Sarcoidosis is a disease most commonly affecting the lungs, but it can also involve lymph
nodes, skin, liver, spleen, eyes, bones, and glands. The cause of the disease is unknown.
When it occurs it can produce an inflammatory reaction leading to irreversible organ damage
In sarcoidosis granulomas can form in various organs (primarily lung) which can lead to its
dysfunction. Granuloma is formed by clusters of inflammatory cells. The formation of
these granulomas is influenced by the release of a substance called TNF-alpha (tumor
necrosis factor alpha) which is found in some white blood cells. A drug known as
pentoxifylline (POF) is known to markedly reduce the release of TNF-alpha.
The standard medical treatment for sarcoidosis is steroid therapy. However, steroid therapy
is associated with significant side effects and often must be stopped. Unfortunately, some
of these patients can relapse when the steroid therapy is discontinued. Because of this,
researchers are interested in finding alternative therapies for the treatment of
This study will evaluate the effectiveness of giving POF to patients with sarcoidosis
currently taking steroids. Researchers will compare the results between patients taking
steroids with pentoxifylline and those patients taking steroids alone.
Corticosteroids are currently the mainstay of therapy for active pulmonary sarcoidosis and
are used to prevent relapses in many patients with stable disease. The pulmonary
manifestations of sarcoidosis are heterogenous and not all patients require corticosteroid
therapy. Corticosteroids often produce undesirable side effects and, therefore, other
therapies that can reduce or replace corticosteroid use are being sought. As tumor necrosis
factor-alpha (TNF-alpha) plays a pivotal role in the formation of granulomata (the
pathological hallmark of the disease), drugs that inhibit its production/release may prove
effective in the treatment of this disease. Pentoxifylline (POF), a xanthine derivative
used for many years in the treatment of peripheral vascular disease, is known to inhibit
TNF-alpha release by human peripheral blood mononuclear cells and alveolar macrophages from
patients with active sarcoidosis. To evaluate whether this drug is beneficial in the
treatment of sarcoidosis, we propose to conduct a randomized, double-blind,
placebo-controlled trial with POF in patients with pulmonary sarcoidosis on corticosteroid
therapy. The primary objective of this study is to determine whether POF treatment can be
beneficial as an adjunct to corticosteroid therapy in patients with pulmonary sarcoidosis.
The role of TNF-alpha and other cytokines (released from alveolar macrophages) in explaining
treatment responses defined by whether or not a patient improved will be assessed by testing
whether the effect of treatment on the probability of improvement varies with cytokine
1. Admission to this protocol will require a diagnosis of pulmonary sarcoidosis with or
without ocular sarcoidosis based on clinical history, and biopsy of either lung,
intrathoracic or other lymph nodes, or internal organs consistent with sarcoidosis,
with all other causes of granuloma ruled out. Prior to enrollment in the study,
patients will have their biopsy slides reviewed by a pathologist for confirmation of
2. Males or females between 18 and 70 years of age on corticosteroid therapy.
1. Patients with active sarcoidosis of major organs other than the lungs and eyes (e.g.,
central nervous system, cardiac, renal) that require corticosteroid therapy.
2. Patients with uncontrolled hypertension, uncontrolled diabetes, history of cerebral
or retinal hemorrhage, heart failure (New York class III or higher), renal failure
(on dialysis), liver failure (with portal hypertension and ascites), cancer EXCEPT
non-metastatic basal or squamous cell carcinoma of the skin, hematologic disorders,
including severe anemia (hemoglobin less than or equal to 7 g/dl), granulocytopenia,
platelet disorders, or a need for anticoagulation therapy.
3. Patients with concomitant obstructive lung disease (i.e., asthma, COPD, cystic
fibrosis) or other interstitial lung diseases since changes in pulmonary function in
such patients could not be attributed to sarcoidosis alone.
4. Patients who are pregnant or lactating.
5. Women of child-bearing potential without an accepted method of birth control.
6. Patients with a positive serum test for human immunodeficiency virus or hepatitis B
or C virus.
7. Patients incapable of giving informed consent.
8. Patients allergic to POF or methylxanthines such as caffeine, theophylline and
9. Patients currently taking corticosteroids for disease other than pulmonary
sarcoidosis, theophylline, POF, or other xanthines, or patients who have been on
these drugs in the preceding three months.