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None of the conventional treatments used to treat sarcoidosis have been FDA approved for that purpose. They’re used off-label and many have not been studied or have only limited clinical evidence regarding efficacy. None claim to cure sarcoidosis or to treat the cause of sarcoidosis, which many studies suggest is bacterial. All have serious side effects and their use is usually withheld until the disease process has advanced far enough to justify their risk.

Corticosteroids

Corticosteroids are also called glucocorticoids or steroids, and there are many different medicines within the corticosteroid class of drugs, including cortisone, prednisone, and prednisolone. When sarcoidosis is deemed to need treatment, corticosteroid medications are the first drug tried.

The use of steroids to treat sarcoidosis is not FDA approved and many patients will need ongoing steroid therapy for a long time, possibly a lifetime. Steroids can cause side effects including mood swings, weight gain, acne, difficulty sleeping at night and present serious risks (e.g., osteoporosis, diabetes, high blood pressure, cataracts, glaucoma, and other serious conditions).

Oral prednisone

If sarcoidosis symptoms are worrisome prednisone is the first drug used because it aggressively suppresses the body's immune system. But the reduction in inflammatory symptoms comes at the cost of preventing the immune system from fighting the intracellular bacteria that cause sarcoidosis and eliminating these bacteria is the only way to permanent resolution of sarcoidosis symptoms (i.e., Inflammation Therapy).

Prednisone stops the actions of a protein called Nuclear Factor-Kappa Beta which is essential to effective immune system function. The complex mechanism the immune system uses to fight pathogens is disrupted and bacteria can invade the immune system putting patients at increased risk for acute infections. Prednisone also inhibits the body's response to other challenges (including hyperglycemia) and disrupts the delicate balance of bone generation.

In the short term symptoms may be reduced (e.g., chest x-ray clearer, joint pain diminished, liver enzymes lower) but prednisone can’t suppress the immune response indefinitely. Often the amount of prednisone must be increased to maintain the same symptom reduction and there’s growing evidence that use of corticosteroids is linked to relapse in sarcoidosis. It’s clinically proven that 78% of patients relapse (often to a state worse than pre-steroid) after trying to reduce their prednisone dose.

Prednisone often leads patients down a path of increasing oral steroid use and decreasing quality of life. Patients who never took prednisone are healthier in the long run. There is no study which shows that steroids improve long term prognosis but there are studies to show that relapse is frequent when the immunosuppression is withdrawn.

This report states “Then there is also the possibility that corticosteroids prolong the course of the disease by delaying resolution… We suggest.. that corticosteroid treatment itself, rather than the need for treatment, contributed to relapse..."
Outcome in Sarcoidosis - the relationship of relapse to corticosteroid therapy

Pulmonologist Dr. Marc Judson, in his hypothesis on using corticosteroids to treat sarcoidosis, An Approach to the Treatment of Pulmonary Sarcoidosis with Corticosteroids, said, "Relapses occur in 20 to 50% of patients in whom corticosteroid therapy is discontinued." He also stated "prednisone does not cure the underlying disease."

There are no studies documenting the effectiveness of steroids to treat sarcoidosis.

National Jewish Hospital states "The decision to initiate steroid therapy is further complicated by the knowledge that the treatment does not guarantee protection from pulmonary fibrosis and permanent functional impairment."

According to this article from CHEST:
Prednisone Improves Symptoms but not Lung Function in Sarcoidosis.
"Prednisone is used only because there is nothing else for sarcoidosis. It makes the patient feel better (for a while), but doesn't improve lung function."

And from a 2002 JAMA article entitled Corticosteroid Therapy in Pulmonary Sarcoidosis: "There are no data to suggest that corticosteroid therapy alters long-term disease progression."

This study, Corticosteroid treatment in sarcoidosis, states:
"Remarkably, despite >50yrs of use, there is no proof of long-term (survival) benefit from corticosteroid treatment. In addition, there are still no data regarding the optimal dose and duration of corticosteroid or other immunosuppressive therapy."

As one author put it "It is remarkable how cortisone can get a seemingly hopeless patient on his feet again. Sometimes it is so effective that he can walk all the way to the autopsy table."

