SARCOIDOSIS - General Information and FAQs - ABOUT THE MARSHALL PROTOCOL

Not logged in - Login | Register

The Marshall Protocol Study Site > ABOUT THE MARSHALL PROTOCOL > General Information and FAQs > SARCOIDOSIS

SARCOIDOSIS

Moderated by: Dr Trevor Marshall

New Topic

Author

Post

Aussie Barb
Research Team

Joined:	Thu Jul 22nd, 2004
Location:	Australia
Posts:	19547
Status:	Offline

Posted: Sun May 22nd, 2005 06:40

Quote

⁽^filelink⁾
Sarcoidosis and the Marshall Protocol

The only effective treatment for sarcoidosis is the Marshall Protocol

"Sarcoidosis kills. Your doctor is correct in that, but totally incorrect in representing that any (standard) treatment he can offer you will make any measurable difference in the rate of long-term decline. There are no studies showing that any of the treatments he is offering you will be effective. This is because he (and his pulmonologist colleagues) just do not understand the disease. ..........

We know of around 300 sarcoid patients who are recovering on the MP. More than 50 of those have recovered beyond the point of relapse. There are hundreds more that we are not following. You need to understand that killing the bacteria is a CURE, not a therapy.

The conventional treatments are *NOT* FDA approved. They have not even been checked by the FDA for safety.

The prescription of Prednisone, Methotrexate, etc, for Sarcoidosis is ALL off-label. Please see First report from ATS, San Diego

The FDA has never approved any drug for the treatment of Sarcoidosis. Prednisone was never approved, Methotrexate, Humira, NOTHING has ever approved by the FDA for the therapy of Sarcoidosis.

FDA has designated several drugs which appear promising. This Foundation applied for, and received, designation by the FDA of Clindamycin and Minocycline in the treatment of Sarcoidosis.

So now that you have found your caregivers are totally incorrect on one issue, are you prepared to look more closely at the other things they have told you?

Here is the cumulative list of all drugs the FDA has designated might be suitable for Sarcodiosis.
http://www.fda.gov/orphan/designat/alldes.rtf
You will note that our Autoimmunity Research Foundation is responsible for 2 out of the total 5

Dr. Trevor Marshall, Ph.D.

Myths

Sarcoidosis experts continue to perpetuate many myths regarding this disease. This is the result of anecdotal misinformation which has gained credence by repetition. In other words, much of what sarcoidosis 'experts' proclaim about sarcoidosis is not substantiated by science or scientific study.

The MP study site vs other sarc support groups

This site tells you all about how sarc sufferers are getting better by following the Marshall Protocol, a treatment devised by a research scientist, Dr Trevor Marshall. There's a huge amount of information here - don't try to read it all at once!

You can try the other sarc websites if you like, and listen to the despairing cries of those whose doctors have given them no hope, and no treatment but prednisone, which, as you've discovered, does no long-term good. Then come back here and sense the hopefulness and jubilation of those who know they're healing.

The MP isn't easy, but it works, and you can look forward to better health now that you've found it. ~Julia

For a basic explanation of sarcoidosis from Wikipedia, the free encyclopedia, see Sarcoidosis

See also:

What is the Marshall Protocol? The First Basic Questions Answered

The Marshall Protocol -- simple explanations

Why isn't the MP being used by more doctors?

MP Phase One Guideline

Papers for Physicians

(scroll down for up-to-date, accurate information on Sarcoidosis)

Foundation Staff
.

Joined:	Sat Jul 10th, 2004
Location:
Posts:	17283
Status:	Offline

Posted: Thu May 26th, 2005 13:50

Quote

^[filelink]
Pulmonary involvement

Lung involvement may be misdiagnosed as a "respiratory infection" It has to be differentiated from "pneumonia"
http://tinyurl.com/43hqr

and lots of other conditions.
http://tinyurl.com/58rjz

DLco gas transfer factor test

"The best test to show inflammation in pulmonary interstitial tissue is the DLco gas transfer factor test. The DLco is important because it recovers back to 'normal' during the MP, allowing sarcoidosis patients who were needing 24/7 oxygen to be able to discard the oxygen and still function reasonably well. Even if the fibrotic tissue remains, the sarcies recover lung capabilities based on FEV1 (muscle tone) and DLco (gas transfer) improvements.

It my opinion that the biggest single factor in lung effectiveness is the ability of the lungs to transfer gases to and from the blood. This is measured by the DLco test. This capability is significantly reduced during active inflammation, and of course by immunopathology.

The DLCO (diffusing lung capacity) test is usually given at the same time that other pulmonary function tests are given. It is not a self test - it's usually administered by a respiratory therapist in a facility such as a hospital, by a doctor's order.

You inhale a single breath of a known quantity of carbon monoxide, then hold your breath, then exhale. This is all done with special equipment so the exhaled breath can be analyzed to determine the amount of carbon monoxide that was absorbed in the single breath. The results indicate how well oxygen passes from the lung's "air sacs" across to the blood."

...Trevor...

Lung diffusion testing
Illustration of DLco test

Evaluating pulmonary function tests

The overall accuracy of the FVC for restriction is about 60%.(Aaron SD, Dales RE, Cardinal P. How accurate is spirometry at predicting restrictive pulmonary impairment? Chest. 1999;115:869-873.) Based on this sort of accuracy, there is a wide a range of margin for errors.

The PFT results are comparative; they are standardized for standing height, age and gender, and for ethnic group. This is called the predicted value. Predicted values can be selected by the user from amongst 16 sets for adults, and 13 sets of equations for children and adolescents.

"In a healthy population there is great variation in spirometric values even after taking into account age, height, gender and ethnic group. This underlines the need for putting great emphasis on clinical data and the patient’s previous medical history in interpreting spirometric data. The best predicted value for a patient is the personal reference value, i.e. the value obtained in a clinically optimal period; such personal best values may reveal that values which were within the normal range are not the patient’s optimal values." http://www.spirxpert.com/welcome.htm

Obstructive lung disease

It's a little-recognized fact that sarcoidosis can cause PFTs results to indicate obstructive lung disease (sarcoidosis is considered a restrictive lung disease). This is because chest lymph nodes may become so enlarged they compress airways and/or granulomas themselves may obstruct airways.

This article explains the difference between restrictive and obstructive lung disease. http://www.mayoclinic.com/invoke.cfm?id=AN00759

Alveolitis

Inflammation in sarcoidosis does cause fluid in the lungs. Alveolitis is inflammation of the tiny sac-like air spaces where the exchange of carbon dioxide and oxygen take place. When the alveoli are filled with fluid, there is less exchange of gases.

Crackles

This resource says that crackles are sometimes found in sarcoidosis.
http://www.chestjournal.org/cgi/content/abstract/73/3/333 And interstitial lung disease is listed here as one reason for crackles.

i. Crackles (Rales)

Crackles are discontinuous, nonmusical, brief sounds heard more commonly on inspiration. They can be classified as fine (high pitched, soft, very brief) or coarse (low pitched, louder, less brief). When listening to crackles, pay special attention to their loudness, pitch, duration, number, timing in the respiratory cycle, location, pattern from breath to breath, change after a cough or shift in position. Crackles may sometimes be normally heard at the anterior lung bases after a maximal expiration or after prolonged recumbency.

The mechanical basis of crackles: Small airways open during inspiration and collapse during expiration causing the crackling sounds. Another explanation for crackles is that air bubbles through secreations or incompletely closed airways during expiration.
Conditions:
ARDS
asthma
bronchiectasis
chronic bronchitis
consolidation
early CHF
interstitial lung disease
pulmonary edema

Bronchiectasis

Bronchiectasis is the abnormal widening of bronchi damaged by infection and the resulting inflammatory cytokines, or obstruction or traction. Sarcoidosis can result in bronchial obstructions from enlarged chest lymph nodes or granulomas. Traction bronchiectasis can occur when there is pulmonary fibrosis that distorts the airway.

Since bronchiectasis can result in little 'pockets' where infections can take hold, one possibility you may want to discuss is perhaps bacteria cultured from a biopsy were secondary, opportunistic infections. If a decision is made to treat them, the primary goal remains to treat the primary cause of disease: sarcoidosis.

You should be concerned if doctors are most concerned about bronchiectasis - seeing it as more threatening than the primary disease. So you may need to be prepared to dig in your heels to begin the MP, instead of palliative treatments (aimed to help you feel more comfortable) and because you will want to ward off recurring complications.

-I have bronchiectasis - identified in my chest radiology - and I've done quite well on the MP! I've had no episodes of pneumonia, visits to the ER or anything like that. The rationale I used with my doc to convince him to try the MP initially was:
1) Since antibiotics are used to treat bronchiectastis, and
2) there isn't a singular well-defined treatment for bronchiectasis,
3) why not monitor a trial of the MP and see if it treats the sarcoidosis, which caused the bronchiectasis in the first place?

We've never regretted the decision to use the MP. ~Belinda

Atalectasis

Atelectisis refers to collapse of a lung or a portion of one, due to incomplete filling with air. This usually occurs in association with some mechanical blockage of the airway which prevents new air from entering the lung. The air in the lung distal to the block is absorbed by the bloodstream leading to the collapse of the alveoli. Atelectasis can be caused by fibrosis. Sarcoidosis results in fibrosis and can also result in bronchial obstructions from enlarged chest lymph nodes or granulomas. Atelectasis is not a common occurance in sarcoidosis but it does happen. If you google 'atelectasis & sarcoidosis', you will find some cases studies and xrays.

Hyperinflation

A chest x-ray can give a general idea as to whether a patient is hyperinflating, as explained here. Dynamic hyperinflation, discussed here (you will need to register to read the article) occurs in COPD and other diseases. Pulmonary function tests may be used to give more information about this condition.

Hyperinflation is sometimes called "air trapping" and may be helped by measures such as pursed lip breathing. Pursed lip breathing can help release air trapped in the lungs and can help relieve the feeling of shortness of breath, if it's due to hyperinflation.

In some cases, supplemental oxygen might be useful in overcoming hyperinflation. The Medscape article discusses how supplemental oxygen facilitates lung emptying. ~Belinda

Lymph nodes

I personally wouldn't worry too much if lymph nodes are still swollen. Lymph nodes play a criticial role in removing bacteria, abnormal cells and other matter as part of the immune system. That means they are still working. ~Belinda

Enlarged lymph nodes are usually a sign of infection and the way to treat is to treat the underlying cause when possible. ie MP is doing that.

What happens in later stages of sarcoidosis is the lymph nodes shrink down; they stop doing their part. This may be because they become too damaged to function. It's not unusual for lymph nodes to be calcified in sarcoidosis patients.
FAQ My lymph nodes are growing. Is this normal? Should I be concerned about cancer?

Photos of sarcoidosis gross pathology

Neurological inflammation can cause impairment of respiratory function and affect test results

Breathing diffusion difficulties from neuro-muscular disease is a broad statement that could have many causes. Since Sarc is a restrictive disease when affecting the lungs, many times the expiratory phase is longer, making it difficult to exhale enough to register adequate numbers on their equipment. The reduced musculature effort could be translated to poor innervation which would be another way of saying the above. The words neuro muscular apply to all muscle as without innervation from the brain muscles would not work. ~VEZ R.N.

See also:

Improvement in pulmonary function tests

Assessing lung function

Pulmonary Function Tests (PFTs)

Foundation Staff
.

Joined:	Sat Jul 10th, 2004
Location:
Posts:	17283
Status:	Offline

Posted: Sun May 29th, 2005 20:19

Quote

^filelink
Symptoms of sarcoidosis

Many sarcoidosis patients experience symptoms long before they are correctly diagnosed, since their individual symptoms can sound vague (fatigue, for instance) and benign. Sarcoidosis is often misdiagnosed. Patients are often told they probably have cancer before they are correctly diagnosed, because the chest imaging in sarcoidosis looks similar to cancer and/or tuberculosis.

One of the most frequent and universal symptoms of sarcoidosis is fatigue that is not relieved by sleep. Lack of concentration is one of the most frustrating symptoms, but neither of these is specific to sarcoidosis. They occur in other diseases. The relentless fatigue of sarcoidosis may be discounted by medical professionals because "everyone gets tired" and there is no good way to measure fatigue.

The most common sarcoidosis symptoms listed by the Cleveland Clinic are:
* Tender reddish bumps or patches on the skin
* Red and teary eyes or blurred vision
* Swollen and painful joints
* Enlarged and tender lymph glands in the neck, armpits and groin.
* Enlarged lymph glands in the chest and around the lungs
* Nasal stuffiness and/or hoarse voice
* Pain in the hands, feet or other bony areas
* Kidney stone formation
* Enlarged liver (or spleen)
* Development of abnormal or missed beats (arrhythmias), inflammation of the covering of the heart (pericarditis) or heart failure
* Nervous system effects, including hearing loss, meningitis, seizures or psychiatric disorders (for example, dementia, depression, psychosis)

There are many other symptoms that may be due to sarcoidosis, because it can damage or alter the function of any body organ.

Physicians like to have a tissue biopsy to diagnose sarcoidosis, and this is largely due to the fact that the common treatments for sarcoidosis are so fraught with side effects that biopsy proof is needed to justify their use. Biopsy is not always required, though, and now the serum D-metabolite tests are a good tool for measuring systemic inflammation.

Sarcoidosis patients have a dysregulated vitamin D metabolism and produce excessive Hormone D, 1,25-D, in unregulated amounts due to activated macrophages. This can cause symptoms of Hypervitaminosis D (see the article below). Fatigue, sleepiness, and mood or mental changes can be due to hypervitaminosis D. We suggest you talk to your doctor about getting your D-metabolites measured. Get a copy of the lab test results and post them on our study website for help in understanding them.

