Richard Sontheimer, MD
University of Iowa
Specialist in Dermatologic Immunology
First Published: April 2000
Last Revised: September 2003
Peer Review Status: Internally Peer Reviewed
Why are there skin problems that occur in rheumatoid patients?
Almost all of the diseases in this category are thought to be diseases in which
one's immune system is not working properly. The immune system is a normal part
of one's body that is designed to protect us from infections with germs and
viruses from the environment. Our immune system also helps us ward off cancer
cell development in our bodies. When one's immune system gets out of control
and starts attacking one's own bodily tissues, this is called "autoimmunity."
In this situation, blood proteins called autoantibodies are produced that bind
to and injure one's own bodily tissues. Rheumatic diseases such as rheumatoid
arthritis, lupus, dermatomyositis, and scleroderma are thought to be autoimmune
In a disease like rheumatoid arthritis, the immune system abnormalities can
attack the lining of the joints. This produces arthritis or inflammation in
the joints. (The term "inflammation" means a combination of pain, tenderness,
swelling, and redness.) The same type of immunological abnormalities that occur in the
joint of a rheumatoid arthritis patient also can occur in the skin. As a result,
we can see skin lesions in patients with rheumatoid arthritis
that can reflect the state of activity of the immunological abnormalities inside
of that patient.
What do the following tests mean: ANA, C&P ANCA, LP, and CFS?
There are some blood tests one can do that can reflect how active the immunological
disease is inside our bodies in diseases like rheumatoid arthritis, lupus,
and scleroderma. These tests are routinely ordered by doctors who are treating
such patients. This information can be very helpful at times both in the diagnosis
of the specific problem and in guiding treatment of the problems over time.
In a disease like rheumatoid arthritis, the most common blood test abnormalities
are the presence of rheumatoid factor. Rheumatoid factor is a type of autoantibody
present in the blood of almost all patients with rheumatoid arthritis who have
the really destructive form of the disease. This particular tests also indicates
a risk for some of the complications that can occur in rheumatoid arthritis,
in parts of the body outside of the joints. A test like the rheumatoid factor
certainly can be helpful in making the initial diagnosis of rheumatoid arthritis.
In addition, the amount of rheumatoid factor in the blood can be an indication
of the state of activity of the immunological illness inside the body.
Another test is the antinuclear antibody assay (the "ANA test" for short).
The ANA test is almost always positive in rheumatic diseases such as lupus.
In addition, it is often positive in rheumatoid arthritis, dermatomyositis,
and scleroderma. This test, since it can be positive in a number of these diseases,
is not diagnostic of any one particular disease. A physician will use the ANA
test to screen for this general group of illnesses, and if that is positive,
then will do more specific tests to make a specific diagnosis such as lupus.
However, one thing that must be kept in mind in interpreting the results of
the ANA test is that it can also be positive in other disease settings that
are not related to arthritis. Even normal individuals, on occasion, will have
abnormal ANA test results. This occurs even more frequently in older healthy individuals. Certain medications can trigger a positive ANA test.
The point is that the physician must be very careful in interpreting the results
of the ANA test and should counsel patients about the true meaning of an ANA
test result. I see a lot of confusion produced as a result of physicians in
the community not being fully aware of the various pluses and minuses of the ANA test.
I will mention one other laboratory test in this context. That is the ANCA
test. ANCA stands for "antibody to neutrophil cytoplasmic antigens." This test
is often positive in forms of blood vessel inflammation such as vasculitis.
One of the strongest disease associations of the ANCA test is a disease called
Wegener's granulomatosis. This is a disease that can attack blood vessels in different parts
of the body including the skin. Recognizing the characteristic patterns of skin
changes can be a clue to the diagnosis of this disease and getting patients
on proper treatment for the internal complications that can be very severe (lung
and kidney injury). However, like the ANA test, one must be careful in interpreting
the ANCA test results. The ANCA test can be positive in other conditions besides
vasculitic illnesses like Wegener's granulomatosis.
How are these skin conditions commonly treated?