The Corticosteroids for Pulmonary Sarcoidosis (Cochrane Review) reports that "Oral steroids improved the chest X-ray and a global score of CXR, symptoms and spirometry over 6-24 months., but there is little evidence of an improvement in lung function. There are no data beyond two years to indicate whether oral steroids have any modifying effect on long-term disease progression."

Non-oral steroid use

Steroids are also given by injection, topically, nasally, inhaled and via eye drops. The use of all steroid products is strongly discouraged because they’re absorbed systemically and will, to some degree, inhibit the immune system. Occasionally they must be used on a short-term basis to ameliorate intolerable symptoms or dangerous acute inflammation. Patients should consult with their doctor to devise a plan to substitute other medication for symptom relief or to discontinue the use of the steroid product as soon as the acute inflammation is under control.

Use of non-oral steroids can cause diverse side effects.

For example, steroid injections into arthritic hips offer questionable benefit, and by inducing immunosuppression they may actually put patients who later undergo total hip replacement at risk of infection. A retrospective matched cohort study of infections after arthroplasty in patients who had received a steroid injection and those who hadn't (40 in each group) showed that there had been five revisions in the injected group (four due to deep infection), but none in the matched group ( Journal of Bone and Joint Surgery 2005;87B: 454-7).

Inhaled corticosteroids: past lessons and future issues.

Inhaled corticosteroids are absorbed from the lungs into the systemic circulation, in which they can acutely decrease growth velocity in children, an effect that fortunately appears to be temporary and might have no effect on final adult height. In sufficient dosages, they also produce bone mineral loss leading to osteoporosis and might increase the risk of cataracts, glaucoma, skin atrophy, and vascular changes that increase the risk of ecchymoses. Effective evaluation of the severity and significance of these complications is challenging because highly sensitive tests do not reliably predict clinically significant events, and short-term observations do not predict long-term consequences. Also, compliance wanes with long-term treatment, and susceptibility to a particular adverse event can vary over time, even in the same individual, because of developmental or hormonal changes.

See also this study:
Evidence Growing that Inhaled Steroids, Like Pills, Can Cause Bone Loss

Steroid side effects

Steroids have many unpleasant immediate side effects, they’re addictive and when used long-term (as little as a month in some cases), they can destroy hip bones and cause diabetes, cataracts, glaucoma, opportunistic infections and osteoporosis.

Side effects are dose and duration dependent. Possible side effects from oral corticosteroids (prednisone) include:

  • increased risk of infection
  • fluid retention and increase in weight
  • thinning/softening of bones (osteoporosis)
  • diabetes
  • indigestion or worsening of peptic ulcer
  • changes in mood
  • impaired healing
  • stretch marks
  • skin thinning
  • bruising
  • increased facial hair
  • avascular necrosis
  • muscle weakness
  • eye cataracts

This Johns Hopkins website describes and illustrates the many adverse effects of prednisone.

Some of the questions patients should ask their doctor are:

  • Whether you’re suffering any of the above treatment-induced diseases or damage as a result of taking high-dose steroids.
  • Whether they are familiar with reports that corticosteroids do not halt the advancement of sarcoidosis.
  • Whether they realize that withdrawal from corticosteroids causes relapse of sarcoid symptoms that may be worse than the original symptoms.

Studies demonstrating side effects and risks of steroid therapy

Adrenal
Suppression and recovery of adrenal response after short-term, high-dose glucocorticoid treatment.

Diagnosis and therapy of patients with adrenocortical insufficiency

Adrenal insufficiency and diabetes mellitus secondary to the use of topical corticosteroids for cosmetic purpose.

Brain
Steroids and brain atrophy in multiple sclerosis.

Corticosteroids: sculptors of the hippocampal formation. (cognition, learning and memory)

Bone
Current management of corticosteroid-induced osteoporosis: variations in awareness and management.

Avascular bone necrosis. A complication of long-term corticosteroid therapy.

Malpractice and avascular necrosis: legal outcomes.

Endocrine System
[Endocrine consequences of corticotherapy. Weaning from long-term corticotherapy]
 
Eyes
Corticosteroids and glaucoma risk.

