Sarcoidosis

Epidemiology

  • Prevalence: varies from 0.04/100 K in Spain to 64/100 K in Sweden
  • Sex: slight F>M
  • Race: American blacks have 10-17x incidence that of whites
  • Age of onset: most commonly between 20-40 y/o (can occur in children and elderly: elderly are usually chronic cases)
  • Tobacco: higher incidence of Sarcoid in non-smokers (compared to smokers)
  • Genetics: slightly increased (possibly due to low penetrance) incidence in twins (monozygotic > dizygotic) and other family members (including spouses)
    • Increased incidence in blacks with HLA-Bw 15
    • Alleles which increase risk of disease: HLA DR 11, 12, 14, 15, and 17
    • Alleles which are protective: HLA DR1, DR4, and possibly HLA DQ 0202
    • Resolution of disease is linked to HLA-B8 (this antigen also occurs more commonly in patients with sarcoid arthritis and E. nodosum)

Physiology

  • Immunologic Disease of Unknown Etiology

  • T-cell alveolitis: initial process (BAL shows increased CD4 cells and increased amount of alveolar macrophages)

  • Decreased peripheral blood CD4: CD8 ratio
  • Granuloma formation (found in most organs): alveolar macrophages are incorporated into granulomas (alveolar macs take up Gallium when scanned)
    • Even early in disease, granulomas can be found in lungs and liver [Hunninghake; Sarc Vasc Diff Lung Dis, 1999]
  • PCR has detected Mycobacteria Tuberculosis in tissue from 7/16 patients in one series
  • Upper Airway Involvement: laryngeal/ posterior pharyngeal/ vocal cord infiltration by granulomas
  • Lower Airway Involvement: granulomatous involvement of trachea/ bronchi (or stenosis due to scarring associated with disease)
    • Extrinsic compression of bronchus by adenopathy is rare in Sarcoidosis

Pathology

  • Non-caseating granulomas (typically along lymphatic routes)
  • Whorls of elongated fibroblasts/ epithelioid cells with mononuclear cells
  • Extensive necrosis is rare
  • Giant cells (may be either Langhan or foreign-body type) with multinucleated crystalline or cellular inclusions (inclusions: Asteroid bodies, Schaumann bodies, or Hamasaki-Wesenberg bodies)
  • Similar granulomas may also be seen in Berylliosis/ certain malignancies/ immune deficiencies/ Foreign Body Granulomatosis
  • Nodular/Necrotizing Sarcoid: confluent granulomas/necrotic granulomatous vasculitis of pulmonary arteries, veins

Diagnosis

Arterial Blood Gas (ABG)/Oximetry

  • Exercise-Related Desaturation: due mainly to diffusion defect
    • Exercise pO2 correlates with right ventricular ejection fraction

Serum Chemistry

Purified Protein Derivative (PPD)

  • Usually Partial or Complete Anergy: PPD is negative in >66% of patients
    • Sometimes positive PPD seen initially or with remission
    • Previously positive PPD may revert to negative during active disease, returning to positive with cure of sarcoidosis
    • Strongly positive PPD is rare in sarcoidosis

Kveim Test

  • Positive: although not currently used

Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests, [[Pulmonary Function Tests]])

  • No correlation of PFT’s with CXR Findings, Disease Activity, and Disease Reversibility
    • Radiographic Stage 1: PFT’s are abnormal in 20% of cases
    • Radiographic Stage 2-3: PFT’s are abnormal in 40-70% of cases
  • Spirometry: obstruction is observed in 30% of cases
  • Lung Volumes
    • TLC: correlates with RV-EF
    • VC: decreased
  • DLCO: decreased early (due to interstitial and pulmonary vascular disease)

Bronchoscopy (see Bronchoscopy, [[Bronchoscopy]])

