Previous work described Borrelia burgdorferi sensu lato group DN127 as a new genospecies, Borrelia bissettii, and prompted the present study to identify the Borrelia spp. that exist in northern Colorado.
To determine the genospecies present, we analyzed two specific intergenic spacer regions located between the 5S and 23S and the 16S and 23S ribosomal genes.
Phylogenetic analysis of the derived sequences clearly demonstrated that these isolates, originating from rodents captured in the foothills of northern Colorado, diverged from B. burgdorferi sensu stricto by 5 to 5.5% and were members of the new genospecies B. bissettii.
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Melanie Reber
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Three multiplex assays for detection of Borrelia burgdorferi sensu lato and Borrelia miyamotoi sensu lato in field-collected Ixodes nymphs in North America. [Journal Article] Ullmann AJ, Gabitzsch ES, Schulze TL, Zeidner NS, Piesman J J Med Entomol 2005 Nov; 42(6):1057-62.
Two hundred fifty New Jersey field-collected Ixodes scapularis Say ticks and 17 Colorado Ixodes spinipalpis Hadwen & Nuttall ticks were tested using three separate multiplex real-time polymerase chain reaction (PCR) assays.
One assay targets the rrs-rrlA IGS region of Borrelia spp. to detect Borrelia burgdorferi sensu lato (s.l.) and Borrelia miyamotoi s.l. The second assay targets the ospA region of B. burgdorferi s.l. to detect B. burgdorferi sensu stricto (s.s.), Borrelia bissettii, and Borrelia andersonii. The final assay targets the glpQ region of B. miyamotoi s.l. to differentiate B. miyamotoi LB-2001 and Borrelia lonestari.
A testing scheme combining these tests yielded 18% of tested I. scapularis ticks surveyed from New Jersey positive for B. burgdorferi s.s., 3.2% I. scapularis ticks positive for B. miyamotoi LB-2001, and 41.2% I. spinipalpis ticks positive for B. bissettii surveyed from Colorado.
...........
41.2% is rather high considering... don't you think? Posts: 7052 | From Colorado | Registered: Mar 2003
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Truthfinder
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I'll write more later on, but.....
Great information about Borrelia carolinensis, Melanie. Borrelia b. may be just the tip of the iceberg.
Oh, I hadn't seen that 2005 article - wow! 41.2% of Borrelia bissettii in Colorado ticks seems pretty darn high to me, for sure! Nice work, Melanie.
In fact, isn't that a much higher incidence rate (in ticks) than we see in the Northeast for most Borrelia burgdorferi strains?
This could be very important information!
The first article you posted in one that I have, and then there's another one that is similar from 2002. I'll send you what I have, but it won't be until later. I have more info somewhere about B. bissetti and I can't seem to find it. Grrr. And I see that to my articles don't take you to the article itself..... grrr. Well, I've copied enough info from the articles that it can be found using a Google search, I guess.
Here's an excerpt that I thought was extremely interesting..... it confirms why there are so many negative serological results out there......
quote:......strains genetically similar to those of B. bissettii from New York, California, South Carolina, and Florida have been isolated from several humans in Slovenia . Those patients had clinical presentations ranging from relatively benign illness to some severe afflictions. Some of the patients had variable and unpredictable serologic responses, including a lack of antibody response despite disseminated disease (29). Interestingly, some of the Lyme disease patients in the southern United States also lacked a serologic response to antigens derived from B. burgdorferi sensu stricto (9).....
Gotta go finish another post and get busy here......
-------------------- Tracy .... Prayers for the Lyme Community - every day at 6 p.m. Pacific Time and 9 p.m. Eastern Time � just take a few moments to say a prayer wherever you are�. Posts: 2966 | From Colorado | Registered: Dec 2005
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Melanie Reber
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Hi Trish, I'm so sorry, I wasn't trying to ignore you, I just somehow missed your reply.
If you have ACA treat Babesia if you have not.
Yes, Babs has been a difficult one for me to treat. It took me way too long to admit that I even had it, and when I did treat, it was for about a year and a half.
Now, it has returned, and has apparently teamed up with a second strain of Duncani as well. So, yes, we have been going after it pretty aggressively.
I have also had the hands ITCH like heck from this Mepron and Azithromyin where the ACA is...
I did ask my LLMD about this insane itching that happens to me on my legs anytime I try to go for a walk. I was told it is a manifestation of neuropathy! Well, of course I have the numb and tingling PN, but had no clue that the itching was also PN.
This does make sense, because an early symptom of ACA IS PN of the extremities. So perhaps this will help to explain why your areas of ACA itch?
I'm very pleased to know that you are doing better with treatment!
Hey Roz, sorry I somehow missed your last reply as well.
Your skin coloring looks like mine, how is your circulation? I am doing much better. I believe 100% you can go into remmision with ACA as well. I am 65% percent better and have been in treatment for 2 years. How are you doing as far as detoxing goes?
My circulation stinks. I am so pleased you are doing so well! This is what I have been told as long as you get straight to treating effectively. My detox ability stinks too. Posts: 7052 | From Colorado | Registered: Mar 2003
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Melanie Reber
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Thanks for the additional info Tracy.
Ya know what... this really disturbs me. This is NOT rocket science! If WE can find the info we need to connect the dots after only looking for a few minutes... and only having access to very limited information...
WHY can't the 'powers that be' do the same?????
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Carol in PA
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quote:Originally posted by Melanie Reber:
During the period from 1986 to 2000, 85 adult patients with solitary borrelial lymphocytoma were diagnosed....
Borrelial lymphocytoma was located on the ear lobe in...9.4%...
I have had little "blind pimples" on my earlobes since my teen years. I have some right now. The LightWorks healed them in a few days, after more than six months, but there is still something there.
This is the best pic I could find:
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Melanie Reber
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Hey there Miss C, That is actually a great picture of Borrelial lymphocytoma. (and rated G as well, thanks)
I know we have spoken before about overlapping symptoms... I so wish we could get you on some ABX to see what would happen with you.
Love, M
PS...I know I owe you an email, actually a few. Just know that I appreciate them and you so much!
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Truthfinder
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Melanie, I just sent you some Colorado info via your e-mail addy at the Lyme Memorial Project. I hope it was okay to use e-mail...... it will be more readable than through the PM system here (which still appears to be a bit unreliable).
Well, I still don't have time to post much this morning - and we've got some thunder and lighting going on close by, so I'll probably have to shut down the computer pretty soon anyway.
I'll get back here eventually.......!
-------------------- Tracy .... Prayers for the Lyme Community - every day at 6 p.m. Pacific Time and 9 p.m. Eastern Time � just take a few moments to say a prayer wherever you are�. Posts: 2966 | From Colorado | Registered: Dec 2005
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Melanie Reber
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Thank you SO much Tracy,
I'm afraid I am really dragging on the newest meds, but will get back with you as soon as I can.
Truthfinder
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Thanks for the camera tip, Melanie. I actually printed that out. I actually bought some little USB cable thingie so that I wouldn't have to use the camera batteries to download..... and it is still in the package, lol. I just want to make sure that I can edit photos once they are off the camera. Somebody told me that they couldn't do that on the computer. That didn't sound right, but again, it's probably a software issue.
Yes, I think eating small meals through out the day would probably be the best. But like you, I just have trouble doing this.
My temperature fluctuations are not only annoying but because they vary so much, I never know how to dress for the weather if I go somewhere! Gee, will I be freezing today or not? Like you said, the actual temperature is only a starting point; it's my internal temp that dictates my comfort level. I've acquired so many clothes that a `normal' person doesn't need because I must wear at least 2 layers, even in summer.
Example of the madness: Just a couple of hours ago, I was wearing a winter watch cap here at the computer! Yep, it's true. I ate a small `vegetable' meal last night, had trouble getting warm in bed, and then, of course, when I got up this morning, it felt like an icy breeze was blowing on my head. But its 68 degrees here at the computer. Craziness!
No, I have no Lyme doc, even an alternative one. I'm just sort of winging it at the moment. If I treat with someone, it will be a homeopath. I don't tolerate drugs or herbs or supplements well so it's the best choice for me, really. Not only that, I think homeopathy is a terrific system of medicine. Thanks for your concern - I appreciate that.
One thing I thought of re the `source' of my Lyme and probable ACA.....
Though I've never been to Europe, the man I married (since divorced) was from Oklahoma and spent a couple of years at Ramstein Air Force Base in Germany. He did considerable traveling and camping throughout Europe. It was AFTER I began a serious relationship with him that my symptoms started to manifest.
That is only one factor of many things that all happened about the same time, though. Still, it's possible that he had been exposed to some European TBI strain that set my symptoms in motion. I hadn't thought of him as a possible factor.
(BTW, ex-hubby was a physical mess when I met him and had all kinds of musculoskeletal problems, mostly spinal - which is where my worst physical symptoms are. He'd been disabled for 2 years with back problems, had 2 cervical fusions, 5 knee surgeries plus later had both knees replaced, surgery on one wrist for compartment syndrome, and a couple of other surgeries that I can't recall.)
Also, I'm having peripheral neuropathy or something similar in my feet. I figure it was diabetes (no, don't have that yet) or circulation. Maybe another clue there.
So, I guess I can add that information to my list of things that make me go, ``Hmmmm''.
-------------------- Tracy .... Prayers for the Lyme Community - every day at 6 p.m. Pacific Time and 9 p.m. Eastern Time � just take a few moments to say a prayer wherever you are�. Posts: 2966 | From Colorado | Registered: Dec 2005
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Melanie Reber
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Hey there Tracy,
Your story just gets more interesting by the day!
About editing. Do you have PhotoShop loaded on your comp? That would make life a whole lot easier for you, but only if you know how to use it I suppose.
Most comps do have a built in editing program, you may have to search and experiment to find it though.
Another option would be to send the unedited pics to me and I can edit for you?
I'm SO behind already for the day and it isn't even 7am yet! So, I have to shut down windows so I can concentrate on work a bit. Just let me know IF you would like any help with the pics, OK? M
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Tracy, my husband has the exact same diagnosis and you describe his sores exactly. I asw similar loking pics in Schaller's bart book.
My husband has never been to CO, but has hiked quite a bit in the western states: alaska, montana mostly. I dont think he remembers a tick bite.. we know how that goes.
We are from the east coast.
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Truthfinder
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Thanks for the offer, Melanie. We'll see how it goes. No, I don't find Photoshop on here - just 2 other photo programs, one is a Microsoft product, the other is some Dell program.
R62, Bart, huh? Interestingly, I LIVED in interior Alaska for 10 years..... and it was there that the skin on my face started doing weird things.....
-------------------- Tracy .... Prayers for the Lyme Community - every day at 6 p.m. Pacific Time and 9 p.m. Eastern Time � just take a few moments to say a prayer wherever you are�. Posts: 2966 | From Colorado | Registered: Dec 2005
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Tracy, he doesnt have other bart symptoms, esp not neuro symptoms. His only symptoms are headaches and muscle pain in his thighs. And these sores that you described to a tee.
