Medication Summary
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Class Summary
NSAIDs are indicated for arthralgias and other rheumatic complaints and not for significant pulmonary disease. Patients with stage I sarcoidosis require only occasional treatment with NSAIDs.
Naproxen (Aleve, Anaprox, Naprelan, Naprosyn)
Naproxen is used for relief of mild to moderate pain; it inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.
Flurbiprofen
Flurbiprofen may inhibit cyclo-oxygenase, which, in turn, inhibits prostaglandin biosynthesis. These effects may result in analgesic, antipyretic, and anti-inflammatory activities.
Ibuprofen (Motrin, Ibuprin, Advil, Addaprin, Neoprofen)
Ibuprofen and other NSAIDs are useful in the management of joint complaints. It inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.
Ketoprofen
Ketoprofen is indicated for relief of mild to moderate pain and inflammation. Small initial dosages are indicated in small and elderly patients and in those with renal or liver disease. It inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.
Indomethacin (Indocin)
Indomethacin inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis. It is rapidly absorbed and metabolism occurs in the liver by demethylation, deacetylation, and glucuronide conjugation.
Corticosteroids
Class Summary
Corticosteroids are the cornerstone of therapy. They have potent immunologic effects that ameliorate many signs and symptoms.
Prednisone (Rayos)
Prednisone is an immunosuppressant used for the treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Prednisone stabilizes lysosomal membranes and suppresses lymphocytes and antibody production. The response may be rapid but often is seen over 12-16 weeks.
Antimetabolites
Class Summary
Given the adverse effect profile of corticosteroids, methotrexate has recently received significant attention as either a corticosteroid alternative or a corticosteroid-sparing agent.
Methotrexate (Folex PFS, Rheumatrex, Otrexup)
Methotrexate is an antimetabolite that interferes with folate metabolism. It is cell cycle specific. Actively proliferating cells are more susceptible to its effects.
Antimalarial agents
Class Summary
Antimalarial agents have previously been used for the treatment of rheumatoid arthritis. Literature supporting its use in sarcoidosis is limited to case series. They have a relatively benign adverse effect profile.
Hydroxychloroquine (Plaquenil)
Hydroxychloroquine may be most useful in the management of osseous involvement. It inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions.
Immunosuppressants
Class Summary
These agents may be of benefit in patients whose conditions have not responded to steroids or in patients unable to tolerate prednisone.
Chlorambucil (Leukeran)
Chlorambucil is a bifunctional slow-acting aromatic nitrogen mustard derivative that interferes with DNA replication, transcription, and nucleic acid function by alkylation. It alkylates and cross-links strands of DNA. Alkylation takes place through the formation of a highly reactive ethylenimonium radical. The probable mode of action involves cross-linkage of the ethylenimonium derivative between two strands of helical DNA and subsequent interference with replication. Chlorambucil is known chemically as 4-[bis(2chlorethyl)amino]benzene butanoic acid.
The dosage must be carefully adjusted according to the response of the patient and must be reduced as soon as an abrupt fall in the white blood cell count occurs.
Azathioprine (Azasan, Imuran)
Azathioprine is an imidazolyl derivative of 6-mercaptopurine. Many of its biological effects are similar to those of the parent compound. Both compounds are eliminated rapidly from blood and are oxidized or methylated in erythrocytes and the liver. No azathioprine or mercaptopurine is detectable in urine 8 hours after it is taken.
Azathioprine antagonizes purine metabolism and inhibits the synthesis of DNA, RNA, and proteins. The mechanism whereby azathioprine affects autoimmune diseases is unknown. It works primarily on T cells. It suppresses hypersensitivities of the cell-mediated type and causes variable alterations in antibody production. Immunosuppressive, delayed hypersensitivity, and cellular cytotoxicity tests are suppressed to a greater degree than antibody responses. It works very slowly; it may require 6-12 months of trial prior to effect. Up to 10% of patients may have idiosyncratic reactions disallowing use. Do not allow the WBC count to drop below 3000/μL or the lymphocyte count to drop below 1000/μL.
Azathioprine is available in a tablet form for oral administration or in 100-mg vials for intravenous injection.
Cyclophosphamide
Cyclophosphamide is a cyclic polypeptide that suppresses some humoral activity. It is chemically related to nitrogen mustards. It is activated in the liver to its active metabolite, 4-hydroxycyclophosphamide, which alkylates the target sites in susceptible cells in an all-or-none type reaction. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells.
Cyclophosphamide is biotransformed by cytochrome P-450 system to hydroxylated intermediates that break down to active phosphoramide mustard and acrolein. The interaction of phosphoramide mustard with DNA is considered cytotoxic.
When used in autoimmune diseases, the mechanism of action is thought to involve immunosuppression due to destruction of immune cells via DNA cross-linking.
In high doses, it affects B cells by inhibiting clonal expansion and suppression of the production of immunoglobulins. With long-term low-dose therapy, it affects T-cell functions.
Cyclosporine (Gengraf, Neoral, Sandimmune)
Cyclosporine is an 11-amino acid cyclic peptide and natural product of fungi. It acts on T-cell replication and activity.
It is a specific modulator of T-cell function and an agent that depresses cell-mediated immune responses by inhibiting helper T-cell function. Preferential and reversible inhibition of T lymphocytes in the G0 or G1 phase of the cell cycle is suggested.
Cyclosporine binds to cyclophilin, an intracellular protein, which, in turn, prevents the formation of interleukin 2 and the subsequent recruitment of activated T cells.
It has about 30% bioavailability, but there is marked interindividual variability. It specifically inhibits T-lymphocyte function with minimal activity against B cells. Maximum suppression of T-lymphocyte proliferation requires that the drug be present during the first 24 hours of antigenic exposure.
Cyclosporine suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft-vs-host disease) for a variety of organs.
Infliximab (Remicade)
Infliximab neutralizes cytokine TNF-alpha and inhibits its binding to the TNF-alpha receptor. Mix it in 250 mL of normal saline for infusion over 2 hours. It must be used with a low-protein-binding filter (1.2 micron or less). Infliximab is indicated to reduce the signs and symptoms of active ankylosing spondylitis
Thalidomide (Thalomid)
Thalidomide is an immunomodulatory agent that may suppress excessive production of TNF-alpha and may down-regulate selected cell-surface adhesion molecules involved in leukocyte migration.
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Stage I sarcoidosis.
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Stage II sarcoidosis.
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Stage III sarcoidosis.
Tables
Stage |
Remission (%) |
Asymptomatic at 5 y (%) |
Chest Radiograph Clearing (%) |
Mortality (%) |
Stage I |
60-90 |
95 |
54 |
0 |
Stage II |
40-70 |
58 |
31 |
11 |
Stage III |
10-20 |
25 |
10 |
18 |
Stage IV |
0 |
N/A |
0 |
N/A |
Characteristics |
Group La |
Group Sb |
P |
Dyspnea score (range 1-4) |
0.24 |
0.47 |
NS |
Fibrosis score (range 0-16) |
0.83 |
1.47 |
NS |
FEV1c (% predicted) |
95.9 |
86.9 |
0.05 |
VCd (% predicted) |
99.8 |
90.8 |
0.02 |
DLCOe (% predicted) |
84.3 |
77.7 |
NS |
Weight gain (kg) |
+3.26 |
+0.99 |
0.02 |
a Long-term steroids. b Short bursts of steroids. c Forced expiratory volume in 1 second. d Ventilatory capacity. e Diffusing capacity of lung for carbon monoxide. |
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