Sarcoidosis is often referred to as the "snowflake" disease because patients present with so many different symptoms. The clinical picture can be complicated by intermittent inflammation in many different organs. While the symptoms may vary from patient to patient, the underlying cause is the same. The disease is really very simple when you realize that sarcoidosis inflammation has only one cause: intracellular bacteria. The MP is designed to deal with all intra-phagocytic bacteria, regardless of the species.

Hypervitaminosis-D

Sarcoidosis results in abnormally high levels of dihydoxyvitamin-1,25-D, a powerful hormone which affects many other hormones. This diagram summarizes some of the key relationships between the body's hormones and 1,25-D.

List of Hypervitaminosis-D symptoms

"Signs of mild Vit D toxicity include hard stools, constipation, metallic taste, "weakness, headache, muscle pain, bone pain, somnolence (sleepiness), nausea, vomiting, dry mouth, constipation, polyuria, polydipsia, anorexia, weight loss, nocturia, conjunctivitis (calcific), pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated SGOT and SGPT, ectopic calcification, nephrocalcinosis, hypertension, cardiac arrhythmias and rarely, overt psychosis" and facial paralysis."

Bell's Palsy

Bell's Palsy occurs as a result of the high levels of 1,25-dihydroxyvitamin-D which are associated with Lyme, and all the Th1 diseases. IMO, One of the earliest and best papers on the various issues is
Muler H, et al: "Facial Paralysis in Children" Ann Otolaryngol Chir Cervicofac. 1975 May-Jun;92(4-5):229-34. PMID: 1217818
Unfortunately the paper is in French, but it is pretty easy to work through it with only High School French as a background. You can get it on Inter Library Loan. It also links Bell's palsy to the hypervitaminosis D of Tuberculosis. We see it in Sarcoidosis as well. Several patients have had their paralysis resolve as they worked down their bacterial load.
Dr. Trevor G Marshall, PhD

Granulomas

Inflammation, including granulomas, seems to settle in injured tissues. Most of us have had some experience with that whether it was 'tennis elbow' or 'football shoulder' or carpal tunnel syndrome. Granulomas tend to make scar tissue pink. But intracellular bacteria also resides in noninjured tissues. Therefore, Th1 inflammation can and does occur in tissues that have not been injured. I'm sure there are many areas of your body that have never been injured that have sarcoidosis inflammation.

Heerfordt's syndrome is the association of facial nerve palsy with anterior uveitis and parotid gland enlargement. It is caused by sarcoidosis.

Sjogren's (sicca) syndrome

Sjogren's and Sarcoidosis are both described in the standard literature as a collection of symptoms. Sjogren's is known to be related to diseases such as rheumatoid arthritis, sarcoidosis, lupus, scleroderma and polymyositis. Many Sarcoidosis patients manifest the same symptoms as described in Sjogren's syndrome (dry eyes and mouth, decreased tears and saliva, and resulting dental caries).

Mouth

Sarcoidosis can affect any organ, and the mouth is not exempt. We know sarcoidosis affects these areas because biopsy of these leads to diagnosis. Here, briefly, are some of the symptoms:

- sores on or swelling of the face, tongue, mouth, gums or inside the cheeks
Orofacial Manifestations and Systemic Sarcoidosis
Facial Swelling and Systemic Sarcoidosis
Oral manifestations of sarcoidosis.
Granulomatous cheilitis (lip swelling) can lead to a sarcoidosis diagnosis

- gingivitis is simply inflammation of the gums. Sarcoidosis is an inflammatory disease.

- affected salivary glands can produce too much saliva or (more commonly) too little saliva
Sarcoidosis with Involvement of the Salivary and Lacrimal Glands

- too little saliva when inflammation impairs or blocks the function of the salivary glands can result in

-gum disease and increased dental cavities. The term "xerostomia" means dryness of the mouth due to a decreased function of the salivary glands.

It is not unusual for people with sarcoidosis or other Th1 disease to experience dysphagia, difficulty swallowing as a symptom. It is possible for dysphagia to begin abruptly, but you can be on the alert for alterations in the functioning of your throat and voice which would signal you might also have a problem if you ate at that time. The vocal cords must be able to close properly to avoid choking.
Acute reversible dysphagia and dysphonia as initial manifestations of sarcoidosis.

Dysphonia

Dental Fractures
Since sarcoidosis causes a dysregulation of Hormone D (1,25-dihydroxyvitamin D), a condition which causes calcium to be pulled from bones and teeth, the teeth can become weakened and susceptible to cracking easily. Sarcoidosis patients may experience multiple non-traumatic tooth fractures. Calcium pulled from bones and teeth is carried by the blood and deposited in soft tissues like the lungs, kidneys or dental pulp. Dental stones (pulp stones) can result from calcium deposits within the dental pulp. These may be found when root canal therapy is performed.

See also: Dental Problems and Dental problems and sarcoidosis

Eye Involvement

See EYE INFLAMMATION

The lacrimal glands

In the eye, the lacrimal gland is a common area of manifestation for sarcoidosis. produce tears to moisten and protect the eyes. It's not unusual for sarcoid patients to have uncontrolled tearing of the eyes, dry eyes or blurry vision.

Cataracts

Sarcoidosis itself can cause cataracts, because sarcoid inflammation of the eye can result in a cataract.

Uveitis

Uveitis is a symptom, and has many identified causes and associations at this point. Some cases are widely accepted to be due to bacteria or viruses. Other cases are associated with “autoimmune diseases” like Crohns disease and rheumatic arthritis. Researchers found cell-wall deficient bacteria (sometimes called mollicute-like organisms) in the vitreous fluid of patients with sardoidosis, Crohn’s disease, ulcerative colitis, juvenile rheumatoid arthritis, etc.

You can read about eye inflammation (uveitis)at this URL for the Cleveland Clinic: http://www.clevelandclinic.org/eye/patient_info/uveitis.asp
It says, "Complications of uveitis may include glaucoma, cataract, abnormal blood vessel growth, fluid within the retina and vision loss."

Conjunctiva
http://tinyurl.com/55z7e

A patient with sarcoidosis diagnosed by biopsy of scleral nodules.
http://tinyurl.com/4mypt

Wirostko papers on eye disease

Lymphadenopathy

Sarcoidosis can result in abdominal lymphadenopathy. Like any sarcoidosis symptom, lymphadenopathy may flare with Herxing, resulting in enlarged and/or tender lymph nodes. Muscle spasms and cramps often are worse at night. One explanation that was offered for this was an increase in lymphadic edema.

Links to sarcoidosis in other organs:

Nose and sinuses
http://tinyurl.com/4wwsh

Sinonasal sarcoidosis
http://tinyurl.com/63ffa

Central Nervous System (Yes, they sometimes want a brain tissue biopsy which isn't necessary)
http://tinyurl.com/62zcb

Muscle
http://tinyurl.com/3wbbo

Maxillary Involvement
http://tinyurl.com/6jyqt

Renal
http://tinyurl.com/47z5f

Pancreas
http://tinyurl.com/57cdc

Splenomegaly (Enlarged Spleen)
http://tinyurl.com/3azaqd

Anemia

See Anemia and Th1 Disease

Depression

There is limited and controversial evidence that changes in the expression of cytokines and other molecules usually associated with immune function may be involved in the pathogenesis of depression. Cytokines are expressed in the brain, and during development they play important roles in normal brain embryogenesis.

A recent study revealed that induction of increased cytokine activity was associated with depressed mood in normal volunteers (Duman et al 1997). Elevated IL-6 concentrations in plasma have been reported in depressed patients (Musselman et al 2001). Should further work confirm a relationship between cytokines and depression, medications directed at cytokines might represent novel antidepressants. See Depression

Neuropathy

One bacterial species which has shown an affinity to cluster around nerve fibres is Mycobacterium leprae. It is possible that this characteristic has been acquired by less pathogenic 'cousins' of that species, or that the species itself is one of the players in Th1 disease. See Will the MP treat paresthesia and neuropathy?

Sleep apnea

Th1 inflammation can cause dysfunction in any tissue of the body. The upper airway is often affected which could cause obstructive sleep apnea. In central sleep apnea, the airway is not blocked but the brain fails to signal the muscles to breathe due to instability in the respiratory control center. Central sleep apnea is usually observed in patients with central nervous system dysfunction, such as following a stroke or in patients with neuromusclular diseases like amyotrophic lateral sclerosis (which is a Th1 inflammatory disease).

According to the following article, sarcoidosis patients have a higher incidence of sleep apnea than the general population.

Sleep apnea in sarcoidosis
Sarcoidosis Vasc Diffuse Lung Dis 1997, No. 14 (1), March 1997
Turner GA, Lower EE, Corser BC, Gunther KL, Baughman RP.
see also sleep file link

Liver involvement

Extrapulmonary sarcoidosis primarily diagnosed in the liver.
http://tinyurl.com/4ap64

Asymptomatic organ involvement is quite common in sarcoidosis. An article from Medscape Gastroenterology http://www.medscape.com/viewarticle/405532_4 says:
"The prevalence of hepatic granulomas in sarcoidosis is 65%. In a study of 100 patients with hepatic sarcoidosis, the majority of patients were asymptomatic and had normal abdominal examinations. Abdominal pain and hepatosplenomegaly were seen in 15% and 8% of these patients, respectively. Much less common were features of chronic liver disease and cirrhosis."

Sarcoidosis of the liver
http://tinyurl.com/6ew3q

Th1 inflammation commonly affects the liver, although it may be subclinical. Patients may be told they have "fatty liver disease" or cirrhosis.

Angiotensin receptor blocking drugs are known to have organ-protective effects.
An angiotensin II type 1 receptor antagonist, olmesartan medoxomil, improves experimental liver fibrosis by suppression of proliferation and collagen synthesis in activated hepatic stellate cells.

Cardiac Involvement

http://tinyurl.com/46l2g

Chest pain is, in fact, a common symptom endured by sarcoidosis patients, substantiated by reports such as this one, http://tinyurl.com/4hg48, which found that about 30% of sarcoidosis patients suffer from chest pain. While it is true that chest pain can be due to cardiac involvement, it may simply be due to other problems brought on by sarcoidosis such as enlarged lymph nodes which can cause pressure, crowding and pain in the chest.

20 to 30 percent of sarcodiosis patients are found to have cardiac involvement upon autopsy. This is why we caution patients to assume they may have unrecognized cardiac involvement and to control their Herxing accordingly.

This report found that perhaps 50% of sarcoidosis patients have cardiac involvement that is not diagnosed. Cardiac sarc can cause chest pain.

Pulmonary Hypertension

Pulomonary Hypertension is a severe condition that may develop as a result of sarcoidosis. PH is a form of high blood pressure in the pulmonary artery, which connects the heart to the lungs.

Pulmonary hypertension associated with sarcoidosis:
mechanisms, hemodynamics and prognosis.
Thorax. 2005 Oct 14; [Epub ahead of print]
PMID: 16227329 [PubMed - as supplied by publisher]
http://tinyurl.com/d74hs

Sudden death with clinically undiagnosed pulmonary
hypertension.
J Clin Forensic Med. 2005 Oct;12(5):264-7. Epub 2005
Mar 28.
PMID: 16198969 [PubMed - in process]
http://tinyurl.com/7pgqr

Pulmonary hypertension in advanced sarcoidosis:
epidemiology and clinical characteristics.
Eur Respir J. 2005 May;25(5):783-8.
PMID: 15863633 [PubMed - indexed for MEDLINE]
http://tinyurl.com/dbmwn

CT findings in severe thoracic sarcoidosis.
Eur Radiol. 2005 Jan;15(1):23-30. Epub 2004 Sep 24.
Review.
PMID: 15449010 [PubMed - indexed for MEDLINE]
http://tinyurl.com/8shc4

Cutaneous manifestatios of sarcoidosis

Cutaneous manifestations of sarcoidosis are common and varied, and one patient can have different types of sarc skin lesions at the same time. Sarcoidosis is a systemic inflammatory disease, so be suspicious of sarcoidosis if you have a skin problem and you've already been diagnosed with sarcoidosis.

The reason Sarcoidosis is called a "masquerader" is to alert physicians to be more suspicious in investigating skin lesions and rashes that generally indicate something else in normal (non-sarcoid) people. I guess you could say sarcoidosis is more than "skin deep."

Cutaneous immunopathology

The body of folks with systemic Th1 infection severe enough to cause sarcoid granuloma is going to exhibit wierd physical phenomena as it heals. These include spots on the skin which are often red. Although these manifestations can be scary but there is nothing we know which can help you get through the 'Herx' phase of this disease any faster than the slow, steady, bacterial killoff of the MP.

Lupus pernio, first described by Ernest Besnier, is the most characteristic of all sarcoid lesions. Lupus Pernio is a skin manifestation of sarcoidosis. Lupus Pernio is not another disease (and is not related to lupus), it's simply a name for the red-to purplish lesions that can appear on the nose, face, ears or hands of sarcoidosis patients. These lesions can occur when the nose, face or hands are exposed to cold or wind, so it's a good idea for sarcies to keep these areas protected from wind and cold. Avoiding exposure to bright lights is also an important preventative measure.

Sometimes lupus pernio lesions will have an appearance of small "beads" along their edge, especially if the sore is on the rim of the nose. If left untreated, lupus pernio lesions can be disfiguring and cause a patient to feel embarrassed, particularly since they may be noticeable on facial areas so visible to the public.

Like some other cutaneous sarcoidosis lesions, lupus pernio can appear at sites of old scars or trauma.

Lupus pernio lesions, like other sarcoid manifestations in the upper respiratory tract, can be quite resistant to the standard immunosuppressive therapies.

Lupus pernio is said to be the skin lesion most characteristic (a diagnostic indicator) of sarcoidosis, but not all sarcoidosis patients have these skin lesions.

