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Lymphland International Lymphedema Online
| Morgellons disease: Managing a mysterious skin condition Morgellons disease is mysterious and controversial. Here you'll find answers to common questions about Morgellons disease and suggestions for coping with it. Morgellons disease is a mysterious skin disorder characterized by disfiguring sores and crawling sensations on and under the skin. Although Morgellons disease isn't widely recognized as a medical diagnosis, experts from the Centers for Disease Control and Prevention (CDC) are investigating reports of the condition. If you suspect that you have Morgellons disease, you may have many questions about the condition. Here's what you need to know about Morgellons disease, including practical tips for managing your signs and symptoms. What are the signs and symptoms of Morgellons disease? According to the Morgellons Research Foundation, primary signs and symptoms of Morgellons disease include: Skin lesions, often accompanied by pain or intense itching Fibers which may be white, blue, red or black in and on the lesions Crawling sensations on and under the skin, often compared to insects moving, stinging or biting Joint and muscle pain Fatigue significant enough to interfere with daily activity Inability to concentrate and difficulty with short-term memory Behavioral changes Other signs and symptoms may include: Changes in vision Stomach pain or other gastrointestinal symptoms Changes in skin texture and color Morgellons disease shares characteristics with various recognized conditions, including attention-deficit disorder, chronic fatigue syndrome, Lyme disease, obsessive-compulsive disorder and a mental illness involving false beliefs about infestation by parasites (delusional parasitosis). How long has Morgellons disease been around? In 1674, English physician and writer Sir Thomas Browne used the term "Morgellons disease" to describe "black hairs" emerging from childhood skin lesions. Today, the Morgellons Research Foundation doesn't claim that the disorder described by Browne is the same as Morgellons disease. Rather, the foundation adopted the term as a convenient label for a set of signs and symptoms. How widespread is Morgellons disease? Reports of Morgellons disease have been made in every state in the United States and various countries around the world. Most reported cases are clustered in California, Texas and Florida. What do researchers know about Morgellons disease? Beyond anecdotal reports, researchers know little about Morgellons disease. The Morgellons Research Foundation reports no known causes of Morgellons disease and no successful treatment for the condition. Whether Morgellons disease is contagious remains a mystery. How controversial is Morgellons disease? Current attitudes toward Morgellons disease fall into various categories: Some health professionals believe that Morgellons disease is a specific condition likely to be confirmed by future research. Some health professionals believe that signs and symptoms of Morgellons disease are caused by another condition, often mental illness. Other health professionals don't acknowledge Morgellons disease or are reserving judgment until more is known about the condition. Some people who suspect Morgellons disease claim they've been ignored, criticized as delusional or dismissed as fakers. In contrast, some doctors say that people who report signs and symptoms of Morgellons disease typically resist other explanations for their condition. How can you cope with the signs and symptoms of Morgellons disease? The signs and symptoms linked to Morgellons disease can be distressing. Even though health professionals disagree about the nature of the condition, you deserve compassionate treatment. While research continues, take positive steps to manage your signs and symptoms. Establish a caring health care team. Find a doctor who acknowledges your concerns and does a thorough examination. Since Morgellons disease often requires frequent follow-up visits, a local health care team may be most convenient. Be patient. Your doctor will likely look for known conditions that point to evidence-based treatments before considering a diagnosis of Morgellons disease. Keep an open mind. Consider various causes for your signs and symptoms, and follow your doctor's recommendations for treatment which may include long-term mental health therapy. Seek treatment for other conditions. Get treatment for anxiety, depression or any other condition that affects your thinking, moods or behavior. Keep track of the latest news about Morgellons disease. Supplement the information you find online with articles published in peer-reviewed medical journals. Remember that some sources are more reputable than are others. RELATED Web Resources http://www.mayoclinic.com/health/morgellons-disease/SN00043 Centers for Disease Control and Prevention -------------------------------------------- http://www.healthatoz.com/healthatoz/Atoz/common/standard/transform.jsp? requestURI=/healthatoz/Atoz/ency/lymphadenitis.jsp Lymphadenitis is the inflammation of a lymph node. It is often a complication of a bacterial infection of a wound, although it can also be caused by viruses or other disease agents. Lymphadenitis may be either generalized, involving a number of lymph nodes; or limited to a few nodes in the area of a localized infection. Lymphadenitis is sometimes accompanied by lymphangitis, which is the inflammation of the lymphatic vessels that connect the lymph nodes. Description Lymphadenitis is marked by swollen lymph nodes that are painful, in most cases, when the doctor touches them. If the lymphadenitis is related to an infected wound, the skin over the nodes may be red and warm to the touch. If the lymphatic vessels are also infected, there will be red streaks extending from the wound in the direction of the lymph nodes. In most cases, the infectious organisms are hemolytic Streptococci or Staphylococci. Hemolytic means that the bacteria produce a toxin that destroys red blood cells. The extensive network of lymphatic vessels throughout the body and their relation to the lymph nodes helps to explain why bacterial infection of the nodes can spread rapidly to or from other parts of the body. Lymphadenitis in children often occurs in the neck area because these lymph nodes are close to the ears and throat, which are frequent locations of bacterial infections in children. Causes and symptoms Streptococcal and staphylococcal bacteria are the most common causes of lymphadenitis, although viruses, protozoa, rickettsiae, fungi, and the tuberculosis bacillus can also infect the lymph nodes. Diseases or disorders that involve lymph nodes in specific areas of the body