Lupus In 'Overlap' With Other Connective Tissue Diseases

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Adminஐﻬ:
Lupus In 'Overlap' With Other Connective Tissue Diseases

Thomas A. Medsger, Jr., M.D.
University of Pittsburgh School of Medicine

Pittsburgh , PA


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Connective Tissue Disease And Overlap Syndromes
Lupus and Rheumatoid Arthritis
Lupus and Myositis
Lupus and Scleroderma
Mixed Connective Tissue Disease
Sjogren's Syndrome and Lupus
Frequency Of Overlap Syndromes In People With Lupus
Heredity And Overlap
Prognosis For People With Lupus And Overlap Syndromes
The Lupus Foundation of America
Related Information

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Connective Tissue Disease And Overlap Syndromes
The connective tissue diseases are a family of closely related disorders. They include:

rheumatoid arthritis (RA)
systemic lupus erythematosus (SLE or lupus)
polymyositis-dermatomyositis (PM-DM)
systemic sclerosis (SSc or scleroderma)
Sjogren's syndrome (SS)
various forms of vasculitis.
These diseases have a number of common features:
They affect females much more frequently than males.
They are "multisystem" diseases, capable of affecting the function of many organs.
They "overlap" with one another, sharing certain clinical symptoms, signs, and laboratory abnormalities.
Blood vessels are the most common target of injury in all of these diseases.
The immune system is abnormal and accounts, at least in part, for the observed tissue damage.
Although lupus most often occurs alone, many people with lupus also have symptoms characteristic of one or more of the other connective tissue diseases. In this circumstance, a physician may use the term “overlap” to describe the illness. There are several well-recognized overlaps that may affect people with lupus.




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Lupus and Rheumatoid Arthritis

Lupus

Joint pain (arthralgia) is common.
Joint swelling (arthritis) may be present in some cases.
The majority of those with lupus experience joint pain without swelling or only intermittent swelling.
If a person with lupus develops severe arthritis with joint deformities, he/she should be considered to have rheumatoid-like arthritis.
RA
Joint swelling is always present.
Joint pain is common but less prominent.
Because rheumatoid arthritis is more likely than lupus to cause joint deformities and bone destruction, joint replacement or reconstructive surgery is more often required in RA than in lupus.
Overlap
In some instances, the physician might have reason to believe that both diseases-SLE and RA-have occurred in the same person.

Treatments

When arthritis develops in the course of lupus, treatment with these agents can be helpful:
- non-steroidal anti-inflammatory drugs (NSAIDs)
- low doses of cortisone
- the antimalarial drug hydroxychloroquine (Plaquenil).
People with lupus who have typical rheumatoid arthritis are prescribed the standard forms of RA treatment:
- methotrexate
- sulfasalazine
- In some cases, more potent drugs to suppress inflamation




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Lupus and Myositis

Lupus
Many persons with lupus have muscle pain (myalgia), but few have muscle weakness due to inflammation (myositis).
The "muscle weakness" that people with lupus report is most commonly due to fatigue or high doses of cortisone.
Myositis
In polymyositis-dermatomyositis, the primary problem is muscle weakness due to muscle inflammation.
Weakness especially affects:
- the hips (inability to rise from a chair or toilet seat, or to climb stairs unassisted)
- the shoulders (inability to lift a weight onto a high shelf or comb one's hair).
- typically, there is little or no pain associated with the weakness.
People with myositis also have:
- increased blood levels of creatine kinase (CK), a substance that leaks from injured muscle
- abnormal electrical activity of muscles detected by electromyogram (EMG)
- muscle biopsy showing muscle cell degeneration and inflammation that is found in a muscle biopsy.

Treatments

Prednisone or other cortisone-like drugs are most often recommended for the treatment of myositis, and may be used in combination with other immune-suppressing drugs..
Cortisone itself, in high doses, may actually cause muscle weakness of the hips and shoulders, very similar to what occurs in myositis. But in this condition, called "steroid myopathy," the CK, EMG, and the muscle biopsy do not suggest inflammation, and recovery of strength promptly follows reduction of the cortisone dose.