He has been to Alaska twice. Once in Denali with me and the other hiking the Brooks Range. He just told me that he had these before he went to Alaska...
???
He also has the fry mystery bug.
I have also wondered if they are gluten related.
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Truthfinder
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Well, sort of glad to know that Alaska probably didn't have anything to do with it.
Bart is certainly a possibility for me, though I don't know about the Fry bug or gluten.
-------------------- Tracy .... Prayers for the Lyme Community - every day at 6 p.m. Pacific Time and 9 p.m. Eastern Time � just take a few moments to say a prayer wherever you are�. Posts: 2966 | From Colorado | Registered: Dec 2005
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Melanie Reber
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The spirochetal etiology of acrodermatitis chronica atrophicans Herxheimer. [Journal Article] Asbrink E, Hovmark A, Hederstedt B Acta Derm Venereol 1984; 64(6):506-12.
Spirochetes were recovered from the skin lesion of 1 out of 10 acrodermatitis chronica atrophicans patients (ACA). Spirochetes from this skin isolate and from Ixodes (I.) ricinus and I. dammini spirochetes were used as antigens in indirect immunofluorescence tests. All sera from 17 ACA patients showed high antibody titers to the three antigens.
Seven of the 17 sera which had the highest titers had crossreactive antibodies to treponemal antigen detectable in the FTA-ABS test.
The results indicate that spirochetes are of importance for ACA and probably the causative agent of this disease. The connection between ACA and tick bites and the relationship to erythema chronicum migrans Afzelius (ECMA) and Lyme disease are discussed.
The results are consistent with the hypothesis that ECMA and ACA are different manifestations of the same spirochete, with ACA as a late manifestation.
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Melanie Reber
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Many times ACA, Scleroderma and Raynaud's Phenomenon go hand in hand. Here is an excellent overview of Scleroderma. I realize this is very long...but it contains some very valuable information. As with most overviews, please be cautious re: some suggestions, and talk everything over with your treating physician before any decisions are made re: your healthcare.
Symptoms * Because significant depression can affect more than 50% of people with scleroderma, researchers say it may be beneficial for scleroderma patients to get routine screening for depression.
Causes * Researchers have discovered a gene called connective-tissue growth factor (CTGF), which they say is more common in people with systemic scleroderma than in those without the disease.
Prognosis * The prognosis for patients with systemic scleroderma has improved since the 1970s. Ten-year survival rates are up, and deaths from kidney crises have dropped. However, deaths from pulmonary fibrosis have increased during this time period.
Treatment * High-dose immunosuppressant therapy with cyclophosphamide significantly improved skin and overall function in patients with scleroderma.
* Evidence shows that intravenous iloprost given in progressively increasing doses can reduce the duration and frequency of Raynaud's phenomenon attacks.
* A potential new therapy using PVAC, a substance derived from the bacterium, Mycobacterium vaccae, can improve skin symptoms without causing significant side effects.
Introduction The name scleroderma comes from the Greek words skleros, which means hard, and derma, which means skin. The disease is categorized as a rheumatologic disorder because it affects the connective tissues in the body.
Scleroderma is a rare disease marked by the following:
* Damage to the cells lining the walls of small arteries
* An abnormal buildup of tough scar-like tissue in the skin
Patients with scleroderma may develop either a localized or a systemic (body-wide) form of the disease.
Localized Scleroderma
Localized scleroderma usually affects only the skin on the hands and face. Its course is very slow, and it rarely, if ever, goes throughout the body (becomes systemic) or causes serious complications. There are two main forms of localized scleroderma: morphea and linear scleroderma.
Morphea Scleroderma. In morphea scleroderma, patches of hard skin form and can last for years. Eventually, however, they may improve or even disappear. There is less than a 1% chance that this disorder will progress to systemic scleroderma.
Linear Scleroderma. Linear scleroderma causes bands of hard skin across the face or on a single arm or leg. Linear scleroderma may also involve muscle or bone. Rarely, if this type of scleroderma affects children or young adults, it may interfere with growth and cause severe deformities in the arms and legs.
Systemic Scleroderma
Systemic scleroderma is also called systemic sclerosis. This form of the disease may affect the organs of the body, large areas of the skin, or both. This form of scleroderma has two main types: limited and diffuse scleroderma. Both forms are progressive, although most often the course of the disease in both types is slow.
Limited Scleroderma (also called CREST Syndrome). Limited scleroderma is a progressive disorder. It is classified as a systemic disease because its effects can be widespread throughout the body. It generally differs from diffuse scleroderma in the following ways:
* Most often the internal organs are not affected.
* Patients with scleroderma have a less serious course, unless they develop pulmonary hypertension (a particular danger with the CREST syndrome). Pulmonary hypertension is high blood pressure in the lungs (see the Lung Complications section).
Limited scleroderma is commonly referred to by the acronym CREST, whose letters are the first initials of characteristics that are usually found in this syndrome:
* Calcinosis. With this condition, mineral crystal deposits form under the skin, usually around the joints. Skin ulcers filled with a thick white substance may form over the deposits.
* Raynaud's phenomenon. In this syndrome, the fingers of both hands are very sensitive to cold, and they remain cold and blue-colored after exposure to low temperatures. This occurs in nearly all cases of scleroderma, both limited and diffuse. It is caused by abnormal changes in small blood vessels. These changes cause the vessels to narrow, and blood flow is temporarily interrupted, usually in the fingers.
* Esophageal motility dysfunction. The esophagus carries food from the mouth to the stomach. In esophageal motility dysfunction, the muscles in the esophagus become scarred by scleroderma and do not contract normally. This can cause severe heartburn and other symptoms of gastroesophageal reflux disorder (GERD).
* Sclerodactylia (also called acrosclerosis). This is the stiffness and tightening of the skin of the fingers, a classic symptom of scleroderma. Bone loss may occur in the fingers and toes.
* Telangiectasia. In this situation, widening of small blood vessels causes numerous flat red marks to form on the hands, face, and tongue.
In general, people with limited scleroderma develop Raynaud's phenomenon long before they develop any of the other symptoms. One or more of the CREST conditions can also occur in other forms of scleroderma.
Diffuse Scleroderma. Diffuse scleroderma, the other systemic sclerosis, has the following characteristics:
* It can affect wide areas of the skin, connective tissue, and other organs.
* It can have a very slow course, but it also may start quickly and be accompanied by swelling of the whole hand. If it gets worse quickly early on, the condition can affect internal organs and become very severe -- even life threatening.
* Diffuse scleroderma can overlap with other autoimmune diseases, including systemic lupus erythematosus and polymyositis. In such cases, the disorder is referred to as mixed connective disease.
Symptoms and Complications
Raynaud's Phenomenon
Raynaud's phenomenon is often the first sign of the scleroderma disease process. With this condition, small blood vessels narrow in the fingers, toes, ears, and even the nose.
Attacks of Raynaud's phenomenon can occur several times a day, and are often brought on or worsened by cold. Warmth relieves these attacks. In severe cases, attacks can develop regardless of the temperature. Severe cases may also cause open sores or damage to the skin and bones, if the circulation is cut off for too long. Stress also can trigger the syndrome.
Typically, the fingers go through three color changes:
* First, they become very pale.
* As the blood flow is cut off, they turn a bluish color, usually in the top two sections of the second and third fingers.
* Finally, when blood flow returns, the fingers become red.
Tingling and pain can occur in the affected regions.
Raynaud's is very common and occurs in 3 - 5% of the general population. It's important to note that more than 80% of patients with Raynaud's phenomenon do not have scleroderma, lupus, rheumatoid arthritis, or other more serious illnesses. Raynaud's is more likely to be a symptom of scleroderma or some other connective tissue disease if it develops after age 30, if it is severe, and if it is accompanied by other symptoms (such as skin changes and arthritis).
Skin Changes
Course of Typical Skin Changes. The primary symptoms of scleroderma occur in the skin. They often take the following course:
* Typically, pitted scars appear first on the hands. The skin begins to thicken and harden on the hands, feet, and face. The fingers may swell. This condition is called sclerodactylia or acrosclerosis. Patients with diffuse scleroderma may have swelling of the whole hand before the skin significantly thickens.
* Thickened or hardened patches may also develop on other areas of the body. (Their appearance on the trunk and near the elbows or knees tends to be a sign of a more severe condition.)
* For the first 2 or 3 years, the skin continues to thicken and feel puffy.
* This process then stops, and can even get better. The skin may soften.
* As the disease progresses further, however, the skin loses its ability to stretch, and becomes shiny as it tightens across the underlying bone, particularly in the fingers, toes, and around the mouth.
* Eventually, in severe cases, the fingers may lose the ability to move, and can be difficult to bend. The hands and feet may curl from the tightness of the skin. It may be difficult to open the mouth widely.
Other Skin Changes. The following skin symptoms may also occur:
* Flat red marks, known as telangiectasis, may appear in various locations, usually the face, palms, lips, or the inside of the mouth.
* In calcinosis, small white lumps form beneath the skin, sometimes oozing a white substance that looks like toothpaste. Calcinosis can lead to infections.
* Small blood vessels at the base of the fingernails may be lost in some places, and may widen in other places. This is an indication that internal organs might be involved.
* The entire surface of the skin may get darker over time, and contain patches of abnormally pale skin.
* Hair loss may occur.
* About 1% of patients have Sjogren syndrome, a group of symptoms that include dry eyes and dry mucus membranes (such as those in the mouth).
* Inside the mouth, scleroderma can also cause changes that impair gum healing.
Bone and Muscle Symptoms
Changes in bones, joints, and muscles can cause the following symptoms:
* Mild arthritis. The condition is usually distributed equally on both sides of the body.
* Bone loss in the fingers. The destruction is not as severe as it is in rheumatoid arthritis, although the fingers may shorten over time.
* Trouble bending the fingers, if the disease has affected the tendons and joints.
* Muscle weakness may occur, especially near the shoulder and hip.
Digestive Tract Symptoms and Complications
Complications in the Upper Digestive Tract.
* Esophageal motility disorder develops when scarring in the muscles of the esophagus causes them to lose the ability to contract normally, resulting in trouble swallowing, heartburn, and gastroesophageal reflux (also known as GERD). Some experts believe that patients with severe GERD may breathe in microscopic amounts of stomach acid, which in turn may be a major cause of lung scarring.
* About 80% of patients also experience impaired stomach activity. A delay in stomach emptying is very common.
* Some patients develop "watermelon stomach" (medically referred to as CAVE syndrome), in which the stomach develops red-streaked areas from widened blood vessels. This causes a slow bleeding that can lead to anemia (low red blood cell counts) over time.
* There may be a higher risk for stomach cancer.
* Problems with movement of the food through the intestines (motility) also develop. Patients may experience an increase in bacteria and have trouble absorbing nutrients from foods through the intestines.
Complications in the Lower Digestive Tract. Complications in the lower tract are uncommon. If they do occur, they can include the following:
* Scarring can cause blockages and constipation. In rare cases, constipation can become so severe that the bowel develops holes or tears, which can be life threatening.
