Sarcoidosis

Last Updated: 2020-11-23

Author(s): Anzengruber, Navarini

  • Jonathan Hutchinson 1875
  • Ernest Besnier 1889
  • Cäsar Boeck 1899
  • Schaumann 1916-1917

Boeck disease, Besnier-Boeck-Schaumann disease.

Granulomatous multisystemic disease characterized by non-caustic epithelial cell granulomas.

  • Women > Men.
  • North-South gradient.
    • 10-14/100,000/year (Caucasians in the USA)
    • 35-64/100,000 per year. (African-Americans in the USA)
    • 64/100,000/year (Sweden)
    • 20/100,000 per year (UK)
    • 1.4/100,000/year (Spain and Japan)

Classification into acute, subacute and chronic form. By organ infestation.

Forms of skin sarcoidosis:

  • Large-nodular form
    • Special form: Lupus pernio
  • Small nodular disseminated form
  • Erythema nodosum
  • Anular, circular form
  • Subcutaneous nodular form
  • Scar sarcoidosis
  • Angiolupoid sarcoidosis
  • It is an immune disease. CD4+ helper cells (Th1 subtype) are activated, which leads to a shift in the CD4/CD8 ratio (↑CD4+ cells over 3.5 times). This results in ↑ production of Th1- cytokines and B-cell stimulation with consequent hypergammaglobulinemia. This leads to the initiation of a tissue reaction.
  • A genetic component is regarded as certain, because there is a familial accumulation.
  • Association: 
    • HLA-B8, -q, -B8, -B13, DR3 and -DR5. HLA DR 11, 12, 14, 15, 17 Comment: Here are very different data depending on the source.
  • Collectives of sarcoidosis patients also contain polymorphisms of the gene coding for the angiotensin converting enzyme.

  • Cutaneous symptoms occur in up to 35% of cases

Classification

  • Acute form (Löfgren's syndrome)
    • 5% of cases
    • Triad:
      • Erythema nodosum (associated with benign course, often spontaneous regression after years)
      • Arthritis
      • Bihilary adenopathy 
        • Stage I: Bihilar lymph node enlargement
        • Stage II: Parenchyma involvement
        • Stage III: Fibrosis
      • Familial blue syndrome --> Start < 5 years of age. Triad of granulomatous changes in skin, joints and eyes.
  • Subacute form
  • Chronic form
    • In 95% of cases
    • Progression over years
    • Organ involvement:
      • Lungs (60%)
      • Lymphatic system (20%)
      • Liver (20%)
      • Eyes (18%)
      • Parotid gland (5%)
      • Tear gland (Heerfordt's syndrome)
      • Bones (ostitis multiplex cystoid youth)
      • Joints (oligoarticular arthritis)
    • General symptoms
      • Reduced general condition
      • Fever
      • Fatigue
      • Flu-like symptoms
    • Skin symptoms 
      • Large nodular form:
        • Especially on the face and extremities, reddish, bluish, sometimes brownish, coarse palpable nodules and plaques with teleangectasia. In some cases a central regression is possible.
      • Small nodular form:
        • Erytheamous, partly bluish papules and nodules are mainly visible on the face and on the extensor sides of the extremities. 
      • Anular or circular form:
        • Polymorphic, partly roundish/annular/angular or circinate erythematous to brownish plaques and nodules with central atrophic regression.
      • Subcutaneous nodular form:
        • Subcutaneously localized, indolent, nodular masses under mostly inconspicuous, in some cases slightly livid discolored skin.
  • Clinical picture
  • Diascopy  ("apple jelly" colour of infiltrates on print)
  • Biopsy
  • Chest X-ray
  • Pulmonary function
  • Hand X-ray
  • ECG
  • Laboratory
    • ESR ↑
    • Angiotensin converting enzymes (ACE) ↑ in about 75% of the untreated patients. However, they are not very specific and sensitive and their role as a progression parameter is unclear
    • Soluble interleukin-2 receptor (sIL2R) ↑ in up to 80% of patients
      • Laboratory parameters with the highest sensitivity.  Possible marker for extrapulmonary infestation.
    • Increased values can also occur in other T-cell-mediated diseases
    • Adenosine deaminase and serum amyloid A ↑ (low specific/sensitive)
    • Procollagen III peptide (marker for pulmonary fibrosis)
    • Calcium ↑ in urine (30-60%), hypercalcemia (15%)
      eosinophilia (3%)
    • Leukopenia (5-10%), but hypergammaglobulinemia (30-80%)
    • Lymphocytopenia
    • Antinuclear antibodies are elevated in 1/3 of patients - do not be confused, does not speak against sarcoidosis. 
  • Upper abdomen sonography
  • Liver biopsy, if necessary
  • Neck sonography
  • Ophthalmologic consultation
    • Exclusion of involvement with impairment of the field of vision
  • In case of primarly pulmonary involvement
    • Bronchoscopy with bronchoalveolar lavage (T4/T8 quotient increased)
    • PE from mediastinal or pulmonary LK
    • Mediastinoscopy with LK-exstirpation
    • TBc exclusion
  • n case of primarily cardiac involvement
    • Echocardiography
    • Long-term ECG
    • Cardio-MRI
    • Heart scintigraphy
  • In the case of primarily neurosarcoidosis
    • Cerebrospinal fluid puncture and cranial MRT