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Lupus and Scleroderma

Lupus
The variety of skin rashes seen in lupus are due to inflammation, rather than fibrosis. Features of these rashes are limited to the skin surfaces exposed. They include:
- the facial "butterfly" rash
- a photosensitivity reaction (rash, hives or blisters) seen immediately after exposure to sunlight or other sources of ultraviolet light.
An exception is "discoid" or "cutaneous" lupus, which consists of spots or patches of rash, mostly in sun-exposed areas (face, ears, extremities), which typically cause scarring and skin pigment changes. The appearance of scleroderma and discoid lupus are entirely different, and should be easily distinguished from one another by your physician.
Scleroderma
The hallmark of scleroderma (SSc) is thickened skin (sclero=hard; derma=skin). If skin thickening is widespread, it may extend to the upper arms, thighs, chest, and abdomen.
These changes are due to the excessive production and uncontrolled "laydown" of collagen, the substance normally present in scar tissue.

If skin fibrosis (hardening) is widespread, it may extend to:
- the upper arms
- thighs
- chest
- abdomen.

The variety of skin rashes seen in lupus are due to inflammation, rather than fibrosis. These include the facial “butterfly” rash and photosensitivity reaction (rash, hives or blisters ) seen immediately after exposure to sunlight or other sources of ultraviolet light ). The latter is limited to the skin surfaces exposed. An exception is discoid lupus , which consists of spots or patches of rash, mostly in sun exposed areas (face, ears, extremities), which typically cause scarring and skin pigment changes. The appearance of scleroderma and discoid lupus are entirely different, and should be easily distinguished from one another by your physician.

Other features less common in lupus than in SSc include:
- pulmonary fibrosis: scarring of the lower portions of the lung
- difficulty in swallowing solid foods such as bread or meat
- heartburn or indigestion from stomach acid "refluxing" ( coming back) into the esophagus. Difficulty swallowing and reflux are due to sluggish and uncoordinated motion of the muscle layer of the esophagus (esophageal dysmotility).
-Scleroderma often leads to finger and hand deformities as well, due to the combination of skin thickening, arthritis, tendinitis and tenosynovitis (inflammation and scarring of tendons and their lining tissues). These processes ultimately result in limited movement of the fingers-Raynaud's phenomenon: fingers turn blue or white with cold. This occurs in 95 percent of persons with scleroderma and in 40 percent of persons with lupus.
Treatment
The primary treatment approaches to SSc are quite different from those for lupus.
Therefore, treatment for scleroderma like problems in persons with lupus should be individualized and directed at the particular problems present at any given time.



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Mixed Connective Tissue Disease

Some individuals have symptoms and signs of three connective tissue diseases:
lupus
polymyositis-dermatomyositis
scleroderma.
At any given time, the combination of problems encountered by the patient may vary considerably, from no active disease to features of one, two, or all three of these conditions at the same time.
These persons often (but not always) have one specific blood antibodyin their blood (anti-U1RNP antibody) but not the other antibodies commonly associated with SLE, SSc, or PM-DM.
Whether this is an entirely separate disease, or a situation in which one person has three diseases, remains uncertain. However, the presence of a single blood antibody is a strong point in favor of a distinctive disease.
Treatment

Treatment should be individualized and directed at the particular problems present at any given time.




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Sjogren's Syndrome and Lupus
Sjogren's syndrome
Henrik Sjögren was a Swedish ophthalmologist and the first to recognize that dry eyes and dry mouth were often found in people with connective tissue diseases.