* Scarring can also damage the absorption of fats in the intestines. This can lead to an increase in the number of bacteria, which causes watery diarrhea.
* Fecal incontinence (the inability to control bowel movements) may be more common than studies indicate, because patients are reluctant to report it.
Many patients, however, have few or even no lower gastrointestinal symptoms.
Lung Symptoms and Complications
In severe cases, the lungs may be affected, causing shortness of breath or difficulty in taking deep breaths. Shortness of breath may be a symptom of pulmonary hypertension, an uncommon but life-threatening complication of systemic scleroderma.
Lung problems are usually the most serious complications of systemic scleroderma. They are now the leading cause of death in scleroderma patients. Two major lung conditions associated with scleroderma, pulmonary fibrosis and pulmonary hypertension, can occur either together or independently.
Interstitial Pulmonary Fibrosis. Scleroderma involving the lung causes scarring (pulmonary fibrosis). Pulmonary fibrosis occurs in about 70% of scleroderma patients, although the progression is very slow and patients have a wide range of symptoms:
* Some patients may not experience any symptoms.
* When pulmonary fibrosis progresses, patients develop a dry cough, shortness of breath, and reduced ability to exercise.
* Severe pulmonary fibrosis occurs in about 16% of patients with diffuse scleroderma. About half of these patients experience the most profound changes within the first 3 years. In such cases, lung function worsens rapidly over that period, and then the progression slows down.
This condition also places the patient at higher risk for lung cancer. One study suggested that interstitial lung disease may be due to severe dysfunction in the esophagus, which causes patients to breathe in tiny amounts of stomach acid.
The most important indication of future worsening in the lungs appears to be inflammation in the small airways (alveolitis). Doctors detect alveolitis by using a lung test called bronchoalveolar lavage.
Pulmonary hypertension is the narrowing of the pulmonary arteries in the lung. The narrowing of the arteries creates resistance and increases the workload of the heart. The heart becomes enlarged from pumping blood against the resistance. Some symptoms include chest pain, weakness, shortness of breath, and fatigue. The goal of treatment is to control the symptoms, although the disease usually develops into congestive heart failure.
Pulmonary Hypertension. The primary symptom of pulmonary hypertension is shortness of breath, which becomes severe over time.
Pulmonary hypertension can develop in one of two ways:
* As a complication of pulmonary fibrosis
* As a direct outcome of the scleroderma process itself. In this case, it is most likely to develop in patients with limited scleroderma after many years.
Kidney Symptoms and Complications
Signs of kidney problems, such as increased levels of protein in the urine and mild high blood pressure (hypertension), are common in scleroderma. As with pulmonary hypertension, the degree of severity depends on whether the kidney problems are acute or chronic.
Slow Progression. The typical course of kidney involvement in scleroderma is a slow progression that may produce some damage but does not often lead to kidney failure.
Renal Crisis. The most serious kidney complication in scleroderma is renal crisis. It is a rare event that occurs in a small number of patients with diffuse scleroderma, most often early in the course of the disease. This syndrome includes a life-threatening condition called malignant hypertension, a sudden increase in blood pressure that can cause rapid kidney failure. This condition may be fatal. However, if the condition is successfully treated, it rarely recurs.
Until recently, renal crisis was the most common cause of death in scleroderma. Aggressive treatment with drugs that lower blood pressure, particularly those known as ACE inhibitors, is proving to be successful in reducing this risk.
Heart Symptoms and Complications
Many patients with even limited scleroderma have some sort of functional heart problem, although severe complications are uncommon and occur in only about 15% of patients with diffuse scleroderma. As with other serious organ complications, they are more likely to occur within 3 years after the disease begins.
Fibrosis of the Heart. The most direct effect of scleroderma on the heart is fibrosis (scarring). It may be very mild or it can cause pain, low blood pressure, or other complications. By damaging muscle tissue, the scarring increases the risk for heart rhythm problems, problems in electrical conduction, and heart failure. The membrane around the heart can become inflamed, causing a condition called pericarditis.
Pulmonary hypertension and hypertension associated with kidney problems in scleroderma can also affect the heart.
Other Symptoms and Complications
Other complications of scleroderma may include the following:
* Patients with CREST may be at increased risk for biliary cirrhosis, an inflammatory autoimmune disorder of the liver.
* Nerve damage may occur in the extremities (legs and feet, arms and fingers), causing numbness and pain. This damage can progressively worsen and lead to severe open sores (ulcerations), particularly in the hands. The feet are less often affected, but when they are, the disease tends to affect the joints and cause pain.
* Bone loss (osteoporosis) can occur because of impaired blood flow.
* About half of patients develop underactive thyroid gland (hypothyroidism).
* Impotence, usually due to scarring of the penis, may be one of the first complications of the disease in men.
* Some studies using imaging techniques have found changes in brain tissue, but because the brain has little connective tissue, scleroderma appears to have little effect on mental functioning, except possibly in the late stages of severe disease.
* Systemic scleroderma does not generally affect fertility in women. Pregnant women with scleroderma, however, have a slightly increased risk of premature birth and low-birth-weight babies. Although they can carry a baby to term, because complications such as kidney crisis can occur with the disease, pregnant women with scleroderma need to be monitored closely in a high-risk obstetric facility.
* More than half of scleroderma patients are likely to experience significant depression. Researchers say it may be beneficial for scleroderma patients to be routinely screened for depression.
Causes
Most likely this disease is caused by a number of inherited (genetic) abnormalities, which are triggered by environmental factors.
Researchers have found a gene, called connective-tissue growth factor (CTGF), which they say regulates the production of a protein that may be a key to systemic scleroderma. This gene is more common in scleroderma patients than in people without the condition. However, researchers say the gene is just one factor that affects the development of the disease.
Research published in 2005 also showed that the growth of new blood vessels is abnormal in people with scleroderma, particularly those whose disease affects the blood vessels in the lungs. Researchers now know that cells in the blood vessels and skin of scleroderma patients make too much of certain chemicals, and not enough of others. Studies revealed that the cause is an alteration in the hereditary material, DNA. These changes "turn off" some genes and "turn up" others. It is hoped that certain drugs, some of which are already used in cancer treatments, can some day be used to stop these DNA changes.
Inflammatory Response and Autoimmunity
The disease process leading to scleroderma appears to occur as an autoimmune response, in which an abnormal immune system attacks the body itself. In scleroderma, this response produces swelling (inflammation) and too much production of collagen. Collagen is the tough protein that helps build connective tissues such as tendons, bones, and ligaments. Collagen also helps scar tissue form. When normal tissue from skin, lungs, the esophagus, blood vessels, and other organs is replaced by this type of abnormal tissue, none of these body parts work as well, and many of the symptoms previously described occur.
Antigens are large molecules (usually proteins) on the surface of many cells -- both human cells, and cells of viruses, fungi, bacteria, and some non-living substances such as toxins, chemicals, drugs, and foreign particles. When the immune system recognizes an antigen as being foreign (not part of the human body), it starts offensive and defensive actions against them by producing antibodies and other chemicals such as cytokines that destroy any cells in the area.
Much of this activity is directed by T cells, which are categorized as killer T cells or helper T cells (TH cells).
The actions of the helper T cells are of special interest in scleroderma. For some unknown reason, the T cells become overactive in scleroderma and mistake the body's own collagen as a foreign antigen. This triggers a series of immune responses to destroy the collagen. When the body creates antibodies against itself in this way, it is called an autoimmune response.
Cytokines and the Inflammatory Response. Helper T cells also release powerful immune factors called cytokines. In small amounts, cytokines are necessary for healing. If overproduced, however, they can cause serious damage, including inflammation and injury.
Neutrophils. Cytokines attract to the scene large numbers of other white blood cells known as neutrophils. Neutrophils help activate chemicals known as leukotrienes. Scleroderma patients have high levels of specific leukotrienes that may contribute specifically to lung disease in scleroderma.
Fetal Cell Theory and Microchimerism
A process called microchimerism has been proposed as a cause of scleroderma. The theory arose from the fact that scleroderma occurs mostly in women, and its symptoms resemble those of graft-versus-host disease (GVHD). GVHD occurs in bone marrow transplant patients who have received cells from another person. It happens when the transplanted donor immune cells launch an attack against the patient's cells.
Chimerism occurs when cells from two different individuals exist in the same body. When there is a low number of cells of one body in another, the condition is referred to as microchimerism.
However, if microchimerism plays a role, it most likely does so only in a subset of patients.
Triggering the Immune Response
It is still not clear why the immune system responds abnormally in people with scleroderma. Some experts believe that environmental factors, such as a virus or a chemical, may trigger the response in individuals with a genetic vulnerability.
Oxygen-Free Radicals and Abnormal Metal Accumulation. One focus for researchers investigating scleroderma involves an observation that, as blood vessels narrow and become inflamed, destructive particles known as oxygen-free radicals are produced. Oxygen-free radicals are made by natural processes in the body. They cause harm by setting off a chemical chain reaction, which can damage any type of cell in the body. Environmental toxins, infections, and other factors may cause very high amounts of these oxygen-free radicals to build up in the body.
Chemicals. Occupational exposure to certain chemicals can cause blood vessel constriction and attacks of Raynaud's phenomenon. Despite the fact that women are at higher overall risk for scleroderma, among people who are exposed to solvents at work, men face a higher risk for the disease. However, no specific work-related factors have been proven to cause the disorder.
It is nearly impossible to determine whether specific chemicals may actually cause systemic scleroderma, primarily because few people develop the disease, even though many people are exposed to such chemicals. In addition, research has been unable to consistently repeat studies that have reported links with chemicals.
Studies have found, however, that certain industrial toxins are significantly associated with severe lung problems in people with scleroderma. The toxins most likely to be associated with severe disease include epoxy resins, white spirit, solvents, and silica mixed with welding fumes.
Repetitive Stress Injuries. Raynaud's phenomenon and symptoms of scleroderma have been associated with jobs that require intense repetitive hand and arm movements, such as working jackhammers or other vibrating tools. However, many workers are involved in such occupations, yet scleroderma is still very rare, even in this group. If there is a link, the disease would most likely develop in individuals with genetic factors that make them susceptible to the disease in the first place.
Radiation. Radiation therapy has been reported to cause local patches of scleroderma (morphea) or worsen preexisting scleroderma in a few patients. In some cases, scleroderma may occur years after radiation treatments.
Infections
Researchers think that infections may play a role in triggering the process leading to some cases of scleroderma. There is no real evidence of any single type of bacteria or other organism that might be responsible, although some are of particular interest.
Some studies reported an association between Borrelia burgdorferi, the cause of Lyme disease, and some cases of morphea (localized scleroderma). However, the evidence is weak. If there is a connection, it is possibly limited to a specific type of the bacteria in Europe and Asia. There is no connection between systemic scleroderma and Lyme disease.
Other infections associated with scleroderma include parvovirus and hepatitis C. However, there is no evidence of a cause-and-effect relationship.
Risk Factors
Scleroderma is uncommon. It afflicts about 300,000 Americans, but only about 49,000 have the systemic form of the disease. The cause of scleroderma has not been determined, and there are few specific risk factors. The incidence tends to be higher in certain groups, however.