include rabbit fever (tularemia), cat-scratch disease, lymphogranuloma venereum, chancroid, genital herpes, infected acne, dental abscesses, and bubonic plague. In children, tonsillitis or bacterial sore throats are the most common causes of lymphadenitis in the neck area. Diseases that involve lymph nodes throughout the body include mononucleosis, cytomegalovirus infection, toxoplasmosis, and brucellosis. The early symptoms of lymphadenitis are swelling of the nodes caused by a buildup of tissue fluid and an increased number of white blood cells resulting from the body's response to the infection. Further developments include fever, often as high as 101-102°F (38-39°C) together with chills, loss of appetite, heavy perspiration, a rapid pulse, and general weakness. Diagnosis Physical examination The diagnosis of lymphadenitis is usually based on a combination of the patient's history, the external symptoms, and laboratory cultures. The doctor will press (palpate) the affected lymph nodes to see if they are sore or tender. Swollen nodes without soreness are often caused by cat-scratch disease. In children, the doctor will need to rule out mumps, tumors in the neck region, and congenital cysts that resemble swollen lymph nodes. Although lymphadenitis is usually diagnosed in lymph nodes in the neck, arms, or legs, it can also occur in lymph nodes in the chest or abdomen. If the patient has acutely swollen lymph nodes in the groin, the doctor will need to rule out a hernia in the groin that has failed to reduce (incarcerated inguinal hernia). Hernias occur in 1% of the general population; 85% of patients with hernias are male. Laboratory tests The most significant tests are a white blood cell count (WBC) and a blood culture to identify the organism. A high proportion of immature white blood cells indicates a bacterial infection. Blood cultures may be positive, most often for a species of staphylococcus or streptococcus. In some cases, the doctor may order a biopsy of the lymph node. Treatment Medications The medications given for lymphadenitis vary according to the bacterium or virus that is causing it. If the patient also has lymphangitis, he or she will be treated with antibiotics, usually penicillin G (Pfizerpen, Pentids), nafcillin (Nafcil, Unipen), or cephalosporins. Erythromycin (Eryc, E-Mycin, Erythrocin) is given to patients who are allergic to penicillin. Supportive care Supportive care of lymphadenitis includes resting the affected limb and treating the area with hot moist compresses. Surgery Cellulitis associated with lymphadenitis should not be treated surgically because of the risk of spreading the infection. Pus is drained only if there is an abscess and usually after the patient has been started on antibiotic treatment. In some cases, a biopsy of an inflamed lymph node is necessary if no diagnosis has been made and no response to treatment has occurred. Prognosis The prognosis for recovery is good if the patient is treated promptly with antibiotics. In most cases, the infection can be brought under control in three or four days. Patients with untreated lymphadenitis may develop blood poisoning (septicemia), which is sometimes fatal. Prevention Prevention of lymphadenitis depends on prompt treatment of bacterial and viral infections. Key Terms Hemolytic Able to break down or dissolve red blood cells. The bacteria that cause lymphadenitis are hemolytic. Hernia The bulging of a part of the intestine or other organ through its surrounding wall of tissue. Most hernias are in the abdominal cavity. An inguinal hernia is located in the groin area. Lymph nodes The glandlike masses of tissue in the lymphatic system that contain lymphocytes. The lymph nodes also filter lymph, which is a clear yellowish tissue fluid that carries lymphocytes and fats throughout the body. Lymphangitis Inflammation of the lymphatic vessels. It often occurs together with lymphadenitis. Septicemia The presence of bacteria and their toxins in the bloodstream. Septicemia is sometimes called blood poisoning. For Your Information McPhee, Stephen, et al., editors. "Blood Vessels & Lymphatics." In Current Medical Diagnosis and Treatment, 1998. 37th ed. Stamford: Appleton & Lange, 1997. ------------------------------------------------------ What Is Sarcoidosis? Sarcoidosis (sar"koi-do'sis) involves inflammation that produces tiny lumps of cells in various organs in your body. The lumps are called granulomas (gran"u-lo'mahs) because they look like grains of sugar or sand. They are very small and can be seen only with a microscope. These tiny granulomas can grow and clump together, making many large and small groups of lumps. If many granulomas form in an organ, they can affect how the organ works. This can cause symptoms of sarcoidosis. Sarcoidosis can occur in almost any part of your body, although it usually affects some organs more than others. It usually starts in one of two places: Lungs Lymph nodes, especially the lymph nodes in your chest cavity. Sarcoidosis also often affects your: Skin Eyes Liver. Less often, sarcoidosis affects your: Spleen Brain Nerves Heart Tear glands Salivary glands Bones and joints. Rarely, sarcoidosis affects other organs, including your: Thyroid gland Breasts Kidneys Reproductive organs. Sarcoidosis almost always occurs in more than one organ at a time. Sarcoidosis has an active and a nonactive phase: In the active phase, the granulomas form and grow. In this phase, symptoms can develop, and scar tissue can form in the organs where the granulomas occur. In the nonactive phase, the inflammation goes down, and the granulomas stay the same size or shrink. But the scars may remain and cause symptoms. The course of the disease varies greatly among people. In many people, sarcoidosis is mild. The inflammation that causes the granulomas may get better on its own. The granulomas may stop growing or shrink. Symptoms may go away within a few years. In some people, the inflammation remains but doesn't get worse. You may also have symptoms or flare-ups and need treatment every now and then. In other people, sarcoidosis slowly gets worse over the years and can cause permanent organ damage. Although treatment can help, sarcoidosis may leave scar tissue in the lungs, skin, eyes, or other organs. The scar tissue can affect how the organs work. Treatment usually does not affect scar tissue. Changes in sarcoidosis usually occur slowly (e.g., over months). Sarcoidosis does not usually cause sudden illness. However, some symptoms may occur suddenly. They include: Disturbed heart rhythms Arthritis in the ankles Eye symptoms. In some serious cases in which vital organs are affected, sarcoidosis can result in death. Sarcoidosis is not a form of cancer. There is no known way to prevent