These symptoms are caused by the accumulation of immune system cells (lymphocytes) in and around tear and saliva producing glands.
The build-up of cells disturbs the function of these glands and leads to reduced production of tears and saliva.
This condition also interferes with the protective mechanisms of the eye and mouth.
Eye inflammation and ulcers of the cornea, as well as fungal infections of the mouth (thrush), occur with increased frequency in those with Sjogren's.
Rarely, a person with this disorder develops a malignancy (cancer) affecting lymphocytes (lymphoma).
Today, Sjogren's syndrome is itself accorded the status of a distinct connective tissue disorder.
Lupus
Sjogren's syndrome also occurs in some people with lupus:
They have an increased frequency of sun-sensitive rashes and Sjogren's-related blood antibodies (anti-SSA and anti-SSB antibodies).
Women with anti-SSA antibodies are at increased risk of having babies with "neonatal lupus." Symptoms in the infant can be as minor as a temporary lupus-like skin rash, or as serious as permanent damage to the electrical system of the heart which results in a very slow heart rate (complete heart block)
Treatments

The best treatments for Sjogren's syndrome include : artificial tears (usually satisfactory) and either artificial saliva (most often unsatisfactory) or a saliva stimulant such as pilocarpine and hydroxychloroquine (Plaquenil). Eye drops containing cyclosporin have also just been introduced and have significant benefit for dry eyes in some cases . Arthritis, fatigue and skin rash in people with Sjogren's is often treated with Plaquenil.

 



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Frequency Of Overlap Syndromes In People With Lupus
The majority of people with lupus have lupus alone. Between 5 and 30 percent of people with lupus report having overlap symptoms. The likelihood of a person with lupus also having an overlap disease is 15 percent, distributed as follows:

Overlap Disease Rate of Occurrence
Rheumatoid Arthritis  1%
Polymyositis-Dermatomyositis 2%
Mixed Connective Tissue Disease 3%
Scleroderma 4%
Sjogren's syndrome  5%





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Heredity And Overlap

It is unusual (less than 10 percent of the time) for a person with lupus to have a close family member (parent, child, brother, or sister) who also suffers from lupus.
However, it is common for persons with lupus to have relatives (including grandparents, aunts/uncles, cousins) with other connective tissue diseases such as rheumatoid arthritis, Sjogren's syndrome, scleroderma, etc.
These co-occurrences raise the possibility that heredity may be a factor in all of the connective tissue diseases.
Most scientists agree that important hereditary associations with these diseases are present in some families. Additional research is needed to shed light on this important question.



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Prognosis For People With Lupus And Overlap Syndromes
It is important for those with lupus to be aware of the symptoms that might indicate the development of "overlap" features, since these symptoms and abnormalities may be best managed with treatments not typically used for lupus. Fortunately, when an overlap syndrome is present, the symptoms characteristic of the other connective tissue diseases involved are usually mild and not life-threatening.




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The Lupus Foundation of America
The Lupus Foundation of America (LFA) was established in 1977 to educate and support those affected by lupus and find the cure. The LFA supports research, education, awareness, patient services, and advocacy.

The Lupus Foundation of America is the only nationwide organization exclusively serving individuals, families and friends affected by lupus. The LFA has local chapters and support groups throughout the United States, as well as international affiliates around the world. Contact the LFA or the chapter that serves your area to find out how you can become involved in our mission.

Become a Lupus E-Advocate and help pass federal legislation that will benefit people with lupus. You'll receive periodic advocacy updates and other breaking lupus news and information.

For more information about lupus of to lacate the chapter nearest you, visit our website at www.lupus.org or call our information request line toll-free at 1-800-558-0121. (en Espanol, 800-558-0231).


Approved by the Lupus Foundation of America's
Patient Education Committee

Adminஐﻬ:
What are connective tissues?

The connective tissues are the structural portions of our body that essentially hold the cells of the body together. These tissues form a framework or matrix for the body. The connective tissues are composed of two major structural molecules, collagen and elastin. There are many different collagen proteins that vary in amount in each tissue of the body. Elastin is another protein that has the capability of stretching and returning to original length like a spring. Elastin is the major component of ligaments (tissues which attach bone to bone).

Connective tissue diseases are disorders featuring abnormalities involving the collagen and elastin. Connective tissue diseases are often characterized by a variety of immune abnormalities that are common for each particular type of illness.