Mostly where reduced blood flow occurs, for example:

  • Forehead, nose, cheeks, earlobes as well as sides of extremities (flexion sides are not affected).
  • Scars
  • Spontaneous healing often in over 50%.
  • Lung involvement is predicted.

Topical therapy

  • Clobetasol propionate cream / ointment
  • Triamcinolone injection suspension 10/40 mg

 

Radiation therapy

  • PUVA therapy

 

Systemic Therapy

  • Indication for systemic treatment:
    • General symptoms
    • Chron. rec. fever episodes
    • Decreased general condition
    • Weight loss
  • Organ involvement:
    • Lungs
      • Symptomatic lung disease (if lasting for more than 2 years)
    • Liver/Spleen
      • Transaminases increased
      • Hepatosplenomegaly
    • CNS involvement
    • Heart
      • Myocardial involvement
    • Lymph nodes
      • Lymphadenopathy
      • Serological
    • Hypercalcemia
    • Muscles
      • Myopathy
      • Myositis
  • Systemic glucocorticoids

    • Prednisolone p.o. 40-60 mg once a day for 6 months.
    • Methylprednisolone 40 mg p.o. once a day for 6 months.
    • CAVE: Systemic glucocorticoid treatment longer than 6 weeks should be accompanied by medication with PPI, calcium substitution and amphotericin.
  • Methotrexate (MTX) s.c. 15 mg once a week

    • Start with 10 mg once a week.
    • Weekly increase of 2.5 mg to 15 mg is achieved.
    • Folic acid p.o. 5 mg 1-0-0 the following day to reduce side effects.
  • Azathioprine p.o. 1x daily.

    • Initial: 1-3 mg/kg bw
    • Course: Reduction by approx. 0.5 mg/kg bw to the lowest still effective dosage.
    • CAVE: If allopurinol is administered simultaneously, a reduction of the azathioprine dose to a ¼ is indicated.
  • Mycophenolate mofetil p.o. 1-1.5 g 2x a day.

 

Experimental:

  • Allopurinol p.o. 300 mg 1x a day
  • Ciclosporin p.o. 3-5 mg/kg bw 1x a day
  • To be taken independently of meals
  • Fumarates (fumaric acid ester)
  • Biologicals
  • TNF-alpha inhibitors:
    • Etanercept s.c. 50 mg once a week
    • Adalimumab 
    • Infliximab i.v. 5mg/kg bw 

 

Surgical therapy

  • Cryosurgery 
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