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Scleroderma & Stem Cells by Alex Carmody

By at January 1, 2012 | 3:59 am | Print

Scleroderma is referred to as the “stone man’s disease”. An excessive amount of collagen production leads patients to become stiff. Due to the stiffness, they essentially become rendered of mobility, hence the phrase “stone man”. However, stone “man” is not necessarily accurate. Although, scleroderma can affect men, it predominately manifests in women, usually women in their late 30’s to 50’s (National Institute of Arthritis and Musculoskeletal and Skin Diseases).

It is an extremely uncommon autoimmune disease. According to the NIAMS, only about 300,000 people in the United States have the condition. People with scleroderma have either one of two types: systematic or localized scleroderma. Systematic scleroderma is the more devastating of the two because it affects the internal organs, whereas localized scleroderma solely tightens the skin. Doctors and scientists have yet to figure out the exact cause or reasons for this rare, autoimmune disease. However, some things we can be certain of. We know why scleroderma is classified as an autoimmune disease, the symptoms that arise from scleroderma and the semi-effective procedures for treatment specifically stem cells.

There is a wide spectrum of autoimmune diseases; however they all share a similar feature. Autoimmune diseases attack the body instead of working cohesively within it. Unlike a virus or flu that you can catch, these abnormal cells live inside you, but are unable to function correctly. A person with an autoimmune disease might produce less/more cells than a healthy human which causes their bodies to react differently. For example, scleroderma patient’s immune system triggers fibroblasts. Fibroblasts produce an excess of collagen; the extra collagen leaves the skin rigid (NIAMS). You need collagen to help you move, but when you have too much then you no longer produce harmony within your body. Without this essential balancing act, a scleroderma patient will become rigid instead of mobile. For example, a person with scleroderma won’t be able to flex their fingers open and closed. Instead, their hands will remain rigid with limited movement. Part of this limited movement is due to one of the symptoms of scleroderma called sclerodactyly.

However, the most predominant symptom and one of the first to occur with scleroderma patients is raynaud’s phenomenon. Similar to scleroderma it affects mostly women. Raynaud’s phenomenon can easily be correlated to autoimmune diseases, specifically scleroderma because it is a symptom in 90% of people with scleroderma (NIMAS). It is not to be confused with raynaud’s disease which occurs without any other disease or illness. Raynaud’s disease is solely an annoyance and acts on its own, while secondary raynaud’s or raynaud’s phenomenon is a part of a larger problem. With scleroderma patients, raynaud’s phenomenon is the first red flag. They start to feel a tingling in their finger; they also will notice a stark white or blue color followed by their finger feeling ice cold. The reason for the chilling finger is because of the lack of blood getting into the body. For unknown reasons, excess collagen will restrict the blood flow to digits. Raynaud’s phenomenon, in particular, affects hands, feet, nose and ears. The disease will flare up during extreme weather (hot or cold) and when people experience powerful emotions. Therefore, in winter or cold temperatures, it’s important to always make sure scleroderma patient’s hands or feet are warm, because once the blood rushes toward the fingers or infected area it, will turn the fingers red and then they will return to normal.

CREST is a very common way to identify scleroderma. These symptoms are calcinosis, raynaud’s phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia. Calcinosis refers to calcium deposits found on the fingers (NIAMS). The calcium deposits come from the connective tissues. Raynaud’s phenomenon, once severe enough, can create digital ulcers. The ulcers appear from the lack of oxygen reaching the cells. This isn’t a detrimental problem, but ulcers can be painful. The esophagus (a part of the gastrointestinal tract) will lose some of its contracting motion which makes it hard to swallow. Sclerodactyly refers to the rigidity of the hands due to the extra collagen production. Lastly, telangiectasia produces tiny blood vessels to appear as red spots. This isn’t painful, but is not very common so a scleroderma patient might stand out (NIAMS).

CREST symptoms aren’t the only issues to arise in people with scleroderma. Scleroderma patients have a wide range of issues to go along with their illness. Most of these problems can occur along the gastrointestinal tract. Research done by the Indian Journal of Rheumatology, addresses these issues and how to alleviate the symptoms. For example, a scleroderma patient might face sjögren’s syndrome. This affects liquids in the body. For example, people might have constant dry eyes or difficulty swallowing. Sjögren’s syndrome effects 20% of patients (Khanna). One recommendation is to take in small amounts of food in, eat soft foods and to stay hydrated (Khanna). Small portions are necessary to fix down the suffocated esophagus.