  • Appearance of Airways: granular “cobble-stoning” of airways
  • Bronchoalveolar Lavage (BAL): lymphocytosis (>35%) may be seen
    • High CD4/CD8 ratio >3.5 (ratio >5 is highly suggestive of sarcoidosis)
      • Especially high in Lofgren syndrome patients
    • Previous studies suggest that BAL lymphocytosis >28% predicts clinical deterioration: however, this is controversial
    • Neutrophilic predominance: may correlate with presence of end-stage pulmonary fibrosis
  • Endobronchial Biopsy (EBB): indicated for gross airway findings
  • Trans-Bronchial Biopsy (TBB)
    • Positive in 50-60% of cases with normal CXR
    • Positive in 85-90% with abnormal CXR

CXR/Chest CT Pattern

  • Usually, adenopathy precedes parenchymal disease (rare for adenopathy/parenchymal disease to recur after spontaneous clearing)
  • CXR Patterns
    • Hilar Lymphadenopathy
    • Interstitial Lung Disease
    • Bullous-Cystic Disease
    • Lung Nodules: may cavitate
  • Radiographic Staging: however, disease does not progress temporarily through these “stages”
    • Stage 0 (5-10% of cases): normal
      • In these cases, HRCT may demonstrate parenchymal abnormalities and adenopathy
    • Stage 1: bilateral hilar adenopathy
    • Stage 2a: bilateral hilar adenopathy + diffuse lung disease
    • Stage 2b: diffuse lung disease without hilar adenopathy
    • Stage 3: fibrosis + distortion of lung parenchyma

High-Resolution Chest CT (HRCT)

  • May show nodules along bronchovascular bundles, particularly in mid-upper lung fields (”beading”), pleural or subpleural nodules, septal lines, confluent opacities with air bronchograms, cystic or bronchiectatic lucencies, honeycombing, or bullae

Bone Scan

  • xxx

Gallium Scan

  • “Panda Pattern”: uptake in hilar and mediastinal nodes, lacrimal glands, and salivary glands
  • Non-specific
  • May guide biopsy site
  • Does not reliably predict prognosis or responsiveness to therapy
  • May aid in monitoring of disease

Cardiac MRI

  • Useful to Evaluate Cardiac Sarcoid

Brain MRI

  • Useful to Evaluate Neurosarcoid

Serology/Inflammatory Markers

  • ANA/RF/Anti-Lymphocyte Ab: may be positive
  • Circulating Immune Complexes: may be seen (increased levels may occur with symptoms)
  • Polyclonal Hyperglobulinemia/Macroglobulinemia: may be present
  • Lysozyme/Thermolysin-Like Metallopeptidase: elevated

Serum Angiotensin Converting Enzyme (ACE) Level (see Serum Angiotensin Converting Enzyme, [[Serum Angiotensin Converting Enzyme]])

  • Elevated >2 Standard Deviations in 41-80% of Sarcoidosis Cases
    • However, ACE level may also be elevated in HIV, hepatitis, miliary TB, Gaucher’s, Histoplasmosis
    • May be decreased with corticosteroid or ACE inhibitor use
  • May Be Useful to Monitor Disease Activity

Biopsy

  • Liver/Lymph Node Biopsy: high Incidence of false-positives
  • Skin/Conjunctival Biopsy: low sensitivity, but high specificity
  • Nasal Mucosal/Muscle/Spleen/Lacrimal Gland/Salivary Gland Biopsy: may be useful in some cases

Clinical Manifestations

Cardiovascular Manifestations

General Comments

  • General Comments: cardiac involvement may occur in the absence of other organ involvement

Conduction Defects (see Heart Blocks, [[Heart Blocks]])

  • Epidemiology
  • Clinical
    • Syncope (see Syncope, [[Syncope]])

Arrhythmias

  • Epidemiology
  • Clinical
    • Premature Ventricular Contractions (PVC’s)/Ventricular Tachycardia (VT) (see Ventricular Tachycardia, [[Ventricular Tachycardia]])
    • Syncope (see Syncope, [[Syncope]])

Restrictive Cardiomyopathy

  • Epidemiology:

Pericardial Effusion/Tamponade (see Pericardial Effusion, [[Pericardial Effusion]] and Tamponade, [[Tamponade]])

