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Sarcoidosis

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Sarcoidosis is a multisystem inflammatory disorder of unknown etiology characterized by the formation of noncaseating granulomas in affected organs, most commonly the lungs, lymph nodes, skin, and eyes
Etiopathogenesis
  • Unknown
  • Saurat: result of a T-cell immune response, mainly CD4 in response to an unknown antigen presented by the host’s monocytes/macrophages
    • Immune response Th1
  • Infectious agents: Mycobacterium tuberculosis and other atypical M. species, Propionibacterium acnes and Chlamydia species
  • Mineral dust, such as silical and titanum
  • Genetic factors are also important in defining the pattern clinical presentation, severity and prognosis
    • Class I HLA B6 antigen: association with acute sarcoidosis
    • HLA-DRB I and DQB I
    • Suscetibility genes are present on chromosome 3p and 5q 11.2 and protective genes on region of 5p 15.2
  • Fármacos que induzem sarcoidoses: imunoterapia, anti-TNF
 
Epidemiologia
  • Adult onset, childhood rare
 
Clinical presentation
  • Envolvimento cutâneo in 30% of cases, sometimes 1st manifestation
    • Various morphologies → “great imitator”
    • Reddish-brown to violaceous papules and plaques
    • Favor the nose on the alar rim
    • Muitas vezes as lesões surgem sobre cicatrizes antigas
    • Usually smooth
      • There is an ichtiosiform variant, usually on the legs, can have scale - unique because sarcoid is usually dermal process
    • Based on the presence or not of noncaseating granulomas on histology, cutaneous lesions have been classified into
      • Specific (9-15% of all sarcoidosis patients)
          • Maculopapular sarcoidosis (small nodular sarcoids in Saurat)
          • Lesions
            • Red-brown to purple
            • Variants may be skin-colored, yellow-brown or hypopigmented
            • <1cm in diameter
            • Slightly infiltrated with minimal epidermal changes
            • Usually on the face: eyelids, periorbital, nasolabial folds and scalp
          • Mean age: 47 years (range 9-83 years)
          • Disease onset and progression
            • Lesions can be transient, often at the onset of the disease
            • Disease typically resolves in less than 2 years
          • Associated symptoms and conditions
            • Acute organ involvement: sudden lymphadenopathy, acute arthritis, acute uveitis
            • Abnormal chest radiographs
            • Early disease stages often feature intrathoracic involvement
              • Bilateral hilar lymphadenopathy with or without parenchimal infiltation (up to stage II)
              • Lymphadenopathy in 50% of patients
          Nodular and plaque sarcoid (large nodular sarcoids in Saurat)
          • Frequently occurs on the face
          • Also on the back, buttocks, extensor surfaces of the extremities
          • Lesions
            • Multiple round or oval infiltrated plaques
            • Reddish-brown color
            • >1cm in diameter
            • More indurated and elevated than papular sacoid lesions
            • Sometimes mammillated and associated with nodular dermal lesions
          • Over 90% of cases are chronic (>2 years)
          Lupus pernio (infiltrative sarcoids in Saurat)
          • is not lupus, is not pernio
          • Most characterictic cutaneous manifestation of sarcoidosis
          • Lesions: diffuse, reddish to violaceous, telanfiectatic plaques
            • May merge into disfiguring nodular plaques
          • Commonly affects:
            • Plaques on face
            • Nose (can cause nasal ulceration, obstruction or perforation of the nasal septum)
            • Cheeks
            • Ears
            • Fingers
            • Alar rim lesions = airway involvement hallmark
          • More frequent in:
            • Older individuals
            • Black women
          • Typically follows an extremely chronic course (2-25 years)
          • Often resistant to treatment with systemic corticosteroids and other immunosuppressants
          • 75% with pulmonary involvement
          • 50% with upper respiratory tract involvement
          • Why the name Lupus pernio? In the old days, lupus vulgaris was a manifestation of TB. Lupus pernio has also granulomatous inflammation. Pernio is considered for the ends of the body, such as nose and digits.
          Scar sarcoidosis
          • Can manifest at disease onset
          • Erythematous swelling in or around old scars
          • Development of papules and nodules within original scars
          • On sites of skin trauma due to:
            • Mechanical injuries
            • Venipuncture and intramuscular injections
            • Inoculations
            • Infections (herpes zoster) - wolf isotopic response
            • Tattoos
            • Foreign material
          • Often associated with systemic involvement
          Darier-Roussy subcutaneous sarcoidosis
          • Usually multiple
          • Asymptomatic
          • Diascopy: apple-jelly color (usually more opaque than in lupus vulgaris)
          • Women are more commonly affected that men (2:1)
          • More often in black people
          • Woody induration of the skin
          • No color change
          Annular sarcoid
          • Red-brown induated papular lesions with central clearing → may coalesce into annular patterns
          • Predominantly affects photoexposed areas, such as the forehead
          • Alopecia may develop in the center of lesions
          Angiolupoid sarcoidosis
          • Accounts for 8% of cutaneous sarcoidosis cases
          • Lesions: initially present as single plaques that evolve into annular shapes with prominent telangiectasias and central hypopigmentation
          • Typically appears on photo-exposed areas: face, ears & scalp
          • More commonly observed in women
          • Can be an early indicator of systemic sarcoidosis
          • Associated organ involvement
            • Lungs (often at stage 2)
            • Glandular systems
          • Refractory to treatment
      • Non-specific
    • Hypopigmented, alopecic, ulcerative variants (?)
  • Systemic manifestations are protean (can affect many things)
    • 90% of patients have lung involvement
      • Hilar lymphadenopathy
      • Alveolitis
      • Granulomatous inflammation of alveoli, septi, and blood vessels
      • End stage fibrosis (with bronchiectasis) and honeycombing
    • Pulmonary and mediastinal involvement
    • Uveitis
    • Peripheral lymphadenopathy
    • Bony cysts
    • Parotid infiltration
    • Nerve damage
 