Age. Systemic scleroderma usually develops between the ages of 35 and 55. Localized scleroderma is more common in children than adults, but is extremely rare even in the young age group. It occurs in between 0.2 and 0.4 per 100,000 people. Systemic scleroderma in children is even more rare.
Gender. The incidence of scleroderma is three to eight times higher in women than in men. This may reflect a different cause of the disease in these two genders. (It should be noted that pregnancy itself is not a risk factor for scleroderma.)
Family History. A family history is the strongest risk factor for scleroderma, but even among family members, the risk is very low (less than 1%).
Genetics. Genetic factors appear to play a role in triggering the disease, but most cases are unlikely to be inherited. Preliminary research suggests that patients with certain gene variations may be more susceptible to scleroderma than those who do not carry these variations.
Ethnicity. Limited data on risk by ethnic group in the United States suggests that the risk from highest to lowest is the following: Choctaw Native Americans (highest), African-Americans, Hispanics, Caucasians, Japanese Americans. African-Americans have a higher rate of diffuse scleroderma, lung involvement, and a worse prognosis than Caucasians. Other studies also found lower survival rates among Japanese Americans.
Genetic factors affect population groups differently. Studies are finding that ethnic groups differ in the number of specific scleroderma-related antibodies they produce. Caucasians, for instance, have a higher rate of anti-centromere antibodies, which are associated with limited disease, while African-American patients have higher rates of autoantibodies and genetic factors that are associated with a more severe condition.
Geography. There appears to be certain geographic clusters of scleroderma, or specific types of scleroderma related to location. This may suggest an infectious or genetic factor at work, but the reasons are largely unknown. The following are some examples:
* Studies reported significantly higher-than-average scleroderma mortality rates in male patients (both African-American and Caucasian) who live in two specific regions of the Southeast: one cluster around Coffee, Tennessee, and two others near Northampton, North Carolina.
* A cluster of scleroderma cases has been observed in South Boston, Massachusetts.
Prognosis
At this time there is no cure for scleroderma and no treatment to change its course, but outlook varies widely. Many patients, even those with systemic scleroderma, can expect a normal lifespan.
General Outlook of Localized Scleroderma. Localized scleroderma nearly always carries a good prognosis and a normal life span. Even localized scleroderma, however, can cause some severe effects in children, including impaired growth, limb imbalance, and problems in flexing and bending muscles.
General Outlook of Systemic Scleroderma. The outlook for patients with systemic scleroderma has generally improved over the years. Ten-year survival rates rose from 54% in 1972 to 66% in 2001.
The causes of death related to systemic scleroderma also have changed. The proportion of deaths from kidney crises dropped significantly, from 42% to just 6% in that time period; however, the proportion of deaths from pulmonary fibrosis increased from 6% to 33%. Today, lung complications account for 60% of scleroderma-related deaths.
* Limited Scleroderma. Patients with limited CREST scleroderma can usually expect a favorable outlook and normal lifespan if the disease affects only the hands and face. The course of this type of scleroderma still tends to be slowly progressive and, in some cases, may affect internal organs.
* Diffuse Scleroderma. The severity of diffuse scleroderma varies widely, and it is very difficult to predict its course. It generally follows one of two paths: If it is acute or rapidly progressing, it may be a life-threatening condition that affects internal organs. The most critical period for rapid progression is usually within the first 2 - 5 years of the start of the disease. In the absence of rapid progression, or if the patient survives the initial acute progression, the disease tends to progress very slowly. The more severe the condition of the skin is at the start of the disease, the poorer the survival rates.
Many patients with systemic scleroderma experience a plateau in which the condition stabilizes. This plateau is followed by a period of improvement and skin softening. No one knows why this occurs, and it can happen regardless of treatment. In one study, patients with systemic scleroderma who experienced such improvements also had better survival rates (80% at 10 years) than those whose skin did not improve (60% 10-year survival rate).
Impact on Quality of Life
The many complications of scleroderma can have a major impact on a person's sense of well-being. Patients are greatly concerned about changes in their appearance, particularly those changes caused by tightening of the facial skin. A 2002 study on scleroderma patients reported that 63% experienced at least mild pain, and half of them had some degree of depression. Depression had the greatest impact, even more than pain, in reducing patients' ability to function socially.
Diagnosis
There are no specific tests for scleroderma. The doctor may suspect scleroderma after taking a history of the symptoms and performing a physical examination. As part of this examination, the doctor does the following:
* Checks the skin for thickened and hardened areas. The major signs of scleroderma are hardening and thickening of the skin in any areas on the fingers and toes.
* Presses affected tendons and joints to detect crackling or grating sensations, which can indicate changes related to scleroderma beneath the skin.
* Examines the fingernails underneath a microscope. The doctor may find changes in capillaries that are characteristic of scleroderma and mixed connective tissue disease.
Scientists recently found that antibodies that are often found in patients with scleroderma and systemic lupus erythematosus (SLE) bind to different parts of a single protein. Scientists hope this finding will one day lead to a specific diagnostic test for scleroderma.
Tests for Antinuclear Antibodies
Tests may be done to detect immune factors called antinuclear antibodies (ANAs). Detecting specific types of ANAs may help diagnose scleroderma. ANA subtypes include the following:
* Rheumatoid factor, anti-single-stranded DNA, and antihistone antibodies are autoantibodies associated with scleroderma, but they are also common in other autoimmune disorders, such as rheumatoid arthritis and systemic lupus erythematosus. Some ANAs attack RNA or DNA, the genetic material in cells.
* Anti-RNA polymerase III, anti-topoisomerase I (also called anti-DNA topo 1) and anti-centromere antibodies (ACA) are three other autoantibodies. Most patients with systemic scleroderma (but not localized scleroderma) have one or more of these autoantibodies. They do not appear at the same time, and seem to relate to different phases of the disease process. For example, anti-DNA topo 1 often occurs with diffuse skin scleroderma and lung complications. Anti-centromere antibodies usually occur with a less severe form of the disease.
* Higher-than-normal levels of autoantibodies to fibrillin 1, a protein found in muscle and other connective tissues, is more common in patients with both systemic and localized scleroderma. This autoantibody in localized scleroderma is more common in some ethnic groups (such as Japanese and Native Americans) than in others (Caucasians). It is not found in other autoimmune diseases.
These antibodies are also found in other rheumatologic disorders, so detecting them does not necessarily prove that a patient has scleroderma. At the same time, studies have found that specific antibodies are associated with specific aspects of the disease. Therefore, identifying their presence could help diagnose, treat, and monitor people with scleroderma. Here are a few examples:
* Anti-U1-RNP and anti U3-RNP are associated with muscle inflammation.
* ACA is commonly associated with pulmonary hypertension and vascular disease.
* TOPO is associated with pulmonary fibrosis.
* RNA Polymerase III (Pol 3) is rarely linked to severe interstitial fibrosis, although this autoantibody is strongly present in patients with kidney crisis.
* Patients with diffuse scleroderma who have Pol 3 have the best survival rate.
Diagnosing Systemic Complications
Diagnosing Lung Complications. Changes in the lungs may occur early in scleroderma lung disease, and prompt treatment is very important to prevent complications. For this reason, once a diagnosis is made, the doctor will check for lung changes in the following ways:
* Listen to the lungs through a stethoscope. Rales, a crackling sound at the base of the lungs as the patient breathes in, is a sign of pulmonary fibrosis, even if breath function is normal.
* Perform respiratory function tests to determine lung capacity.
* Take a chest x-ray (however, x-rays do not always find lung disease, especially in children).
* Have patients inhale nitric oxide to test the ability of blood vessels to open.
* Perform more extensive tests, such as high-resolution computed tomography (CT) scans and bronchoalveolar lavage, if the doctor suspects severe lung scarring.
Newer tests showing promise in diagnosing lung complications include:
* The induced sputum test, which looks at cells taken from coughed-up phlegm
* Another test that uses the inhaled chemical, technetium-labeled diethylenetriamine pentaacetate (99mTC-DTPA), to detect lung damage.
Diagnosing Heart Complications. Patients with suspected heart complications should have the following tests:
* Electrocardiography (ECG): A test of the heart's electrical activity
* Echocardiography: A look at the beating heart through the use of sound waves
* Radionucleotide ventriculography: An evaluation of the working heart using a radioactive dye
Advanced imaging techniques, which provide a more detailed picture of the heart, may also be useful to determine the extent of heart complications in scleroderma patients.
Diagnosing Pulmonary Hypertension. Echocardiography is a noninvasive imaging technique for detecting pulmonary hypertension, a common and life-threatening complication of scleroderma. (Neither materials nor equipment are put into the body.) To confirm the diagnosis, doctors sometimes use an invasive procedure called right-heart catheterization. Right-heart catheterization involves the passage of a catheter (a thin flexible tube) into the right side of the heart to get diagnostic information about the heart.
Diagnosing Gastrointestinal (Digestive) Complications. Endoscopy may detect gastrointestinal problems. Endoscopy is an invasive procedure in which a tube is inserted down the esophagus. The tube contains a small camera and other instruments. Another diagnostic test is manometry, which measures the pressure that the muscles in the esophagus apply.
Electrogastrography (EGG) measures the electrical activity in muscles in the stomach, and may be an effective method for detecting stomach problems.
Diagnosing problems in growth of blood vessels. Capillaroscopy is the microscopic examination of blood vessels under the skin. It is now considered a useful tool for identifying problems with the growth of blood vessels, because more than 95% of patients will have some capillary abnormalities. Such problems can show the severity and progression of scleroderma. In a technique called nailfold capillaroscopy, the doctor places a drop of oil on the nailfolds (the skin at the base of the fingernails), and then looks at the nailfold under a microscope for signs of changes in the capillaries that may indicate a connective tissue disease such as scleroderma.
Ruling out Other Conditions
Other Autoimmune and Connective Tissue Disorders. Several other autoimmune conditions that affect connective tissue can strongly resemble, or occur together with, scleroderma. They include the following:
* Rheumatoid arthritis
* Systemic lupus erythematosus
* Polymyositis
Symptoms of such diseases may also include fever, arthritis, muscle aches, rash, and lung and heart problems.
Eosinophilic Fasciitis. Eosinophilic fasciitis is a muscle disorder that is known to occur after intense hard work. It can cause symptoms similar to scleroderma, including pain, swelling, and tenderness in the hands and feet, as well as skin thickening. The disorder can be ruled out with blood tests.
Although Raynaud's phenomenon occurs in most scleroderma patients, over 80% of the cases of Raynaud's phenomenon are harmless. In one study, only 12% of Raynaud's cases were associated with some other condition, and few of those were scleroderma. The following are other problems that might accompany or cause Raynaud's phenomenon:
* Other autoimmune connective tissue diseases
* Diabetes (patients with diabetes may develop Raynaud's phenomenon and other scleroderma-like symptoms)
* Certain drugs, including bleomycin, ergot derivatives (used for migraines), and methysergide
* Hereditary hemorrhagic telangiectasia (a very rare condition that is very similar to CREST syndrome)
* Repetitive stress injuries (particularly from vibrating tools)
* Hypothyroidism
Treatment
Scleroderma treatments vary depending on these variables:
* Is it local or systemic, and if systemic, is it limited or diffuse?