sarcoidosis. Sarcoidosis was once thought to be an uncommon condition. It's now known to affect tens of thousands of people throughout the United States. Because many people who have sarcoidosis have no symptoms, it's hard to know how many people have the condition. Sarcoidosis was identified in the late 1860s. Since then, scientists have developed better tests to diagnose it and made advances in treating it. The cause of sarcoidosis is not known. And, there may be more than one thing that causes it. Scientists think that sarcoidosis develops when your immune system responds to something in the environment (e. g., bacteria, viruses, dust, chemicals) or perhaps to your own body tissue (autoimmunity). Normally, your immune system defends your body against things that it sees as foreign and harmful. It does this by sending special cells to the organs that are being affected by these things. These cells release chemicals that produce inflammation around the foreign substance or substances to isolate and destroy them. In sarcoidosis, this inflammation remains and leads to the development of granulomas or lumps. Scientists have not yet identified the specific substance or substances that trigger the immune system response in the first place. They also think that sarcoidosis develops only if you have inherited a certain combination of genes. You can't catch sarcoidosis from someone who has it. More research is needed to discover what causes sarcoidosis. Sarcoidosis affects people of all ages and races worldwide. It occurs mostly in: Adults between the ages of 20 and 40 African Americans (especially women) People of Asian, German, Irish, Puerto Rican, and Scandinavian origin. In the United States, sarcoidosis affects African Americans somewhat more often and more severely than Caucasians. Studies have shown that sarcoidosis is more likely to affect certain organs in certain populations. For example, Sarcoidosis of the heart and eye appears to be more common in Japan. Painful skin lumps on the legs occur more often in people from Northern Europe. People who are more likely to get sarcoidosis include: Health care workers Nonsmokers Elementary and secondary school teachers People exposed to agricultural dust, insecticides, pesticides, or mold Firefighters. Brothers and sisters, parents, and children of people who have sarcoidosis are more likely than others to have sarcoidosis. What Are the Signs and Symptoms of Sarcoidosis? Many people who have sarcoidosis have no symptoms. Often, the condition is discovered by accident only because a person has a chest x ray for another reason, such as a pre-employment x ray. Some people have very few symptoms, but others have many. Symptoms usually depend on which organs the disease affects. Lung Symptoms Shortness of breath A dry cough that doesn't bring up phlegm (flem), or mucus Wheezing Pain in the middle of your chest that gets worse when you breathe deeply or cough (rare). Lymph Node Symptoms Enlarged and sometimes tender lymph nodes—most often those in your neck and chest but sometimes those under your chin, in your arm pits, or in your groin. Skin Symptoms Various types of bumps, ulcers, or, rarely, flat areas of discolored skin, that appear mostly near your nose, eyes, back, arms, legs, and scalp. They usually itch but aren't painful. They usually last a long time. Painful bumps that usually appear on your ankles and shins and can be warm, tender, red or purple-to-red in color, and slightly raised. This is called erythema nodosum (er"i-the'mah nodo'sum). You may have fever and swollen ankles and joint pain along with the bumps. The bumps often are an early sign of sarcoidosis, but they occur in other diseases too. The bumps usually go away in weeks to months, even without treatment. Disfiguring skin sores that may affect your nose, nasal passages, cheeks, ears, eyelids, and fingers. This is called lupus pernio (loo'pus per'nio). The sores tend to be ongoing and can return after treatment is over. Eye Symptoms Burning, itching, tearing, pain Red eye Sensitivity to light Dryness Floaters (i.e., seeing black spots) Blurred vision Reduced color vision Reduced visual clearness Blindness (in rare cases). Heart Symptoms Shortness of breath Swelling in your legs Wheezing Coughing Irregular heartbeat, including palpitations (a fluttering feeling of rapid heartbeats) and skipped beats Sudden loss of consciousness Sudden death. Joint and Muscle Symptoms Joint stiffness or swelling—usually in your ankles, feet, and hands. Joint pain. Muscle aches (myalgias). Muscle pain, a mass in a muscle, or muscle weakness. Painful arthritis in your ankles that results from erythema nodosum. It may need treatment but usually clears up in several weeks. Painless arthritis that can last for months or even years. It should be treated. Bone Symptoms Painless holes in your bones. Painless swelling, most often in your fingers. Anemia that results from granulomas affecting your bone marrow. This usually should be treated. Liver Symptoms Fever Fatigue Itching Pain in the upper right part of your abdomen, under the right ribs Enlarged liver. Parotid (pah-rot'id) and Other Salivary Gland Symptoms Swelling, which makes your cheeks look puffy Excessive dryness in your mouth and throat. Blood, Urinary Tract, and Kidney Symptoms Increased calcium in your blood or urine, which can lead to painful kidney stones Confusion Increased urination. Nervous System Symptoms Headaches. Vision problems. Weakness or numbness of an arm or leg. Coma (rare). Drooping of one side of your face that results from sarcoidosis affecting a facial nerve. This can be confused with Bell's palsy, a disorder that may be caused by a virus. Paralysis of your arms or legs that results from sarcoidosis affecting your spinal cord. Weakness, pain, or a "stinging needles" sensation in areas where many nerves are affected by sarcoidosis. Pituitary (pi-tu'i-tar"e) Gland Symptoms (Rare) Headaches Vision problems Weakness or numbness of an arm or leg Coma (rare). Other Symptoms Nasal obstruction or frequent bouts of sinusitis. Enlarged spleen, which leads to a decrease in platelets in your blood and pain in your upper left abdomen. Platelets are needed to help your blood clot. Sarcoidosis may also cause more general symptoms, including: Uneasiness, feeling sick (malaise), an overall feeling of ill health Tiredness, fatigue, weakness Loss of appetite or weight Fever Night sweats Sleep problems These general symptoms are often caused by other conditions. If you have these general symptoms but don't have symptoms from affected organs, you probably do not have sarcoidosis. How Is Sarcoidosis Diagnosed? Your doctor will find out if you have sarcoidosis by taking a detailed medical history and conducting a physical exam and