Sarcoidosis

• 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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