sarcoidosis%20-%20pulmonary
SARCOIDOSIS - PULMONARY
Sarcoidosis is a multisystem disease which may present with non-specific symptoms or symptoms related to organ-specific involvement.
Non-specific symptoms include fever, malaise, fatigue and weight loss.
Pulmonary involvement is seen in >90% of sarcoidosis patients.

Principles of Therapy

  • Decision to treat sarcoidosis depends on the presence of symptoms & stage of the disease

Pulmonary Disease

  • Pulmonary disease is a relative indication for treatment

Stage 1

  • Studies show that no treatment is necessary for patients w/ stage 1 disease

Stage 2-3

  • Asymptomatic patients w/ stage 2 or 3 disease may not benefit from systemic therapy
    • Treatment may be required in asymptomatic patients w/ progressive loss of lung function & persistent infiltrates

Symptomatic Disease

  • Treatment w/ corticosteroids provides acute relief & reversal of organ dysfunction

Absolute Indications for Treatment of Sarcoidosis Include the following:

  • Cardiac involvement
  • Neurosarcoidosis
  • Hypercalcemia
  • Ocular disease that is refractory to topical therapy

Other Extra Pulmonary Diseases

  • Treatment is usually administered in progressive, symptomatic, extrapulmonary disease

Pharmacotherapy

Corticosteroids

Systemic Corticosteroids

  • The mainstay in the treatment of pulmonary sarcoidosis
  • Recommended for patients w/ hypercalcemia, stage II/III pulmonary sarcoidosis w/ moderate-severe or progressive disease, & those w/ radiographic evidence of pulmonary changes
  • Usually results in improvement of respiratory symptoms, lung function studies & CXR findings
    • Reappearance of symptoms & CXR abnormalities are frequent after discontinuation of treatment
  • A meta-analysis concluded that corticosteroid use in pulmonary sarcoidosis results in improvement of CXR & spirometry over 6-24 months, but there is minimal proof of improvement in lung function
    • It is not clear whether these improvements are maintained beyond 2 years
    • It is not known whether corticosteroids improve long-term pulmonary function or favorably alter disease progression
  • Corticosteroid use should be reserved for those w/ clear clinical indication because of its known potential toxicity & lack of evidence of sustained benefit

Follow-Up & Duration of Therapy

  • Patient should be evaluated after 1-3 months of corticosteroid therapy
    • Patients who fail to respond after 3 months are unlikely to respond to a longer course of therapy
  • Patients who respond should have their corticosteroid dosages tapered & treatment continued for a minimum of 12 months
  • After a treatment period of 6-24 months, withdrawal of corticosteroids should be considered, w/ continued monitoring for relapse
    • Certain patients may still require long-term low-dose therapy to prevent recurrent disease

Complications of Therapy

  • Patients receiving chronic corticosteroid therapy are at risk for osteoporosis
    • Bisphosphonates & Calcitonin may be used for prevention of osteoporosis complications

Inhaled Corticosteroids

  • An alternative to oral corticosteroids
  • May be used for patients w/ pulmonary symptoms especially chronic coughing, & for those whose systemic steroid medications are due for reduction/tapering
  • Studies show that patients experienced symptom improvement while on inhaled Budesonide treatment

Immunosuppressants

  • Eg Azathioprine, Methotrexate, Cyclophosphamide, Chlorambucil, Cyclosporine, Leflunomide
  • May benefit patients who fail to respond to corticosteroids
  • Usually given in combination w/ corticosteroids but may also be used as monotherapy

Azathioprine

  • Second-line treatment for sarcoidosis; as a corticosteroid-sparing agent
  • Preferred agent, along w/ Methotrexate, because of a more favorable safety profile
  • Usual dose: 50-100 mg daily initially, then up to 3 mg/kg daily as maintenance

Chlorambucil

  • Rarely used because of its increased risk of malignancy

Cyclophosphamide

  • Decreases lymphocyte proliferation & function thereby decreasing the immune response
  • Seldom used as 3rd-line treatment because of increased appearance of pancytopenia
  • Has been effective in some patients who have failed therapy w/ corticosteroids & Methotrexate
  • Significant toxicity limits its use in patients w/ severe, refractory disease

Leflunomide

  • Recommended for patients w/ chronic sarcoidosis intolerant to Methotrexate therapy
  • May also be used in combination w/ Methotrexate in patients w/ chronic pulmonary sarcoidosis refractory to other therapies

Methotrexate

  • Recommended as 1st-line treatment when in combination w/ steroids
  • Recommended 2nd-line treatment for steroid-refractory patients as a steroid-sparing agent
    • Used especially w/ the presence of adverse effects of corticosteroid therapy
  • Usual dose: 10 mg once a week initially, then 2.5-15 mg once a week as maintenance

Immunomodulators

  • 3rd-line treatment option for patients unresponsive to corticosteroids &/or immunosuppressants
  • Lacks evidence for the treatment of sarcoidosis
  • Adequate tests for presence of ongoing infection (eg latent tuberculosis) should be done prior to initiation of treatment

Tumor Necrosis Factor-Alpha (TNF-alpha) Inhibitors

  • Eg Infliximab, Adalimumab
  • Evidence to support Adalimumab’s efficacy for pulmonary chronic sarcoidosis are limited
  • Infliximab is used as an alternative pulmonary & extrapulmonary sarcoidosis therapy for patients refractory to corticosteroids
  • Studies show that Infliximab is an effective TNF-alpha inhibitor not only against pulmonary, but also for other types of sarcoidosis (ie skin, kidney, muscle, bone), & for patients w/ hypercalcemia, neuropathy & disabling fatigue

Etanercept

  • Further studies are needed to prove the efficacy of Etanercept therapy against sarcoidosis

Pentoxifylline

  • Studies show that patients w/ acute pulmonary sarcoidosis respond well to Pentoxifylline

Thalidomide

  • Studies proving the efficacy of Thalidomide for pulmonary sarcoidosis is lacking

Anti-malarial Agents

Chloroquine & Hydroxychloroquine

  • Action: May inhibit macrophage production of TNF-α
  • Efficacy for the treatment of chronic sarcoidosis has been established
  • Effect on disease activity is more likely suppressive than curative
  • Chloroquine has been shown to be particularly helpful in hypercalcemia & lupus pernio
  • Hydroxychloroquine is usually preferred because of lower risk of ocular toxicity
  • Usual dose:
    • Chloroquine: 500 mg daily initially then 250 mg daily as maintenance
    • Hydroxychloroquine: 200-400 mg daily
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