several diagnostic tests. The purpose is to: Identify the presence of granulomas in any of your organs Rule out other causes of your symptoms Determine the amount of damage to any of your affected organs Determine whether you need treatment. Medical History Your doctor will ask you for a detailed medical history. He or she will want to know about any family history of sarcoidosis and what jobs you have had that may have increased your chances of getting sarcoidosis. Your doctor may also ask whether you have ever been exposed to inhaled beryllium metal, which is used in aircraft and weapons manufacture, or organic dust from birds or hay. These things can produce granulomas in your lungs that look like the granulomas that are caused by sarcoidosis but are actually signs of other conditions. Physical Exam Your doctor will look for symptoms of sarcoidosis, such as red bumps on your skin; swollen lymph nodes; an enlarged liver, spleen, or salivary gland(s); or redness in your eyes. He or she will also listen for abnormal lung sounds or heart rhythm. Your doctor also will check for other likely causes of your symptoms. Diagnostic Tests There is no one specific test for diagnosing sarcoidosis. It is harder to diagnose sarcoidosis in some organs (e.g., heart, nervous system) than in others. Your doctor will probably conduct a variety of tests and procedures to help in the diagnosis. These include: Chest X Ray. A chest x ray takes a picture of your heart and lungs. It may show granulomas or enlarged lymph nodes in your chest. About 95 out of every 100 people who have sarcoidosis have an abnormal chest x ray. Doctors usually use a staging system for chest x rays taken to detect sarcoidosis: Stage 0: Normal chest x ray Stage 1: Chest x ray showing enlarged lymph nodes but otherwise clear lungs Stage 2: Chest x ray showing enlarged lymph nodes and shadows in your lungs Stage 3: Chest x ray showing shadows in your lungs, but the lymph nodes are not enlarged Stage 4: Chest x ray showing scars in the lung tissue. In general, the higher the stage of the x ray, the worse your symptoms and lung function are. But there are a lot of differences among people. If your x-ray results show Stages 0, 1, 2, or 3, you may not have symptoms or need treatment, and you may get better and have normal chest x rays again over time. Blood Tests. These tests can show the number and type of cells in your blood. They also will show whether there are increases in your calcium levels or changes in your liver, kidney, and bone marrow that can occur with sarcoidosis. Lung Function Tests. One test uses a spirometer (spi-rom'e-ter), a device that measures how much and how fast you can blow air out of your lungs after taking a deep breath. If there is a lot of inflammation and/or scarring in your lungs, you will not be able to move normal amounts of air in and out. Another test measures how much air your lungs can hold. Sarcoidosis can cause your lungs to shrink, and they will not be able to hold as much air as healthy lungs. Electrocardiogram (EKG). This test will help show if your heart is affected by sarcoidosis. Pulse Oximetry. A small clip attached to your finger tip can show how well your heart and lungs are moving oxygen into your blood. Arterial Blood Gas Test. This test is more accurate than pulse oximetry for checking the level of oxygen in your bloodstream. Blood is taken from an artery (usually in your wrist). It is then analyzed for its oxygen and carbon dioxide levels. Fiberoptic Bronchoscopy. In this procedure, your doctor inserts a long, narrow, flexible tube with a light on the end through your nose or mouth into your lungs to look at your airways. This tube is called a bronchoscope. You most likely would have this procedure as an outpatient in a hospital under local anesthesia. Bronchoalveolar Lavage (brong"ko-al-ve'o-lar lah-vaje') (BAL). During bronchoscopy, your doctor may inject a small amount of salt water (saline) through the bronchoscope into your lungs. This fluid washes the lungs and helps bring up cells and other material from the air sacs deep in your lungs where the inflammation usually starts to develop. The cells and fluid are then examined for signs of inflammation. Biopsy. Your doctor may take a small sample of tissue from one of your affected organs. For example, when breathing tests or chest x rays show signs of sarcoidosis in your lungs, your doctor may do a fiberoptic bronchoscopy biopsy. This will help confirm the diagnosis. Your doctor inserts a tiny forceps through the bronchoscope to collect tissue that will be examined. Because the granulomas may be spread out in your lungs, the bronchoscope may miss some of them. Biopsies of your skin and liver are sometimes done to detect granulomas in these organs. You may have sarcoidosis in other organs as well and multiple biopsies may be necessary. However, every organ involved does not need to be biopsied for a diagnosis to be made. Computerized Tomography (CT) Scan. This test provides a computer-generated image of your organs that has more detail than a regular chest x ray. It can provide more information about how sarcoidosis has affected an organ. Your doctor may do a CT scan to: Obtain more information about how much of your lung is affected by sarcoidosis. Detect sarcoidosis in your liver. A CT scan of your abdomen will show if your liver is enlarged and if there is a pattern suggesting granulomas. Magnetic Resonance (MR) Scan. This test is also called nuclear magnetic resonance (NMR) scanning or magnetic resonance imaging (MRI). This scan uses powerful magnets and radio waves to make images of some of your organs that your doctor doesn't want to risk doing a biopsy on. For example, an MR scan can be used to diagnose sarcoidosis in your brain, spinal cord, nerves, or heart. Thallium and Gallium Scans. These scans are often done to see if sarcoidosis is affecting your heart. Thallium and gallium are radioactive elements. Your doctor injects a small amount of one of them into a vein in your arm. The elements collect at places in your body where there is inflammation. After awhile, your body is scanned for radioactivity. Increased radioactivity at any place may be a sign of inflammation. This test gives information on the tissue in your body that has been affected by sarcoidosis and the amount of damage to it. But since this test shows all inflammation in your body, even inflammation caused by conditions other than sarcoidosis, it does not give a definite diagnosis of sarcoidosis. Positron Emission Tomography (PET) Scan. This test also uses radioactive injections. It may be more sensitive than gallium in detecting areas of inflammation. Some doctors are using it instead of gallium scans. Your doctor may not need to find every one