  • Epidemiology: uncommon

Constrictive Pericarditis (see Constrictive Pericarditis, [[Constrictive Pericarditis]])

  • Epidemiology: uncommon

Pulmonary Hypertension with Cor Pulmonale (see Pulmonary Hypertension, [[Pulmonary Hypertension]])

  • Epidemiology:

Superior Vena Cava (SVC) Syndrome (see Superior Vena Cava Syndrome, [[Superior Vena Cava Syndrome]])

  • Epidemiology: uncommon
  • Physiology: due to mediastinal lymphadenopathy

Substernal Chest Pain (see Chest Pain, [[Chest Pain]])

  • Epidemiology: common

Constitutional Manifestations

  • Fever (see Fever, [[Fever]])

Dermatologic Manifestations

  • Erythema Nodosum (see Erythema Nodosum, [[Erythema Nodosum]]): painful, nodular panniculitis, and vasculitis
  • Subcutaneous Nodules: on extremities
  • Nodular or Flat Plaques/Papules
  • Lupus Pernio: bluish-purplish elevations
  • Loffgren’s Syndrome
    • Arthralgias
    • Bihilar Lymphadenopathy
    • Erythema Nodosum

Endocrine Manifestations

  • Parotid Gland Enlargement
  • SIADH/DI/primary polydipsia
  • Hypercalcemia (see Hypercalcemia, [[Hypercalcemia]]): due to increased calcium absorption, enhanced sensitivity to vit. D, or increased vit. D metabolite production by granulomas)
    • Hypercalciuria
    • PTH may be decreased (due to hypercalcemia)
  • Involvement of pituitary/ thyroid/ parathyroid/ adrenal glands/ testes/ epididymis/ uterus (rare): no direct effect on fertility
  • Pregnancy: disease probably improves during pregnancy, with disease exacerbation post-partum

Gastrointestinal Manifestations

  • Anorexia (see Anorexia, [[Anorexia]])
  • Appendiceal Involvement: pain may mimic appendicitis
  • Dysphagia Due to Infiltration of Esophageal Wall and/or Esophageal Compression by Lymphadenopathy (see Dysphagia, [[Dysphagia]])
  • Esophageal Achalasia (see Esophageal Achalasia, [[Esophageal Achalasia]]): due to involvement of Auerbach’s plexus
  • Gall Bladder Involvement: pain may mimic cholecystitis
  • Malabsorption: due to jejunal atrophy/non-necrotizing granuloma of stomach, small intestine, colon
  • Pancreatic Involvement: pain may mimic pancreatitis
  • Weight Loss (see Weight Loss, [[Weight Loss]])

Hematologic Manifestations

  • Cervical/Supraclavicular/Epitrochlear Lymphadenopathy (see Lymphadenopathy, [[Lymphadenopathy]]): usually small, discrete, mobile nodes
  • Hypersplenism (see Splenomegaly, [[Splenomegaly]]): marked splenomegaly occurs more often with chronic disease/ may produce pancytopenia
  • Thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]]): may occur without splenomegaly

Hepatic Manifestations

  • General Comments: usually asymptomatic
  • Hepatic Parenchymal Lesions (see Hepatic Mass, [[Hepatic Mass]])
    • RUQ Pain
    • Jaundice
    • Hepatomegaly (see Hepatomegaly, [[Hepatomegaly]])
  • Portal fibrosis
  • Cirrhosis (see End-Stage Liver Disease, [[End-Stage Liver Disease]]): rare
  • Hepatitis: rare
  • Portal Hypertension (see Portal Hypertension, [[Portal Hypertension]]): due to damaged hepatic veins

Neurologic Manifestations (5% of cases)