Another problem for 20-50% of patients with systemic scleroderma is constipation or diarrhea. Diarrhea can lead to bacteria overgrowth syndrome, then to anorectal involvement which is reported in 50-70% of scleroderma patients (Khanna). If the patient is constipated they don’t suggest a high fiber diet, in fear that it might make the condition worse. They recommend patients take laxatives two to three times a day to be regular (Khanna). If the patient suffers from diarrhea, doctors might recommend stimulating the nerves to make the GI tract constrict; however, this requires a procedure to place a pulse generator in the anus (Khanna).

However, the worst issue to come from scleroderma is pulmonary hypertension. Pulmonary hypertension combined with limited blood flow is the leading cause of death in people with scleroderma (Donald). The arteries become so narrow, due to the collagen that the heart has to double its work. Since the heart is already working overtime any extraneous activity can be deadly. Hypertension combined with limited lung capacity leaves patients unable to be active for long periods of time. If a patient tries to overwork themselves they could end up having a heart attack. The downside is that it forces them to be unhealthy by being inactive.

There is no exact gene or cause for scleroderma. Many believe scleroderma lies dormant until major phases in a person’s life that will alter the body. These phases include puberty or menopause. Other doctors believe that environmental factors play a part in people developing scleroderma because of the high number of European descendents and African American women who have scleroderma (NIAMS). Studies have shown people who have been exposed to fumes are more susceptible to scleroderma. Jobs that expose people to these toxic fumes would be coal miners or gold miners. Other types of chemicals that have been associated with scleroderma include vinyl chloride or trichloroethylene (NIAMS).

Although there is no cure for systematic or localized scleroderma, there are ways to alleviate some of the symptoms. These approaches range from oral medication to drastic means such as, chemotherapy (low to high doses) and stem cell transplants. Every scleroderma patient is unique, so not ever procedure will work and/or be as effective. Doctors will either use a pill form or chemotherapy or hook patients up to an IV containing the drug. Cyclophosphamide (chemotherapy drug) kills cell division. Cancer cells divide without any control from DNA or RNA cells. These types of drugs kill all cells from dividing. They mainly target dividing cells. The cells that divide the most rapidly are the cancerous ones. Thankfully, these are the ones that the chemotherapy drugs will latch onto. These cancer cells end up dying off, because if they can’t divide then they won’t thrive or survive. This wipes the body (specifically the immune system) clean. The drug leaves relatively no cells present; therefore the body can rebuild itself on the new bone marrow it has received. This bone marrow will be from a healthy person whose cells will function correctly. The hope is that these new cells will make copies from the new bone marrow.

Bone marrow can be found inside your bones; which is also where hematopoietic stem cells are found. Stem cells are used to develop into three types of blood cells: white blood cells, which protect your body against viruses; red blood cells, which you breathe by carrying oxygen; and platelets, which help the blood to clot (NIAMS). Even though bone marrow can be extracted from many places, the most common way is through an allogeneic transplant. Allogenic transplants are more useful because they come from a relative (brother, sister, mother, father) or a donor. Most scleroderma patients can’t use their own stem cells because they’re compromised which would be an autologous transplant. The other is called a syngeneic transplant which comes from an identical twin which is extremely uncommon.

For most patients, stem cell transplants are a last resort, because it’s a very taxing procedure on patients already weakened bodies. Not to mention, doctors have to do rigorous testing to determine good candidates. They must check their heart, lungs, gastrointestinal tract to see if they can handle such an intense procedure. If they meet all the requirements, then they will be put onto chemotherapy to begin the procedure. Some studies have been done to show stem cells affects on scleroderma. For example, Dr. Arnold used autologous stem cell transplant to see how it affected people with scleroderma. He found a 25% increase in skin scores occurred in 20/29 or 69% of his patients. Lung function did not improve; however it did not get worse. Lung function remained stable for most patients. Only 24% saw a decrease in lung functioning. Kidney failure is common among people with severe scleroderma. One of five renal cases deteriorated, but after the transplant they had no new occurrences. Another extraordinary discovery was made during the trial too. There was no progression in pulmonary hypertension after the transplant either. Overall, the stem cells did help. Even with a 10% mortality rate, the people who survived will live life without declining in health. After the procedure, most of the patients hit a plateau; therefore it seems to be a success, because of the fact they aren’t deteriorating (Arnold).

A study done by The New England Journal of Medicine, narrowed their use of cyclophosphamide to just scleroderma patients lungs. The reason they focused on the lungs of scleroderma patients is because their lungs cannot fill to maximum capacity, due to the scar tissue blocking the flow. They found similar results to Dr. Arnold’s findings. The drug can slow the deterioration or help improve the amount of oxygen a scleroderma patient can intake.