of your organs affected by sarcoidosis, only those that cause symptoms. Often the organs affected by the condition continue to function well and don't need to be treated. How Is Sarcoidosis Treated? The goals of treatment are to: Improve how the organs affected by sarcoidosis work Relieve symptoms Shrink the granulomas. Treatment may shrink the granulomas and even cause them to disappear, but this may take many months. If scars have formed, treatment may not help, and you may have ongoing symptoms. Your treatment depends on: What symptoms you have How severe your symptoms are Whether any of your vital organs (e.g., your lungs, eyes, heart, or brain) are affected How the organ is affected. Some organs must be treated, regardless of your symptoms. Others may not need to be treated. Usually, if you don't have symptoms, you don't need treatment, and you probably will recover in time. Drugs The main treatment for sarcoidosis is prednisone. Prednisone is a corticosteroid, or anti-inflammatory drug. Sometimes it is used with other drugs. Sometimes other corticosteroids are used. Prednisone almost always relieves symptoms of inflammation. If a symptom doesn't improve with prednisone treatment within a couple of months, consult your physician. Prednisone is usually given for many months, sometimes for a year or more. Low doses of prednisone can often relieve symptoms without causing major side effects. When used at high doses, prednisone can cause serious side effects. Side effects can include: Weight gain. Diabetes. High blood pressure. Mood swings (depression). Difficulty sleeping at night. Heartburn. Acne. Thinning of the skin and bones (called osteoporosis). Cataracts. Glaucoma. Adrenal gland insufficiency, which occurs when these glands don't make enough of certain hormones. This requires treatment by an endocrinologist (en"do-kri-nol'o-jist), a doctor who specializes in the diagnosis and treatment of the endocrine glands. The endocrine glands include your adrenal and pituitary glands. Aseptic (a-sep'tik) or avascular (ah-vas'ku-lar) necrosis (ne-kro'sis) of the hip, the development of cysts and hardened and dead tissue in the hip. Your doctor can usually help you manage these side effects. When it is time to stop taking prednisone, you should cut back slowly, with your doctor's help. This will help prevent flare-ups of sarcoidosis and allow your body to adjust to life without the drug. You may also want to see an endocrinologist to make sure that your endocrine glands are making enough hormones. The endocrinologist may prescribe certain hormones for you to take until your endocrine glands are working well again. Other Drugs Used To Treat Sarcoidosis Other drugs are sometimes used to treat sarcoidosis. Your doctor may prescribe one of them if: Your condition gets worse while you are taking prednisone You can't stand the side effects of prednisone. Most of these other drugs are immune system suppressants. This means that they prevent your immune system from fighting things like bacteria and viruses. As a result, you may have a greater chance of getting infections. Most of these drugs also can cause serious side effects. Some also could increase your chances of getting cancer, especially if you take them at high doses. You and your doctor must weigh living with the symptoms of sarcoidosis against the side effects of the drugs. Some drugs work better than others for different people. You may be given more than one drug. Some drugs used to treat sarcoidosis are taken by mouth. Others are applied locally to an affected area. Local therapy is the safest way to treat sarcoidosis. The drug is applied directly to the affected area. As a result, only small amounts of the drug reach other parts of your body. Drugs used for local therapy include: Eye drops Inhaled drugs for your lungs Skin creams. Drugs can be used locally only if the affected area is easily reached. For instance, inhaled steroids can ease coughing and wheezing in the upper airways, but they don't seem to relieve these symptoms when the affected lung tissue is deep within your chest. Talk with your doctor about these treatments and the side effects that may occur. The other drugs used to treat sarcoidosis include: Hydroxychloroquine (Plaquenil). This drug can usually help people who have sarcoidosis in the skin or a high level of calcium in their blood. This drug can irritate your stomach. It also can cause eye problems. Before starting on this drug, you should see an ophthalmologist (of"thal-mol'o- jist), or eye doctor, for some baseline tests. Once you start taking it, you should have your eyes examined every 6 months. Methotrexate. This drug is taken once a week by mouth or injection and usually takes up to 6 months to relieve symptoms. This drug may cause side effects, especially if you take high doses. These include: Nausea. Mouth sores. A decrease in infection-fighting white blood cells. You then have a greater chance of getting an infection. If you take this drug, you should have regular blood tests to check the levels of your white blood cells. An allergic reaction in your lungs that goes away when you stop taking the drug. This is extremely rare. Liver damage. This is the most serious side effect. If you take methotrexate you should be followed regularly by your physician. If you are pregnant, you should not take this drug. Taking folic acid can help you reduce your chances of having bad side effects from methotrexate. Azathioprine (Imuran). This drug may work in about half of the people who have sarcoidosis. You usually take it for at least 6 months. Side effects include: Nausea Reduced white blood cell levels, which increases your chances of getting an infection. This drug has caused cancer in some people, especially when they have taken it at high doses. If you are pregnant, you should not take this drug. Cyclophosphamide (Cytoxan). This is a very toxic drug. It is rarely used to treat sarcoidosis. It is given only to people who have serious forms of sarcoidosis, such as sarcoidosis in their central nervous system (neurosarcoidosis). This drug is more likely to cause nausea and reduce your white blood cell levels than either methotrexate or azathioprine. Your doctor should check your white blood cell levels often while you are taking this drug to make sure you have a high enough level to fight infection. Cyclophosphamide can also irritate your bladder. Some people who have taken it for more than 2 years have developed bladder cancer. If you are pregnant, you should not take this drug. Cyclophosphamide can be given intravenously (through one of your veins), which lessens some of its side effects, but this doesn't reduce the risk of cancer. Treatments for Specific Types of Sarcoidosis Eyes. Sarcoidosis in your