What diseases characteristically affect connective tissue?

Diseases of connective tissue that are strictly inheritable (due to genetic inheritance) include Marfan syndrome (can have tissue abnormalities in the heart, aorta, lungs, eyes, and skeleton), and Ehlers-Danlos syndrome (may have loose, fragile skin or loose [hyperextensible] joints).

Other diseases of connective tissue do not have specific gene abnormalities as their sole cause. These connective tissue diseases occur for unknown reasons. They are characterized as a group by the presence of spontaneous over activity of the immune system, which results in the production of unusual antibodies into the blood.

The classic immune-related connective tissue diseases include systemic lupus erythematosus, rheumatoid arthritis, scleroderma, polymyositis, and dermatomyositis. Each of these diseases has a characteristic presentation with typical clinical findings that doctors can recognize during an examination. Each also has characteristic blood test abnormalities and abnormal antibody patterns. However, each of these diseases can evolve slowly or rapidly from very subtle abnormalities before demonstrating the classic features that help in the diagnosis. When these conditions have not developed the classic features of a particular disease, doctors will often refer to the condition as "undifferentiated connective tissue disease." This implies that the characteristic features that are used to define the classic connective tissue disease are not present, but some symptoms or signs of connective disease exist. Individuals with undifferentiated connective tissue disease may never develop a fully definable condition or they may eventually develop a classic connective tissue disease.

Adminஐﻬ:
What is mixed connective tissue disease?

Mixed connective tissue disease, as first described in 1972, is "classically" considered as an "overlap" of three diseases, systemic lupus erythematosus, scleroderma, and polymyositis. Patients with this pattern illness have features of each of these three diseases. They also typically have very high quantities of antinuclear antibodies (ANAs) and antibodies to ribonucleoprotein (anti-RNP) detectable in their blood. The symptoms of many of these patients eventually evolve to become dominated by features of one of three component illnesses, most commonly scleroderma features.

It is now known that overlap syndromes can occur that involve any combination of the connective tissue diseases. Therefore, for example, patients can have a combination of rheumatoid arthritis and systemic lupus erythematosus (hence, the coined name "rhupus").

How is MCTD diagnosed?

Today, true mixed connective tissue disease is diagnosed when patients demonstrate the clinical features (exam findings) of overlap illnesses (as described above) and have high amounts of the antibodies ANA and anti-RNP in their blood. MCTD patients do not typically have antibodies such as dsDNA, Scl70, which are particularly common in systemic lupus erythematosus and scleroderma respectively.

How is MCTD treated?

The treatment of mixed connective tissue disease is based on which features are causing symptoms. The prognosis (outlook) varies accordingly. Therapies must be targeted for each of the organ systems affected. In general, treatment is often directed at suppressing the inflammation present in the tissues by using anti-inflammatory and immunosuppressive medications. These medications include nonsteroidal anti-inflammatory drugs (NSAIDs), cortisone drugs/steroids (such as prednisone), antimalarial drugs (hydroxychloroquine), and cytotoxic drugs (such as methotrexate, azathioprine, and cyclophosphamide). Organ damage, such as in the kidneys, can require additional treatments directed at high blood pressure, etc.

For the joint and muscle pains of MCTD, treatment options include NSAIDs, low-dose prednisone, hydroxychloroquine, and methotrexate can be helpful. Physical therapy for certain joints is sometimes helpful. For pulmonary hypertension, prednisone, angiotensin converting enzyme inhibitors, and cyclophosphamide are used. For interstitial lung disease, prednisone and cyclophosphamide are considered. To prevent damage to the kidneys, angiotensin converting enzyme inhibitors, such as captopril (Capoten), enalapril (Vasotec) are used, especially if blood pressure is elevated. Esophagus irritation and heartburn can be prevented by elevating the head of the bed and relieved with omeparazole (Prilosec) or lansoprazole (Prevacid). Antacids can also be helpful. Constipation, cramping and diarrhea is sometimes caused by bacteria that can be treated with tetracycline or erythromycin.