-My experience with lupus pernio is that it flares with exposure to light plus cold and wind. I suspect you have still been having a good bit of cool wind and weather in your part of the world. You may need to keep your nose better protected. I know that's hard to do, so if nothing else, you can stay indoors during daytime as much as possible and wrap a scarf around your nose if it is cool or windy.

Warning of the risk of scarring, whether on the skin or in the lungs, is a common tactic to pressure patients to use the treatment a physician prefers. Lupus pernio has a reputation for being difficult to treat. In reality, the doctor has no way to know whether you will scar. Certainly I sustained no scars from my winter bouts with lupus pernio.

Within a month, you will probably have this lupus pernio flare behind you and you can deal more assertively with your doctor to reassure him you are on the correct treatment, MP.

Continuing to take Benicar allows your immune system to work more efficiently and provides protection of organs. Prednisone injections will have a systemic effect, but less than if you took an oral dose. ~Belinda

Skin rash

I was diagnosed with sarcoidosis several years ago, after testing that included a tissue biopsy. Now I've had a skin rash biopsied and was told the result indicated no granulomas, so this can't be sarcoidosis. I think there is a mistake.

This article by a practicing dermatologist explains that both "specific" and "non-specific" skin lesions are found in sarcoidosis, explaining, "Specific skin lesions are generally associated with chronic disease and demonstrate noncaseating granulomas in the dermis on histological examination. Nonspecific skin lesions are seen primarily with acute disease and noncaseating granulomas are absent."

Erythema Nodosum is a common manifestation of acute sarcoidosis.

Subcutaneous Nodules

Subcutaneous nodular sarcoid lesions are sometimes called Darier-Roussy sarcoidosis, named for the French physicians Darier and Roussy who described these subcutaneous nodules in 1904.

Here is a photo of skin tags.

According to this source, alternate names for skin tags are:
* Acrochordons
* Papillomas
* Soft fibromas
* Pedunculated (this means they are on a stalk)
* Filiform (this means they are thread-like)

"Skin tags develop in both men and women as they grow older. They are skin coloured or darker and range in size from 1mm to 5cm. They are most often found in the skin folds (neck, armpits, groin). They tend to be more numerous in obese persons and in those with type 2 diabetes mellitus."

Sarcoidosis manifests in a wide variety of skin lesions. You can find links to photos of cutaneous sarcoidosis on this SarcInfo thread. Here is a photo of sarc lesions around the eye.

Some of the types of skin lesions encountered in sarcoidosis, and the other diseases these resemble are:
Papules (little bumps) resembling
Granulomatous rosacea
Acne
Benign appendageal tumors

Plaques resembling
Psoriasis
Lichen planus
Nummular eczema
Discoid lupus
erythematosus
Granuloma annulare
Cutaneous T-cell lymphoma
Kaposi's sarcoma
Secondary syphilis

Lupus pernio resembling
Scar
Discoid lupus erythematosus
(more info on lupus pernio can be found in a later post)

Erythema nodosum resembling
Cellulitis
Furunculosis
Other inflammatory panniculitis

Sarcoid skin lesions can be painful, itchy, oozy or dry and peeling. They can also make your hair fall out. You can find more information and lots of pictures of skin sarcoidosis (to compare with your rashes) in the thread "Skin Sarc, What Does it Look Like?" or in the list later on in this thread.

Sweat glands

"Alan Cantwell, MD (dermatologist) wrote a paper on the skin in Th1. http://www.joimr.org/phorum/read.php?f=2&i=2&t=2

Alan told me that he always found bacteria in the sweat glands, that bacteria loved the skin, in all these diseases. That is in line with what I think we are seeing." ..Trevor..

Nails

Onycholysis is the loosening (lifting) of the nail, starting at the border. Sarcoidosis can cause oncholysis. See: Derm Net NZ (with photos) and Internet Journal of Dermatology. If you click here, you will find a list of four PubMed-indexed articles about sarcoidosis nail disorders.

Cancer

Sarcoidosis is a multi-systemic disease that can be confused with benign or malignant tumors.

Patients should make their doctors aware of any previous sarcoidosis diagnosis (even if only suspected) so sarcoidosis can be investigated as a possible cause of any lumps or tumors. See Cancer and Th1 inflammation

Foundation Staff
.

Joined:	Sat Jul 10th, 2004
Location:
Posts:	17283
Status:	Offline

Posted: Sun May 29th, 2005 20:29

Quote

^{SARCOIDOSISlink}

REMISSION
......

It is a myth that sarcoidosis goes away on its own:

NIH ACCESS study shows that Sarcoidosis does not go away

Lessons Learned from the NIH ACCESS Study

There were no spontaneous remissions in the placebo group of the NHLBI Trental study
.......

from Dr Marshall: What causes Sarcoidosis to sometimes go into remission?
is it possible?
......

MP.com thread Sarcoidosis and Remission

FAQ: Does sarcoidosis go away on its own without treatment?

.............

"Even though you may still be feeling terrible (while on the Marshall Protocol), a CT scan might well show that the lymph nodes are steadily shrinking. Granuloma shrink too, but not those which have been calcified or turned fibrotic. The body encases pathogens which have been missed by the immune system in collagen (fibrosis) commonly called 'scarring'. Angiotensin blockade inhibits the formation of new fibrotic tissue.

The lungs also are really good at healing, even though they may be badly scarred from years of fibrosis. The PFTs usually improve, particularly the DLco, or gas diffusion capability."

..Trevor..

====================

Lungs

Q-I have calcified granuloma in my lungs which indicates old infection. I wanted to know if the MP will clear this up. I have not had any symptoms to indicate any herxheimer reaction in my lungs, but everywhere else that I have had active inflammation or infection, I am having herxheimer reactions.

A-You will probably get Lung Herx when you get to phase 3. The bugs there are aerobic (they like oxygen) and more difficult to kill.

I am not sure you want the calcified granuloma to clear up, as that may indicate that calcium is being absorbed into your bloodstream, which is not good for the bones

But the lungs will function well despite the fibrotic scar tissue and any small calcifications.

..Trevor..

==============================

"In sarc patients we find that those who have been aggressively treated (mostly with prednisone, cyclosporin, etc) do take longer to heal than those who have just tried to live with their symptoms."

..Trevor..

==================================

What degree of healing is possible with the MP?

==================================================

Evaluating progress with chest xrays

The ACCESS study showed that X-rays are not a good measure of disease, and Meg and I heard this verified as the current thinking when we attended the Cleveland Clinic's professional conference on Sarcoidosis last summer.

Remember that symptoms get worse before they get better. X-rays picture lung inflammation and enlarged lymph nodes, which are symptoms. Since you had significant lung involvement, after about six months on the MP, it seems reasonable to me that your x-rays may seem a little worse or the same, rather than significantly improved.. because of the Herxheimer reaction.

The impression from the radiology report is that you have only slightly more inflammation in your lungs, possible more adenopathy on the right side and stable adenopathy on the left side. All in all, it sounds pretty good. If your doctor is concerned, it may be that he still needs to get used to the concept of Herxheimer, which is very different from the effect of Prednisone, which may rapidly clear pulmonary imaging - yet allow and lead to disease progression. One possible explanation for the difference between the right and left sides is that there was originally more involvement on the right side, but I am only speculating. I know that there was a difference like this in my own case.

My suggestion would be that you review your recent posts which discussed your improvement in symptoms, and rely on your assessment of symptoms to evaluate your progress. I believe that a frank evaluation of your progress along these lines will reassure both you and your physician. This is the point where your physician will really need to listen to your assessment of your symptoms because an improvement in lung imaging will probably not manifest for another 6-12 months.

Belinda Fenter

=====================================

Chest CT is a computed tomography scan of the chest and upper abdomen. It can be useful for diagnosing sarcoidosis. This scan relies on x-ray radiation in higher doses than a standard x-ray but allows better pictures of the lung. The patient lies very still on a gurney in the machine while a tube rotates around the chest to produce images.

A contrast material may be used to provide superior image quality of some features, it is administered intravenously. The contrast material usually contains iodine. This may be pose a risk to patients who have renal insufficiency. Usual precautions are to drink plenty of water before and after a CT.

Report of improved CT scan

You are likely to see the most change in the gas transfer coefficient,
the DLco, which most doctors don't measure because it can't be done
with the simple office spirometer.

Foundation Staff
.

Joined:	Sat Jul 10th, 2004
Location:
Posts:	17283
Status:	Offline

Posted: Sun May 29th, 2005 20:34

Quote

^[filelink]
Diagnosis

You only need ONE positive biopsy to obtain a definitive diagnosis of sarcoidosis. If you have already had a biopsy, you do NOT need another. If your doctor is recommending a biopsy, please inform him/her that patients are recovering on the MP without the need of this invasive procedure that can have long-term consequences to the status of your lungs and your body will have to heal the damage caused by the biopsy.

Please see: Explanation of biopsy

You could go have a bronchoscopy with transbronchial biopsy done and the pathology might show granulomatous inflammation or even inflammation. The closest you will get to "seeing sarcoidosis" would be a pathology report saying the findings are consistent with sarcoidosis. There are risks in understaking this procedure, including possibility of a punctured lung or uncontrolled bleeding.

It isn't necessary to undergo a Bronchoscopy with transbronchial biopsy or an invasive and risky open-lung biopsy for a proven diagnosis of sarcoidosis or expensive tests to locate inflamed tissues in order to prescribe the MP. A thoracotomy is major surgery that can take months to recover from and can leave you with permanent neurological pain.

Dr Marshall wrote on having a biopsy for diagnosis?: "I am sorry to say the skeptics will never take you seriously. You see, pulmonologist folklore says that Sarcoidosis goes away on its own. So it is clear that you are one of the lucky 60% whose sarcoidosis has gone away without needing any treatment.

That is why the Foundation has put so much effort into exposing these lies and myths, and trying to get the pulmos to cite the studies which show these statements are true. But they have not proven to be reasonable people, I am afraid. I think they are going to have to be dragged kicking and screaming into the 21st century.

Don't put yourself out to prove anything. It really will not matter. We are not dealing with scientists, today's 'experts' are not interested in 'proof' or 'facts.'"

Lung biopsies are risky

See Allan Abrahams went into Wellington Hospital for what he thought would be a straightforward biopsy. Which details an adverse event:

In 2003, Mr Abrahams was suffering from an unknown illness, later confirmed as sarcoidosis, which produces clumps of inflammatory cells in many organs.

He was admitted to Wellington Hospital so surgeons could take a tissue sample. "I was supposed to be back at work in two days' time."

But he began bleeding excessively during a mediastinotomy - a procedure in which a viewing tube is inserted into the chest.

The surgeon could not see where the bleeding was coming from and the cut had to be extended.

Alcohol iodine was applied to the wound and, when an electronic diathermy device was used, the iodine ignited.

The fire was extinguished, but Mr Abrahams continued bleeding. The surgeon turned him on his side, opened his chest and managed to stop the bleeding and obtain the biopsy.

Mr Abrahams was later told he had lost two litres of blood, and he ended up spending a week in hospital.

....when he woke up, his surgeon told him there had been "big flames" in the operating theatre. He had a burn mark on his chest, a result of his skin catching fire during surgery.

-We were warned about having a lung biopsy done but we didn't really understand the MP stuff very well initially so went ahead and had it done. To this day, when my wife has herxheimer reaction, she sometimes feels the pain where she had the biopsy done because they pierced the lung back then. ~Ricco

See Which diagnostic tests do I need?

Granuloma are clumps of white cells-a sarcoid granuloma is less than 0.1mm (about 4 thousands of an inch) in diameter. They survive without a tissue-structure to support them, as the inflammatory Th1 reaction has progressed to the point where the phagocytes can exist in clumps on their own. Any disease where an extremely active bacterial infection is present can form granuloma. This includes Tuberculosis, and a number of the other common infections. But in your case (sarcoidosis) the granuloma were chronic (long lived) and their bacterial pathogenesis is more important than the label a Doctor might attach.

Note that Lymphocytes are expelled to the periphery of granuloma - they play little or no part in the Th1 immune reaction. This observation was the fundamental step in comprehension which led me to an understanding of these Th1 diseases.

..Trevor..

Non-caseating granulomas

There is some confusion about the use of the term "caseating."

Caseation is what happens when necrosis changes what was once normal tissue so it looks "cheese-like" in appearance to the naked eye. (Think of Swiss cheese.) Basically, caseation is what you get when there is necrosis.

A physician, Yale Rosen, M.D., who devoted his life to studying granuloma and granulomatous diseases explains, "The use of the terms "caseating" and "non-caseating" to describe the microscopic appearance of granulomas, although prevalent, is inappropriate since the term "caseous" applies only to the grossly visible cheese-like appearance that may be associated with necrotizing granulomas, necrotic neoplasms and other types of necrotic lesions. There is no typical microscopic appearance that corresponds to the gross appearance of caseation."

You might be interested in knowing that necrosis can occur in sarcoidosis, although it is small and involves few of the granuloma.

To sum it up, non-necrotizing (not dead/dying) is the best term to describe sarcoidosis granulomas viewed under the microscope and non-caseating (not cheese-like) is the best term to describe sarcoid tissue viewed with the naked eye.

Sarcoidosis, or any Th1 disease with elevated 1,25-dihydroxyvitamin D (the D-hormone), can result in calcium being pulled from bones and deposited in soft tissues, resulting in calcification. The lymph nodes are and lungs are areas where calcification may be noted as a result of disease. ~Belinda

Physicians like to have a tissue biopsy of usually non-necrotizing granulomatous inflammation to assist in diagnosing sarcoidosis, because the only way to diagnose the disease is by excluding other diseases that might possibly explain the symptoms. There is no one specific test that can be used to diagnose sarcoidosis. Blood tests are useful in diagnosing sarcoidosis; the two vitamin D metabolites, are some of the latest tests used.

