Pediatric Sarcoidosis Medication

Updated: Sep 17, 2021
  • Author: Girish D Sharma, MD, FCCP, FAAP; Chief Editor: Kenan Haver, MD  more...
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Medication Summary

The current therapy of choice for childhood sarcoidosis with multisystem involvement is corticosteroids, whereas a patient with anterior uveitis may be a candidate for topical steroids alone. The optimal corticosteroid dose and the duration of corticosteroid therapy for sarcoidosis have not been studied in randomized, controlled trials. Dose and duration of therapy must often be individualized.

Oral prednisone or prednisolone is usually initiated at 1-2 mg/kg/day for 4-8 weeks as induction treatment. This treatment is continued until the clinical manifestations of the disease resolve or show significant improvement.

Slowly taper the dose in patients who respond to steroids over a period of 2-3 months to an appropriate maintenance dose (ie, the lowest dose that controls the activity of the disease, which often is in the range of 10-15 mg/d or a qod regimen). Depending on which organs are involved and on the activity of the disease, maintenance treatment is usually required for at least 6 months for most age groups and is then tapered if possible.

Some patients may relapse, either during steroid taper or after discontinuation of the drug. In such cases, resume treatment with a dosage similar to that used in the induction treatment. In a few cases, patients are steroid-dependent and need long-term treatment with relatively high doses to achieve satisfactory responses. In such cases, serious complications due to chronic corticosteroid therapy, such as growth failure and bone disease, may occur. Moreover, a subset of patients with persistent active or progressive sarcoidosis may be unresponsive to corticosteroids; therefore, steroid-sparing agents are needed.


Immunosuppressive agents, such as low-dose MTX, have been used to treat rheumatoid arthritis for the last 2 decades. In patients with JRA, a double-blind, controlled study showed that MTX was efficacious and had little toxic effect. Randomized, controlled trials have demonstrated that MTX has clinically important benefits and steroid-sparing properties in many chronic inflammatory disorders, including Crohn disease, multiple sclerosis, and asthma. Most reports on MTX therapy in sarcoidosis have involved adults.

Lacher's initial case report in 1968 described the successful use of MTX in a 27-year-old woman with sarcoidosis who was unresponsive to glucocorticoids and vinblastine treatment. Since this report, numerous small, uncontrolled clinical trials have consistently shown MTX to be beneficial in patients with steroid-resistant disease or in those with unacceptable adverse effects from glucocorticoids.

Lower and Baughman treated 15 adult patients on prednisone who had progressive disease or excessive steroid adverse effects with MTX for 6 months and found that 12 patients had improvement in objective parameters. Five relapses occurred as treatment was withdrawn. [27]

In a larger, subsequent series, these investigators treated 50 symptomatic patients for 2 years with MTX and showed an improvement in pulmonary function and a reduction in steroid dosage in 66% of patients. Although MTX is steroid-sparing, however, its use has been associated with significant adverse effects, including hepatotoxic effects (it may lead to fibrosis or cirrhosis), neutropenia, cough, obstructive lung disease, and hypersensitivity pneumonitis. It is also teratogenic and has been shown to cause spontaneous abortions in early pregnancies.

Advise male and female patients to use appropriate birth control for as long as 6 months after discontinuation of MTX. Although some concern exists that the drug has the potential to cause malignancy, several large series have failed to show an increase in malignancy in cases of MTX-treated patients followed for up to 10 years.

In a study, Gedalia et al found symptom improvement in pediatric patients treated with MTX. In the report, the investigators described their experience with 6 months of low-dose oral MTX following a strict protocol in 7 children with biopsy-proven sarcoidosis. [28] Corticosteroids were used for the first 6 weeks only in 6 of 7 cases. The patients were treated with low-dose MTX for 1 year, and the clinical response was scored using a composite of the various symptoms encountered.

In the study, MTX therapy resulted in improvement in clinical symptom score and decreased mean daily steroid dosage. Additionally, parallel decreases in the ESR and the mean serum ACE concentrations were observed. No adverse effects occurred in these patients, all of whom received folate supplementation. The authors suggested that MTX administered orally in low doses in childhood sarcoidosis was effective, safe, and had steroid-sparing properties.

However, because of significant concerns regarding the risk of long-term adverse effects of MTX therapy and the lack of a randomized, controlled trial, some experts have questioned the therapeutic index of MTX for corticosteroid-resistant sarcoidosis in children. Liver biopsy performed after a cumulative MTX dose of 1-1.5 g has been proposed to monitor liver toxicity. MTX toxicity can be minimized by the use of folic or folinic acid. Successful steroid-sparing treatment with mycophenolate mofetil was described in an adolescent with renal-limited sarcoidosis complicated by renal failure.

Additional medications

Alternative immunosuppressive agents, such as azathioprine, cyclophosphamide, chlorambucil, and cyclosporine, have been tried in adult cases of sarcoidosis with questionable efficacy. The high toxicity profile of these agents, including an increased risk of lymphoproliferative disorders and carcinomas, has limited their use to patients with severe disease that is refractory to other agents. Studies have failed to demonstrate any beneficial effect of inhaled corticosteroids in pulmonary sarcoidosis.

Hydroxychloroquine has been used with success in adults for chronic disfiguring cutaneous sarcoidosis that is unresponsive to corticosteroids, with serial monitoring for ocular toxicity. The quinolones also are efficacious in the management of hypercalcemia in sarcoidosis. Although clinical trials and case reports support the use of antimalarial agents in sarcoidosis, no double-blind placebo-controlled studies have been conducted. Several other agents, such as melatonin, thalidomide, and pentoxifylline, have been reported as useful in some adult patients with refractory sarcoidosis.

Newer treatment strategies have included the use of monoclonal antibodies to TNF-α, such as infliximab. Anecdotal case reports about the use of infliximab in renal sarcoidosis are found in the literature.



Class Summary

Pharmacologic therapy inhibits the lymphokine IL-2 from activated helper T lymphocytes (CD4), which controls T cell proliferation and recruitment of these cells from the blood. Therapy decreases the release of IL-1 monocyte chemotactic factor, an initiating event in granuloma formation.


Oral corticosteroids are indicated in patients with pronounced symptomatic disease and/or evidence of progressive damage to involved organs. Systemic therapy is clearly indicated for extrapulmonary sarcoidosis (eg, cardiac disease, neurologic disease, eye disease not responding to topical therapy, hypercalcemia, hepatosplenomegaly, sarcoid hepatitis, marked lymphadenopathy).

Corticosteroid therapy is not indicated for asymptomatic patients with isolated bilateral hilar adenopathy. In contrast, severe respiratory symptoms, decreasing lung function, and progressive pulmonary infiltrates on chest radiograph warrant corticosteroid therapy.


Immunosuppressive agents

Class Summary

These agents have been proposed as an alternative therapy for refractory sarcoidosis in adults, particularly low-dose MTX. Although randomized controlled trials are lacking, recent reports in adults and children suggest that low-dose MTX is effective, safe, and has long-term corticosteroid-sparing properties. Because low-dose MTX displays far fewer adverse effects than other alternative agents, such as cyclosporin A or cyclophosphamide, select MTX first in refractory sarcoidosis.

Methotrexate (Trexall, Rheumatrex)

Low-dose MTX therapy has been used to treat various manifestations of sarcoidosis in adult patients, such as skin disease, musculoskeletal complications, progressive pulmonary sarcoidosis, and neurosarcoidosis. In pediatric sarcoidosis, low-dose MTX has been used to treat a subset of patients with persistent active or progressive disease that is unresponsive to corticosteroids.