Sarcoidosis

Last Updated: 2022-02-25

Author(s): Anzengruber F., Navarini A.

ICD11: 4B20.Z

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

Boeck's morbus, Besnier-Boeck-Schaumann's morbus, sarcoidosis.

Granulomatous multisystem disease characterised by non-caseating epithelioid cellular granulomas.

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

Division into acute, subacute and chronic form. According to organ involvement.

Types of skin sarcoidosis:

  • Large nodular form
    • Special form: lupus pernio
  • Small nodular disseminated form
  • Erythema nodosum
  • Anular, circular form
  • Subcutaneous nodular form
  • Scarring sarcoidosis
  • Angiolupoid sarcoidosis
  • It is an immune disease. CD4+ helper cells (Th1 subtype) are activated, leading to a shift in the CD4/CD8 ratio (↑CD4+ cells over 3.5-fold). There is ↑ production of Th1- cytokines and B-cell stimulation with consequent hypergammaglobulinaemia. This leads to an initiation of a tissue reaction
  • A genetic component is considered certain, as there have been familial clusters reported
  • Association:
    • HLA-B8, -q, -B8, -B13, DR3 and -DR5. HLA DR 11, 12, 14, 15, 17
      • Comment: very different information here depending on the source
  • In addition, polymorphisms of the gene encoding angiotensin-converting enzyme are found in collectives of sarcoidosis patients

  • Cutaneous symptoms show up in about up to 35%

Division

  • Acute form (Löfgren's syndrome)
    • 5% of cases
    • Trias:
      • Erythema nodosum (associated with benign course, often spontaneous regression after years)
      • Arthritis
      • Bihilar adenopathy
        • Stage I: Bihilary lymph node enlargement
        • Stage II: Parenchymal 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
    • Years-long course
    • Organ involvement:
      • Lung (60%)
      • Lymphatic system (20%)
      • Liver (20%)
      • Eyes (18%)
      • Parotis (5%)
      • Tear gland (Heerfordt syndrome)
      • Bones (ostitis multiplex cystoides Jüngling)
      • Joints (oligoarticular arthritis)
    • General symptoms
      • ↓ general condition
      • Fever
      • Fatigue
      • Flu-like symptoms

Skin symptoms

  • Large nodular shape:
    • Mostly on the face and extremities, there are reddish, bluish, sometimes brownish, derb palpable nodules and plaques with telangectasias. In some cases, central regression is possible
  • Small nodular form:
    • Erythematous, sometimes bluish papules and nodules are visible, especially on the face and extensor sides of the extremities
  • Anular or circular form:
    • Polymorphous, partly roundish/ring-shaped/annular or circine erythematous to brownish plaques and nodules with central atrophic regression
  • Subcutaneous nodular form:
    • Subcutaneously localised, indolent, nodular space-occupying lesions under mostly inconspicuous, in some cases slightly livid discoloured skin
  • Clinical image
  • Diascopy ("apple jelly" colour of infiltrates on pressure)
  • Biopsy
  • Chest X-ray
  • Pulmonary function
  • X-ray of the hands
  • ECG
  • Laboratory
    • BSG ↑
    • Angiotensin converting enzyme (ACE) ↑ in about 75% of non-treated patients. but poorly specific and sensitive, role as a progression parameter unclear.
    • Soluble interleukin-2 receptor (sIL2R) ↑ in up to 80%
      • Lab parameter with the highest sensitivity. Possible marker for extrapulmonary involvement.
    • ↑ Levels may also occur in other T-cell mediated diseasesAdenosine deaminase and serum amyloid A ↑ (low specificity/sensitivity)
    • Procollagen III peptide (marker for pulmonary fibrosis)
    • Calcium ↑ in urine (30-60%), hypercalcaemia (15%)
    • Eosinophilia (3%)
    • Leukopenia (5-10%), but hypergammaglobulinaemia (30-80%)
    • Lymphocytopenia
    • Antinuclear antibodies are elevated in 1/3 of patients - do not be confused, does not argue against sarcoidosis.
  • Upper abdominal sonography
  • If necessary, liver biopsy
  • Neck sonography
  • Ophthalmological consultation
    • Ruling out involvement with visual field impairment
  • When pulmonary involvement is suspected
  • Bronchoscopy with bronchoalveolar lavage (T4/T8 quotient ↑)
  • Biopsy from mediastinal or pulmonary lymph node
  • Mediastinoscopy with lymph node extirpation
  • Tbc exclusion
  • When cardiac involvement is suspected
    • Echocardiography
    • Long-term ECG
    • Cardiac MRI
    • Cardiac scintigraphy
  • In cases of suspected neurosarcoidosis
    • Liquor puncture & cranial MRI

Mostly where ↓ blood flow e.g.:

  • Front, nose, cheeks, earlobes, as well as the extensor sides of the extremities (flexor sides are not affected)
  • Scars
  • Spontaneous healing frequent in over 50%
  • Lung involvement prognostic

Topical therapy

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

Radiation therapy

  • PUVA therapy

Systemic therapy

  • Indication for systemic treatment:
    • General symptomatology
    • repearting febrile episodes
    • ↓ general condition
    • Weight loss
    • Organ involvement:
      • Lung
        • Symptomatic lung disease (if present for more than 2 years)
      • Liver/ Spleen
        • Transaminases ↑
          • Hepatosplenomegaly
      • CNS involvement
      • Heart
        • Myocardial involvement
      • Lymph node
        • Lymphadenopathy
      • Serologic
        • Hypercalcaemia
      • Muscles
        • Myopathy
        • Myositis
  • Systemic glucocorticoids
    • Prednisolone per os 40-60 mg once daily to be phased out over 6 months
    • Taper off methylprednisolone per os 40 mg once daily over 6 months
    • CAVE: In case of systemic glucocorticoid treatment longer than 6 weeks, concomitant medication with PPI, calcium substitution and amphotericin should be given.
  • Methotrexate (MTX) s.c. 15 mg once weekly
    • Start with 10 mg once weekly.
    • Increase by 2.5 mg weekly until 15 mg is reached.
    • Folic acid per os 5 mg 1-0-0 the following day to reduce side effects.
  • Azathioprine per os once daily
    • Initially: 1-3 mg/kg bw
    • Progression: reduction by approx. 0.5 mg/kg bw to the lowest still effective dosage.
    • CAVE: With concomitant administration of allopurinol, a reduction of the azathioprine dose to a ¼ dose is indicated.
  • Mycophenolate mofetil per os 1-1.5 g twice daily.
  • Experimental:
  • Allopurinol per os 300 mg once daily.
  • Ciclosporin per os 3-5 mg/kg bw daily
    • Take independently of meals
  • Fumarates (fumaric acid esters)
  • Biologicals
    • TNF-alpha inhibitors:
    • Etanercept s.c. 50 mg once weekly
    • Adalimumab
    • Infliximab i.v. 5mg kg bw

Operative therapy

Cryosurgery

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