If symptoms involve tissues that are not easily biopsied (heart, liver, eye, joints for example), a presumptive diagnosis may be declared based on medical history and clinical signs such as symptoms and labwork.

All biopsies are invasive and uncomfortable to some extent, even a simple skin biopsy. It isn't necessary to have a biopsy when you are already on the only treatment plan that will cure sarcoidosis, MP. Your D-metabolites results are definitive for extensive systemic inflammation.

Pulmonologists are trained to verify sarcoidosis inflammation with a biopsy in order to justify using the standard medications which are often so toxic and have never cured anyone.

Belinda Fenter had this to say about diagnosing sarcoidosis:

"Naming a disease is sort of like "matching colors." Doctors try to get as close as they can to describe what they see, but (just like with colors) there can be disagreement about what the name is. Sometimes two names can describe the same or similar colors (or diseases). It's easy to differentiate shades from opposite sides of the color wheel. Only the color-blind would get confused there. On the other hand, people argue over similar color-names all the time. What my mother calls teal I call blue-green, and what I call a purple, my daughter insists is a shade of blue.

You need to understand that any diagnosis that ends in "-itis" is indicating inflammation. The part of the diagnosis before "-itis" indicates where the inflammation is located. For example, "spondylitis is inflammation of the spondyles, which are joints in the backbone. Sarcoidosis is a disease that can result in inflammation in any part of the body. If you read my earlier answer... you will probably recognize that the symptoms associated with akylosing spondylitis are also symptoms of sarcoidosis, and there is "no known cause" of ankylosing spondylitis. It won't hurt to try the MP to see if it improves these symptoms that are very similar to sarcoidosis. It's a good idea to talk to your doctor about the similarity of these symptoms."

Cardiac

Sarcoidosis cardiac inflammation is very difficult to diagnose. It is only picked up by echo or MRI in its advanced stages. A biopsy of the heart is dangerous, often imprecise and unnecessary. Th1 inflammation in the heart is subclinical long before the damage it causes is detected by tests. A diagnosis of sarcoidosis heart involvement is usually based on symptoms which can include most heart symptoms, including but not limited to... chest pain, tachycardia, bradycardia, mitral valve prolapse, atrial fibrillation and premature beats.

PET (Postitive Emission Tomography) Scan

"In a PET (Positive Emission Tomography) scan, a radioactive marker is combined with a metabolite, usually glucose, and the degree of release of positron energy is supposed to be an indicator of the usage of glucose in that area.

I wish more folks would be given PET scans rather than CT or MRI. PET is the best available imaging technology, and it images the metabolic activity within the body rather than just the shape of water-rich structures (organs and tissue), as MRI and CT scanning do.

But the PET scanner is expensive, and many physicians don't like to believe what it tells them; that sarcoidosis is systemic.

In about 1994 I visited Hamamatsu Photonics, in Japan, where they had been using some high-power computer modules I had designed. Their prototype PET scanner had its own building, including a cyclotron for making the radioactive 'sugar'. That was produced (by the cyclotron) in a room right adjacent to the scanner (and the patient). The computing power to image the weak particles emitted by the sugar as it was being metabolized inside the patient was really quite incredible, for the early 90's. PET is amazing technology. And it works.

All imaging is imprecise and only a crude approximation of the inflammatory process. I think of it as a crutch for folks who are not able to visualize the progress of this disease by bloodwork alone - the same folks who failed to find either the pathogenesis or the cure."

..Trevor..

This article explains a bit more about PET scans and how they work. It states that this diagnostic tool is not specific for differentiating sarcoidosis or tuberculosis from cancerous tumors. In a PET scan, FDG may accumulate in non-neoplastic tissue such as new granulation tissue, areas of inflammation, and early post-op scarring.

Gallium Scan

"I have never really paid much attention to gallium scans. Most sarcoidosis patients have weakened kidneys, and I question the ethics of performing any test, such as a gallium scan, which is likely to hurt those weakened kidneys even more. Even though the coming of Ga67 scintillography has reduced the risk, there are safer alternatives available. For example, a PET scan. It gives better contrast (for systemic sarcoidosis) and is far less likely to make the patients sicker.

Soluble Interleukin 2 Receptor (sIL2R) and 1,25-dihydroxyvitamin-D bloodwork tests are much cheaper, non-invasive, tests for Th1 inflammation, without causing any danger to the patient."

Dr. Trevor Marshall

Chronic fatigue

"Nearly all sarcoidosis patients suffer from chronic fatigue, even if
it is not clinically diagnosable as CFS.

In Sarcoidosis the Th1 inflammation has gotten so energetic that the
immune cells no longer need to gather in the inflamed tissue, they can actually form colonies (sometimes polyps) comprised solely of
monocytes, macrophages and polymorphonuclear cells (collectively, phagocytes). They no longer need any tissue structure, but are self-sustaining colonies of phagocytes. These are called 'granuloma'. But the cause of all the Th1 diseases is Th1 inflammation, due to the intracellular bacterial pathogens.

So it really doesn't matter what you want to call yourself. A doctor
would say that if you have biopsy-proven granuloma then you probably have Tuberculosis. If you don't have TB, then maybe Sarcoidosis. It is more complex than that, but I am sure you get the picture.

All I care about is how to get better. And it seems that for all the
Th1 diseases the same approach works, regardless of the label we might place on the disease."

..Trevor..

Multiple diagnoses

"If you get to know the disease sarcoidosis, arguably the most virulent of the inflammatory diseases because the phagocytes no longer need to gather in tissues, but can form colonies called 'granuloma', you will find folks who have been diagnosed with MS, Lupus, Crohn's, RA and a host of other ailments as they progressed to the sarcoid granuloma. All these diseases have a bacterial pathogenesis, with the species of bacteria and the genetic predispositions varying during the course of the diseases, and between individuals."

..Trevor..

Kveim test

Anybody who knowlingly injects the ground-up spleens of dead sarcoidosis patients into a living human being, knowing full well that sarcoidosis has been proven to be communicated by transplanted lungs and other organs, needs to be hung, drawn and quartered.

I have no sympathy whatsoever for the idiots who are promoting, and enriching their institution, using the Kveim test. They know that their own studies have shown the test is not 100% definitive, and also that Kveim is a very high risk procedure. Words fail me...

..Trevor..

See also What is the best way to assess lung function?

Last edited on Fri Apr 11th, 2008 09:33 by Foundation Staff

Foundation Staff
.

Joined:	Sat Jul 10th, 2004
Location:
Posts:	17283
Status:	Offline

Posted: Sun May 29th, 2005 21:02

Quote

^{SARCOIDOSISlink}

STAGING SYSTEM

Dr. Marc Judson had this to say about staging sarcoidosis:

"It is important to make several points about the staging system. First, is only a chest X-ray staging system. It tells you nothing about involvement of sarcoidosis outside of the lungs. Second, it is in general, a poor staging system. Most sarcoidosis experts do not use it because it's so poor. It has a few major problems. The first is that it's inaccurate. When you do much better views of the lungs by chest CT scans, you find out that the actual stage is different than what appears on chest X-ray. The next problem with the staging system is that it does not predicit the need for therapy, the level of disability, or the prognosis IN AN INDIVIDAL PATIENT with any good degree of accuracy. That is, if you had 100 patients with stage 1 disease and 100 with stage 2, the stage 1 would have better pulmonary function, less pulmonary symptoms, and a better prognosis. BUT many in the stage 2 group would have better pulmonary function, less pulmonary symptoms, and a better prognosis than in the stage 1 group...you can't tell what will happen to one specific patient. Probably the most useful part about the staging system is that patients with stage 4 generally have poor pulmonary function and have the worst prognosis. But I don't put too much weight on this staging system...it is antiquated and doesn't help me much at all." 14 August 2003

and on 3 September 2003
"you will learn that the ACE level and the stage of sarcoidosis give little information concerning who should be treated and the prognosis of the patient. They are both antiquated systems...especailly the X-ray staging system."

and on 30 Oct 2003
"Please realize that I personally think that this whole stage system is antequated and offers very little today (please scroll down and see previous threads about the staging system). It was developed prior to 1960 when there were no CT scans and we knew much much less about sarcoidosis."

Foundation Staff
.

Joined:	Sat Jul 10th, 2004
Location:
Posts:	17283
Status:	Offline

Posted: Sun May 29th, 2005 21:07

Quote

^{SARCOIDOSISlink}

ACE TEST
Serum Angiotensin Converting Enzyme or S.A.C.E.
......

While serum ACE level is elevated in some sarcoidosis patients, not all sarcoidosis patients have elevated ACE levels. As a result, serum ACE is not a reliable diagnostic tool or measure of disease activity. The ACE level is less likely to be elevated in those with chronic sarcoidosis, for example.

You can read a simple explanation of the ACE test and what it may indicate on Medline. The serum ACE test is a non-specific test used in helping diagnose sarcoidosis. The major problem is that it is unreliable -- in the sense that some people who are very ill with sarcoidosis do not *always* produce a high number on the ACE test. So the ACE test is not clinically reliable, either as a diagnostic tool, or to monitor how well a patient is doing. There are also genetic differences among individuals that affect the normal range of ACE, which confounds the problem.

An elevated ACE test result *is* significant. If someone has an elevated ACE test, they should press on to understand why. The results of any blood test have to be considered in their clinical context.

A high level of ACE is not meaningless. Angiotensive converting enzyme is only an enzyme, not the actual end-product that causes the body harm. The harmful end-product that causes damage is Angiotensin II, with ACE catalyzing the conversion of Angiotensin I to Angiotensin II. So a high level of ACE in the blood is an indication that there is a high conversion of Ang I to Ang II taking place.

Many patients with serious Th1 inflammation have a normal ACE. ACE is an intermediate biochemical. It is a precursor to Angiotensin. It has no direct action in the inflammatory cycle other than to cause the release of quantities of Angiotensin II. That is probably why it is relatively insignificant in some patients; it depends on your Renin Angiotensin System activity level.

See this article for a list of diseases with a high ACE level.
......

Why ACE sometimes elevates on the MP

"The more your ACE is initially elevated, the more ACE is being generated in your inflammation, and the higher the ACE will go when the Angiotensin II receptors are blocked. We have had one report of ACE greater than 400.

The serum ACE usually rises to quite high levels when you have an Angiotensin Receptor Blockade in place (eg with Benicar).

This is because the inflamed tissue can't get any Angiotensin II binding at its receptors, so it puts out extra ACE to try and convert more Renin/A-1 into Angiotensin II (the Angiotensin-II level rises too). But even though all that Angiotensin II is manufactured, there are no receptors left for it to bind to, so it can do no harm.

Note that ACE is not the same as Angiotensin II. They are different chemicals and have vastly different functions. Our paper "New Treatments Emerge..." describes the biochemistry as "the Angiotensin Hypothesis". Although put as a 'hypothesis' in that (old) paper, a Spanish group recently validated my etiology in-vitro and in rats."

...Trevor...

===============
See also:

Why has my ACE gone up since I started the MP?

What do my lab tests mean?

===================================

Q-Why do some patients with Th1 disease would have normal blood work for all tests other than 1,25D? My SED rate and CPK are normal.

A-In sarcoid patients, the pathogens are so well secreted in the granuloma that the immune system does not touch them. There are no antibodies formed, and, since the pathogens delay apoptosis, the SED rate is almost always very low.

When the MP antibiotics start killing the pathogens, then the SED rate shoots up, usually above the upper end of normal.

I would expect the CRP to behave in the same way, as it is part of the body's reaction to infection, and so CRP would not be generated until the body can recognize that it is dealing with infective pathogens. This often doesn't happen until you start killing the pathogens, and the DNA fragments start to enter the bloodstream.

..Trevor..

Foundation Staff
.

Joined:	Sat Jul 10th, 2004
Location:
Posts:	17283
Status:	Offline

Posted: Sun May 29th, 2005 21:31

Quote

^{SARCOIDOSISlink}
Infectious etiology of sarcoidosis

"The only thing that can cause the granuloma of Sarcoidosis is the intraphagocytic Microbiota of antibiotic-resistant bacterial pathogens." Dr. Trevor Marshall, Ph.D.

There is a wealth of proof linking mycoplasma bacteria to sarcoidosis. There are many studies that have convinced me of the validity of the bacterial etiology. Here are just a few. I hope that you will share them with your doctor.