Overall, scleroderma is an incurable disease. The only helpful solution that doctors have come up with for systemic scleroderma is stem cells. The excess collagen that is produced by the body will deteriorate the gastrointestinal tract, skin, lungs, kidneys and heart. All these can contribute to the inevitable 10 years scleroderma patients’ face, while declining in health (NIAMS). From research the only way patients can maintain their health or slightly increase is from stem cells. They are the most effective way to keep a baseline of symptoms without progressing in a downward spiral.

 

Work Cited

Arnold, R. Bacon, P. Besenthal, C. Binks, M. Black, C. Breedveld, W. Emery, P. Espigado, B. Farge, D. Fibbe, F. Finke, J. Furst, D. Gluckman, E. Gratwohl, A, Hertenstein, I. Hiepe, F. Hoogen F. Kashyap, A. Kooter, I. Laar, J. Locatelli, F. Marmont, A. Martinez, A. Martini, A. McSweeney, P. Pascual, M. Passweg, J. Peter, H. Prentice, H. Putte, L. Schattenberg, A. Sullivan, K. Tyndall, A. “Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: procedure related mortality and impact on skin disease.” National Center for Biotechnical Information, 6 March. 2001. PubMed. Web. 18 Nov. 2011.

Donald P. Tashkin, M.D., Robert Elashoff, Ph.D., Philip J. Clements, M.D., M.P.H., Jonathan Goldin, M.D., Ph.D., Michael D. Roth, M.D., Daniel E. Furst, M.D., Edgar Arriola, Pharm.D., Richard Silver, M.D., Charlie Strange, M.D., Marcy Bolster, M.D., James R. Seibold, M.D., David J. Riley, M.D., Vivien M. Hsu, M.D., John Varga, M.D., Dean E. Schraufnagel, M.D., Arthur Theodore, M.D., Robert Simms, M.D., Robert Wise, M.D., Fredrick Wigley, M.D., Barbara White, M.D., Virginia Steen, M.D., Charles Read, M.D., Maureen Mayes, M.D., Ed Parsley, D.O., Kamal Mubarak, M.D., M. Kari Connolly, M.D., Jeffrey Golden, M.D., Mitchell Olman, M.D., Barri Fessler, M.D., Naomi Rothfield, M.D., and Mark Metersky, M.D. “Cyclophosphamide versus Placebo in Scleroderma Lung Disease.” The New England Journal of Medicine. 22 June. 2006. Web. 18 Nov. 2011.

Khanna, D. Melikterminas, E., et al. “Gastrointestinal involvement in systemic sclerosis.” Indian Journal of Rheumatology 3.1 (2008): 13-10. Science Direct. Web. 18 Nov. 2011.

United States. Dept. of Health and Human Services. National Institute of Health. “Scleroderma.” National Institute of Arthritis and Musculoskeletal and Skin Diseases. May. 2010.Web. 18 Nov 2011.

 

 

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One Comment


  1. Holly Hauser, 5 years ago Reply

    Dear Alex,

    Thank you for taking the time to study scleroderma. A couple of corrections to your article. Stone man syndrome is a different disease, although some think biblical references about being turned to stone could represent scleroderma. Many of us feel stone-like; however, there is a different syndrome which carries that name.

    The internal manifestations of scleroderma are known as systemic disease– not systematic disease.

    Your explanation of chemotherapy is reasonable for cancer. In scleroderma, chemotherapy is used differently. Basically, the chemotherapy drugs are used to target normal immune system cells. Scleroderma is, at it’s root, an autoimmune disease characterized by an immune system which attacks normal body tissues. It’s a little like taking a shotgun to a problem that needs a pocket knife, though. We need to find more refined treatments.

    Additional stem cell research was published by Dr. Richard Burt in 2011 demonstrating no mortality and lung improvement. This good news, likely a result of improved patient selection and process, is coupled with about a 30% recurrence rate.

    Because scleroderma comes in many forms (see Dr. Virginia Steen’s paper titled The Many Faces of Scleroderma), death is not inevitably 10 years from diagnosis. Many patients live long lives, while some continue to face early, aggressive and deadly complications.

    The more we can do to spread the word, educate ourselves and others, fund research, and look for more potent and targeted therapies, the greater chance scleroderma patients will have of living well with the disease.

    Thanks, again, for spreading the word about scleroderma.

    Warmly,
    Holly Hauser, M.D.


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