eyes almost always responds well to treatment. Often, the only treatment you need is eye drops containing corticosteroids. You should have yearly eye exams, even if you think your eyes are doing well. Spleen. Sarcoidosis can cause your spleen to become larger. This can lead to a decrease in your red or white blood cells or platelets and increase your chances of infection and blood clotting disorders. Treatment is usually given to increase the number of your blood cells and ease your pain. In rare cases, your spleen may need to be removed. Liver. Sarcoidosis rarely causes permanent liver damage. As a result, your liver usually isn't treated unless it's causing major symptoms (e.g., fever). Drug treatment can usually reduce granulomas in your liver. Liver transplantation has been successful in those rare cases in which the condition has become worse. Followup care includes regular blood tests to find out how well your liver is working. You should check with your doctor to find out how often you need these tests. Nervous system. Sarcoidosis in your nervous system (neurosarcoidosis) usually needs treatment. Nerve tissue heals slowly, so treatment often takes a long time. You may need to take several drugs at high doses. Erythema nodosum. These painful bumps on your shins often go away in weeks to months without treatment. Your doctor probably will not give you medication unless you are very uncomfortable. Aspirin or ibuprofen, an anti-inflammatory drug that you can buy without a prescription, will usually help. Heart. Sarcoidosis in your heart is usually treated with steroids. You may also be given heart drugs to improve your heart's pumping ability or to correct a disturbed heart rhythm. If you have a severe heart rhythm disturbance, your doctor may prescribe one of these devices: A cardiac pacemaker, a small battery-operated device, often put under your skin, that regulates your heartbeat A defibrillator, an implanted device that shocks your heart into a normal heartbeat or, if it has stopped, into beating. If your heart is severely affected and doesn't respond to treatment, a transplant may be done. But this is rarely needed. Lupus Pernio. This rash on your face, especially your cheeks and nose, can be distressing because it's in a very visible area. It often occurs with loss of your sense of smell, nasal stuffiness, and sinus infections. Options for treatment include: Local treatment with skin creams Oral drugs (plaquenil or prednisone, for example) Local injections of steroid preparations. Lupus pernio is often treated by dermatologists, doctors who specialize in skin diseases, working with a sarcoidosis specialist. Because sarcoidosis varies so much among different people, your doctor may find it hard to tell whether the treatment is helping. Other Drugs Being Studied for Possible Use in Treating Sarcoidosis Scientists also are studying drugs that are used for other conditions to see if they can help people who have sarcoidosis. These drugs include: Etanercept (Enbrel). This drug is an immune system suppressant. It's injected under the skin to reduce symptoms of rheumatoid arthritis. It may also be used to treat psoriasis (so-ri'ah-sis) or ankylosing spondylitis (ang"ki-lo'sing spon"di-li'tis), a type of arthritis that affects the joints in the spine. Early studies suggest that it will not be useful in treating sarcoidosis, but research is ongoing. Infliximab (Remicaide). This drug is an immune system suppressant. It's injected into a vein in your arm. It's used to treat Crohn's Disease, rheumatoid arthritis, and ankylosing spondylitis. Some studies have shown it to help sarcoidosis patients who also have lupus pernio, eye disease, or neurosarcoidosis. This drug has serious side effects but may improve lung function in some people who aren't helped by corticosteroids. More research is needed. Pentoxifylline. This drug is an immune system suppressant. Stomach and gastrointestinal side effects are common. Early studies show that it has helped some people who have sarcoidosis in their lungs reduce their doses of prednisone while taking it. More research is needed. Tetracycline. Tetracycline antibiotics are used to treat Lyme Disease, some types of pneumonia, and acne. A few small studies suggest that they may help in treating sarcoidosis in the skin. Research is ongoing. Thalidomide. This immune system suppressant can cause bad side effects. It is effective against other conditions that involve granulomas of the skin (e.g., leprosy, tuberculosis). Scientists are studying this drug to see if it can be used to treat sarcoidosis in the skin. More studies are needed. What Does the Future Hold? Scientists worldwide are trying to learn more about sarcoidosis and how to improve its diagnosis and treatment. Some recent studies have led to possible new treatments, which, in turn, are being studied. Current research includes studies of: The agent or agents that cause sarcoidosis Why sarcoidosis seems to act differently in people of different races Why sarcoidosis appears in some families How genes, passed from one generation to another, may make some people more likely than others to develop sarcoidosis How cells act and communicate with each other to cause sarcoidosis symptoms. Living With Sarcoidosis You should take steps to stay healthy. This includes: Don't smoke. Avoid substances like dusts and chemicals that can harm your lungs. Try to follow a healthy eating plan. Be as active as you can but don't strain yourself. Joining a patient support group may help you adjust to living with sarcoidosis. Talking to others who have the same symptoms can help you see how they have coped with them. To find a local support group, check your telephone directory or contact one of the sarcoidosis groups listed under Links. Your regular doctor may be able to diagnose and treat your sarcoidosis, but diagnosis and treatment by a doctor who specializes in sarcoidosis is recommended. If you prefer to use your regular doctor, you should see a doctor who specializes in the organs that are affected by your sarcoidosis at least once. For example, see an ophthalmologist if your eyes are affected or a pulmonologist if you have sarcoidosis in your lungs. These specialists are often found at major medical centers. They will work with your regular doctor to help make a diagnosis, develop a treatment plan, and schedule periodic exams and lab tests. . Pregnancy Many women give birth to healthy babies while being treated for sarcoidosis. Pregnancy usually doesn't affect the course of sarcoidosis, and you can continue corticosteroid treatment through your pregnancy. None of the other drugs are recommended for use during pregnancy. Sometimes your sarcoidosis may get worse after the baby is delivered. Women with