  • Cranial Nerve Palsies (most common presentation): usually facial nerve (CN-7)
    • Heerfordt’s syndrome (Uveoparotid fever): CN-7 palsy+ parotid involvement + uveitis
  • Fatigue (see Fatigue, [[Fatigue]])
  • Hearing Loss/Vestibular Dysfunction (due to neuropathy or vasculitis of cranial nerve)
  • Peripheral Neuropathy (see xxxx, [[xxxx]]): parasthesias
  • Meningitis (see Meningitis, [[Meningitis]]): CSF may be normal (or may demonstrate increased protein, pleocytosis, hypoglycorrhachia, elevated CSF pressure)
  • Manifestations of Space-Occupying Lesions
    • Headache (see Headache, [[Headache]])
    • Seizures (see Seizures, [[Seizures]])
    • Obtundation-Coma/Encephalopathy (see Obtundation-Coma, [[Obtundation-Coma]])
    • Cerebellar Dysfunction (se xxxx, [[xxxx]])
    • Spinal Cord Compression (see xxxx, [[xxxx]])
    • Brainstem Dysfunction: due to brainstem lesions

Ophthalmologic Manifestations

  • Uveitis: most common ophthalmologic manifestation of sarcoidosis
    • Anterior Uveitis: inflammation in the portion of the uveal tract extending forward from the iris and ciliary body -> asymptomatic or red painful eye with photophobia
      • Exam: “mutton fat” in anterior chamber and/or posterior cornea
    • Intermediate Uveitis: inflammation in the vitreous, pars plana, or peripheral retina -> floaters or other visual disturbances
    • Posterior Uveitis: involves central portions of the retina (with venulitis that causes exudation of protein out of the retinal veins) -> retinal scarring and permanent vision loss
      • Fluorescence Angiogram: leaking retinal veins, leads to appearance of candle wax drippings
  • Optic Neuritis (rare): usually presents with sudden loss of vision or color vision
    • Exam: papillitis, papilledema, neovascularization with optic atrophy
  • Vitreous Opacities/Choroiditis/Conjunctival Granulomas: photophobia, eye pain, visual loss
  • Lacrimal Gland Enlargement (25% of cases): may produce sicca-like syndrome
    • Biopsy of Lacrimal Gland: may be useful
  • Exophthalmos: due to orbital disease

Otolaryngologic Manifestations

Nasal Polyps (see Nasal Polyps, [[Nasal Polyps]])

  • Clinical: nasal congestion

Laryngeal/Posterior Pharyngeal/Vocal Cord Granulomas

  • Clinical
    • Hoarseness (see Hoarseness, [[Hoarseness]])
    • Upper Airway Obstruction (see Obstructive Lung Disease, [[Obstructive Lung Disease]]): laryngeal granulomas seen mostly with lupus pernio, but occur with other dermatologic manifestations

Pulmonary Manifestations

General Comments

  • Predominant Anatomic Sites of Pulmonary Involvement
    • Bronchovascular Bundles: lesions along airways are common (and lesions involving the pulmonary vasculature may explain the occasional development of pulmonary hypertension)
    • Perilymphatic Areas: subpleural lesions are common
  • Distribution: upper lobe-predominant

Alveolar Sarcoidosis (see Pneumonia, [[Pneumonia]])

  • Diagnosis
    • CXR/Chest CT
      • Fluffy alveolar densities
      • “Reverse pulmonary edema” peripheral infiltrates, resembling chronic eosinophilic pneumonia or COP, have been reported
      • “Fairy Ring”/”Atoll Sign”/”Reverse Halo Sign”: normal or ground-glass region of parenchyma surrounded by dense ring of alveolar consolidation

Bullous-Cystic Sarcoid (see Cystic-Cavitary Lung Lesions, [[Cystic-Cavitary Lung Lesions]])

  • Clinical
    • Cavities may become colonized with Aspergillus
    • Severe bullous disease may cause the “Vanishing Lung Syndrome”
  • Treatment/Prognosis: cavities may resolve with or without therapy

Hilar/Mediastinal Lymphadenopathy (see Mediastinal Mass, [[Mediastinal Mass]])

