria, propionibacterium acnes and Rickettsia however no real evidence for this!

 

Morphology

• Noncaseating granulomas composed of epitheloid cells and Langhans type giant cells
• Central necosis is unusual
• May become fibrous
• Other microscopic features;
  • Laminated concretions composed of calcium and proteins called Schaumann bodies
  • Stellate inclusions known as asteroid bodies enclosed within giant cells and found in 60% of granulomas
• Asteroid and Schaumann bodies may also be found in other granulomatous disease e.g. TB
• Organs of pathological involvement;
• Lungs
  • Commonly involved
  • Granulomas may coalesce to form large non caseating noncavitating lesions
  • Lesions form along lymphatics, blood vessel and brochi generally although alveolar lesions are seen
  • Strong tendency for lung lesions to heal leaving fibrosis and hyalinisation. The pleural surface might also be involved
• Lymph nodes
  • Involved in almost all cases, specifically hilar and mediastinal
  • Nodes are enlarged discreet and sometimes calcified
  • Tonsils may also be involved
• Spleen
  • Can be involved and enlarged
  • Capsule not involved
• Liver
  • May be enlarged
• Bone marrow
  • Radiological visible bone lesions involving phalangeal bones of hands and feet creating small circumscribed areas of bone reabsorbtion throughout the cavity and a diffuse reticulated pattern throughout the cavity
• Skin lesions
  • Can assume a variety of macroscopic appearances
  • Lesions may also appear on the mucous membranes of the oral cavity, larynx and URT
• Eye
  • Iritis resulting in corneal opacities, glaucoma and loss of vision
  • Associated with lacrimal gland inflammation and suppression of lacrimation
  • Salivary glands may also be involved
• Muscle
  • Symptoms of muscle weakness, aches, tenderness and fatigue
• Other organs that might be involved; heart, kidney, CNS and endocrine glands

 

• Before diagnosis can be made other causes of granulomatous inflammation must be ruled out e.g. TB and fungal infection

 

Investigations

• CXR and CT
• FBC – normochromic normocytic anaemia and raised CRP
• Serum biochemistry – calcium may be raised
• Transbronchial biopsy
• Raised serum levels of ACE
• Lung function tests showing a restrictive lung defect

 

Clinical course

• May be discovered unexpectedly on routine CXR
• Mostly patients seek medical attention for respiratory symptoms or constitutional signs, weight loss, fever, night sweats, fatigue and anorexia
• Unpredictable course. May be progressive or have periods of activity followed by remission
• Pulmonary infiltration may lead to cor pulmonale and death
• If severe can be treated with corticosteroids