* If the disease is systemic, what organs, if any, are involved?
Although there is still no treatment for the underlying process of scleroderma, specific drugs and treatments help combat the various mechanisms and consequences of the disease.
* Some medications keep blood vessels open (prostacylins, endothelin receptor antagonists, ACE inhibitors, phosphodiesterase 5 inhibitors, and others) and are used to treat Raynaud's phenomenon, heart and kidney problems, and pulmonary hypertension.
* Other drugs reduce inflammation and block damaging immune factors. These treatments, which include cyclophosphamide, penicillamine, bone marrow transplantation, and others may be helpful for improving skin thickness and reducing scarring, even in the lungs.
* Doctors use other treatments for specific complications, such as proton pump inhibitors and pro-kinetic agents for gastrointestinal problems, or light treatments for skin thickening.
* Various investigative approaches exist, including stem-cell transplants.
Patients should receive treatments for specific complications as early as possible in the course of the disease, to reduce progression before irreversible hardening of tissues occurs.
There is no cure for scleroderma. Many drugs that are useful for other autoimmune inflammatory disorders have not proven to be very effective for scleroderma. Experimental work is ongoing to develop procedures or to find drugs that can treat the underlying processes that cause damage. Developing effective treatments for scleroderma is very problematic, however, for the following reasons:
* The course of scleroderma is hard to predict, making it one of the most difficult rheumatic diseases to treat. It also makes drug development complicated.
* The disease, when advanced, affects many organs. Designing treatment strategies that will improve symptoms in some organs without affecting other organs is very difficult.
* The disease is so uncommon that there are few patients available for clinical trials. Studies, then, are very small, sometimes having only four or five patients. It is very difficult to design studies of this size that can provide strong evidence on treatment effects. Drugs that seem promising on small groups of patients often fail to show effectiveness on larger groups.
Treating the Whole Patient
The disease can evolve slowly over time with few symptoms, or progress rapidly and become very severe. The patient, then, must live with considerable uncertainty and emotional stress. Support associations, non-medical aids to help relieve symptoms, and other lifestyle measures can be extremely important and helpful.
Medications
Calcium-channel blockers are the standard drugs to open the blood vessels, and may be used for pulmonary artery hypertension and Raynaud's phenomenon. Short- or sustained-release nifedipine (Adalat, Procardia) is the gold standard.
Other drugs used include diltiazem (Cardizem, Dilacor), and the newer dihydropyridines (felodipine, amlodipine, and isradipine). Side effects vary among different medications, and may include fluid buildup in the feet, constipation, fatigue, gingivitis, impotence, flushing, and allergic symptoms. Calcium channel blockers should not be taken with grapefruit juice, as it appears to boost the effects of these drugs. [The medications listed below are also discussed under many of the sections covering treatment complications.
Nitrates
Nitrates relax smooth muscles and open arteries, and are therefore sometimes used for the short-term management of Raynaud's phenomenon. They are available in topical and oral (by mouth) forms. Side effects of nitrates include headaches, dizziness, nausea, blurred vision, fast heartbeat, and sweating. Lying down with the legs elevated can relieve low blood pressure and dizziness.
Alcohol, beta blockers, calcium-channel blockers, and certain antidepressants can significantly worsen these side effects. Withdrawal from nitrates should be gradual. Some severe reactions have occurred when people have stopped taking these drugs too quickly.
Prostacyclins (also called Prostaglandins)
Prostacyclins open blood vessels and also have anti-blood-clotting properties. One or all of these drugs is used to treat pulmonary artery hypertension and Raynaud's phenomenon. Several prostacyclins are being used for scleroderma, although none have been approved specifically for the condition. Promising prostacyclins or similar drugs include iloprost (Ventavis), alprostadil (prostaglandin E1), epoprostenol (Flolan), and treprostinil (Remodulin).
Endothelin Receptor Antagonists
Bosentan (Tracleer) is a drug taken by mouth. It is called an endothelin receptor antagonist. It controls endothelin, a powerful molecule that causes blood vessels to narrow. It improves blood flow and is becoming important for treating patients with scleroderma, especially for preventing finger ulcers and improving hand function. This drug is also a treatment option for pulmonary hypertension.
ACE Inhibitors and Angiotensin II Receptors
The most effective approach at this time for preventing kidney (renal) crises is to start aggressive blood pressure-lowering treatment before blood tests show kidney damage has occurred.
Angiotensin Converting Enzyme (ACE) Inhibitors. Many medications are available for controlling blood pressure, but ACE inhibitors appear to be the most effective for scleroderma patients, because of their protective actions in the kidney. These drugs are also used to treat patients with evidence of kidney damage, whether or not they have high blood pressure.
ACE inhibitors include captopril (Capoten), enalapril (Vasotec), quinapril (Accupril), benazepril, and lisinopril (Prinivil, Zestril). Side effects are uncommon, but may include an irritating cough, large drops in blood pressure, and allergic reactions. The drug picotamide can help reduce the frequency of coughs.
Angiotensin II Receptor Antagonists. Angiotensin II receptor antagonists (losartan, candesartan cilexetil, and valsartan) have benefits similar to ACE inhibitors and may have fewer or less severe side effects, including coughing. They may also have positive effects on blood vessels.
Small studies showing improvement in Raynaud's phenomenon warrant further research.
Treatments that Affect the Immune System
One major approach to scleroderma is to use treatments that suppress the immune system, and therefore reduce the activity of the harmful processes that lead to scleroderma. Such treatments are used effectively in other autoimmune diseases. Their use in scleroderma varies, depending on the location and severity of the disease process.
Cyclophosphamide (Cytoxan). Cyclophosphamide is the most important immunosuppressant currently used for scleroderma. This drug can be taken through a vein (intravenous) or by mouth. It blocks some of the destructive actions of scleroderma in the lungs. Intravenous cyclophosphamide can be life-saving for patients with pneumonia caused by interstitial lung disease. Side effects of this drug include hair loss, infection, and bleeding into the urinary tract. To date, no other immunosuppressive drugs have shown any significant benefits for scleroderma.
Other drugs used to suppress the immune system may be useful in specific cases. They include D-penicillamine (which may be useful for skin symptoms), methotrexate (Rheumatrex), corticosteroids, cyclosporine (Sandimmune, Neoral), and chlorambucil (Leukeran). All of these drugs have potentially severe side effects.
Other Treatments
Tumor-Necrosis Factor Modifiers. Tumor-necrosis factor (TNF) modifiers are major breakthroughs in the treatment of rheumatoid arthritis. They interfere with specific parts of TNF, a powerful immune factor. Researchers believe they should be tested in other inflammatory conditions, including scleroderma. The current agents include infliximab (Remicade), etanercept (Enbrel), alefacept (Amevive), and adalimumab (Humira).
Blood Exchange (Plasmapheresis or photopheresis). Plasmapheresis is a process in which the liquid part of the blood, called plasma, is separated from blood cells. The procedure involves first withdrawing blood from the patient. The plasma, which contains the active immune factors, is discarded and replaced with other fluids. The blood is then returned to the patient.
Autologous Stem-Cell Transplantation. Researchers are investigating a possible benefit of transplanting the patient's own stem cells (an autologous transplant). (Patients with autoimmune diseases cannot be given cells from donors.) The transplant procedures introduce normal white blood cells that replace the abnormal autoimmune cells. The procedure has improved or stabilized systemic scleroderma in some patients, with remissions lasting up to 5 years or more, and improvements in skin and overall function.
Initial results of ASTIS, a major study evaluating stem-cell transplants and high-dose immunosuppressive therapy in severe scleroderma, indicate that this combination has led to sustained remission in more than one-third of patients. Randomized controlled trials comparing stem cell transplants to monthly cyclophosphamide therapy are underway in Europe and the U.S.
Although the risk of death from having a transplant is now less than 10%, the procedure has serious side effects. Experts suggest that the best candidates are those at high risk for complications from scleroderma. In general, such patients would have diffuse scleroderma, experienced their first symptoms within the previous three years, and have evidence of at least mild abnormalities in the heart, lungs, or kidney. In general, patients with advanced scleroderma would not be the best candidates, because the risks of the procedure would outweigh the risks from the disease.
Extracorporeal Photopheresis: Another phototherapy treatment under investigation, extracorporeal photopheresis, involves withdrawing the patient's blood and treating it with ultraviolet light. Little data exists on its effectiveness. One study found that the therapy improved skin and joint symptoms, but the authors say it's possible that a placebo effect was at least partly responsible for the results. Experts do not recommend photopheresis at this time, but some feel that it does hold promise and warrants more research.
Intravenous immunoglobulin (IVIg). Animal studies have found that administration of IVIg, an agent that modifies the immune system, may reduce the severity of scleroderma and other autoimmune diseases. So far, only extremely small studies including fewer than 10 patients have been conducted, but the treatment is showing promise for relieving joint pain and tenderness and improving function. The exact role of this therapy in scleroderma treatment, if any, has yet to be determined.
Herbs and Supplements
Because of the difficulty in treating scleroderma, many patients are tempted to try high-dose supplements or other alternative treatments. Some natural treatments have been evaluated for the treatment of scleroderma, including para-aminobenzoic acid, vitamin E, evening primrose oil, and an avocado/soybean extract. However, these treatments have not been proven effective, and using alternative remedies can be dangerous.
There is almost no published research on the use of herbal remedies for patients with scleroderma. Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been numerous reported cases of serious and even deadly side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.
Treatment for Raynaud's Phenomenon
The following are some lifestyle tips for managing Raynaud's phenomenon:
* Keeping warm is the primary goal for preventing the onset of Raynaud's phenomenon. Air-conditioning and exposure to refrigeration can trigger this syndrome. If patients go out in cold weather, they should dress warmly with many layers. Wearing a hat is essential.
* Living in a warm climate may help relieve symptoms, although a recent study found that weather changes themselves had little effect on the disorder.
* Exercise is helpful for maintaining a sense of well-being, keeping warm, and sustaining skin flexibility. Patients with Raynaud's phenomenon may want to avoid exercising outdoors in cold weather, however.
* Quitting smoking is, of course, essential for anyone, but it is critical for people with scleroderma.
* Learning relaxation and anti-stress techniques might help reduce some triggers of Raynaud's phenomenon.
* Using moisturizers and antibiotic ointments may be helpful for keeping skin flexible and preventing infections in the fingers.
* Avoiding medications such as nonselective beta blockers (such as propranolol), certain common cold preparations, and narcotics, can help avoid aggravating Raynaud's phenomenon.
Medications Used in the Treatment of Raynaud's Phenomenon
Vasodilators. Vasodilators open blood vessels and so are important for Raynaud's phenomenon.