For Raynaud's phenomenon, patients are recommended to use hand and body warming techniques while protecting the fingers from injury. Nifedipine (Procardia), losartan (Cozaar, Hyzaar) and nitroglycerin cream are used to dilate the constricted blood vessels. Severe RP can lead to gangrene and the loss of digits. In rare cases of severe disease, nerve surgery called "sympathectomy" is sometimes considered. In order to prevent blood vessel spasming, the nerves that stimulate the constriction of the vessels (sympathetic nerves) are surgically interrupted. Usually this is performed during an operation that is localized to the sides of the base of the fingers at the hand. Through small incisions the tiny nerves around the blood vessels are stripped away. This procedure is referred to as a digital sympathectomy.

Mixed Connective Tissue Disease At A Glance
Connective tissues are the framework of the cells of the body.
MCTD is an "overlap" combination of connective tissue diseases.
Diagnosis of MCTD is supported by detecting abnormal antibodies in the blood.
Treatment of MCTD is directed at suppressing immune-related inflammation of tissues.
For more specific information related to the individual connective tissue diseases, please read the following articles: Systemic Lupus Erythematosus, Rheumatoid Arthritis, Scleroderma, and Polymyositis.

Reference:
Clinical Primer of Rheumatology, Lippincott Williams & Wilkens, edited by William Koopman, et. al., 2003.
Kelley's Textbook of Rheumatology, W B Saunders Co, edited by Shaun Ruddy, et.al.,  www.LupusMCTD.com

Adminஐﻬ:
Symptoms, Signs and Tests
Because many symptoms of systemic lupus erythematosus (SLE) mimic those of other illnesses, lupus can be a difficult disease to diagnose. Diagnosis is usually made by a careful review of three factors:
the individual's entire medical history
an analysis of the results obtained in routine laboratory tests and
some specialized tests related to immune status.

To make a diagnosis of SLE, an individual must show clinical evidence of a multi-system disease (i.e. has shown abnormalities in several different organ systems). Typical symptoms or signs that might lead to suspicion of SLE are:

*Skin: Butterfly rash across the cheeks; ulcers in the mouth; hair loss.

*Joints: Pain; redness, swelling.
*Kidney: Abnormal urinalysis suggesting kidney disease.
*Lining membranes: Pleurisy (inflammation of the lining of the lung); pericarditis (inflammation of the heart lining); and/or peritonitis (inflammation around the abdomen). Taken together, these types of inflammation are known as polyserositis.
*Blood: Hemolytic anemia (the red cells are destroyed by autoantibodies); leukopenia (low white blood cell count); ஐﻬthrombocytopenia (low number of platelets).
*Lungs: Infiltrates (shadowy areas seen on a chest x-ray) that come and go
*Nervous system Convulsions (seizures); psychosis; nerve abnormalities that cause strange sensations or alter muscular control or strength.
*
If an individual has several of these symptoms, the physician will then usually order a series of tests to examine how well the individual's immune system is functioning. In general, physicians look for evidence ஐﻬof autoantibodies. Although there is no one test that can definitely say whether or not a person has lupus, there are many laboratory tests which aid the physician in making a lupus diagnosis.

Routine clinical tests which suggest that the person has an active systemic disease include:

sedimentation rate (ESR) and CRP (C-reactive protein) binding, both of which are frequently elevated in inflammation from any cause
serum protein electrophoresis which may reveal increased gammaglobulin and decreased albumin
routine blood counts which may reveal anemia and low platelet and white cell counts
routine chemistry panels which may reveal
kidney ஐﻬinvolvement by increases in serum blood urea nitrogen and creatinine
abnormalities of liver function tests
increased muscle enzymes (such as CPK) if muscle involvement is present.
These kinds of abnormalities alert the doctor to the presence of a systemic disease with multiple organ involvement.