Locally administered ocular corticosteroids: benefits and risks.

Corticosteroid-induced cataracts.

[Corticosteroid-induced glaucoma following treatment of the periorbital region]

Females: Menstruation Disturbances
[The most frequent complications during long-term corticotherapy]

Gastrointestinal Hemorrhage
[Immunosuppression--a tightrope walk between iatrogenic harm and therapy]

Males: Decreased Testosterone
Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment.

Decreased testosterone levels in men with rheumatoid arthritis: effect of low dose prednisone therapy.

Reduction of serum testosterone levels during chronic glucocorticoid therapy.

Muscles
Chronic corticosteroid administration causes mitochondrial dysfunction in skeletal muscle.

Corticosteroid myopathy: a clinical and pathological study.

Impact of physical training on the ultrastructure of midthigh muscle in normal subjects and in patients treated with glucocorticoids.

[The effect of corticotherapy on respiratory muscles]

[Clinical investigation of diaphragmatic function. Relationships with the biology of muscle]

Skin
Corticosteroid-induced atrophy and barrier impairment measured by non-invasive methods in human skin.

Risks of steroid use in children

Allergic reaction
Steroid allergy: report of two cases.

Appetite and weight
Cushing syndrome
"All patients receiving pharmacologic glucocorticoid treatment develop Cushingoid features if exposed to a high enough dose for long enough (usually 1 mo or more). With the exception of abnormal growth, the signs of hypercortisolism are frequently subtler in pediatric patients than in adults. In children, the most common features that are observed include an increase in body weight due in part to an increase in
appetite and a decrease in linear growth."

Bone
Children and the risk of fractures caused by oral corticosteroids.

Growth suppression
Effect of corticoid therapy on growth hormone secretion.

Inhaled corticosteroid therapy for asthma in preschool children: growth issues.


Treatment of glucocorticoid-induced growth suppression with growth hormone. National Cooperative Growth Study.

Eye
Intraocular pressure profile of a child on a systemic corticosteroid.

Psychological effects
Adverse psychological effects of corticosteroids in children and adolescents.

The effects of corticosteroids on behavior in children with nephrotic syndrome.

Skin
New aspects of the mechanism of corticosteroid-induced dermal atrophy.

Adverse skin reactions to inhaled corticosteroids.


Adrenal suppression
Monitoring growth in asthmatic children treated with high dose inhaled glucocorticoids does not predict adrenal suppression.

Inhaled steroids and the risk of adrenal suppression in children.

Dental
Use of asthma-drugs and risk of dental caries among 5 to 7 year old Danish children: a cohort study.

Eyes
Cataract and ocular hypertension in children on inhaled corticosteroid therapy.

Steroids and Inflammation Therapy

Prednisone must be weaned before using Inflammation Therapy antibiotics. See Weaning from Steroid Medications. Occasionally the use of steroids may be necessary during Inflammation Therapy in specific cases such as severe Crohn’s disease or active uveitis.

During Inflammation Therapy (IT), limited use of sniffed, inhaled or topical steroids is acceptable for intolerable symptoms of nasal congestion, shortness of breath or itching if management of IT medications fails to dampen these Herxheimer symptoms.

Other immunosuppressant drugs

  • CellCept (mycophenolate mofetil
  • Imuran, Azasan (azathioprine)
  • Cytoxan, Neosar (cyclophosphamide)

The use of immunosuppressants is exactly the opposite of what should be done to treat sarcoidosis. Suppressing the immune system allows the intracellular bacteria that cause sarcoidosis to thrive. Their reported effectiveness is limited and due to the reduction of the symptoms that result when bacteria are being killed by the immune system (Herxheimer reaction).

Sandimmun (cyclosporin-A)

Cyclosporin-A is used to suppress rejection of transplanted organs by the body's immune system and some doctors use it to treat sarcoidosis. This study showed cyclosporine-A to be ineffective for the treatment of sarcoidosis. Treatment of Progressive Pulmonary Sarcoidosis with Cyclosporin A

The Cochrane Database of Systematic Reviews published this review of the use of immunosuppressive and cytotoxic therapy for sarcoidosis and concluded that there is not enough evidence that immune-suppressing drugs are beneficial in the treatment of pulmonary sarcoidosis.