The Center for Disease Control has published, in Emerging Infectious Diseases, a 2002 report from Vanderbilt University School of Medicineand Veterans Affairs Medical Center. It is titled Molecular Analysis of Sarcoidosis Tissues for Mycobacterium Species DNA. Their study "provide(s) evidence that one of a variety of Mycobacterium species, especially organisms M. tuberculosis, is found in most patients with sarcoidosis".
http://www.cdc.gov/ncidod/EID/vol8no11/02-0318.htm

R.M Du Bois, et al, of the Royal Brompton Hospital and Imperial College in London have written a Review titled Is There A Role For Microorganisms he Pathogenisis of Sarcoidosis? which was published in 2003 in the Journal of Internal Medicine. They concluded "that microbes are a likely trigger (but not as an infection) in a genetically predisposed individual and that this initial event culminates in the sarcoidosis granulomatous response.
http://tinyurl.com/bdjdp

In 2001, Dubois,et al, published an article, Sarcoidosis: genes and microbsoil or seed?, in the WASOG journal Sarcoidosis, that concludes "that one or more microbes behaving in a non-infectious fashion in a genetically predisposed individual trigger the sarcoidosis granulomatous response". http://tinyurl.com/8n7jo

A landmark Swedish study from 2002, Presence of Rickettsia Helvetica in Granulomatous Tissue of Patients With Sarcoidosis, reports finding Rickettsia andious bacteria in 86% of tissue samples. They conclude "these results support the hypothesis that rickettsiae may contribute to a granulomatous process, as is seen in sarcoidosis." http://tinyurl.com/vahsu

Lida Mattman's study Growth of Acid Fast L Forms From the Blood of Patients With Sarcoidosis, was published in Thorax and reports that various Cell Wall Deficient bacteria were found in 95% of sarcoid biopsy samples. http://tinyurl.com/akjs4

The 1999 German study by Grosser M, Luther T, Muller J, Schuppler M, Bickhardt J, Matthiessen W, Muller M., Detection of M. Tuberculosis DNA in Sarcoidosis: Correlation With T-cell Response, found Mycobacteria in 64% of tissue samples.
http://tinyurl.com/ada4c

D.R. Moller from Johns Hopkins University School of Medicine, concludes in his paper titled Treatment of Sarcoidosis- from a basic science point of view published in the Journal of Internal Medicine in 2003, "Given evidence for a genetic predisposition to sarcoidosis, these findings suggest that the etiology of systemic sarcidosis is linked to genetically determined enhanced Th1 immune responses to a limited number of microbial pathogens."
In plain English Dr Moller says:
1. Sarcoidosis is caused by microbes and bacteria ("microbial pathogens")
2. The immune system response in sarcoidosis is a response to bacteria. It is a Th1 type reaction (which means is can be blocked with angiotensin receptor blocker medications)
4. It is accepted that there is a genetic predisposition to this immune reaction
5. Dr. Moller is limiting his observations to 'systemic' sarcoidosis
http://tinyurl.com/d5g4b

Live bacteria have been found, with significant frequency of occurrence, in sarcoid tissue. But they are of a variety called "Cell Wall Deficient" (CWD), or "L-Forms", or "Coccoid Forms". They have adapted with a resistance to the Penicillins, which attack bacterial cell walls. The bacteria that have been repeatedly and consistently found in sarcoid tissue do not have cell walls, they are much smaller, and very difficult to see in pathology unless special stains are used. can be cultured, but it usually takes several months for the culture to grow. They are consequently not usually identified during conventional lab testing.

A description of which Pathology stains work best, and examples of CWD Coccoid forms (including photographs of cultures) are in the SarcInfo tutorial:

"How a Pathologist can see Bacteria causing Sarcoidosis"
http://www.sarcinfo.com/pathology.htm

There is an excellent Canadian Radio show on which the World's leading scient were interviewed regarding Cell Wall Deficient mycoplasma. Although it is pretty long (two hours) you will find it an amazing eye-opener. The links to it are from URL
http://sarcinfo.com/phorum/read.php?f=1&i=5320&t=5320

Bacteria in Sarcoidosis and a Rationale for Antibiotic Therapy in this Disease

There is abundant evidence, some dating back to the 1930s and 1940s by various investigators (such as Gullberg, Hollstrom, Schaumann, and others) showing that bacteria, related to tuberculosis bacteria, are associated with sarcoidosis. This research has been largely ignored, prompting Moscovic to declare in 1982: "Had all the work and effort spent on proving a non-mycobacterial nature of the disease been channeled into pursuing these clues, the etiology of sarcoidosis may have long been clearly established and a more rational approach to diagnosis and treatment could by now have been developed.

I would like to know why this early research has been ignored and why the latest studies documenting bacteria in sarcoidosis tissues are being denigrated. Scientists could spend another 100 years (while patients are dying) trying to identify each of the cell wall deficient bacteria that trigger the abnormal sarcoidosis immune system reaction in predisposed individuals. Luckily, it isn't necessary to know the identity of these offending organisms in order to eliminate them. Sarcoidosis provides a unique clue to the presence of mycoplasma in the cells of the immune system when a Jarisch-Herxheimer reaction is elicited with antibiotics.

"Jarisch-Herxheimer is in fact the maximum of evidence possible in search of occult microbes." Dr. Friedrich Flachsbart, MD. Initiating treatment with antibiotics to provide a therapeutic probe (a time-honored medical technique) can verify the presence of these bacteria without expensive testing and validate the necessity of antibiotic treatment.

I believe it's time to stop arguing about the cause of sarcoidosis and pursue this promising avenue of antibiotic therapy. It may not satisfy all of the scientific criteria but sarcoidosis patients don't care about that, they just want to get better.

Alan Cantweill, M.D.

Donor-Acquired Sarcoidosis Indicates Infectious Origin

Sarcoidosis has developed in non-sarcoidosis transplant recipients who have recieved tissues or organs from donors who were not suspected or known to have active sarcoidosis. This article said, "We draw upon these cases to discuss etiologic considerations for sarcoidosis, and suggest that donor-acquired sarcoidosis strengthens the view that sarcoidosis is caused by a transmissible agent, perhaps of infectious origin. Since not all recipients of organs from donors with active sarcoidosis develop sarcoidosis, host factors also appear to be important in disease pathogenesis. Less credence is ultimately given to external or environmental factors" [as a cause of sarcoidosis].

Here are some of the reported cases:
Transmission of sarcoidosis via cardiac transplantation.
Possible transmission of sarcoidosis via allogeneic bone marrow transplantation.

Antibacterial Therapy Induces Remission in Sarcoidosis
Authors: Trevor G Marshall, PhD1, Belinda J. Fenter1, and Frances E Marshall, GradDipPharm, RPh2

See also:

Cell Wall Deficient Bacteria and the Marshall Protocol

Papers and Presentations for Physicians

Studies Citing Bacterial Cause for Sarcoidosis

All these diseases have a bacterial pathogenesis, with the species of bacteria and the genetic predispositions varying during the course of the diseases, and between individuals.

"If you get to know the disease sarcoidosis, arguably the most virulent of the inflammatory diseases because the phagocytes no longer need to gather in tissues, but can form colonies called 'granuloma', you will find folks who have been diagnosed with MS, Lupus, Crohn's, RA and a host of other ailments as they progressed to the sarcoid granuloma.

..Trevor..

Experimental Skin Sarcoidosis In A Doctor Volunteer proves pathogenic cause of sarcoidosis.

Bacteria in spinal fluid

"The presence of detectable bacteria in the spinal fluid is common. Indeed, Emil Wirostko (whose group took those ownderful photos of the bacteria) was convinced that stem cells become infected at an early stage of Th1 disease, and that is why is spreads so evenly throughout the body."

..Trevor..

There are many species of CWD bacteria

Many types of bacteria work together to cause sarcoidosis. Not all of them are necessarily present in any one patient. Here are some papers he can get species info from:

http://www.cdc.gov/ncidod/EID/vol8no11/02-0318.htm

http://tinyurl.com/anovw

http://tinyurl.com/br7zp

http://tinyurl.com/dybhe

..Trevor..

Mycobacteria isolated from a majority of sarcoidosis patients

"Mycobacterium" is a species of bacteria which are very similar in many ways. Mycobacterium tuberculosis causes - you guessed it - TB. Mycobacterium leprae causes Leprosy. This species are very nasty little bugs indeed. Neverthless, very little is known about the members of the species other than M. tuberculosis. Yet they seem to be pretty ubiquitous, being isolated from a majority of sarcoidosis patients "Molecular analysis of sarcoidosis tissues for mycobacterium species DNA" http://tinyurl.com/4c8fh

BCG vaccination against TB

To state the significance of M. bovis...it is well documented to cause sarcoidosis when injected as the BCG vaccination against Tuberculosis. There are lots of studies from the 60's and 70's documenting this. Do a PubMed search.

That is one of the reasons why BCG has fallen out of favor in the USA.

Heavy metals do not cause Th1 inflammation

"While there is no doubt that heavy metals cause the body's biochemistry to malfunction, and that metals are attracted to the active sites of inflammation, there is no reason to believe that the heavy metals actually cause the inflammation, even though they may help fuel it. An excellent example of this is Berylliosis, which, until recently, was thought to be an environmental disease. Now it is recognized as a Th1 disease. Early investigators found the beryllium in the inflamed tissue, and thought that beryllium caused the inflammation, but now those ideas are having to be entirely re-thought as we understand more and more of the human genome."

..Trevor..

Foundation Staff
.

Joined:	Sat Jul 10th, 2004
Location:
Posts:	17283
Status:	Offline

Posted: Sun May 29th, 2005 21:33

Quote

^{SARCOIDOSISlink}
Cutaneous anergy

Cutaneous anergy

In 1916, Boeck first described cutaneous anergy to tuberculin in patients with sarcoidosis. It was later on realized that this phenomenon was not limited to tuberculin alone, but that anergy to a variety of other skin tests-antigens such was also typical.

In 1994, Kataria and Holter proposed a mechanism for the cutaneous anergy seen in sarcoidosis. At sites of granulomatous inflammation, there is a predominance of helper T lymphocytes, which proliferate and secrete large amounts of lymphokines, including interleukin (IL)-2, monocyte chemotactic factor (MCF) and migration inhibition factor (MIF). These lymphokines induce and amplify the immune response by enhancing T-lymphocyte proliferation as well as recruiting and retaining monocytes from the circulation. The lymphokines and monokines produced at sites of granulomatous inflammation have their highest concentration locally. Nevertheless, the protein molecules diffuse into blood, establishing a concentration gradient between the granulomatous inflammatory site and the remote site of the delayed type hypersensitivity (DTH) skin test.

As a result, the traffic of T-helper lymphocytes and monocytes is preferentially directed towards site of granuloma formation. That leads to a preponderance of suppressor cells in the peripheral blood and competitively depletes the T-helper cells and monocytes available to sites of DTH.

TB tests

Foundation Staff
.

Joined:	Sat Jul 10th, 2004
Location:
Posts:	17283
Status:	Offline

Posted: Sun May 29th, 2005 21:44

Quote

^{SARCOIDOSISlink}

BLOODWORK

Low white blood cell count

"Th1 diseases are lymphopenic, which means a lack of T-cells. This is because the T-cells play only a minor role in Th1 disease. The bacteria inside the phagocytes directly activate the phagocytes, there is no need for any T-cell recognition of pathogens, and so the body down-regulates the number of T-cells it manufactures (hence the lymphopenia).

The bacteria living inside your phagocytes cause the phagocytes to emit the Th1 cytokines without the need for Lymphocytes, Neutrophils, or indeed any other cells of the immune system, to be present. Some of the secreted cytokines cause down-regulation of Lymphocytes.

In Sarcoidosis this causes the Lymphocytes to leave the area of highest inflammatory action (in the center of a granuloma) and migrate to the periphery. The down-regulation also reduces the number of Lymphocytes being generated from stem cells. In less intense Th1 inflammation, that does not form granuloma, the down-regulation of the T-cells is observable primarily by the down-regulation of the Lymphocytes.

These Th1 diseases are therefore fundamentally Lymphopenic diseases. That is what your bloodwork shows.

You can all expect your WBC count and the balance of monocyctes, lymphocytes, NK cells, and etc, to change a lot as the Th1 bacteria are killed.

It is best not to get fixated on any expectation of "bad figures" and "good figures". If Doc gets too concerned about the numbers then, IMO, you should back off your antibiotic dose and take the therapy a bit slower."

..trevor..

Anemia

The granuloma sequester Ferritin and iron, and the low assay is closely tied to the presence of inflammatory granuloma.

Mild 'anemia' is expected in the Th1 diseases, as inflammatory macrophages accrete ferritin. Supplementation usually doesn't correct the 'anemia' and it feeds the inflammation.

This article indicates that one of the potential *benefits* of the anemia of chronic disease is that bacteria are being starved of the iron essential for their proliferation.
http://tinyurl.com/c95vv
Bacterial pathogens, however, sequester iron from the host so it is available for their own use and reproduction. If we use iron supplements, we will provide iron not only for us (the host) but also for our parasitic pathogens -- who will in turn hoard the iron from us. http://tinyurl.com/4o847

The fatigue from chronic disease is a common symptom that will resolve if you stick with the protocol. It will gradually get better, but it may be one of your longer-lasting symptoms. The best thing is to persevere and treat the root cause of disease because once the bacteria are killed off, your iron will be available for your own body once again.

Hemoglobin and serum ferritin are the most common ways to test for anemia. A new test called serum transferrin receptor is a good way to determine iron deficiency anemia because this test is not affected by inflammation.

Triglycerides

Elevated Triglycerides indicates (most probably) liver inflammation which will resolve during the MP.

CRP

"CR protein (CRP) is generated by the body to help it fight bacterial infection. This was in one of the papers presented at the recent Budapest conference. So it being high in Th1 disease and atherosclerosis is really no surprise

Take a look at this abstract - it will change your view of CRP:"
http://tinyurl.com/64cm5

In sarcoidosis patients, the CRP is part of the body's reaction to infection, but it would not be generated until the body can recognize that it is dealing with infective pathogens. This often doesn't happen until you start killing the pathogens with the MP, and the DNA fragments start to enter the bloodstream.

..trevor..

Many persons with Th1 inflammation have normal or low C-Reactive Protein. Our bodies respond to inflammation in a variety of ways depending on many factors.

BUN

"It is reasonable for BUN to be elevated, as the bacterial endotoxins cause Nitric Oxide (NO) to be generated in the inflamed tissues. It will almost certainly go higher once the antibiotics start to kill off the bacteria. Please ask Doc to call me if he is unduly worried about your kidney metabolites. ARBs are renoprotective, but the Th1 bacteria have to be killed off before Doc will see creatinine or BUN improve, I am afraid."

...Trevor...

Creatinine and Potassium

"These kidney function tests may increase to show inflammation which is to be expected with long-standing disease and the Herxheimer reaction.

This article, Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: what to do if the serum creatinine and/or serum potassium concentration rises, explains that long-term benefits have to be the focus when using ARBs.

Alkaline phosphatase

This article says, "In the serum of many patients with sarcoidosis, alkaline phosphatase activity is increased due to sarcoid liver involvement."