Commonly used blood tests in the diagnosis of SLE are:

Anti-nuclear antibody test (ANA) to determine if autoantibodies to cell nuclei are present in the blood
Anti-DNA antibody test to determine if there are antibodies to the genetic material in the cell
Anti-Sm antibody test to determine if there are antibodies to Sm, which is a ribonucleoprotein found in the cell nucleus
Serum (blood)ஐﻬ complement test to examine the total level of a group of proteins which can be consumed in immune reactions
Complement proteins C3 and C4 test to examine specific levels


The Antinuclear Antibody (ANA or FANA) Test
Positive ANA
The immunofluorescent antinuclear antibody (ANA or FANA) test is positive in almost all individuals with systemic lupus (97 percent), and is the most sensitive diagnostic test currentlyஐﻬ available for confirming the diagnosis of systemic lupus when accompanied by typical clinical findings. When three or more typical clinical features are present, such as skin, joint, kidney, pleural, pericardial, hematological, or centralஐﻬ nervous system findings as described above, a positive ANA test confirms the diagnosis of systemic lupus.

However, a positive ANA test, by itself, is not proof of lupus since the test may also be positive in:

other connective tissue diseases, such as:
scleroderma
Sjogren's syndrome
rheumatoid arthritis
thyroid disease
liver disease
juvenile arthritis
individuals being treated with certain drugs, including:
procainamide
hydralazine
isoniazid
chlorpromazine
viral illnesses, such as:
infectious mononucleosis
other chronic infectious diseases, such as:
hepatitis
lepromatous leprosy
subacute bacterial endocarditis
malaria
other autoimmune diseases, including:
thyroiditis
multiple sclerosis
as many as 30-40 percent of asymptomatic first-degree relatives of people with lupus (siblings, parents, and children).
Weakly positive ANA
The test can even be weakly positive in about 20 percent of healthy individuals. While a few of these healthy people may eventually develop ஐﻬlupus symptoms, the majority will never develop any signs of lupus or related conditions. The chances of a person having a positive ANA test increases as he or she ages.

Negative ANA
A negative ANA test is strong evidence against lupus as the cause of a person's illness, although there are very infrequent instances where SLE is present without detectable antinuclear antibodies. ஐﻬANA-negative lupus can be found in people who have anti-Ro (SSA) or antiphospholipid antibodies.

ANA Titers and Patterns
ANA laboratory reports include a titer (pronounced TY-tur) and a pattern.

The titer indicates how many times the lab technician had to dilute plasma from the blood to get a sample free of the antinuclear antibodies.
For example, a titer of 1:640 shows a greater concentration of anti-nuclear antibodies than a titer of 1:320 or 1:160.
The apparent great difference between various titers can be misleading.

Since each dilution involves doubling the amount of test fluid, it is not surprising that titer numbers increase rather rapidly.
In actuality, the difference between a 1:160 titer and a 1:320 titer is only a single dilution. This does not necessarily represent a major difference in disease activity.

ANA titers go up and down during the course of the disease, and a high or low titer does not necessarily mean the disease is more or less active.
Therefore, it is notஐﻬ always possible to determine the activity of the disease from the ANA titer.
A titer above 1:80 is usually considered positive.
Some laboratories may interpret different titer levels as positive, so one cannot compare titers from different laboratories.


The pattern of the ANA test can sometimes be helpful in determining which autoimmune disease is present and which treatment program is appropriate.
The homogeneous, or smooth pattern is found in a variety of connective tissue diseases, as well as in people ஐﻬtaking particular drugs, such as certain antiarrhythmics, anticonvulsants or antihypertensives.
This homogenous pattern is also the one most commonly seen in healthy individuals who have positive ANA tests.
The speckled pattern is found in SLE and other connective tissue diseases
The peripheral, or rim pattern is found almost exclusively in SLE.
The nucleolar pattern, with a few large spots, is found primarily in people who have scleroderma.
 

Because the ANA is positive in so many conditions, the results of the ANA test have to be interpreted in light of the person's medical history, as well as his or her clinical symptoms. Thus, a positive ANAஐﻬ alone is never enough to diagnose lupus. On the other hand, a negative ANA argues against lupus but does not rule out the disease completely.