The answer to this question is complex. The skin lesions in a large number
of the 100 or so diseases that cause arthritis are treated differently. For
example, in a disease like lupus, the skin lesions can be treated quite nicely
with cortisone-containing creams and oral medications such as the antimalarials.
However, these same forms of treatment usually do not help the skin changes
that we see in scleroderma. The treatment really has to be individualized to
the specific disease and to the specific conditions related to a given case.
Some drugs might be riskier in women compared to men, for example.
What about the following tests: Ro and La antibody titers?
The Ro and La antibody tests give information somewhat similar to the results
of an ANA test. However, the Ro and La antibodies are specific autoantibodies
that can reflect a risk for certain types of rheumatic disease. For example,
the Ro antibody test, when positive, can indicate a risk for certain forms of
lupus skin disease such as subacute cutaneous lupus erythematosus and neonatal
lupus erythematosus. In addition, Ro antibodies also can indicate risk for Sjogren's
syndrome. Perhaps I should be more specific in describing what I mean by these
Subacute cutaneous lupus erythematosus (also known in its abbreviated form
as SCLE) is a form of lupus skin disease that is made worse by exposure to sunlight
or artificial sources of ultraviolet radiation and does not produce scarring.
It produces scaly red patches on the skin that can simulate the appearance of
psoriasis occurring in sun-exposed areas of the body. Patients with this form
of skin lupus have a somewhat higher risk for developing the more severe internal
complications of systemic lupus erythematosus compared to another common form
of lupus skin disease named discoid lupus erythematosus. Discoid lupus erythematosus
(also referred to as DLE) produces scaly coin-shaped lesions most commonly occurring
on the face or scalp, although other parts of the body can be affected. This
type of skin lupus often produces scarring of the skin and hair loss that can
be permanent. In addition, discoid lupus skin lesions often produce darkening
and/or lightening of the skin color. When lupus shows itself initially only
as discoid lupus skin lesions, such patients are at very low risk for later
developing serious internal problems from systemic lupus.
Neonatal lupus is a condition in which newborn babies develop skin lesions
often simulating the appearance of subacute cutaneous lupus erythematosus. However,
this occurs only when the mother of the newborn baby also had an immunological
abnormality during pregnancy that resulted in her body producing Ro autoantibodies.
It is thought that the mother's Ro autoantibodies cross over into the baby's
blood circulation while still in the womb. These autoantibodies appear to be
actually causing the skin lesions that occur after the baby is born and exposed
to sunlight and other forms of ultraviolet light. Normally neonatal LE is a
mild condition and the skin lesions go away on their own as the child gets older
when the autoantibodies from the mother's blood disappear from the baby's blood.
However, there is another complication that can occur in this setting and that
is congenital heart block. Rather than developing skin lesions after delivery,
babies develop damage in the conduction system in their hearts while still in
the womb. This can be a very severe complication requiring permanent pacemaker
placement in the heart of the baby.
The third condition I mentioned that is associated with Ro antibodies is Sjogren's
syndrome. This is a condition that produces dryness in the eyes and dryness
in the mouth, most commonly in adult women. This dryness results from autoimmune
damage to the glands that make tears and saliva. This is one of the most common
of all rheumatic or arthritis-associated diseases but among the most difficult
to diagnose--it is very often not diagnosed until it is quite advanced. Patients
who have Sjogren's syndrome also experience body tenderness and lethargy that can simulate
conditions such as fibromyalgia. In addition, internal organ damage can occur
in Sjogren's such as kidney problems, nerve injury, and blood vessel injury.
I have not said anything so far about the La autoantibody; however, everything
I have said so about the diseases that are associated with Ro autoantibodies
also applies to the La autoantibody. These two autoantibodies almost always
occur as a pair. However, the Ro autoantibody occurs more frequently than the
What is an LP test? A doctor I am seeing asked if I had an LP and if so
what does the CSF show--can you explain?