severe sarcoidosis, especially if they are older, may have trouble becoming pregnant. It's important for you to discuss this issue with your doctor. If you become pregnant, you should be sure to get both good prenatal care and regular sarcoidosis checkups during and after pregnancy. Followup Care Regular followup care is important, even if you aren't taking medication for your sarcoidosis. New symptoms can occur at any time, and your condition can get worse slowly, without your noticing. Followup exams usually include: A review of your symptoms A physical exam A chest x ray and CT scan Breathing tests An eye exam Blood tests An electrocardiogram (EKG). How often you have your examinations and tests depends on: How severe your symptoms are Which organs were affected at diagnosis What treatment you are using Any complications that may develop during treatment. You will probably need routine followup care for several years. Whether you see your regular doctor or a sarcoidosis specialist for this depends on your symptoms during the first year of followup. Here are some examples of how your followup care can be managed. They are based on either your condition when you were diagnosed with sarcoidosis or the treatment used. Followup After Initial Diagnosis If at diagnosis, you have no symptoms, a normal breathing test, and an abnormal chest x ray: You should plan on having a followup exam every 6 to12 months until your condition is stable or improving. Your breathing test may need to be repeated. The need to repeat it depends on your symptoms and ability to be active. If at your first followup visit, you have no new symptoms and your chest x ray is normal, you can go to your regular doctor for future followup care. If at diagnosis, you have some symptoms, an abnormal chest x ray, but you don't need treatment: You should plan on having a followup exam in 3 to 6 months. If at your followup exam, your condition has gotten worse (i.e., you now have more symptoms, an abnormal x ray, or abnormal lab tests) you may need treatment. If treatment is started, you may need followup tests more often. Followup Based on Your Drug Treatment If treatment is begun with prednisone: You should be checked for the side effects of high blood pressure, too much weight gain, diabetes, loss of calcium from your bones, and pain in one or both hips. If treatment is begun with hydroxychloroquine: You should have an eye exam every 6 months while taking this drug. If treatment is begun with methotrexate: You should have blood tests every month or every other month to see if you have anemia, low white blood cell or platelet levels, or liver inflammation. Other Followup Tests Depending on how serious your condition is and what organs are affected, you may also need to have certain tests done regularly. Eye Tests Everyone who is diagnosed with sarcoidosis, even if they don't have eye symptoms, should see an ophthalmologist (eye doctor) for eye tests. This is important because you may have eye damage even if you don't have symptoms. These tests may include: A slit lamp examination. Your doctor uses an instrument with a high-intensity light source to look at the front of your eyes. A visual fields examination. Your doctor will ask you to you to look at a light through an instrument. Inspection of your retina and optic nerve. If you develop eye symptoms, your doctor will have you repeat the tests. You should also have regular eye exams if you are being treated with: Chloroquine or hydroxycholoroquine (Plaquenil) Corticosteroids. Breathing Tests These tests are used to check the course of sarcoidosis in your lungs. The results are compared over time. Blood Tests A blood test for calcium should be done. If your calcium level is high, you probably will need to be treated. You also should not take vitamin and mineral supplements containing calcium or vitamin D, and you should avoid too much exposure to the sun. Electrocardiogram This test is needed to make sure that your heart is still not affected by sarcoidosis. The heart can be affected at any time if the sarcoidosis is active. www.nhlbi.nih.gov/health/dci/Diseases/sarc/sar_whatis.html --------------------------------------------------------- microlymphatic hypertension LYMPHOEDEMA Microlymphatics of human skin. Int J Microcirc Clin Exp. 1993; 12(1):1-15 (ISSN: 0167-6865) Bollinger A Department of Internal Medicine, University Hospital, Zurich, Switzerland. Microlymphatics of human skin form two superposed networks. The superficial one located at the level of dermal papillae may be visualized by fluorescence microlymphography. Microlymphatics fill from a subepidermal depot of minute amounts of FITC-dextran 150,000. In primary lymphedema with late onset the depicted network with vessels of normal size is significantly larger than in healthy controls, whereas in congenital lymphedema (Milroy's disease) microlymphatics are aplastic or ectatic (diameter > 90 microns). Lymphatic microangiopathy with obliterations of microvessels develops in chronic venous insufficiency, in lipedema (preliminary results) and after recurrent erysipelata. In healthy controls microlymphatics are permeable to FITC-dextran 40,000 and impermeable to the larger molecule 150,000. Preserved fragments of the network in chronic venous insufficiency exhibit increased permeability to FITC-dextran 150,000. After visualization of the vessels by the fluorescent dye microlymphatic pressure may be measured by the servo-nulling technique. First results indicate that microlymphatic hypertension contributes to edema formation in patients with primary lymphedema. PreMedline Identifier: 8473066 http://www.ewma.org/pdf/fall05/focus_eng.pdf ---------------- Anti-fibrosclerotic effects of shock wave therapy in lipedema and cellulite. Biofactors. 