A Positive ANA Does Not Equate to Having a Disease
The ANA should be ஐﻬlooked at as a screening test. If it is positive in a person who is not feeling well and who has other symptoms or signs of lupus, the physician will probably want to conduct further tests for lupus.

If the ANA is positive in a person who is feeling well and in whom there are no other signs of lupus, it can be ignored. If there is any doubt, a consultation with a rheumatologist should clarify the situation.


Other Autoantibodies
In those individuals with a positive ANA, additional tests can be done for certain particular antibodies that may better establish a diagnosis of SLE. The knowledge of which particular antibody is responsible for the positive ANA test can sometimes be helpful in determining which autoimmune disease is present.

Antibodies to DNA (the protein that makes up the body's genetic code) are found primarily in SLE.
Antibodies to histones (DNA packaging proteins) are usually found in people with drug-induced lupus (DIL), but may also be found in those with SLE.
Antibodies to the ஐﻬSm antigen are found almost exclusively in lupus, and often help to confirm the diagnosis of SLE.
Antibodies to RNP (ribonucleoprotein) are found in a number of connective tissue diseases. When present in very high levels, RNP antibodies are suggestive of mixed connective tissue disease (MCTD), a condition with symptoms like those of SLE, ஐﻬpolymyositis, and scleroderma.
Antibodies to Ro/SS-A are found in people with either lupus or Sjogren's syndrome, and are almost always found in babies who are born with neonatal lupus.
Antibodies to Jo-1 are associated with polymyositis.
Antibodies to PM-Scl are associated with certain cases of polymyositis that also have features of scleroderma.
Antibodies to Scl-70 are found in people with a generalized form of scleroderma.
Antibodies to the centromere (a ஐﻬstructure involved in cell division) are found in people with a limited form of scleroderma which tends to have a chronic course.


Complement
Laboratory tests which measure complement levels in the blood may also be helpful to the physician in making a diagnosis of SLE.

Complement is a blood protein that destroys bacteria and also influences inflammation.
Complement proteins are identified by the letter "C" and a number.
The most common complement tests are C3, C4, and CH50.
If the total blood ஐﻬcomplement level is low, or the C3 or C4 complement values are low and the person also has a positive ANA, some weight is added to the diagnosis of lupus. Low C3 and C4 complement levels in individuals with a positive ANA may signify the presence of active disease, especially kidney disease.

Biopsy
Sometimes examination of a tissue sample (biopsy) can be helpful in making a diagnosis. The biopsy is one of ஐﻬthe best ways to evaluate an organ or tissue. The procedure involves removal of a small sliver of tissue, which is then examined under a microscope.

The doctor can use the biopsy to identify the amount of inflammation and damage to the tissue.
Further tests can be performed on the specimen to determine whether the problem is due to lupus or is caused by some other factor such as infection or medication.
Almost any tissue can be biopsied. The most ஐﻬcommon sites biopsied in lupus are the skin and kidney.
The results of the biopsy, like any other laboratory test, should be examined in combination with the individual's medical history and clinical findings.


Tests to Assess Disease Activity
When a person diagnosed with lupus develops new or recurring symptoms, laboratory testing of blood or urine can help determine if the symptoms are due to an increase in lupus activity.

Disease activity correlates with a rise in:

CRP (C-reactive protein) binding
ESR, or sedimentation rate
Anti-DNA
Liver and kidney function tests (AST, ALT, BUN, creatinine)
CPK (muscle enzyme)
Urine protein or cellular casts
Disease activity also correlates with a fall in:

CBC or complete blood count (white blood cell count, hemoglobin, platelets)
Complement components
Serum albumin

Putting It All Together
The interpretation of all these tests, and their relationship to symptoms, can be difficult. When a person has many symptoms and signs of lupus and has positive tests for lupus, it is easier for physicians to make a correct diagnosis and begin treatment. However it is more common for an individual to report vague, ஐﻬseemingly unrelated symptoms of achy joints, fever, fatigue, or pain, and to have negative or borderline test results.