There can be several reasons for an elevated alkaline phosphatase level. The basic Alkaline Phosphatase (ALP) test is explained here: http://www.nlm.nih.gov/medlineplus/ency/article/003470.htm

When that basic ALP test is elevated, there is another test a doctor can order to measure the different forms of alkaline phosphatase present, to help analyze the problem. As Medline explains http://www.nlm.nih.gov/medlineplus/ency/article/003497.htm "Alkaline phosphatase is an enzyme in the blood, intestines, liver, and bone cells. Its chemical structure varies (called isoenzymes) depending on where it is produced. This makes it possible to determine where a problem has originated. When bones are growing, liver cells are damaged, or a biliary obstruction occurs, alkaline phosphatase levels rise considerably... The isoenzymes can reveal whether the increase is in "bone" ALP or "liver" ALP."

==============================

See also:

What do my lab tests mean?

Foundation Staff
.

Joined:	Sat Jul 10th, 2004
Location:
Posts:	17283
Status:	Offline

Posted: Sun May 29th, 2005 21:48

Quote

^{SARCOIDOSISlink}

CALCIUM LEVELS

"In 94% of sarc patients (approx) there is absolutely no connection between the 1,25-dihydroxyvitamin-D level and the serum calcium level. But Calcium is a pretty easy thing for Doctors to measure. So, in the other 6% of patients they see hypercalcemia (high serum calcium). They then are told to look at the 1,25-D and find it is often high. So they go away and assume that 1,25-D is solely assicated with calcium -WRONG - THEY ARE TOTALLY ABSOLUTELY WRONG

It is this misconception that has kept the true cause of sarcoidosis hidden for so long. In 1949 The Royal College of Physicians was told that Sarc patients are hypersensitive to Vit D, and that the ones with the highest Vit D levels are the ones least likely to remit. Yet here we are, 54 years later, and Doctors still do not realize that 1,25-dihydroxyvitamin-D3 is one of the most important hormones in the body, and it drives the thyroid hormones, and a host of other body control systems.

Many doctors, even so-called sarcoidosis experts, who may not have not cracked a textbook since medical school think that sarcoidosis causes people to absorb too much calcium in the gastrointestinal tract, and that can lead to too much calcium. They have a simplistic, inaccurate explanation of sarcoid's deranged calcium metabolism. They totally overlook/exclude the abnormal synthesis of 1,25-dihydroxyvitamin D by the activated macrophages that occurs in sarcoidosis and its effect on our bones. It's amazing that most doctors actually think that the complete story of sarcoid's abnormal calcium homeostasis is that it simply causes increased gut absorption of calcium, and that's all!

Doctors without a proper understanding of Vitamin D biochemistry might think that sarcoid patients who try to discuss deranged vitamin D metabolism in sarcoidosis are a little strange, and erroneously believe it is impossible to have elevated vitamin D levels. If doctors were taught an old-fashioned understanding of calcium metabolism - that didn't include vitamin D metabolism or the role of 1,25-dihydroxyvitamin D in calcium metabolism - and they've never done further study of it, then we might as well be speaking Greek! This is simply a lack of education, and it indicates more realistically the amount of work to be done with doctors before there is widespread understanding of sarcoidosis.

The (once) unknown is 1,25-dihydroxyvitamin D, and as this article explains, "The hormonal metabolite 1,25-dihydroxyvitamin D3 stimulates intestinal calcium absorption and "resorption of calcium and phosphates from bone..." There is so much more to 1,25-dihydroxyvitamin than digestive absorption of dietary calcium. Yet, that limited view is what led to vitamin D being added to all our milk in the USA. I can see now that it is a widely-held misconception.

We have no choice but to be educators as well as patients."
.....

"Blood may be drawn to test the level of 1,25 Dihydroxyvitamin D3 in your body at any doctor's office in the USA. This is the only test that can tell you if you are having this problem, although you need to have your 25 Hydroxyvitamin D measured at the same time, for comparison. It used to be thought that hypercalcaemia was the only result of excess Vitamin D, we now know it is far more complex than that. Many otherwise normocalcemic sarc patients have been suffering from kidney stones and calcium deposition into the soft tissue as a result of excess levels of this hormone in their tissue. We can only measure its level in the blood, which is still an approximation, but the best we can get."

OSTEROPOROSIS
....

"Excess amounts of 1,25 Dihydroxyvitamin D3 can result in bone resorption. This means that your bones and teeth can be absorbed into your blood stream and then be deposited into soft tissue, such as the lungs (and kidneys). Sarc patients should avoid all Vitamin D supplementation unless you have been tested to have normal values of the hormone. Here is an explanation for you to discuss with your doctors explaining why sarc patient's metabolism is different. As if the osteporotic side-effect of prednisone wasn't enough, we now learn that sarc patients may also have to contend with bone wastage due to the inflammatory biochemistry itself."

...Trevor...

BMJ and Lancet recently published studies showing that Vit D and Calcium supplements do not strengthen bones:

http://www.medicalnewstoday.com/medicalnews.php?newsid=23534

why sarcoidosis patients get hypercalcemia:
There have been plenty of published reports such as this one. Elevated hormone D can cause symptoms even without hypercalcemia.

Hyperhydration does lower the level of circulating calcium so thirst is a protective reaction.

I would think that discussing Benicar and how ARBs are reno-protective (often used in CKD for this reason) would provide an opening so someone might be willing to write the prescriptions for you. See Uses of Benicar. ~ Belinda

Foundation Staff
.

Joined:	Sat Jul 10th, 2004
Location:
Posts:	17283
Status:	Offline

Posted: Mon May 30th, 2005 16:02

Quote

^{SARCOIDOSISlink}

SUNLIGHT

Sarcoidosis is a chronic progressive disease that is rarely diagnosed in its early stages. Someone who is exposed to excessive sunlight (such as on a vacation or moving to a sunnier climate) may have a symptom exacerbation that leads to a doctor visit and a diagnosis. This doesn't mean that the sunlight caused the saroidosis. It just made it more apparent.

4-30-02
"One of the topics that has often been too much of a "hot potato" to talk about is the extreme sensitivity of many sarc patients to sunlight, and the Vitamin D it produces in our skin.

I am not talking about UVA or UVB or sunscreen or sunburn, I am talking about hormones being produced that play havoc with your body and mind.

This is not a newly discovered phenomenon, it was detailed in 1950 by Scadding and in 1954 by Anderson. In 1968 a paper by Winnacker, et al, reported that sarc patients can be 20 times as sensitive to sunlight and dietary Vitamin D as the 'normal' population, in fact, only 9000 IU of Vitamin D was a toxic dose to some sarcoid patients, whereas 'normal' people could take in in 150,000 IU without a problem. Scadding (in 1950) reported that some sarc patients were intolerant to any dosage of Vitamin D at all...

"25 hydroxyvitamin D" is produced as Sunlight strikes the skin. It is also produced after consuming Vit D from an artificial food source. This is then converted to 1,25 dihydroxyvitamin D3, the active Vit D hormone in our bodies.

Most importantly, we now know that 1,25 dihdroxyvitamin D3 is secreted by the inflammatory macrophages that make up granuloma[/url]. It is a cytokine, and it has an essential task in maintaining the number of monocytes, which make up the macrophages, by catalysing the hematopoetic Stem Cells to produce monocytes.

In the past I personally have stated that I believe it is a major cause of sarc relapses, and I have been ridiculed and pilloried for holding that opinion. However, the evidence is becoming overwhelming. Researchers are now starting to document and explain the hormone's key role in the formation of granulomas, and as an element of the immune system. So you will read more and more about this hormone as the research results come in.

Meanwhile, The Canadian Lung Association has now joined National Jewish in warning sarc patients to stay out of the sun:
"If you have sarcoidosis, it is best to avoid too much direct sunlight. Vitamin D sensitivity may occur with sarcoidosis, and excessive exposure to sunlight can result in increased calcium in the blood which may in turn produce kidney damage"

It is almost impossible for most sarc patients to realize that exposure to sunlight is making them ill. This is because the time taken to generate monocytes and for the 1,25 dihydroxyvitamin D3 to clear your body, is a matter of days, not hours. If you are exposed on Monday you will still be suffering on Wednesday. Very difficult to correlate cause and effect.

I have observed that sarc patient's eyes have to be shielded from bright light by wearing dark shades. 1,25 Dihydroxyvitamin D3 interacts with the cornea in ways which are yet to be fully explained."

..Trevor..

Foundation Staff
.

Joined:	Sat Jul 10th, 2004
Location:
Posts:	17283
Status:	Offline

Posted: Mon May 30th, 2005 20:39

Quote

^{SARCOIDOSISlink}

STANDARD TREATMENTS

Prednisone

Prednisone is used as a first line treatment because it ruthlessly suppresses the body's immune system. It stops the body from fighting the bacteria, and consequently reduces the inflammation the body produces during that fight.

Prednisone stops the actions of a protein dimer called NuclearFactor-kappaB. This protein is essential to the immune system, to the body's response to other challenges (including hyperglycemia) and is vital for balance of bone generation.

In the short term (a few months) your chest x-ray may "clear up" and your liver enzymes may drop.

But you cannot shut down the body's immune response for very long. The bacteria multiply in the tissues without any hindrance once the Prednisone has shut down the body's immune reaction. At some time the sheer amount of toxin they are generating will become uncontrollable, even if the dose of Prednisone is continually increased. If the patient stops taking the Prednisone then their condition will relapse, to a state much worse than when they started on the steroid.

The body has a complex mechanism for keeping the pathogenic bacteria out of the immune system. Prednisone destroys this mechanism, and bacteria can quickly invade the immune system while a person is using prednisone. It is clinically proven that 78% of patients relapse after trying to ease up their prednisone dose: Outcome in sarcoidosis-the relationship of relapse to corticosteroid therapy. Patients who never took prednisone end up healthier in the long run. Now we know why.

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 recently noted on the MUSC forum that "prednisone does not cure the underlying disease."

Prednisone will lead you down a path of increasing oral steroids and decreasing quality of life. This report states " Then there is also the possibility that corticosteroids prolong the course of the disease by delaying resolution,": Outcome in Sarcoidosis: the Relationship of Relapse to Corticosteroid Therapy Your doctor will be hard pressed to show you studies documenting the effectiveness of steroids in sarcoidosis because there are none. Here are some references that illustrate the reality of Prednisone therapy.

National Jewish Jewish Hospital states in this article "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 a 2002 JAMA article entitled Corticosteroid Therapy in Pulmonary Sarcoidosis: "There are no data to suggest that corticosteroid therapy alters long-term disease progression" Side effects are the least of prednisones problems. Steroids are addictive and when used long-term (as little as a month), they can destroy your hip bones and cause diabetes, cataracts, glaucoma, opportunistic infections and osteoporosis.

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

This study, [Corticosteroid]http://tinyurl.com/qyt3w]Corticosteroid treatment in sarcoidosis[/URL], states:
"Remarkably, despite >50yrs of use, there is no proof of long-term (survival) benefit fromcorticosteroid treatment. In addition, there are still no data regarding theoptimal dose and duration of corticosteroid or other immunosuppressive therapy."

There is growing evidence that use of corticosteroids is linked to relapse in sarcoidosis.

-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."

Outcome in Sarcoidosis - the relationship of relapse to corticosteroid therapy
http://www.chestjournal.org/cgi/reprint/111/3/623.pdf
"We suggest.. that corticosteroid treatment itself, rather than the need for treatment, contributed to relapse... Although the answer to whether corticosteroid therapy prolongs the course of disease remains uncertain, the results of the present study add to the growing body of evidence suggest that this potential risk be considered in treatment decisions."

Corticosteroids for Pulmonary Sarcoidosis (Chochrane Review) http://www.update-software.com/abstracts/ab001114.htm
"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."

Trevor Marshall wrote:
The biggest study of Sarcoidosis in history, the NIH 6-year ACCESS study, found that there was no discernible improvement in 2 year outcome whether prednisone was used or not. See our summary at URL
http://autoimmunityresearch.org/access-2yr.htm

There is no study which shows that steroids improve long term prognosis but there are studies to show that relapse is certain when the immunosuppression is withdrawn
http://tinyurl.com/66ahp
Note the sentence in that last paper "Corticosteroids contribute to the prolongation of the disease by delaying resolution"

"Prednisolone is a Vitamin D Receptor (VDR) antagonist. Now we know how Predisone works. And how it downregulates NuclearFactor-kappaB (which is generated by VDR)."

..Trevor..

Steroids will destroy your wife's joints (as well as her soul). Look for example, at this thread from 2002, four years ago, at SarcInfo
http://sarcinfo.com/phorum/topic-1-1515-1515.html

We don't talk about this basic stuff so much any more, it is taken as well-known. But clearly your wife needs to ask a heck of a lot more questions of her Doc about this wonder-drug (at least to her) called "Prednisone." There is a very good reason the NIH/NHLBI is now discouraging its long term use on sarcoidosis patients - it makes them much sicker in the long run.

You might also review some of the forums populated by patients who have taken the road which seems so appealing to your wife right now. Two which come to mind are at
http://tinyurl.com/f7lho
http://tinyurl.com/fm7w8
It isn't any fun being hooked on soul-destroying drugs for the rest of your life, not to mention being totally dependent upon the whims of the pulmonologist prescribing them.

..Trevor..

Why steroids cause weight gain

The acronym "Glucocorticoid" is explained here
http://cancerweb.ncl.ac.uk/cgi-bin/omd?glucocorticoid

Examples include: prednisolone, methylprednisolone, hydrocortisone, betamethasone and dexamethasone.