CellCept

CellCept is widely used as a treatment to prevent organ rejection in patients who’ve had organ transplants. A few very small studies have shown it to have a limited effect in treating sarcoidosis. Side effects can include sore throat, fever, tiredness, tingling or burning in one part of the body, and weakness. CellCept increases susceptibility to infection and the risk of developing certain types of cancer.

Imuran, Azasan (azathioprine)

Imuran and Azasan are most commonly used to prevent the rejection of kidney transplants and to treat inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. What little research has been done on the subject shows that azathioprine is roughly as effective as methotrexate in treating sarcoidosis (that is to say, not very effective). The side effects of azathioprine include upset stomach, stomach pain, mouth sores, muscle aches, flu-like symptoms, yellowing of the skin or eyes, and blurred vision. Like methotrexate, azathioprine increases the risk of getting infections.

Immunosuppressive and Cytotoxic Therapy for Pulmonary Sarcoidosis


"Sarcoidosis is a condition that can affect most of the organs in the body, including the lungs, heart, brain, bones, liver and skin. Patients who have severe disease or those who do not respond to treatment with steroids are often given powerful agents that suppress the immune system in an attempt to control the disease. However, these drugs have severe side effects. There is no evidence at the moment that the benefits of these drugs outweigh their side effects." (The drugs reviewed included methotrexate, chloroquine, pentoxifylline and cyclosporin A.)

Immunosuppressants and Inflammation Therapy

Immunosuppressants are contraindicated for use with Inflammation Therapy and must be discontinued. They don’t need to be weaned and Benicar may be started to help reduce any rebound inflammation. Wait until symptoms are stable before starting Minocycline.

Anti-TNF-a drugs

  • Remicade (infliximab)
  • Enbrel (etanercept)
  • Humira (adalimumab)
  • Trental (pentoxifylline)
  • Thalomid (thalidomide)
  • Simponi (golimumab)

Anti-TNF-a drugs work by suppressing an essential component of the immune system, tumor necrosis factor alpha (TNF-a). They have serious risks and side effects including chest pain, fever, hives, trouble breathing, nausea, headache, abdominal pain, and sore throat. They can also increase the risk of infection, congestive heart failure exacerbation, liver failure and certain types of cancer.

In September, 2008 The Food and Drug Administration ordered stronger warnings on four anti-TNF-a drugs Enbrel, Remicade, Humira and Cimzia stating they can raise the risk of possibly fatal fungal infections.

TNF-alpha inhibitors break down granulomas (which also breaks down the barrier that is one of the body's mechanisms to control pathogens) but this does not lead to recovery from sarcoidosis.
Immunosuppression related to collagen-vascular disease or its treatment.

Lung Sarcoidosis Induced by TNF Antagonists in Rheumatoid Arthritis: A Case Presentation and a Literature Review.

Remicade (infliximab)

Remicade was developed to treat Crohn’s disease. It’s delivered by infusion in a medical setting. Researchers recently found infliximab to be effective in reducing the sarcoidosis symptoms of people who did not respond to other treatments, but these results came from small, short-term studies.

The use of Remicade can reactivate or allow new TB infections. The following story from the AP wire about the new 'black box' warning (the highest level of warning for a medication) for Remicade was on the Johns Hopkins Center for Tuberculosis website:

”Remicade Takers to Get TB Tests [L. Neergaard, August 15, 2001]: WASHINGTON (AP) -- Rheumatoid arthritis patients must be tested for tuberculosis before they begin taking a treatment called Remicade, the drug maker and the government announced Wednesday. Patients using Remicade are at least four times more likely than average Americans to get active tuberculosis, the Food and Drug Administration estimates. The problem: Apparently the drug suppresses users' immune systems enough that if they unknowingly carry the TB germ, the respiratory illness can suddenly flare up. The warning is serious because untreated, TB can kill -- and it's also an airborne illness that these patients could spread to family and friends. Worldwide, 88 cases of tuberculosis have been reported among the estimated 170,000 people who have tried Remicade, FDA's Dr. Bill Schwieterman said Wednesday. Fifteen of those people died. Some 2 billion people worldwide are infected with TB and risk developing an active case of the disease. In the United States, TB cases dropped to a record low of 16,377 last year. But the illness is a continuing threat here, with increased foreign travel and immigration from countries where TB is common. Rheumatoid arthritis afflicts more than 2 million Americans when their immune systems go awry and attack their joints, causing severe swelling, pain and stiffness. Remicade is a bioengineered drug that roams patients' blood to sop up an immune system protein called tumor necrosis, a factor responsible for much of the swelling. But that immune suppression, so important in fighting rheumatoid arthritis, can leave users at a higher risk for serious infections. Remicade's label has long carried warnings about various infections, but it now will carry a boxed warning in bold type about the TB risk the strongest warning possible for a prescription drug. The warning doesn't say people should stop using Remicade. The risk of activating latent TB appears highest in the first three to six months of use, so doctors should carefully evaluate those patients, Schwieterman said. But before prescribing Remicade to a first- time user, doctors should test for TB -- it's a simple skin test -- and treat TB carriers, the FDA concluded. Manufacturer Centocor Inc. will send letters to thousands of doctors who prescribe Remicade, both for rheumatoid arthritis and the bowel ailment Crohn's disease, alerting them to the warning. A similar rheumatoid arthritis treatment called Enbrel also suppresses the immune system and carries warnings that users face the risk of serious infections. But so far, Enbrel users don't seem to face a special TB risk, Schwieterman said.

But as the article below points out, TB skin tests on patients treated with immunosuppressants (routinely used on RA patients) are not reliable, because they result in false-negatives. And due to a phenomenon called cutaneous anergy, sarcoidosis patients may also have false negative TB skin tests even when not treated with immunosuppressants. Thus, the anti-TNF-a drugs can induce tuberculosis in a patient who unknowingly carries the TB bacteria.

See also:

Association Between Treatment with Infliximab and the Development of Tuberculosis

Anti-tumor necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management.

The suggestion by some doctors to treat TB in a sarcoidosis patient so that he could then use Remicade is alarming. TB is treated with Rifampin which is extremely toxic and Rifampin would create more mutant Cell Wall Deficient (CWD) bacteria as it kills the TB (it’s CWD bacteria that trigger the sarcoidosis inflammation).

Remicade can also cause an infection called mycobacterium avium.

Remicade also seems to suppress the body's response to Cell Wall Deficient bacterial infection, allowing an infection to develop from within:
A lupus-like syndrome associated with infliximab therapy.

Some people report an allergic response to Remicade. The chimeric monoclonal antibody in Remicade is part human (70%) and part mouse (30%). The mouse portion could elicit an allergic response from the human immune system.

Congestive heart failure exacerbation is a major side effect of Remicade use in patients with moderate to severe CHF.
Briefing Document for Arthritis Advisory Committee
Infliximab (Remicade®) and Congestive Heart Failure


The FDA issued a Remicade warning on December 22, 2004 regarding severe hepatic reactions - including acute liver failure - in patients receiving Remicade.

An abstract presented at the 2005 American Thoracic Society conference concluded "Given the potential for adverse effects, use of IFX (Infliximab/Remicade) in this patient population should be confined to ongoing clinical trials."

Remicade is a biologic agent approved for marketing in the treatment of rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriatic arthritis and ankylosing spondylitis. The FDA has required warning letters and label changes due to the following adverse events in patients receiving infliximab:

  • the increased incidence of neoplasia and lymphoma
  • hepatotoxicity and liver failure and
  • serious opportunistic infections including tuberculosis and histoplasmosis.

Remicade costs $4,600 per month for one IV treatment, with treatment expected to continue ongoing for a 'lifetime'. Each month about $1000 of the $4600 goes to pay the prescribing physician's clinical group, who provide the IV infusion and any emergency care needed. The New Jersey Citizen Action (NJCA), New Jersey's largest independent citizen watchdog, has filed a lawsuit to stop Remicade being promoted by promising doctors windfall profits when they prescribe the drug.

Remicade does work, in that sarcoidosis patients have reported feeling much better for the first few months but then the problems usually start. Although there are studies reporting that Remicade slows Rheumatoid Arthritis, there is a 50% dropout rate.