Fortunately, with growing awareness of SLE, an increasing number of physicians will consider the possibility of lupus in the diagnosis. While these tests are useful only when their strengths and limitations are understood, in the handsஐﻬ of skilled physicians these are important tools that assist in diagnosing lupus.

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Adminஐﻬ:
MCTD vs. UCTD
(Mixed Connective Tissue Disease vs. Undifferentiated Connective Tissue Disease)
Medical Author: William C. Shiel Jr., MD, FACP, FACR

I note that some viewers have been requesting some clarification of the meaning of the terms "mixed connective tissue disease" (MCTD) and "undifferentiated connective tissue disease" (UCTD).

Connective tissue diseases are a special group of rheumatic diseases (diseases that feature abnormalities of the muscles and/or joints) that can be associated with arthritis. The cause(s) for the connective tissue diseases is (are) unknown. They are characterized as a group by the presence of spontaneous over-activity of the body's immune (defense) system. This over-activity results in the production of unusual antibodies that are found in the blood. The antibodies themselves may or may not cause any problems in patients with connective tissues diseases, but they are commonly found in the blood as an characteristic feature.

The connective tissues are the structural portions of our body that essentially hold the cells of the body together. These tissues form a framework, or matrix, for the body. The connective tissues are composed of two major structural protein molecules, collagen and elastin. There are many different types of collagen protein that vary in amount in each of the body's tissues. Elastin has the capabilityஐﻬ of stretching and returning to its original length - like a spring or rubber band. Elastin is the major component of ligaments (tissues that attach bone to bone) and skin. In patients with connective tissue diseases, it is common for collagen and elastin to become injured by inflammation. Diseases in which inflammation of collagen tends to occur are also referred to as collagen diseases.

The classic connective tissue diseases include systemic lupus erythematosus, rheumatoid arthritis, scleroderma, polymyositis, and dermatomyositis. Each of these diseases affects people in a characteristic way and causes typical findings that doctors can recognize during an examination.ஐﻬ Each also has characteristic blood test abnormalities and abnormal antibody patterns. For example, systemic lupus erythematosus has dsDNA antibodies, while scleroderma has Sc170 antibodies. Additionally, each of these diseases can evolve either slowly or rapidly from very subtle abnormalities before demonstrating the classic features that help in the diagnosis.

When these conditions have not developed the classic features of a particular disease, doctors will often refer to the condition as "undifferentiated connective tissue disease," or UCTD. This designation implies that the characteristic features that are used to define the classic connective tissue diseases are not present, but that some symptoms or signs of a connective tissue disease exist.ஐﻬ For example, a person may have a special antibody in the blood, such as antinuclear antibody and muscle pains, but no other definable features of a classic connective tissue disease. Individuals with undifferentiated connective tissue disease may never develop a fully definable condition or they may eventually develop a classic connective tissue disease.

Mixed connective tissue disease, which was first described in 1972, is "classically" considered as an "overlap," or mix, of three specific connective tissue diseases; systemic lupus erythematosus, scleroderma, and polymyositis. Patients with this pattern of illness (that is, with MCTD) have features of each of these three diseases. They also typically have very high quantities of antinuclear ஐﻬantibodies (ANAs) and antibodies to ribonucleoprotein (anti-RNP) detectable in their blood. The symptoms of many of these patients eventually evolve to become dominated by features of one of the three component illnesses, most commonly the scleroderma features.

It is now known, however, that overlap syndromes can involve any combination of the connective tissue diseases. Therefore, for example, patients can have a combination of rheumatoid arthritis and systemic lupus erythematosus (hence, the coined name "rhupus"). Accordingly, today, true mixed connective tissue disease is diagnosed when patients demonstrate the ஐﻬclinical features (exam findings) of overlap illnesses. These patients also have high amounts of ANA and anti-RNP without having such other antibodies as the dsDNA antibodies of systemic lupus erythematosus and the Scl70 antibodies of scleroderma. 

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