Calcium-channel blockers, including diltiazem (Cardizem, Dilacor) and nifedipine (Adalat, Procardia) are the standard vasodilating drugs used for Raynaud's phenomenon. Nifedipine is the best studied of these drugs, but there are also newer dihydropyridines, including felodipine, amlodipine, and isradipine.
Nitrates, available in topical or oral forms, are vasodilators that are also used for Raynaud's phenomenon, and for short-term relief.
Prostacylins. Iloprost and other prostacylins are proving to be effective agents for Raynaud's phenomenon. Small but well done studies seem to show these drugs to be helpful for this condition, and possibly as effective as calcium channel blocker drugs such as nifedipine.
Evidence shows that intravenous iloprost given at progressively increasing doses over 3-month cycles can reduce the duration and frequency of attacks. In general, these drugs are used when a patient's symptoms are severe, particularly when the doctor is considering amputating a finger.
Endothelin receptor agonists have also been shown to help with Raynaud's phenomenon.
Anti-Platelet Drugs. Aspirin, dipyridamole, and other drugs that prevent blood clotting and keep blood flowing freely are sometimes recommended to patients with Raynaud's phenomenon. However, these drugs haven't shown much benefit in studies.
Estrogen Therapy in Women. Short-term treatment with estrogen may benefit older women with Raynaud's phenomenon and scleroderma. It is important to note, however, that hormone replacement therapy for more than 5 years can increase a woman's risk for breast cancer, heart attacks, strokes, and blood clots.
PDE5 Inhibitors. Studies have suggested that a class of drugs called PDE5 inhibitors, which includes sildenafil, helps improve symptoms and blood flow, and speeds ulcer healing in patients with Raynaud's phenomenon. This treatment is still experimental.
Surgical Treatments for Problems of the Hands
Sympathectomy and Hand Surgeries. Sympathectomy uses procedures that block or remove the nerve responsible for narrowing blood vessels in the hand. The result is increased blood flow in the hand.
The local anesthetics lidocaine or bupivacaine may be very effective in temporarily restoring blood flow and reducing pain.
For finger ulcers that won't heal and are resistant to standard treatments, sympathectomy surgery may be done.
Treatment for Skin Thickening
Nitroglycerin is a quick acting nitrate and is used as an ointment (Nitro-Bid, Nitrol, Nitrong, Nitrostat) to treat hardened skin. Before applying it, remove any ointment that remains from the previous application.
Phototherapy
UVA-1 Phototherapy. Phototherapy (light therapy) is now considered by some experts to be the treatment of choice for local scleroderma. Specifically, doctors favor an approach called ultraviolet A-1 (UVA-1) radiation. This treatment produces long UVA wave lengths that do not cause sunburn and may actually repair DNA in damaged skin cells. Research suggests that UVA-1 therapy blocks inflammatory immune factors and the process leading to over-production of collagen, addressing the underlying mechanisms of scleroderma.
The procedure is effective for all stages of morphea. It increases skin elasticity and in some cases, completely clears up symptoms. In one small study, patients with localized scleroderma received 30 phototherapy treatments over a period of 12 weeks. In the majority of patients, 80% of the skin patches disappeared or significantly improved. There were no side effects.
UVA-1 phototherapy is quite expensive and requires a special light source not available everywhere. In addition, studies are reporting an increased risk with UVA radiation. Whether this applies to UVA-1 phototherapy is not yet clear. Nonetheless, phototherapy is still an effective and important treatment of scleroderma. It may prove to be even more beneficial when combined with certain medications, such as calcipotriene (Dovonex), a form of vitamin D3.
PUVA. An alternative phototherapy regimen called PUVA uses drugs called psoralens taken by mouth before UVA treatment. PUVA has been used for other skin diseases, including psoriasis. It may prove useful for patients with early-onset diffuse scleroderma. In one study, most patients treated with PUVA 2 days a month for up to 8 years experienced improvement or stabilization in nearly all scleroderma symptoms. Tests for kidney function remained normal. This treatment is known to increase the risk for skin cancer.
Phototherapy with Psoralen Water Bath. Yet another procedure uses UVA light therapy after patients take a bath containing a solution of psoralen 8-methoxypsoralen (8-MOP). This treatment is safe and well tolerated, although benefits appear to be minor and occur only in a small subset of patients.
Vitamin D3 Analogs
A form of vitamin D3, calcipotriene (Dovonex), appears to help block skin cell production. This vitamin is called calcipotriol in Europe. It also has anti-inflammatory properties, and is being investigated as a rub-on treatment and oral treatment for local scleroderma. It may prove beneficial when combined with low-dose ultraviolet A1 phototherapy.
Immunosuppressive Agents
D-penicillamine is proving to be an effective agent for softening skin and reducing thickness. (Improvements in thickness with this drug have also been associated with improved survival.) Methotrexate (Rheumatrex) is another commonly used drug, and may be even more effective than penicillamine.
Corticosteroids taken by mouth, such as prednisolone and prednisone, are also often used.
Treatment for Other Complications
Pilocarpine (Salagen) has been approved for treating dry mouth in people with scleroderma and Sj�gren syndrome. In one study, patients with Sj�gren syndrome experienced increased salivation after the first dose. Patients reported improvement in speaking, sleeping, and swallowing food without drinking. Side effects of this drug include sweating, increased need to urinate, chills, and flushing.
Surgical Treatments for Problems of the Hands
Other Surgeries. Disabling deformity of the hand is a common feature of scleroderma. Various surgical procedures can relieve pain, prevent tissue loss, protect hand function, and improve the appearance of the hands.
Treatment for Lung Complications
Pulmonary Fibrosis
Cyclophosphamide. Cyclophosphamide (Cytoxan), an immunosuppressive drug, may be effective for preventing lung deterioration and is the important medication for treating pulmonary fibrosis, particularly when given early in the course of the disease.
Use of this drug may improve survival in patients who show early signs of lung deterioration, notably inflammation in the small lung airways (alveolitis). The drug is not recommended for patents with existing stable pulmonary fibrosis and no signs of inflammation. In one study, patients with early signs of lung inflammation were given a course of intravenous pulses of the corticosteroid methylprednisolone (MP) and cyclophosphamide. Nearly all patients experienced improvement or stabilization during the first year, although the disease had progressed in two-thirds of them after 2 years.
Other Treatments. Lung transplantation may offer hope for people with advanced pulmonary hypertension or interstitial fibrosis that does not respond to conservative treatments.
Pulmonary Hypertension
Several types of drugs are used to treat pulmonary hypertension. Anticoagulants taken by mouth, such as warfarin (Coumadin), are a standard treatment used to prevent blood clots from forming. Diuretic treatment and supplemental oxygen are recommended for patients with fluid retention and low blood oxygen, respectively.
Vasodilators help open blood vessels and relieve pressure in arteries of the lungs. Vasodilators used to treat pulmonary hypertension fall into several different drug classes:
Calcium Channel Blockers (CCBs). Some patients with pulmonary hypertension benefit from these drugs. They help relax blood vessels in the heart and lungs, and increase the supply of oxygen. However, calcium channel blockers are only appropriate for patients who meet certain diagnostic criteria, including those who don't have right-sided heart failure. Long-acting nifedipine or diltiazem, or amlodipine, are the preferred calcium channel blockers.
Prostacyclins (Prostaglandins). Prostacyclins, which open blood vessels, are now the primary agents for treating pulmonary hypertension.
* Iloprost (Ventavis) is available in inhaled and intravenous forms. Studies suggest that the inhaled form improves exercise capacity and survival in some patients with pulmonary hypertension. In addition, infusions of iloprost remain effective over long periods (up to 3 years) of use.
* Treprostinil (Remodulin) is similar to epoprostenol but is more stable. It can also be administered using a portable pump that delivers the drug under the skin. This is less expensive, cumbersome, and invasive than the delivery methods for epoprostenol.
* Epoprostenol (Flolan), which is administered intravenously, has improved exercise capacity and symptoms in both the short and long term in a number of patients. In some patients, survival is increased significantly. However, not all patients respond to this drug. The implanted catheter needed to deliver the drug can also cause serious complications.
Endothelin Receptor Antagonists. Bosentan (Tracleer) was the first drug taken by mouth that was approved for pulmonary hypertension. Bosentan controls endothelin, a powerful substance that causes blood vessels to narrow. Studies have reported improved exercise capacity in patients with pulmonary hypertension. Sitaxsentan and ambrisentan (Letairis) are two new drugs being studied.
PDE5 Inhibitors. Sildenafil (Revatio) was approved in 2005 as the first pill for patients with early-stage pulmonary hypertension.
Sildenafil is the same medication contained in the erectile dysfunction drug Viagra. However, Revatio is prescribed at a lower dosage than Viagra, and is a different color and shape than Viagra pills.
Other Treatments. Lung transplantation may offer hope for people with advanced pulmonary hypertension that does not respond to conservative measures.
Treatment for Gastrointestinal Problems
Treatments for abnormalities in the esophagus and stomach are generally the same as those for gastroesophageal reflux (GERD) or heartburn. Many non-prescription agents are available for the relief of heartburn.
Proton-pump or acid-pump inhibitors are probably the best drug treatments for reflux symptoms related to scleroderma. They work by inhibiting the so-called gastric acid pump that is required for the cells of the stomach to release acid. The standard drug has been omeprazole (Prilosec).
Newer drugs -- including lansoprazole (Prevacid), pantoprazole (Protonix), esomeprazole (Nexium), and rabeprazole (Aciphex) -- are more potent, but few comparison studies have been done on them.
Side Effects. Side effects are uncommon, but can include allergic reaction, headache, stomach pain, diarrhea, and flatulence. Of some concern was a report of a very severe and widespread skin rash caused by omeprazole in a woman with scleroderma. It should be noted that this is only one incident, but patients should be cautious about any skin change when taking this medication.
Agents for Impaired Stomach Muscle Contractions
Metoclopramide. Metoclopramide (Reglan) is sometimes used for patients who have delayed stomach emptying.
Octreotide. Octreotide (Sandostatin) is related to a natural hormone that suppresses growth hormone, and may prove to be very helpful for scleroderma patients. Small studies have reported that this drug improved weight and nutrition. It may even help other symptoms of scleroderma.
Agents for Constipation
Prokinetics. Prokinetics improve the muscle action of the esophagus and enhance stomach emptying. Prucalopride is an investigative pro-kinetic agent that significantly improved symptoms and relieved constipation. Similar medications, such as cisapride (Propulsid), are showing promise; however these types of drugs can have serious side effects.
Treatments for Malabsorption
Antibiotics may be effective for the malabsorption syndrome associated with an increase in bacteria. Octeotride may also be used for this problem.
Surgeries
Strictures (abnormally narrowed regions in the esophagus) may need to be opened with surgery.
Melanie Reber
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"Borrelia-associated early-onset morphea": a particular type of scleroderma in childhood and adolescence with high titer antinuclear antibodies? Results of a cohort analysis and presentation of three cases. Prinz JC, Kutasi Z, Weisenseel P, P�t� L, Batty�ni Z, Ruzicka T. J Am Acad Dermatol. 2009 Feb;60(2):248-55.