However, the function of the receptor called the GCR is not fully known, as mice who are bred without it do not survive gestation. Additionally, some Glucocorticoids are now known to have greater affinity for the MCR (MineralCorticoid Receptor) than they have for the GCR. Just as nomenclature got it all wrong with 'Vitamin' D, so the nuclear receptor names do not uniquely define their function.

As you surmise, any drug that affects PPAR-alpha, and, to a lesser extent, PPAR-gamma, can be expected to affect a patient's weight.

Steroid injections:

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).

Steroids are also given by injection, topically, nasally and via eye drops. The use of all these products is strongly discouraged because they are absorbed systemically and will, to some degree, inhibit the immune system. They can also cause adverse side effects. Occasionally they must be used on a short-term basis to ameliorate intolerable symptoms or dangerous inflammation. Please consult with your 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.
Evidence Growing that Inhaled Steroids, Like Pills, Can Cause Bone Loss
......

Possible side effects from oral cortiocosteroids (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

These side effect are dose- and duration-dependent.

Some of the questions you may ask your doctors are:

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

When Weaning Prednisone: You may not realize that ANY symptoms are due to sarcoidosis inflammation. As the prednisone is weaned, you will experience withdrawal symptoms and an increase in inflammatory symptoms which will be similar to past disease symptoms but may also include new symptoms. If you are having more trouble breathing, or problems sleeping or increased fatigue and weakness, these are all symptoms that the inflammation is increasing due to the decrease in prednisone. Try to keep them manageable by decreasing the prednisone very slowly. We expect that you will not be feeling well but your symptoms should be tolerable enough so that you can continue with the weaning. Then, you will be able to really start zapping those intracellular bacteria.

Last edited on Mon Apr 14th, 2008 13:09 by Foundation Staff

Foundation Staff
.

Joined:	Sat Jul 10th, 2004
Location:
Posts:	17283
Status:	Offline

Posted: Mon May 30th, 2005 21:17

Quote

^{SARCOIDOSISlink}
STANDARD TREATMENTS

Methotrexate (MTX) is used to treat diseases with rapid cell growth such as cancer and some 'autoimmune' diseases.

"Methotrexate is an antibiotic. It has identical actions with Trimethoprim which combines with sulfa to make up Bactrim. Here are Course Notes from University of South Carolina which outline MTX's antibacterial actions.

MTX is an anti-folate (actually it is an anti-dihydrofolate reductase (anti-DHFR)) which inhibits one stage in the formation of DNA. Thus any bacteria dwelling within a body which has MTX in the bloodstream will find it more difficult to replicate, and hopefully the bacteria will gradually die off. Bactrim (Sulfa/trimeth) not only blocks DHFR (with trimethoprim) but also blocks P-ABA with Sulfonamide. Here is a diagram showing the Folate biochemistry in more detail

As you know, Bactrim is not a terribly effective antibiotic against the CWD of Sarc and RA (and Lupus and..etc), at least acting on its own. Neither is MTX especially effective (acting on its own).

The interesting thing is that Folic Acid supplements are often given to ease the "side effects" of MTX. Folic Acid directly reduces the antibiotic action of both Trimethoprim and MTX. Sure, this may reduce pain from the 'herx', but wouldn't it be more sensible to just lower the dose of MTX and reduce the risk of liver damage.

The antibiotic action of MTX is likely to increase the effect of herx with Benicar therapy, and that is why we say that you should wean off MTX before starting the Marshall Protocol."

...Trevor...

Discontinuing methotrexate

Benicar should be started only after MTX has been discontinued to avoid an intolerable Herxheimer reaction due to MTX's antibiotic action.

It is not harmful to the body to discontinue MTX abruptly. This is in contrast to prednisone, where abruptly stopping can cause a number of serious problems, from rebound inflammation to an adrenal crisis as the body has to quickly begin producing adrenal hormone (which is suppressed by prednisone). People are advised to wean very slowly from prednisone.

In conventional medical practice, people are advised to wean from methotrexate in an attempt to see at what dose their symptoms return. Sometimes, they are then advised to continue methotrexate at a lower dose.

Some doctors think there is a risk of rebound inflammation from stopping methotrexate abruptly. Taking a few weeks to wean from MTX, while probably not necessary, is the cautious approach to avoid the symptoms of rebound inflammation.

Some doctors say that the effects of MTX might linger for four to six weeks after stopping. This effect would be rebound inflammation. The Benicar blockade will reduce inflammation so it is not necessary to wait 4-6 weeks after discontinuing MTX to start Benicar.

Last edited on Wed Feb 14th, 2007 04:04 by Foundation Staff

Foundation Staff
.

Joined:	Sat Jul 10th, 2004
Location:
Posts:	17283
Status:	Offline

Posted: Mon May 30th, 2005 22:17

Quote

^{SARCOIDOSISlink}

STANDARD TREATMENTS

Anti-TNF-a drugs

Remicade (infliximab)
Enbrel (etanercept)
Trental (pentoxyfyllene)
Humira (adatimumab)
Cimzia (certolizumab
thalidomide

Sept. 4, 2008 WASHINGTON - The Food and Drug Administration ordered stronger warnings on four medications widely used to treat rheumatoid arthritis and other serious illnesses, saying they can raise the risk of possibly fatal fungal infections. The drugs Enbrel, Remicade, Humira and Cimzia work by suppressing the immune system to keep it from attacking the body.

One problem with the anti-tumor necrosis factor alpha drugs, such as Remicade,is that tumor necrosis factor alpha (TNF-a) plays an essential role in keeping tuberculosis and similar diseases at bay, and suppressing it can reactivate or allow new TB infections. Here are two articles on this topic: Treatment with Remicade (Infliximab) is known to cause TB.
Johns Hopkins Arthritis News 10/19/2001
http://tinyurl.com/4c6h7

A recent study says that TNF-a is essential to the proper expression of acquired specific resistance following infection with Mycobacterium tuberculosis:
http://tinyurl.com/cg8d7

REMICADE (infliximab)

This story from the AP wire about the new 'black box' warning (the highest level of warning for a medication) for Remicade is 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.
http://www.hopkins-tb.org/news/8-13-2001.shtml

But as the article below points out, TB skin tests on patients treated with immunospressants (routinely used on RApatients) 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 tuberculosisin a patient who unknowingly carries the TBbacteria.This is not too thrilling for someone who already has RA or sarcoidosis.
Anti-tumor necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management.
Lancet Infect Dis. 2003 Mar;3(3):148-55. Review.
PMID: 12614731 [PubMed - indexed for MEDLINE]
http://tinyurl.com/4ruzv

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:
http://www.rxlist.com/cgi/generic2/rifampin_wcp.htm And Rifampin would create more mutant Cell Wall Deficient bacteria as it kills the TB. It is this CWD bacteria that trigger the sarcoidosis inflammation.

As if TB weren't enough, Remicade can also cause an infection called mycobacterium avium:
http://jcm.asm.org/cgi/reprint/34/9/2240.pdf

These recent papers imply that suppressing TNF-alpha 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.
http://tinyurl.com/4yxub
Sarcoid-related uveitis occurring during etanercept therapy.
http://tinyurl.com/6bkfq

Some people report an allergic response to Remicade. Here is a possible reason:
The chimeric monoclonal antibody in Remicade is part human, part mouse. Exposed to purely mouse (murine) antibodies, human immune systems naturally develop human antibodies to the foreign mouse proteins, which can trigger an allergic-like response. So, they take parts of a mouse antibody and transplant to a human antibody using recombinant DNA technology, to make an antibody that is about 30% mouse and 70% human. Sounds pretty cool, this biotech stuff - until you realize that the 30% mouse portion of the chimeric antibodies can still elicit a 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. Keep in mind that many sarcoidosis patients do not know that they have cardiac involvement.
"Centocor, Inc. would like to inform you of important new safety information for
REMICADE® (infliximab). Upon review of preliminary results of its ongoing phase 2 trial in 150 patients with moderate to severe (NYHA class III-IV) congestive heart failure (CHF), higher incidences of mortality and hospitalization for worsening heart failure were seen in patients treated with REMICADE, especially those treated with the higher dose of 10 mg/kg. Seven of 101 patients treated with REMICADE died compared to no deaths among the 49 patients on placebo."
http://tinyurl.com/4hehq
"Revision of Package Insert to include a contraindication for patients with congestive heart failure, update the Warnings and Adverse Reactions sections, and update the patient information sheet"
http://www.fda.gov/cder/biologics/biologics_table.htm

The real problem is that TNF-alpha is the wrong target. This recentstudy 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.”
http://tinyurl.com/6o8w8

Remicade costs $4600.00 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 (for the (apparently) all-too-frequent anaphylaxis). So that means Remicade is regularly worth $20,000 per month to prescribing doctors and their clinical team. 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. It is then that the problems usually start. Personally, I don't think any drug which causes death as frequently as Remicade is worth paying $18,000 a year for. Minocycline will only cost you about $300 and promises far less excitement. Although there are studies reporting that Remicade slows Rheumatoid Arthritis, there is a 50% dropout rate:
http://tinyurl.com/4scke

It's understandable that drug companies will promote new drugs with large profit margins rather than new uses for old antibiotics with small profit margins.But we should be truly concerned about the outrageous costs and the risk-benefit ratio of anti-TNF-a drugs. The choice to use them or minocycline to treat Rheumatoid Arthritis is just one example that there are significantly less costly, yet effective drug options available.

There are studies reporting that minocycline produces the same effect as Remicade, but at a fraction of the cost. The difference is that there are no pharmaceutical companies funding huge studies of minocycline. Here is one study, though, that indicates minocyclines effectiveness:
Treatment of early seropositive rheumatoid arthritis with minocycline: four-year followup of a double-blind, placebo-controlled trial.
Arthritis Rheum. 1999 Aug;42(8):1691-5.
PMID: 10446869 [PubMed - indexed for MEDLINE]
http://tinyurl.com/5w7ce

The FDA issued a new warning regarding Infliximab (Remicade) on December 22, 2004. The new FDA warning is regarding severe hepatic reactions - including acute liver failure - in patients receiving Remicade. The FDA-ordered Dear Doctor Letter and label with new safety warning are available at the FDA website.

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

Infliximab 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
http://tinyurl.com/lqq8m

- hepatotoxicity and liver failure and
http://tinyurl.com/n86v3

- serious opportunistic infections including tuberculosis and histoplasmosis.
http://tinyurl.com/rx75w

The half life of Remicade is 9.5 days. The excretion rate is unknown. If you are starting the Marshall Protocol, you may take Benicar to dampen inflammatory symptoms that may flare as Remicade leaves your system. Wait 3 weeks to begin minocycline so your body will be accustomed to the absence of Remicade's immunosuppression before you induce immunopathology with minocycline.

TRENTAL (pentoxyfyllene)

Trental may have a palliative effect which allows patients to reduce their dose of prednisone. But it does nothing to effect a cure as the following abstract reports:

A Randomized Trial of Pentoxifylline in Pulmonary Sarcoidosis

V.C. Manganiello, M.D.,Ph.D, M.K. Park, M.D., Ph, M. Stylianou, Ph.D., R. Litzenberger, R.N., K. Jackson, R.N., Y. Tsygansky, B.S., J. Moss, M.D., Ph, Bethesda, MD

Steroid-sparing drugs which suppress inflammatory cytokines that are associated with the formation and maintenance of granulomas would be very useful therapeutics in management of sarcoidosis. In this regard, pentoxifylline (POF) has been reported to inhibit production of IL-2, IL-12, TNF-alpha and, in an open-label clinical study, to improve or stabilize pulmonary sarcoidosis. We therefore conducted a randomized, double-blinded, placebo-controlled trial to assess whether POF treatment would improve or stabilize pulmonary sarcoidosis, and be beneficial as an adjunct to corticosteroid therapy. In our study (NHLBI Protocol 99-H-0057), POF did not improve primary or secondary endpoints in patients with mild to moderate pulmonary sarcoidosis. Although recurrence of pulmonary sarcoidosis was not considered a formal endpoint, 5/13 POF-treated patients experienced disease recurrence versus 12/14 placebo-treated patients (P < 0.02). There were no spontaneous remissions in the placebo group. After 24 weeks, the mean prednisone dose for POF-treated patients was significantly lower than for placebo-controlled patients (P < 0.006). Adverse effects, primarily gastrointestinal, were reported in 11/13 POF-treated , but in no placebo-treated patients. Thus, although POF may have a corticosteroid-sparing effect in pulmonary sarcoidosis, with concentrations of drug used in this study, gastrointestinal side effects were commonly reported.

You can read more about the anti-TNF-alpha drugs, which also include Trental (Pentoxifylline) and Humira (Adatimumab) at http://www.sarcinfo.com: "Warnings:Enbrel,Remicade,Pentoxyfylline,Thalidomide"on SarcInfo
http://sarcinfo.com/phorum/read.php?f=1&i=3450&t=3450

Here's the latest article about TNF-alpha inhibitors, explaining that these drugs are designed to break down granulomas, which also breaks down the barrier that is one of the body's mechanisms to control pathogens.

Immunosuppression related to collagen-vascular disease or its treatment.
Proc Am Thorac Soc. 2005;2(5):456-60.
PMID: 16322600 [PubMed - in process

With the current standard medical treatment, the aim is to reduce granulomas by whatever means - not to bring about real recovery from disease symptoms. ~Belinda

Infections warning upgraded in etanercept label (Enbrel)

By Eleanor McDermid
21 March 2008
US Food and Drug Administration
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.

The warning has been strengthened from the previous bolded warning. The updated labelling "is similar to labelling for other medicines in the tumour necrosis factor (TNF) inhibitor class," notes a statement from Amgen and Wyeth Pharmaceuticals, the companies that manufacture and market etanercept (Enbrel).

