Page 1026 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPter 73 Sarcoidosis 989

The intensity of surveillance of sarcoidosis depends on the ALTERNATIVE CYTOTOXIC THERAPIES
severity of clinical presentation. When sarcoidosis undergoes
remission, the disease rarely recurs; exceptions often involve Corticosteroid-sparing therapies are frequently used for chronic,
neurological or ocular manifestations. No biomarkers have been progressive sarcoidosis when corticosteroid adverse effects sig-
found to be useful in management decisions. nificantly degrade quality of life. 2,47,48 Low-dose weekly methotrex-
ate (10–20 mg/week) is recommended for pulmonary, cardiac,
TREATMENT ocular (panuveitis), cutaneous, and neurological sarcoidosis
requiring higher doses of corticosteroids. Success rates range
from 50% to 70%, but it may take ≥6 months to be effective.
tHeraPeUtIC PrInCIPLes Potential serious complications include hepatotoxicity, oppor-
Indications for Corticosteroid Therapy in Patients tunistic infections, bone marrow suppression, and pulmonary
With Sarcoidosis toxicity. Azathioprine can also be useful in sarcoidosis with similar
response rates to methotrexate but a slightly increased risk of
• Pulmonary involvement infection. Mycophenolate mofetil and leflunomide have been
• Moderate or severe, symptomatic pulmonary disease used as steroid-sparing agents in small case series. Potential drug
• Progressive, symptomatic pulmonary disease toxicities for all four drugs include bone marrow suppression,
• Persistent pulmonary infiltrates or abnormal lung function for 1–2 gastrointestinal symptoms, skin rashes, and an increased risk of
years with mild symptoms to assess reversibility
• Advanced fibrocystic disease malignancy. Cyclophosphamide has been used in steroid-
• Extrapulmonary involvement recalcitrant sarcoidosis, particularly refractory neurosarcoidosis,
• Threatened organ failure: severe ocular, cardiac, or central nervous but its use is severely limited because of its oncogenic potential.
system (CNS) disease Calcineurin inhibitors suppress T-cell activation but do not work
• Posterior uveitis or anterior uveitis not responding to local in sarcoidosis.
steroids Clinical trials support the effectiveness of biological agents
• Persistent hypercalcemia
• Persistent renal or hepatic dysfunction targeting specific immunological pathways in sarcoidosis.
• Pituitary disease Infliximab (anti-TNF) had a small impact on pulmonary func-
• Myopathy tion over 6 months but was effective for many extrapulmonary
• Palpable splenomegaly or evidence of hypersplenism, such as manifestations. Case series have suggested that adalimumab may
thrombocytopenia also be effective in some patients with sarcoidosis. Etanercept,
• Severe fatigue and weight loss golimumab (anti-TNF), and ustekinumab (anti–IL12/IL23) were
• Painful lymphadenopathy ineffective in pulmonary sarcoidosis. Interestingly, there have been
• Disfiguring skin disease
some case reports of successful use of rituximab (anti–B cell) in
treatment-refractory sarcoidosis, particularly neurosarcoidosis,
47
Current therapies are nonspecific and largely unproven. If there although how it may work in sarcoidosis remains unclear. Further
is no organ-threatening involvement at presentation, a period studies are needed to define the role of biological agents (Chapter
of observation is usually indicated to evaluate whether the disease 89) in sarcoidosis, not least because these therapies carry risks
will remit spontaneously. of serious, life-threatening infections and malignancy.
Corticosteroids remain the mainstay of therapy for progressive
organ-threatening or life-threatening manifestations of sarcoidosis. SPECIFIC SITUATIONS
The optimal doses and duration of corticosteroid treatment have
not been established by rigorous clinical studies. For pulmonary Löfgren Syndrome
and cutaneous disease, initial treatment is usually with no more Nonsteroidal antiinflammatory drugs (NSAIDs) are recommended
than 20–40 mg/day of prednisone for 2–4 weeks, followed by a for relief of constitutional symptoms and joint pains. For disabling
slow tapering regimen over several months to a maintenance arthritis or severe constitutional symptoms, corticosteroids are
dose of 5–15 mg/day. Alternate-day therapy has been suggested, almost immediately effective and can generally be tapered over
although it may be ineffective in a subgroup of patients who a few weeks to months.
subsequently respond to daily dosing. Treatment is normally
continued for at least 6–12 months, as premature tapering is Mucocutaneous and Joint Sarcoidosis
likely to result in relapse. Recurrent, progressive pulmonary and Hypercalcemia
disease occurs in 16–74% of patients as corticosteroid therapy Hydroxychloroquine is often tried as a first-line treatment for
is tapered; patients with repetitive relapses usually need chronic cutaneous, joint, nasal, or sinus manifestations when corticoster-
suppressive therapy to minimize loss of lung function. Weight oids are not immediately needed. Hypercalcemia may also respond
gain, hypertension, hyperglycemia, glaucoma, and osteoporosis to hydroxychloroquine as maintenance therapy. Chloroquine
are serious potential complications. Bisphosphonate therapy is may be effective in some patients unresponsive to hydroxychlo-
recommended for patients on chronic corticosteroid therapy. roquine but has a greater potential for ocular toxicity and is
Inhaled corticosteroids may help reduce symptoms of cough or rarely used. Minocycline and doxycycline have been effective in
airway irritability but are not useful as sole agents in pulmonary a small number of patients with cutaneous sarcoidosis, but wider
sarcoidosis. experience shows that these drugs are rarely effective.
Pentoxifylline, a phosphodiesterase inhibitor, was shown to
be beneficial in one study of mild pulmonary sarcoidosis, although Ocular Sarcoidosis
wider experience suggests only very few patients respond to Anterior uveitis is usually treated with topical corticosteroids.
it. Gastrointestinal side effects often limit the dose that is Oral or intravenous corticosteroids are used initially for posterior
tolerated. uveitis, chorioretinitis, or optic neuritis.