An LP test, at least as that term is used most often, refers to a lumbar puncture
test. This is a test where a needle is placed through the lower part of the
back between the backbones and into the spinal column. However, the needle is
positioned where it does not actually touch the spinal cord. Fluid, called cerebral
spinal fluid, that normally circulates around the spinal cord can be withdrawn
through this hollow needle. Various types of tests can be done on this sample
of cerebral spinal fluid. Abnormalities in these tests can reflect brain and
spinal column involvement with diseases like systemic lupus. Other diseases
such as meningitis (bacterial [germ] infection of the membranes that cover and
protect the brain and spinal column) can also cause abnormalities in the LP
Who is most affected by these conditions, men or women, and is there an
age group more at risk?
The group of diseases that we call "rheumatic diseases" affect women more often
by far. I might also mention that another term that is used to describe this
group of diseases is the "autoimmune connective tissue diseases." Another term
that has been used in the past to describe these diseases is "collagen vascular
diseases." It is not fully understood why women have a greater risk for developing
rheumatic diseases and their associated immunological abnormalities. However,
there is some evidence in experimental animal models of diseases like systemic
lupus that indicate that female sex hormones such as estrogen can potentiate
or aggravate the immunological disturbances of lupus. That information has led
to some concern about patients with immune diseases like lupus taking drug forms
of estrogen such as birth control pills or Premarin. However, the studies that
have been done to date would indicate that if there is a risk from such treatment,
it would appear to be relatively mild.
What are the symptoms of these skin conditions, and how can you distinguish whether
they are caused by rheumatoid related illness and not something else?
Again, the answer to this question is very complex. I will try to keep it as
straightforward as possible. Recall that there are as many as 100 different
medical conditions that can be associated with joint inflammation or arthritis.
All of these conditions are different and seem to represent unique abnormalities
in the human body. Therefore, one would expect that the skin problems that might
occur in these many different disorders would be different and would require
different forms of treatment. However, let me focus on a couple of the major
illnesses in this area and describe how the skin lesions occur and how they
are treated in general.
In rheumatoid arthritis, one of the more common ways that the skin is affected
is through inflammation in the walls of the blood vessels of the skin producing
a condition called vasculitis. Since vasculitis also can occur in internal tissues, like nerves,
in rheumatoid arthritis, it is necessary to treat patients having
this type of skin problem with drugs by mouth or by vein that can dampen down
the autoimmune abnormalities that are producing the inflammation in the blood
Some drugs like the corticosteroids ("steroids") suppress the immune response in a broad
fashion and can be very useful in a number of autoimmune diseases including
the rheumatic diseases (corticosteroids are commonly referred to as "cortisone"
type drugs). Corticosteroids like prednisone taken by mouth can certainly suppress
various manifestations of rheumatoid arthritis including the skin changes like
vasculitis. However, long-term use of corticosteroids by mouth can produce a
lot of troublesome and serious side effects. Therefore, physicians are constantly
trying to find other drugs that will prevent having to rely on corticosteroids
for long periods of time. In the case of rheumatoid arthritis, methotrexate
is a drug that has been found to be able to prevent patients from having to
take so much corticosteroid. Generally, the things a dermatologist does to treat
the surface of the skin, such as applying sunscreens and cortisosteroid-containing
creams or ointments, generally does not help the more severe skin problems such as vasculitis that
are seen in rheumatoid arthritis.
Another common autoimmune rheumatic disease in which the skin is often injured
is lupus erythematosus. There are a number of different types of skin changes
that can be seen in these patients. Interestingly, these different types of
skin lesions can provide different types of information about the risk of a
patient developing the more severe internal complications of lupus. For example,
the presence of discoid lupus erythematosus skin lesions at the beginning of
a patient's illness generally indicates a lower risk for developing the
severe internal complications of systemic lupus such as kidney damage or brain
damage. However, other forms of lupus skin disease, such as the red butterfly-shaped
rash that occurs on the cheeks and nose of the face and is often triggered by
exposure to sunlight, is generally seen in patients who have a higher risk for
developing severe internal complications of systemic lupus. Recognizing the
pattern of skin damage that occurs in patients with lupus can have the additional
benefit of helping to predict the severity of illness that a given patient might experience over time.