Enbrel (etanercept)

Enbrel was developed to treat rheumatoid arthritis and it’s delivered by injection. Researchers have tested it in small studies of people with various sarcoidosis symptoms, but results to date have been mixed.

This recent study from the Mayo Clinic was terminated early and concludes: “In patients with progressive stage II or III pulmonary sarcoidosis, etanercept (Enbrel) was frequently associated with early or late treatment failure. These data would not support the design of a large multicenter randomized trial comparing etanercept with conventional corticosteroid therapy.”
Etanercept for the Treatment of Stage II and III Progressive Pulmonary Sarcoidosis

See also:
Sarcoid-related uveitis occurring during etanercept therapy.

In March 2008 the FDA upgraded the Enbrel label to warn against infections.

MedWire News: “The US prescribing information for the psoriasis treatment etanercept now contains a boxed warning on the risk of infections in patients taking the drug.

Humira

Humira is delivered by injection. Its value as a treatment for sarcoidosis is unknown because it has not been tested in clinical trials of sarcoidosis, nevertheless, some doctors prescribe it for their sarcoidosis patients.

Trental (pentoxifylline)

Trental is used to reduce leg pain caused by poor blood circulation. It has an anti-inflammatory effect because it reduces TNF-a. Doctors prescribe it in conjunction with steroids despite the lack of clinical evidence regarding efficacy in sarcoidosis. Pentoxifylline’s side effects include dizziness, headaches, nausea, and stomach discomfort.

Pentoxifylline may have a palliative effect which allows patients to reduce their dose of prednisone but it does nothing to effect a cure. Recently, a randomized, double-blind, placebo-controlled trial of pentoxifylline in patients with pulmonary sarcoidosis reported no disease improvement or stabilization in the pentoxifylline-treated patients compared with placebo-treated patients.
Current and emerging strategies for the management of sarcoidosis

See also:
Pentoxifylline treatment of mice with chronic pulmonary tuberculosis accelerates the development of destructive pathology.

Thalidomide

Thalidomide (Thalomid) is used to treat certain skin problems. Thalidomide reduces the levels of TNF-α and, in very small studies, it has been found effective to treat chronic cutaneous sarcoid lesions that do not respond to steroids and other immuno-suppressive drugs. But sarcoidosis is a systemic disease (not confined to the skin) and thalidomide does nothing to resolve the cause of sarcoidosis which is intracellular bacteria. Side effects associated with thalidomide include drowsiness, dizziness, slowed heartbeats, rashes, and numbness or tingling in the hands or feet.

Anti-TNF-a drugs and Inflammation Therapy

These drugs are contraindicated with Inflammation Therapy and must be discontinued. They do not need to be weaned. Benicar can be started to reduce any inflammatory rebound effect. The half life of Remicade is 9.5 days and the excretion rate of these drugs is unknown. Wait 3-4 weeks before adding Minocycline.

Anti-malarial drugs

  • Plaquenil (hydroxychloroquine
  • Aralen (chloroquine)

Plaquenil) and Aralen increase pH within intracellular vacuoles and interfere with "antigen processing" in macrophages and other antigen-presenting cells. This immune system suppression reduces inflammatory symptoms. Prolonged treatment can have serious side effects. See this article. http://en.wikipedia.org/wiki/Hydroxychloroquine

Plaquenil efficacy to treat Sjögren's Syndrome has recently been called into question by this study.

Plaquenil and Aralen are contraindicated for use with Inflammation Therapy and may be discontinued without weaning. Benicar may be started but Minocycline should not be started until the drug has cleared the system (about 50 days).

Cytotoxic chemotherapy drugs

Chemotherapy includes drugs used to destroy rapidly growing cancerous tissue. Sarcoidosis is considered by some doctors to be caused by an ‘overactive’ immune system so they have concluded that the same drugs used to stop cancerous cell growth may stop growth of immune cells and damage to major organs.

Drugs used to treat cancer are usually not used on mild sarcoidosis cases, but when prednisone doesn't stop advanced sarcoidosis, physicians who don't know that sarcoidosis is caused by a chronic intracellular bacterial infection may feel desperate to help a worsening patient and consider chemotherapy to be justified.