  • Epidemiology: occurs in 75-90% of cases
  • Diagnosis
    • CXR/Chest CT
      • Usually bilateral and symmetric
      • Involves hilar, paratracheal, subcarinal, and other mediastinal lymph nodes
      • Hilar Nodes: “eggshell” calcification may occur
      • Subcarinal/Other Mediastinal Nodes: non-specific calcification may occur with long-standing disease
      • Posterior Mediastinal Mass: may occur
  • Clinical: substernal chest pain
  • Treatment/Prognosis: may regress, remain stable for years, or grow slowly

Nodular/Necrotizing Sarcoidosis (see Lung Nodule or Mass, [[Lung Nodule or Mass]] and Cystic-Cavitary Lung Lesions, [[Cystic-Cavitary Lung Lesions]])

  • Epidemiology: first described in 1973 by Liebow
    • Rare: only 3 of 150 cases in one series
    • Sex: female predominance
  • Physiology: granulomatous vasculitis -> necrosis may develop within the granulomatous lesion
  • Clinical: may be asymptomatic
    • Chest Pain
    • Cough
    • Dyspnea
    • Fatigure/Malaise
    • Fever
    • Hemoptysis
    • Ocular or Central Nervous System Involvement
    • Weight Loss
  • Diagnosis
    • Chest CT: confluent or diffuse >1 cm solitary or multiple lung nodules (possibly associated with lymphadenopathy)
      • Nodules may cavitate (calcification is usually absent): cavitation (and granulomatous vasculitis or pulmonary arteries and veins/necrosis of nodules) clinically distinguishes nodular/necrotizing sarcoidosis from typical sarcoidosis
      • No lobar predilection
      • Predominantly located subpleural and along bronchovascular bundles (similar to other Sarcoid lesions)
  • Treatment/Prognosis
    • Usually benign clinical course with or without corticosteroids
    • Some cases have severe pulmonary or extrapulmonary involvement
    • Few cases develop pulmonary hypertension due to pulmonary vasculitis

Pleural Involvement

  • Epidemiology: uncommon
  • Clinical
    • Chylothorax (see Pleural Effusion-Chylothorax, [[Pleural Effusion-Chylothorax]]): only 2 reported cases
    • Pleural Effusion (see Pleural Effusion-Exudate, [[Pleural Effusion-Exudate]]): occur in <3% of cases
      • Small and May be Bilateral
      • Lymphocyte-Predominant: may be >80%
      • Exudate (usually): by total protein criteria alone (since pleural LDH is usually normal)
    • Pleural Thickening
    • Pneumothorax (see Pneumothorax, [[Pneumothorax]])
      • Most cases are associated with fibrocystic disease
      • May be recurrent

Pulmonary Hypertension (see Pulmonary Hypertension, [[Pulmonary Hypertension]])

  • Epidemiology: occurs in 1-28% of cases
  • Physiology
    • Likely due to destruction of the capillary bed by fibrosis and/or resultant chronic hypoxemia: however, the severity of pulmonary hypertension does not correlate well with the degree of parenchymal lung disease and blood gas abnormalities
    • Other potential mechanisms: extrinsic compression of large pulmonary arteries by mediastinal and hilar adenopathy, and direct granulomatous infiltration of the pulmonary vasculature (especially the pulmonary veins, which sometimes mimic pulmonary veno-occlusive disease)
    • More rarely, portopulmonary hypertension secondary to hepatic sarcoidosis can occur

Pulmonary Veno-Occlusive Disease (VOD) (see Pulmonary Veno-Occlusive Disease, [[Pulmonary Veno-Occlusive Disease]])

  • Epidemiology: few case reports

Reticulonodular Interstitial Lung Disease (see Interstitial Lung Disease-Etiology, [[Interstitial Lung Disease-Etiology]])

  • Epidemiology: most common CXR pattern in sarcoidosis
  • Diagnosis
    • HRCT (superior to normal CT in assessing fine parenchymal abnormalities and separating alveolitis from fibrosis): lymphadenopathy/focal nodular (usually miliary <3 mm micronodules/ may be up to 3-5 mm nodules) or ground-glass opacities (peribronchovascular distribution/predilection for upper, middle, posterior lung zones)
      • Patchy nodules or segmental ground glass opacities without distortion are characteristic of early alveolitis (with minimal pulmonary dysfunction)
      • HRCT scores do not correlate with the Gallium and BAL scores of disease activity