Dermoscopy
  • Nonspecific (similar findings in other granulomatous lesions)
  • Typical findings
    • Translucent, round or ovoid yellowish or reddish-orange globules, focally or diffusely distributed
    • Linear irregular vessels
    • Branching vessels
    • Arborizing vessels
    • Glomerular or dotted vessels
    • Whitish, structureless areas on a yellow-orange background
    • White scales
 
Pathology
  • Sarcoid granuloma
    • Superficial and deep dermal epithelioid granulomas, minimal associated inflammation, “naked granuloma”, non-caseating
  • Langhans type giant cells with inclusions
    • Asteroid bodies = eosinophilic stellate inclusions, engulfed collagen (EUA) or complex lipids (EADV)
    • Schaumann bodies = rounded basophilic inclusions, degenerating lysosomes with laminated calcium oxalate
    • Crystalline inclusions - colorless, round or oval refractile, nonlaminated inclusion bodies composed of calcium oxalate
 
Workup
  • Serum ACE elevation in 60%
  • Hypercalcemia
  • Rule out TB
  • Assessment of systemic sarcoidosis
    • Focused patient history review of systems, physical examination
    • CXR (anterior & lateral) and CT
    • Pulmonary functions tests
    • ECG +/- echocardiogram
    • Ophtalmologic examination
    • Labs (CBC, serum calcium, hepatic transaminases, alk phos, BUNm serum creatinin, urianalysis)
    • Other tests: ACE levels, serum lysozyme, neopterin, soluble IL-2, osteopontin, Kveim-Siltzbach test
      • not indicated for diagnosis
 
Tratamento
  • Topical
    • Steroids
      • Potent topical steroids recommended for prolonged use (over 8 weeks)
      • Intralesional triamcinolone injections for enhanced efficacy
    • Calcineurin inhibitors
      • 2nd line
    • Camouflage topicals
  • Systemic
    • Corticosteroids
      • First-line treatment, especially with multisystem involvement
      • Oral prednisolone typically started at 1-2mg/kg/d for 4-8 weeks
    • Alternative medications
  • Biologics
  • Surgical modalities
    • Electrodessication
    • Pulse dye laser
    • Carbon dioxide laser
    • Reconstructive surgical techniques
    • Improve cosmetic appearance but do not affect disease progression