Methotrexate

MTX, an antimetabolite and antifolate drug, is used at high doses to treat diseases with rapid cell growth (i.e., cancers). At low doses it is used to treat some autoimmune diseases (e.g., rheumatoid arthritis, lupis, psoriasis, sarcoidosis). MTX is one of the more common substitutes for steroids in the treatment of sarcoidosis. There are no large trials of methotrexate therapy or any alternative drugs in sarcoidosis. 

Although methotrexate for autoimmune diseases is taken in lower doses than it is for cancer, side effects such as hair loss, nausea, headaches, and skin pigmentation are still common.

Acting as an anti-folate (anti-DHFR), MTX inhibits one stage in the formation of DNA which makes cellular (including bacterial) reproduction more difficult. This makes methotrexate’s function similar to an antibiotic. MTX has identical actions with trimethoprim which combines with sulfa to make up Bactrim. These Course Notes from University of South Carolina outline MTX's antibacterial actions. However, neither Bactrim nor MTX is effective at killing intracellular bacteria on its own.

For the treatment of sarcoidosis, inhibition of DHFR is not thought to be the main mechanism, but rather multiple mechanisms appear to be involved including: the inhibition of enzymes involved in purine metabolism, leading to accumulation of adenosine; inhibition of T cell activation and suppression of intercellular adhesion molecule expression by T cells; increasing CD95 sensitivity of activated T cells; inhibition of methyltransferase activity, leading to (de)-activation of enzyme activity relevant to immune system function. In other words, it suppresses the immune system.

MTX may help some sarcoidosis patients feel better but it does not treat the underlying cause as Inflammation Therapy does.

Folic acid supplements are prescribed to patients taking MTX because it inhibits folate synthesis and folate is essential for many metabolic processes. Because folate it is a source of 'fuel' for bacterial growth, we recommend avoiding folic acid supplementation.

We do not advise MTX use because it suppresses the immune system. It may be discontinued without weaning.

Cytoxan, Neosar

Cytoxan, Neosar are best known as a cancer treatment, but they’re sometimes prescribed for sarcoidosis. Cyclophosphamide is more toxic than either methotrexate or azathioprine, however, so most doctors only prescribe it when other medications haven’t worked and a patient’s symptoms are very serious. Preliminary and case studies have shown that cyclophosphamide has limited effect for some people (brain and nervous system symptoms unresponsive to other conventional treatments) but its side effects include nausea, weight loss, hair loss, acne, darkened and thickened skin, mouth blisters, and fatigue. Also, taking the drug increases the risk of developing infections and certain cancers, particularly bladder cancer.

Cytotoxic chemotherapy drugs and Inflammation Therapy

Chemotherapy drugs are contraindicated during Inflammation Therapy and must be discontinued. They don’t need to be weaned and Benicar may be started to help reduce any rebound inflammation. Wait until symptoms are stable before starting Minocycline.

Lung transplant

The average survival of a sarcoidosis patient after a lung transplant is only 30 months, the quality of life during that time is poor, anti-rejection drugs must be taken and very few patients live for 5 years.

A study from Denmark shows that lungs implanted in sarcoid patients are reinfected with granulomas five months later. Furthermore, sarcoidosis reinfection came from the recipient patient.
Recurrent sarcoid granulomas in a transplanted lung derive from recipient 
Lung transplantation for sarcoidosis has significant risks and according to this report the median survival for all the sarcoidosis patients who underwent transplantation was 14 months.

“I was able to get off oxygen (I was using 2 liters) and avoided what the pulmonologist believed was the impending collapse of my right middle lobe using Inflammation Therapy. Fibrosis and bronchiectasis were still visible on my last lung imaging, but I now walk six miles a day without dyspnea.” Belinda Fenter

Radiation

Radiation therapy (even whole-brain radiation) despite its many adverse effects and limited effectiveness has been used to palliate cases of neuro-sarcoidosis unresponsive to conventional treatments.
Neurosarcoidosis: an unusual indication for radiotherapy.

Updated September 9, 2014