Rounded Atelectasis (see Rounded Atelectasis, [[Rounded Atelectasis]])

  • Epidemiology: case reports

Tracheobronchial Airway Obstruction (see Obstructive Lung Disease, [[Obstructive Lung Disease]])

  • Physiology: granulomatosus tracheobronchial involvement
    • May progress to stenotic tracheobronchial scarring
  • Diagnosis
    • CXR/Chest CT: right middle lobe involvement is uncommon
    • PFT’s: obstruction
    • Bronchoscopy: characteristic diffuse granular bronchial mucosa (“cobble-stoning”), obstructing lesions, stenoses
  • Clinical: may present as either large or small airway obstruction

Renal Manifestations

  • Chronic Kidney Disease (CKD) (see Chronic Kidney Disease, [[Chronic Kidney Disease]]): due to renal granulomas, calculi (due to hypercalcemia/hypercalcuria)

Rheumatologic Manifestations

  • Polyarthritis/Monoarthritis (see Arthritis, [[Arthritis]]): usually associated with Loffgren’s syndrome
    • Predominant Anatomic Sites of Involvement
      • Ankles
      • Wrists
  • Myopathy (see Myopathy, [[Myopathy]]): muscle granulomas are usually symptomatic (may occasionally produce acute myopathy with marked CK elevation)
  • Lytic or Sclerotic Bone Lesions: usually associated with skin or visceral disease
    • Predominant Anatomic Sites of Involvement
      • Tubular hand bones: 3% of cases
      • Thoracic spine
      • Ribs
      • Sternum
    • Gallium Scan: increased uptake in “Panda” pattern
    • Bone Scan
  • Asymmetric Pseudoclubbing: due to bone cysts with dactylitis

Treatment

Corticosteroids (see Corticosteroids, [[Corticosteroids]])

  • Dose: prednisone 20-40 mg/day x 6-12 weeks, taper over months to lowest effective dose, continue for months-years
  • Indicated for eye, heart, brain, kidney, lung disease, or persistent hypercalcemia
  • Discontinued due to SE in 5-10% of cases

Chloroquine (see Chloroquine, [[Chloroquine]])

  • Dose: chloroquine 250 mg PO BID x 3 months, then 250 mg PO qday x 3 months
  • Useful for chronic pulmonary and cutaneous disease (particularly Lupus Pernio)
  • Decreases hypercalcemia [Annals, 1989]
  • May be used as steroid-sparing agent
  • Requires q3 month retinal exam to detect retinopathy
  • SE: reversible myopathy or neuropathy

Hydroxychloroquine (see Hydroxychloroquine, [[Hydroxychloroquine]])

  • Dose: plaquenil 200 mg qday-BID PO qday x 3-6 months
  • Useful for skin lesions, hypercalcemia, and neurosarcoid
  • Safer and almost as effective as Chloroquine (has replaced Chloroquine today)
  • Requires q3 month retinal exam to detect retinopathy (although retinopathy has not been reported)
  • SE: decreases blood glucose (may be useful in cases with co-existent DM)/ reversible myopathy or neuropathy

Quinacrine (see Quinacrine, [[Quinacrine]])

  • Effective in cutaneous disease
  • SE: ocular toxicity, psychosis

Methotrexate (see Methotrexate, [[Methotrexate]])

  • Dose: methotrexate 10-15 mg PO q week x 3-6 months or to disease activity
  • Steroid-sparing effect/ improvement in lung function, skin lesions, and lung disease by MRI in non-randomized trials/ particularly effective for musculoskeletal manifestations
  • SE: hepatic fibrosis is rare in low-dose- treated cases

Indomethacin (see Indomethacin, [[Indomethacin]])

  • May be used in acute sarcoidosis (with uveitis, polyarthritis, E. nodosum)