Regarding treatment of lupus skin disease, the topical measures that were discussed
above such as the application of sunscreens and corticosteroid-containing creams
and ointments directly to the skin can be helpful in suppressing the skin inflammation
caused by lupus. However, most skin lupus patients do require some type of oral
therapy in addition to the topical therapy. The safest form of oral therapy
to treat lupus skin disease would be one, or a combination, of the anti-malarial
drugs, such as hydroxychloroquine, which is commonly referred to by its trade
name: Plaquenil. This drug can be used very safely if the common recommended
guidelines concerning total daily dosage are followed. However, patients need to have
their eyes monitored while on this drug since on rare occasion problems can
develop in the retina of the eye while on this form of treatment.
Similar forms of treatment are used for the skin problems seen in patients
with dermatomyositis. This condition causes autoimmune inflammation and damage
in the muscles and in the skin and occasionally other vital organs such as the
lungs. However, dermatomyositis skin disease generally is harder to treat than
is lupus skin disease. In addition, dermatomyositis skin disease is often more
troublesome for the patient by producing symptoms such as itching (lupus skin disease usually
does not itch).
The final condition that I will comment upon in this regard is scleroderma.
Scleroderma is a term that just means 'hard skin.' Like lupus, patients having
scleroderma skin changes have a variable risk for having associated damage to
internal organs, especially the kidneys and lungs. Some patients develop a form
of scleroderma that never goes on to cause damage to internal organs. This form
of the disease is called localized scleroderma or morphea. However, other patients
with scleroderma do develop internal complications relatively soon after the
onset of skin problems. I am often asked how one can distinguish between these
two forms of scleroderma at the bedside. A simple rule of thumb is that patients
having scleroderma who are also at risk for developing internal complications
usually have their disease start with Raynaud's phenomenon, whereas, patients
with the localized form of scleroderma or morphea that only causes skin problems
do not develop Raynaud's phenomenon. Raynaud's phenomenon is a condition resulting
from temporary decrease in the flow of blood to the fingertips and toe tips, and
sometimes even the tips of the ears and tip of the nose. This decreased blood
flow pattern often is triggered by exposure to cold temperatures or when experiencing
stressful situations. Patients often initially notice pain in their fingertips,
followed by discoloration in those areas. The classical combination of color
changes in Raynaud's phenomenon is initially a blanching or whitening of the
fingertips, followed by a bluish discoloration of the fingertips, followed by
redness in these areas.
What is a sed rate test, and what is the reference range for testing?
The sed rate is a non-specific test that, when abnormal, indicates generalized
inflammation somewhere in the body from virtually any cause. The test is done
by measuring the rate of sedimentation (or falling) of the red blood cells to
the bottom of a tube when a sample of blood is placed in an upright position.
The rate at which the blood cells fall is a general reflection of protein changes
in the blood that occur as a result of inflammation in the body. Of course,
inflammation is present in many of the arthritis-associated diseases since arthritis
literally means "inflammation in the joints." The sed rate can be done in one
of several ways. However, values lower than 25 mm per hour generally do not
reflect significant systemic inflammation.
Some rheumatic diseases produce greater abnormalities in the sed rate than
others. In patients having systemic lupus that is very active internally, the
sed rate can be very high, 50 mm and above. Another rheumatic disease in which
very high sed rates can be seen, sometimes above 100 mm per hour, is a condition
called "temporal arteritis" that is often associated with another condition called
"polymyalgia rheumatica." These patients have a condition that causes inflammation
in the walls of the blood vessels, particularly the larger arteries near the
surface of the skin in the temporal areas of the forehead and scalp. Damage
to these blood vessels generally shows itself initially as very severe headaches.
Overt skin changes occur only occasionally in this condition and, when present,
generally consist of ulceration of skin of the scalp. Patients who have temporal
arteritis can develop a great deal of pain and stiffness in their shoulders
and upper trunk as a result of the associated condition polymyalgia rheumatica.
It is very important that temporal arteritis is recognized early since delay
in treatment can result in devastating complications such as stroke or blockage
of the artery that supplies the retina layer in the eye resulting in blindness.