BACKGROUND: Morphea is an inflammatory autoimmune skin sclerosis of unknown etiology. A causative role of Borrelia burgdorferi infection has been controversially discussed, but no conclusive solution has yet been achieved.
OBJECTIVE: Intrigued by 3 young patients with severe Borrelia-associated morphea and high-titer antinuclear antibodies, we retrospectively examined the relationship between Borrelia exposure, serologic autoimmune phenomena and age at disease onset in morphea patients.
METHODS: In 90 morphea patients the presence of Borrelia-specific serum antibodies was correlated to the age at disease onset and the presence and titers of antinuclear antibodies. Patients with active Borrelia infection or high-titer antinuclear antibodies due to systemic sclerosis or lupus erythematosus served as controls.
RESULTS: We observed a statistically highly significant association between morphea, serologic evidence of Borrelia infection, and high-titer antinuclear antibodies when disease onset was in childhood or adolescence.
LIMITATIONS: Because pathogenic Borrelia species may vary in different geographic regions the relevance of Borrelia infection in morphea induction may show regional variations.
CONCLUSION: B burgdorferi infection may be relevant for the induction of a distinct autoimmune type of scleroderma; it may be called "Borrelia-associated early onset morphea" and is characterized by the combination of disease onset at younger age, infection with B burgdorferi, and evident autoimmune phenomena as reflected by high-titer antinuclear antibodies. As exemplified by the case reports, it may take a particularly severe course and require treatment of both infection and skin inflammation.
Melanie Reber
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Borrelial Fasciitis: Diffuse Fasciitis and Peripheral Eosinophilia Associated with Borrelia Infection Granter, Scott R. M.D.; Barnhill, Raymond L. M.D.; Duray, Paul H. M.D. The American Journal of Dermatopathology: October 1996 - Volume 18 - Issue 5 - pp 465-473
Abstract
We present four cases of diffuse fasciitis (DF) associated with peripheral eosinophilia in which spirochetal organisms were identified. Two patients had borderline positive results on serologic evaluation for Borrelia burgdorferi.
Deep biopsy showed dermal sclerosis associated with variable degrees of perivascular mononuclear inflammation. Diffuse fasciitis, septal panniculitis, and myositis with mononuclear cell infiltrates and varying numbers of eosinophils were observed. All cases showed a striking lymphocytic vasculopathy associated with atypical reactive endothelial cells. Using modified Dieterle and Steiner silver stains, multiple organisms were seen in one specimen, a single unequivocal organism detected in two specimens.
In one case, no organisms were detected on silver stain; however, organisms were demonstrated using rabbit polyclonal antibodies against B. burgdorferi. B. burgdorferi-specific DNA was identified in one patient by the polymerase chain reaction.
These results indicate that some cases of eosinophilic fasciitis are an expression of Lyme disease. We have previously proposed the more specific term borrelial fasciitis to describe such lesions.
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Melanie Reber
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Role of Borrelia burgdorferi in the pathogenesis of morphea/scleroderma and lichen sclerosus et atrophicus: a PCR study of thirty-five cases. De Vito JR, Merogi AJ, Vo T, Boh EE, Fung HK, Freeman SM, Cockerell C, Stewart K, Marrogi AJ. Department of Dermatology, Talane University School of Medicine, New Orleans, Louisiana 70112, USA. J Cutan Pathol. 1996 Aug;23(4):350-8.
Morphea (localized scleroderma), and lichen sclerosus et atrophicus (LSA) share common features with acrodermatitis chronica atrophicans (ACA), a known chronic form of borreliosis. These include similar histologic findings such as diffuse dermal fibrosis. These observations have led several investigators to consider the possibility of Borrelia burgdorferi (Bb) as a common etiologic factor among all of these diseases.
The aim of this study is to investigate the role of Bb in the pathogenesis of morphea and LSA, by assaying for its presence in lesional skin biopsies from patients with these diseases. We utilized the nested polymerase chain reaction (PCR) technique to selectively amplify a longer segment of a Bb-specific somatic gene, on DNA from paraffin-embedded, formalin-fixed tissues.
The results revealed no Bb-specific DNA sequence in 28 specimens of morphea/scleroderma and 7 of LSA with varying stages of disease. Furthermore, confirmatory Southern blot of the PCR product, resulted in similar findings.
These data seriously question the role played by this spirochete in the pathogenesis of morphea and LSA, at least in the southeastern part of the USA.
PMID: 8864923 [PubMed - indexed for MEDLINE]
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Melanie Reber
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Chronic borreliosis presenting with morphea- and lichen sclerosus et atrophicus-like cutaneous lesions. a case report. Kaya G, Berset M, Prins C, Chavaz P, Saurat JH. Department of Dermatology, DHURDV, University Hospital of Geneva, Switzerland. [email protected] Dermatology. 2001;202(4):373-5.
We report on a case of chronic cutaneous borreliosis with manifestations clinically compatible with morphea and lichen sclerosus et atrophicus. The histopathologic features of these lesions were those of acrodermatitis chronica atrophicans.
Our case illustrates the concept that clinical aspects of morphea and lichen sclerosus et atrophicus pertain to the spectrum of cutaneous borreliosis.
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Melanie Reber
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Bacterial Infection as the Cause of Scleroderma: A Guide to Antibiotic Therapy
CantwellAR Jr, Ganger P
Abstract Scleroderma is a disease characterized by thickening and hardening of the skin. While most traditional and established treatments provide temporary improvement at best, remission is rare -- and cure impossible. Furthermore, the various medications commonly prescribed have serious side effects. There is urgent need for better treatment.
Scleroderma is erroneously considered an incurable disease of unknown cause. This communication provides evidence implicating infectious bacteria as the cause of scleroderma; and proposes antibiotic therapy as a rational and beneficial treatment for this disease.
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Melanie Reber
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from 14th International Scientific Conference On Lyme Disease And Other Tick-Borne Disorders 2001
Clinical Aspects of Lyme Disease: Dermatologic, Cardiac, GI, and Gestational CME Disclosures
Harry Goldhagen, MS Julie Rawlings, MPH
Morphea and Lyme Disease: Are They Related? Morphea is a rare and untreatable dermatologic condition characterized by thickening and induration of the skin from excess collagen deposition. There are at least 5 forms of the disease: localized, generalized, guttate, linear, and coup de sabre (an indentation that can extend to and damage the underlying muscle and bone). The cause is generally not known, but as with any idiopathic condition, proposed etiologies abound, including radiation damage, autoimmunity, infection, vaccination, trauma, and genetic predisposition. One of the leading infectious disease candidates in the pathogenesis of morphea is B burgdorferi, although this association is a subject of controversy.[1] A number of European studies have found a correlation, while most US studies, including a frequently cited study from the Mayo Clinic,[2] have found no evidence of B burgdorferi in morphea lesions.
Andrew G. Franks, Jr, MD,[3] of New York University School of Medicine (NYU), believes there is a connection between the 2 diseases. For instance, it can be difficult to differentiate between EM and certain morphea lesions, especially if the EM lesion is not the typical bull's-eye with central clearing. The differential diagnosis for EM-like lesions is varied and can include spider bites, herpes simplex or zoster, cellulitis, fungus or tinea, granuloma annulare, drug eruption, erythema multiforme, and subacute lupus erythematosus. In many cases, it can be difficult to culture B burgdorferi from EM lesions.
Part of the disagreement between the US and other studies may be due to differences in B burgdorferi serotypes and strains that cause morphea, according to Dr. Franks. For instance, only the sensu stricto strain is found in the United States, but all 3 pathogenic strains are found in Europe. Two skin diseases -- acrodermatitis (similar in appearance to scleroderma) and lymphocytoma -- have been identified in Europe as linked to B burgdorferi; the former is associated with the B afzelii strain, and the latter with the B garinii strain.
Dr. Franks believes that serologic testing is unreliable in morphea. He said that in published US studies of B burgdorferi antibodies in morphea patients, the investigators did not check whether the subjects received antibiotics recently. Antibiotic treatment can alter the results of serologic testing. Polymerase chain reaction (PCR) testing for B burgdorferi DNA in morphea patients may also be inaccurate in the US. For instance, the PCR tests may have been too specific and missed strains or serotypes more likely to cause morphea-like skin disease. European studies have detected B burgdorferi DNA by PCR in patients with morphea. For instance, a PCR study by Fujiwara and colleagues[4] tested for afzelii and garinii strains and found evidence of B burgdorferi in non-US cases. US PCR amplification has generally only tested for the sensu stricto strain.
Dr. Franks and colleagues at NYU have recently completed an unpublished study of the association of B burgdorferi, autoimmunity, and morphea. In this study, 82 patients (average age of 27 years; range, 2-61 years) with new-onset morphea were enrolled; 14 were male. The investigators tested for antibody to autoimmune disease and to B burgdorferi by IgG and IgM Western blot (WB), with all bands reported. They used their own criteria for diagnosis of underlying Lyme disease: more than 1 IgG band on WB was taken as a positive result for Lyme. None of the subjects had clinically defined Lyme disease during the trial. For autoimmune serology, any positive test was defined as positive.
For treatment purposes, they classified the patients into 4 groups, depending on whether they were positive by WB and/or autoimmune serology. Generally, patients with positive WB received 6 weeks of doxycycline (or an alternative antibiotic), and those with negative WB were given 3 weeks of doxycycline, with an optional additional 3 weeks if improvement was seen during the first 3 weeks.
Of the 61 patients who completed the study, 34 had clinical improvement. The WB-positive, autoimmune serology-negative group was the most likely to respond to antibiotic therapy. The Lyme WB converted to negative in many treated patients.
Dr. Franks and colleagues believe that all patients with morphea are candidates for a therapeutic antibiotic trial, regardless of serologic test results. IgM and IgG WB may be helpful in the diagnosis, but current Lyme tests are unreliable in such patients. Because the risks are minimal with antibiotics, he believes it is worth trying this approach, especially since there is no effective treatment for morphea at the present time.
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Melanie Reber
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Special Thank Yous to...
Lonestartick, Trueblue, Tree-hugger, and 5dana8 for providing the links to some of these latest posts!
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seekhelp
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Melanie, are you a researcher? I've never seen one post so many articles!!! Posts: 7545 | From The 5th Dimension - The Twilight Zone | Registered: Mar 2008
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Melanie Reber
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Good morning Seek,
I mainly do exhaustive research on things that personally affect me or my loved ones. And ACA/ Scleroderma happens to fall within that category.
I am also aware that many here and elsewhere are exhibiting these symptoms but have no clue what is causing them. So we are trying to get the message out to those with ACA so they will not have to suffer needlessly.
SO the research is also an educational tool.
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Melanie Reber
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I would also like to point out that if a patient presents to a 'Normal' Physician... and they actually are diagnosed with Scleroderma...
The 'standard treatment' is then massive amounts of steroids.
The Prognosis is then a 5-10 year (at the most) life expectancy. To me, this is unacceptable. And it should be to others as well.