Azathioprine (Imuran) (see Azathioprine, [[Azathioprine]])

  • Dose: azathioprine 150 mg PO qday x 3-6 months
  • Effective in small subset of steroid and chloroquine-unresponsive cases (long-term effects are unknown)
  • SE: immunosuppression

Chlorambucil (see Chlorambucil, [[Chlorambucil]])

  • Dose: chlorambucil 5 mg PO qday x 3 months
  • May be useful in steroid-unresponsive cases
  • SE: immunosuppression, GI symptoms, azoospermia, amenorrhea, pulmonary fibrosis, hepatitis, seizures

Cyclophosphamide (Cytoxan) (see Cyclophosphamide, [[Cyclophosphamide]])

  • Dose: cyclophosphamide 50 mg PO qday x 3 weeks
  • SE: immunosuppression

Oxyphenbutazone (see Oxyphenbutazone, [[Oxyphenbutazone]])

  • Dose: oxyphenbutazone 400 mg PO qday x 3-6 months
  • Effective in placebo-controlled trial in Lancet, 1967 (50% improvement in steroid and oxy group)/ improvement most evident in patients treated within 2 years of disease onset
  • SE: PUD

Thalidomide (see Thalidomide, [[Thalidomide]])

  • Dose: thalidomide 200 mg PO qday x 2 weeks, then 100 mg PO qday x 11 weeks
  • May be effective in steroid-unresponsive cases with skin and lung disease

Etanercept/Infliximab/Pentoxifylline/Cellcept (see xxxx, [[xxxx]])

  • Useful in patients with poor steroid response or severe steroid side effects

Cyclosporine A (see Cyclosporine A, [[Cyclosporine A]])

  • Effective in neurosarcoidosis, patients refractory to steroids (Neurosarcoid, 1992)

Tranilest (see Tranilest, [[Tranilest]])

  • An anti-allergic agent, may have some anti-fibrotic effects

Allopurinol (see Allopurinol, [[Allopurinol]])

  • Can induce regression in cutaneous and pulmonary sarcoidosis

Radiation Therapy

  • Formerly used to treat hilar and mediastinal adenopathy
  • Whole brain irradiation has been used to control meningeal and neurosarcoid (one case with thalamic, posterior third ventricle granuloma showed improvement)
  • Megavoltage XRT has been used to treat laryngeal Sarcoid refractory to steroids

Lung, Heart, and Liver Transplantation (see xxxx, [[xxxx]])

  • Have been successfully performed in sarcoidosis (granulomas may recur in transplanted organs)
  • 2 cases of donor-organ sarcoidosis led to active sarcoidosis in organ recipient

Monitors of Sarcoid Disease Activity

  • ACE level: decreasing level correlates with remission and response to steroids
  • Gallium scan: may be useful in some settings
  • Lung DTPA: increased clearance correlates with deterioration of lung function
  • BAL CD4/CD8 ratio: persistent elevation for >12 months predicts a greater probability of non-remission or deterioration

Prognosis

  • Course: 30-50% remit (within 3 years)/30% progress/20-30% remain stable (over 5-10 years)

References

Pulmonary Hypertension

  • Pulmonary haemodynamics at rest and during exercise in patients with sarcoidosis. Respiration 1984;46:26–32
  • Pulmonary hypertension in advanced sarcoidosis: epidemiology and clinical characteristics. Eur Respir J 2005;25:783–8
  • Clinical predictors of pulmonary hypertension in sarcoidosis. Eur Respir J 2008;32:296–302
  • Pulmonary hypertension associated with sarcoidosis: mechanisms, haemodynamics and prognosis. Thorax 2006;61:68–74
  • Incidence of pulmonary hypertension and its clinical relevance in patients with sarcoidosis. Chest 2006;129:1246 –52
  • The Clinical Features of Sarcoidosis: A Comprehensive Review. Clin Rev Allergy Immunol. 2014 Oct 2 (Epub ahead of print) [MEDLINE]