An increased infection rate is a theoretical risk associated with any immunosuppressive treatment. One of the main concerns is the risk of new or reactivated tuberculosis infection. The updated prescribing information includes statistics on the rate of tuberculosis infection seen in clinical studies of etanercept: about 0.01% in global studies involving more than 20,000 patients and 0.007% in more than 15,000 US and Canadian patients.

Post-marketing data have shown incidences of tuberculosis infection with drugs targeting TNF, including etanercept. The boxed warning advises evaluating patients for tuberculosis risk factors and latent infection before they begin treatment with etanercept. It recommends treating latent infection to reduce the risk of tuberculosis reactivation during etanercept therapy. The warning also stresses that even patients who test negative for latent tuberculosis infection should be monitored for symptoms of the disease while they remain on etanercept. Etanercept treatment should be stopped in patients who develop a serious tuberculosis infection, the boxed warning states. The warning also notes that the risk of reactivated tuberculosis infection may be lower with etanercept than with monoclonal TNF blockers, however.

Last edited on Fri Sep 5th, 2008 00:45 by Foundation Staff

Foundation Staff
.

Joined:	Sat Jul 10th, 2004
Location:
Posts:	17283
Status:	Offline

Posted: Tue May 31st, 2005 01:01

Quote

^filelink
Standard Treatments

Plaquenil

"Plaquenil is hydroxychloroquine, an anti-malarial, anti-parasite drug with only very weak anti-inflammatory properties. Its use in Lupus and Sarcoidosis is historic, decades old. There are many anecdotal reports that Plaquenil has been effective in treating sarcoidosis. But nobody really seems to know why. It is sometimes useful against sarcoidosis microbes, somewhere under 10% of the time, reportedly. As for why doctors might think it is superior - you would have to ask them. I think you will find that most will not even admit to it being an antimicrobial. According to pulmonology folklore it is supposed to have some (unidentified) magic compound in it that suppresses the immune system.

The flouroquinolones are not terribly effective against mycobacteria. See for example the rickettsia susceptibilities study at
http://tinyurl.com/576az
The full text shows the flouroquinolones are 1/20 as effective against the rickettsia as doxycycline. We don't use flouroquinolones on the MP because we have found that they produce litle or no Herxing in sarcoidosis patients and because their use over the long term raises some issues of bacterial resistance.

Plaquenil has significant risk of side effects, you can about read them here:
http://www.rxlist.com/cgi/generic/hquine_ad.htm
At the dosage given to sarc patients it can cause loss of eyesight, and the FDA recommends frequent checking of a patient's eyes while they are on Plaquenil.

There is an antibiotic, minocycline, which is more effective against the Cell Wall Deficient bacteria which drive the inflammation of Lupus and Sarcodiosis. But it needs to be given in a special dosage and combination. You can read about it at:
http://www.sarcinfo.com/minocin.htm
and the JAMA paper:
http://archderm.ama-assn.org/cgi/content/abstract/137/1/69

Any antimicrobial/antibiotic that has has some effect in Sarc is worth trying - it is just that I would try some of the less drastic than Placquenil antibiotics first. There are several that are much safer. You will note that the FDA http://www.rxlist.com/cgi/generic/hquine_ids.htm gives the same advice - try other drugs first.

My position on the safety of Plaquenil to treat these chronic Th1 diseases is primarily based on a "relative risk" doctrine. I know that COMPLETE recovery from these diseases is possible, and that it can be achieved with common antibiotics and an ARB blocker which have extremely good safety profiles, certainly they have significantly better safety profiles than the literature reports for Plaquenil in Lupus and Sarcoidosis."

...Trevor...

Be aware that about 6% of patients on Plaquenil will lose their eyesight.

This study ( http://tinyurl.com/ac84h ) wasn't the one coming up with a 6% figure, this study found that 20% of patients had to discontinue plaquenil therapy because of noticeable artifacts when their eyes were examined.

There are lots of studies. There are too many people going blind solely because their physicians were too proud to admit defeat.

..Trevor..

Plaquenil and the MP

Plaquenil is an antimicrobial which lingers in the system at least 50 days and cannot be taken while on the MP. Dr. Blaney reports he starts his patients on Benicar while they are waiting for Plaquenil to clear their system and has seen no adverse events. He prefers to wait a couple months before starting minocycline.

Aussie Barb
Research Team

Joined:	Thu Jul 22nd, 2004
Location:	Australia
Posts:	19547
Status:	Offline

Posted: Tue Jun 14th, 2005 08:37

Quote

⁽^filelink⁾
Sarcoidosis is communicable

Can I donate blood, organs, tissue or bone marrow if I have a Th1 inflammatory disease? (click here)

You still have sarcoidosis because it doesn't go away on its own or without treating the underlying bacterial cause. Your blood contains bacteria that would be passed on to someone else. There are documented cases of sarcoidosis developing in patients who received tissue/organs from sarcoidosis patients.

Dr Marshall wrote: One of Lida Mattman's slides in Chicago shows L-forms in supposedly sterile, whole Red-Cross blood.

L-forms seem to survive all attempts at sterilization.

Lida is certain that transfusion is one of the reasons that the chronic diseases have balloned to epidemic proportions over the last 50 years. Remember, the Red Cross blood transfusion service grew at the end of the second world war, and was not around during the first half of this century. Neither were beta-lactam antibiotics, Vitamin D supplementation, the Sun-worshipping ethos, and other factors which, IMO, have all contributed to the Th1 autoimmune diseases spiralling out of control.

..Trevor..

I just saw this letter in CHEST online this morning. I thought you might be interested
"Leukoreduction of transfusions and blood stream infections"
http://www.chestjournal.org/cgi/eletters/127/5/1722

They are advocating the removal of phagocytic cells from blood being transfused. Now the big question is - what could those phagocytes possibly have in them that might promote infection? -LOLOLOL

..Trevor..

===========================================================

Sarcoidosis has been transmitted to organ recipients from organ donors. It's in the bone marrow and stem cells. See below.

Belinda

Lancet published this case report in 1990:
Transmission of sarcoidosis via cardiac transplantation.
Burke W, Keogh A, Maloney P, Delprado W, Bryant D, Spratt P.
Lancet Dec 22-29 1990; 336(8730):1579.
PMID: 1979389
http://tinyurl.com/gdp7u

Other cases:
Heyll A, Meckenstock G, Aul C, Svhngen D, Borchard F, Hadding U, Mvdder U, et al. Possible transmission of sarcoidosis via allogeneic bone marrow transplantation. Bone Marrow Transplant 1994; 14:161-164.

Padilla ML, Schilero GJ, Teirstein AS. Donor-acquired sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2002;19:18-24. http://tinyurl.com/g7ck4

Granulomatous pneumonitis following bone marrow transplantation.
Bone Marrow Transplant. 2001 Sep;28(6):627-30.
PMID: 11607780 [PubMed - indexed for MEDLINE] http://tinyurl.com/fg77e

Pulmonary sarcoidosis following stem cell transplantation: is it more than a chance occurrence?
Chest. 2004 Aug;126(2):642-4.
PMID: 15302757 [PubMed - indexed for MEDLINE]
http://www.chestjournal.org/cgi/content/full/126/2/642

Another thing to consider is: there have been reported cases of sarcoidosis lesions at venipuncture sites (sorta like sarc eruptions in scars and tatoos).

Cutaneous sarcoidosis in venepuncture sites.
Br Med J. 1973 Mar 3;1(5852):547. No abstract available.
PMID: 4692686 [PubMed - indexed for MEDLINE

Hancock BW. Cutaneous sarcoidosis in blood donation venepuncture sites.
Br Med J. 1972 Dec 23;4(842):706-8. No abstract available.
PMID: 4646848 [PubMed - indexed for MEDLINE]

===============================================

The recent ACCESS study, the largest study of sarcoidosis in the US sponsored by the National Institutes of Health, found that the risk for sarcoidosis among parents and siblings of sarcoidosis patients increased five-fold. The researchers also found familial aggregation was much more prominent in whites than African-American families, but an important risk factor in both races.

Since so many physicians (and patients) are not aware of the results from the multi-center ACCESS study that followed newly-diagnosed patients for two years, we have a summary of findings from the ACCESS study in this brochure.

No genetic factor has ever been identified to explain familial occurrences of sarcoidosis, although this has been studied - as noted below. Obviously, the alternative explanation is that family members share environmental bacterial exposure.

[Familial sarcoidosis. Apropos of 22 families]

A sarcoidosis genetic linkage consortium: the sarcoidosis genetic analysis (SAGA) study.

Belinda
How does Th1 inflammation develop? What is successive infection?

Foundation Staff.
.

Joined:	Sun Jul 11th, 2004
Location:
Posts:	1178
Status:	Offline

Posted: Sun Jun 26th, 2005 17:39

Quote

(filelink)
OVERVIEW OF SIDE EFFECTS OF CORTICOSTEROID THERAPY
includes topical, oral, inhaled and eye drop applications

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. 1965 article
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.

Foundation Staff.
.

Joined:	Sun Jul 11th, 2004
Location:
Posts:	1178
Status:	Offline

Posted: Sun Jun 26th, 2005 17:50

Quote

(filelink)
RISKS OF CORTICOSTEROID USE IN CHILDREN

Please read the Overview of Side Effects of Corticosteroid Therapy (the topic above) to understand the known side effects of this treatment in humans.

Oral corticosteroids

Allergic Reaction
Steroid allergy: report of two cases.

Appetite and Weight
From emedicine:
"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.
Treatment of glucocorticoid-induced growth suppression with growth hormone. National Cooperative Growth Study.

More about Growth Suppression
Pharmacy Update
"In children, long-term treatment with oral
corticosteroids can suppress growth."

Article published in the NEJM in 2002
concluded that prolonged alternate day dosing
in pre-pubescent boys with cystic fibrosis led to
growth impairment that persisted after treatment was
discontinued and significantly reduced the height
obtained after 18 years of age.

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.

Reproductive System
"In addition to changes in bone cells, glucocorticoids
reduce the production of gonadal hormones through a
number of mechanisms. Glucocorticoids have inhibitory
effects on the pituitary gland and the gonads."
From An Update on Glucocorticoid-Induced Osteoporosis

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

INHALED CORTICOSTEROIDS

General
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.

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.

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

Skin
Adverse skin reactions to inhaled corticosteroids.

Foundation Staff
.

Joined:	Sat Jul 10th, 2004
Location:
Posts:	17283
Status:	Offline

Posted: Fri Jul 22nd, 2005 03:52

Quote

^{SARCOIDOSISlink}

LUNG TRANSPLANT

My doctor put me on the lung transplant list

"Has your Doctor told you that the average survival of a sarcoidosis patient after a lung transplant is only 30 months? Very few live for 5 years. Has your physician told you that the quality of life during those 30 months is going to be pretty awful, as you will be on cocktails of anti-rejection and immuno-suppressive drugs?

Has your doctor told you that the only way you will breathe comfortably again is with a transplant? Well, he is incorrect. There are recovered sarcies here who used to be on oxygen, and now no longer need it at all.

It is probably a good time to talk with him about this, now, before it is too late.

..Trevor..

ps: I would be happy to discuss these issues with Doc, if he calls me."

==============================

A new 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.
http://tinyurl.com/75mjh

==========================================

"Take a look at 36 years of my own chest xrays.

http://sarcinfo.com/xrays/

You can see that I was stage 4 by 1978, and given 18 months to live. Luckily I figured out Vit D about 1986 and slowed the progression. However, you can see that the fibrosis (scarring) on my xrays (which I urge you to compare with your own) is stage 4++

You will also note that my heart has now shrunk back to a normal size... (it was enlarged through all those years of pulmonary hypertension)

Now take a look at the conference DVDs and you can assess how much all that scarring slows me down these days - virtually not at all..."

Dr. Trevor Marshall, PhD

Belinda wrote: 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. You can read more about viability for sarcoidosis patients after lung transplantation on PubMed or on this thread at SarcInfo.com.

Other patients with "end-stage" sarcoidosis have done well on the MP. If you watch the DVDs of our Chicago conference you will see and hear the story of one woman's recovery from "end-stage" sarcoidosis. You can also read the success stories on SarcInfo and here on the marshallprotocol forum. There are Members here who have chosen to do MP rather than be on the Transplant List.

If I had to choose between a lung transplant or the MP, I would choose the MP because it relies on carefully selected, simple low-cost, low risk antibiotics to treat the chronic infection caused by pleomorphic bacteria, along with Benicar and lifestyle changes to control the runaway 1,25-D. I was able to get off oxygen (I was using 2 liters) and avoided what the pulomonologist believed was the impending collapse of my right middle lobe using the MP. Fibrosis and bronchiectasis were still visible on my last lung imaging, but I now walk six miles a day without dyspnea.

You really need to think carefully about what you are willing to do/endure and how you are willing to live your life at this point. You have to realize that you get the final vote about your medical care; nothing goes without your approval, and you have a significant say in choice of treatment. I would only consider having a lung transplant after I had given the MP my all - like my life depended on it.

Staying out of the sun and taking antibiotics and Benicar for a few years is a comparatively low-risk therapy for a disease that can be fatal. I had to fire my specialist and let my treating doctor know that I was "willing to risk dying from sarcoidosis" before I would accept the risks of the conventional treatment offered to me. If you have your mind made up, you should be able to get a physician to help you implement the MP.

Last edited on Mon Oct 8th, 2007 01:22 by

Current time is 07:36

Page: 1 2 3

* We can help you understand chronic disease, but only your physician is licensed to give you medical care *
Always consult your physician before commencing or changing any treatment he/she has prescribed for you

Powered by WowBB 1.7 - Entire site Copyright © 2004-2007 Autoimmunity Research Foundation, All Rights Reserved
Click here to view our PRIVACY POLICY
Page processed in 0.1290 seconds (10% database + 90% PHP). 16 queries executed.