There are educated organizations who will suggest treating with low dose Minocycline. http://roadback.org/ is one. And the success rate is remarkable.
Now, why would a low dose antibiotic help or actually cure Scleroderma? The answer lies in the above abstracts.
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ping
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Melanie - This is very common in the US among those who acquired LD congenitally. Infection with B. afzelli or garinii in the US is a primary sign of long-running congenital infection, usually over a period of 2 or more generations.
ping "We are more than containers for Lyme"
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Melanie Reber
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Hey Ping,
VERY interesting! Do you have any research to back that up, please? If so, I would love to see it, or if you wouldn't mind posting it yourself... that would be most helpful!
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ping
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PMing you.
-------------------- ping "We are more than containers for Lyme" Posts: 1302 | From Back in TX again | Registered: Mar 2005
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ping
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Melanie - Your PM is full and I can't send you info. I'll try again some other time.
ping "We are more than containers for Lyme"
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Melanie Reber
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Oh Goodness, this is one of life's many little nuisances... I'll make some room now. So sorry.
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ping
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Melanie,
I'll give you a short version as best I can then PM you with docs name where you might still find info. to post. I had the info so long ago, don't know where it is now.
A number of LLMDs, but particularly one that used to practice in Houston came to the conclusion that most of the Lyme pts he had (~75%) were congenitally infected and that it was either a B. afzelli or garinii infection that had been pasted from generation to generation. The only way to tell the 2 apart is by DNA test because presentation was the same (no EM, but rash, discoloration, etc. as you describe) and they both originated in Central Europe. It was part of the LLMD's hypothesis that the infection could be traced back at least 2 generations (sometimes 3 and 4) and was likely also what was referred to at the time as STARI (and might actually be bonafide STARI). Of course, there were always the usual misdiagnoses of PSS (Progressive Systemic Sclerosis), etc.
Another reason that the LLMD knew that the infections were congenital is because B. af and ga have not existed in nature in the southern US is about 30 years. They mutated into other strains such as B. lonestarii, etc., likely to tolerate the heat better.
In conclusion, he found that the vast majority of TBD from about central TX, through the entire eastern Gulf Coast to parts of Georgia & FL has been and continues to be congenitally transmitted. This is very true for East TX, as I am one of those people he talked about. Another example is a lady that I talk with on another forum, also from E. TX who can trace the illness back at least 3 generations and has caused infection in her entire clan of over 100 people (parents, children, aunts, uncles, cousins, grandkids, etc.).
It's a terrible disaster here in TX and I don't doubt the rest of The South. If you think it's difficult getting medical help where Lyme is in any way known to be endemic, try getting help in places down here. Darn near impossible. What a horrible legacy.
ping "We are more than containers for Lyme"
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charlie
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Interesting....and I'm one of those showing some of these symptoms now after being sprayed with herbicide in mid-March by a careless farmer.
I think stress from poisoning (and the ensuing feud) can make things go haywire also.
I didn't realize Dr Harvey was talking about euro strains.
Charlie
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Truthfinder
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Wow, great info, Melanie. Spooky, though.
Ping, that's pretty interesting information, also. I swear my dad had whatever I have and so did his mother, but my mom didn't, so I can't make sense of any congenital transfer, really.
Gee, Charlie - that's awful. How in the world did you get sprayed?
-------------------- Tracy .... Prayers for the Lyme Community - every day at 6 p.m. Pacific Time and 9 p.m. Eastern Time � just take a few moments to say a prayer wherever you are�. Posts: 2966 | From Colorado | Registered: Dec 2005
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charlie
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A guy with a cattle raising hobby in back of our place tried to clean up the fence line by spraying 2,4-D on a windy day....apparently I'm one of the sensitive ones who gets all toxic from that particular chemical...fun, eh???
Not sure if it caused an allergic reaction or a partial relapse of some sort, but it's similar to Melanie's presentation.
My guess is as good as any garden variety duck and I don't want steroids so I guess it's back on meds for awhile..... Posts: 2804 | From Texas | Registered: Oct 2000
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Truthfinder
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Gee, Charlie, you must be thrilled to live so close to a genius who can't follow simple directions on a container of herbicide (wind issues). I'm sure the guy's cattle feel the same way (though they were probably upwind).
Hopefully, this is something your body can throw off within a few weeks.
I can certainly understand the ensuing feud issue. Perhaps we'll see you on Judge Judy or People's Court......
-------------------- Tracy .... Prayers for the Lyme Community - every day at 6 p.m. Pacific Time and 9 p.m. Eastern Time � just take a few moments to say a prayer wherever you are�. Posts: 2966 | From Colorado | Registered: Dec 2005
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Melanie Reber
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Yes Ping, that is so very interesting. I actually grew up in the south and lived many years along the Gulf Coast and have European ancestry on both sides. I've also spent a LOT of time in TX.
I've not the time right now to explore this particular aspect of Dr. H's studies, but am excited to do so when I can. Even w/out reading the studies, I can see where the implications are going from your descriptions, and that alone IS very exciting.
I have to wonder if it is 'congenital' in the strictest sense of the word, as in Mother to child. OR if he has hit on some form of genetically inherited DNA that has been passed down.
Your description seems to favor the latter.
I think we also have to take into consideration that the Atlantic coastline is a migratory flyway and that the Gulf of Mexico including the ports along the Mississippi River are our main stopping places for vessels from every continent.
And what are the main stow-aways on those vessels? Why, rats and mice of course. And what are the main reservoirs of TBDs, not to mention little tick magnets themselves... yes, you see where I am going now.
So, for anyone to conclude that Ba and Bg are ONLY found in Europe... is simply a ridiculous assumption.
(oh, and of course this is my opinion only...however, if you do enough research, you will find it to be true)
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ping
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quote:Originally posted by Melanie Reber: I have to wonder if it is 'congenital' in the strictest sense of the word, as in Mother to child. OR if he has hit on some form of genetically inherited DNA that has been passed down.
Your description seems to favor the latter.
I think we also have to take into consideration that the Atlantic coastline is a migratory flyway and that the Gulf of Mexico including the ports along the Mississippi River are our main stopping places for vessels from every continent.
And what are the main stow-aways on those vessels? Why, rats and mice of course. And what are the main reservoirs of TBDs, not to mention little tick magnets themselves... yes, you see where I am going now.
Melanie - You make excellent points.
With regard to the congenital transfer aspect, at present, I lean more toward the Mother to Child, more than the DNA inheritance factor, although, it has no doubt played a role.
Yes, stowaways were part of the problem, as it was with Yersinia outbreaks when the upper crust thought by going out to their country estates, they would somehow escape the mode of transmission and unknowingly took the pestilence with them. The history of The Americas is clear enough to be able to generally trace the Euro strains. Not only do we have the migration from western Europe (England, Ireland, Scotland) into East Coast US, but Spainish from S. America thru TX. Then, the French throughout Canada and as far south as Louisiana. The Germans and other Central Europeans arrived slightly later.
Since Ba and Bg are esp. suited to cooler climates with actual change of seasons, it would not be a stretch to find it not only in upper US but all over Canada.
Pls keep me informed on your research findings.
ping "We are more than containers for Lyme"
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Melanie Reber
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Yes, on my Mother's side, we are Cajun French and Spanish (Spain). However, with so many generations living in and around New orleans, there is a lot of mixed blood. (Plantation owners and overseers)
So, your point of the French Canadians (or outcast Acadians) migrating south was what I was contemplating as well. This really resonates with me.
My Father's side is pure English and Native American. However, even though I have European ancestry on both sides, my Father was stationed in England as a pilot in the USAF... before marrying my mother.
I've also traveled extensively, so the possibilities are endless. But uncovering those possibilities for myself and others... Ah... that intrigues me!
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ping
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quote:Originally posted by Melanie Reber: I've also traveled extensively, so the possibilities are endless. But uncovering those possibilities for myself and others... Ah... that intrigues me!
Go for it, Melanie! Please share whatever info you find out with us!
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Melanie Reber
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Blue discoloration in fingers, palms and wrists of both hands (indoors)
...
Loss of skin elasticity on inside of foot when edema is reduced. However, edema still pools behind outside ankle of foot (outdoors)Posts: 7052 | From Colorado | Registered: Mar 2003
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ping
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Melanie - My feet look exactly like that, with just the edema problems described. I never had the bluing of the fingers.
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TO LIFE
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posted
Dear Melanie,
I am focused on the red dot under the skin, a bit south of the bracelet.
Melanie Reber
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posted
Ah, that is a Cherry Angioma. If you look that up, you will find that there is no known cause.
However, many LLMDs think this is a sign of Babesia. Especially if found on the trunk and chest. Most of mine are in those areas, but I also have them on my arms and a few on my legs.
They do not hurt at all, but are just slightly raised and if picked at they will bleed profusely.
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ping
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quote:Originally posted by Melanie Reber: Ah, that is a Cherry Angioma.
I have them also; on arms and esp. legs.
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Melanie Reber
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Ping, I wasn't sure if the blue would even show up in such small pictures, but suppose it does? I actually look as if all those areas are terribly bruised, although there is not a lot of pain involved specifically in those areas.
The pain is more dispersed evenly in both hands and feet as if the nerve endings are inflamed and the skin itself hurts. And if I should bump my hands or feet against anything, even slightly, the pain is quite a bit more than one would expect.
If I even hold something too tightly with my hands, they feel bruised. Very strange and very difficult to get use to.
Do your feet also swell quite a lot too? I think this is what causes the loss of elasticity of the skin. Once the swelling decreases, the skin does not go back to normal, but wrinkles up instead to what is termed 'cigarette paper' texture.
If you look at the link to the other photos I have posted, you will see more images of the swelling and skin issues.
ping
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quote:Originally posted by Melanie Reber: Do your feet also swell quite a lot too? I think this is what causes the loss of elasticity of the skin. Once the swelling decreases, the skin does not go back to normal, but wrinkles up instead to what is termed 'cigarette paper' texture.
Oh yes...they do definitely swell.
Melanie, do you have hypertension?
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Melanie Reber
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Yes, unfortunately and a high pulse rate. This is something new for me, as I have always had a very slow rate and low BP. My last apt. readings were BP 159/90, HR 126. I was not nervous and I had been sitting for at least 10 minutes before these were taken.
Most times I can feel my heart beating, and at other times I can actually see beating. I was told that this isn't 'normal'.
My doc believes it is due to my endocrine system being whacked now. Thyroid and adrenals are way off. I am basically in a catabolic state, this explains so many issues I have currently.
We are trying to regulate these with thyroid meds and diet modifications... but I'm not sure any of it is actually helping. Well...especially the diet mod, as I simply forget to eat.
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ping
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Yep. What you've described is what Dr. H. said he found in the majority of advanced Lyme pts. Low BP for most of the pts life, spiking to high BP and fast pulse. Even when you go into remission, these malfunctions remain.
Mine was 180/110 before it was diagnosed. I take beta blocker to help lower BP & pulse and diuretic for the edema. AThyroid also, although my readings are just inside the normal range, my doc says that sort of reading is deceptive and that thyroid is an issue.
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