2005; 24(1-4):275-82 (ISSN: 0951-6433) Siems W; Grune T; Voss P; Brenke R Loges-School of Physiotherapy, Research Institute of Physiotherapy & Gerontology, D-38667 Bad Harzburg, Germany. werner.siems@loges-schule.de In vivo measurements in 26 female patients with lipedema and cellulite parameters were carried out before and after therapy by means of complex physical decongestive therapy (CPDT) including manual lymph drainage and compression as main components and/or shock wave therapy (SWT). Oxidative stress parameters of blood serum and biomechanic skin properties/smoothening of dermis and hypodermis surface were evaluated. Oxidative stress in lipedema and cellulite was demonstrated by increased serum concentrations of malondialdehyde (MDA) and plasma protein carbonyls compared with healthy control persons. Both MDA and protein carbonyls in blood plasma decreased after serial shock wave application and CPDT. The SWT itself and CPDT itself lead to MDA release from edematous tissue into the plasma. Obviously both therapy types, SWT and CPDT, mitigate oxidative stress in lipedema and cellulite. In parallel SWT improved significantly the biomechanic skin properties leading to smoothening of dermis and hypodermis surface. Significant correlation between MDA depletion of edematous and lipid enriched dermis and improvement of mechanic skin properties was demonstrated. From these findings it is concluded, that a release of lipid peroxidation (LPO) products from edematous dermis is an important sclerosis- preventing effect of SWT and/or CPDT in lipedema and cellulite. Expression of factors stimulating angiogenesis and lymphangiogenesis such as VEGF was not induced by SWT and/or CPDT and, therefore, not involved in beneficial effects by SWT and/or CPDT. PreMedline Identifier: 16403988 ----------------------------- Stewart-Treves Syndrome Article Last Updated: Mar 28, 2007 AUTHOR AND EDITOR INFORMATIONSection 1 of 9 Authors and Editors Introduction Clinical Differentials Workup Treatment Follow-up Miscellaneous References Author: Geover Fernandez, MD, FAAD, Staff Physician, Department of Dermatology, University of Medicine and Dentistry New Jersey, New Jersey Medical School Geover Fernandez is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and American Society for MOHS Surgery Coauthor(s): Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School Editors: Abby S Van Voorhees, MD, Assistant Professor, Director of Psoriasis Services and Phototherapy Units, Department of Dermatology, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania; Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center; Christen M Mowad, MD, Assistant Professor, Department of Dermatology, Geisinger Medical Center; Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital; William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System Author and Editor Disclosure Synonyms and related keywords: cutaneous angiosarcoma, postmastectomy angiosarcoma, lymphangiosarcoma in postmastectomy lymphedema, postlymphedema angiosarcoma, hemangiosarcoma in chronic lymphedema, hemangiosarcoma in postmastectomy lymphedema, postmastectomy lymphedema, lymphangiosarcoma, Milroy disease, Milroy's disease, idiopathic lymphedema, congenital lymphedema, traumatic lymphedema, filarial lymphedema INTRODUCTIONSection 2 of 9 Authors and Editors Introduction Clinical Differentials Workup Treatment Follow-up Miscellaneous References Background Stewart-Treves syndrome is a rare, deadly cutaneous angiosarcoma that develops in long-standing chronic lymphedema. Most commonly, this tumor is a result of lymphedema induced by radical mastectomy to treat breast cancer. Unfortunately, although the breast cancer may be cured with such radical surgery, this second primary cancer may be responsible for the patient's worsening course. The term Stewart-Treves syndrome is broadly applied to an angiosarcoma that arises in a chronically lymphedematous region due to any cause, including congenital lymphedema and other causes of secondary lymphedema unassociated with mastectomy. As reported by Durr et al in 2004, this lymphangiosarcoma occurs as a rare complication. Lymphangiosarcoma is a misnomer because this malignancy seems to arise from blood vessels instead of lymphatic vessels. A more appropriate name is hemangiosarcoma. In 1906, Lowenstein first described angiosarcoma in a patient's arm that had been affected by severe posttraumatic lymphedema for 5 years. In 1948, Stewart and Treves reported this rare secondary malignancy in 6 cases of angiosarcoma in postmastectomy lymphedema. They recognized that an edematous arm after radical mastectomy for breast cancer may suggest recurrent breast cancer, but that long-standing chronic edema without recurrent cancer may occasionally produce "a heretofore unrecognized and unreported sequel ... long after the malignant breast neoplasm has apparently been arrested ... a new specific tumor." Stewart and Treves suggested that these angiosarcomas were probably not observed previously because they were mistaken for recurrent, inoperable, cutaneous manifestations of breast cancer. Lymphangiosarcoma has been described in Milroy disease and in idiopathic, congenital, traumatic, or filarial lymphedema. A case of lymphangiosarcoma in hereditary lymphedema of the lower extremity has been reported in a 36-year-old woman. Despite of chemotherapy, local hyperthermia, and later amputation of the extremity, the patient died of progressive disease due to pulmonary metastasis. In respect to this case, the different therapeutic concepts, as reported in the literature, and their results are presented and discussed. Pathophysiology The pathogenic mechanism by which lymphedema may induce angiosarcoma has been the subject of controversy. Stewart and Treves found a high incidence of third malignancies in patients with postmastectomy angiosarcoma. Thus, they speculated that a systemic carcinogenic factor was the main causative factor in the pathogenesis of lymphangiosarcomas. In 1979, Schreiber and others postulated the concept of local immunodeficiency in the presence of lymphedema. This theory is supported by experimental evidence. In 1960, Stark and associates demonstrated that homograft skin transplanted to lymphedematous arms survive much longer than those transplanted to healthy arms. Therefore, lymphedema may cause some degree of local immunodeficiency and lead to oncogenesis. The possibility that radiation therapy has an important role in the induction of lymphangiosarcoma is also postulated. Sternby et al reported that, in their study, the patient with the shortest interval between radical mastectomy and the onset of the tumor (8 mo) received both preoperative radiation therapy of the breast and involved axillary lymph nodes followed by fractionated radiation. Others suggest that irradiation is not an essential factor in the pathogenesis of this tumor. Finally, irradiation may be an indirect cause of lymphangiosarcomas because it may cause axillary node sclerosis and thereby accelerate and aggravate the edema. Frequency International Currently, approximately 400 cases are reported in the world literature. In 1962, Schirger calculated that the incidence of this disease is 0.45% in patients who survive at least 5 years after radical mastectomy. Others have noted a much lower incidence of 0.07% in patients after mastectomy. Mortality/Morbidity Lymphangiosarcomas are extremely aggressive tumors with a high local recurrence rate and a tendency to metastasize early to many areas. Long-term survivors are the exceptions. Metastatic angiosarcoma to the lungs and chest wall are the most common cause of death in patients with Stewart- Treves syndrome. Metastases to the liver and bones can also occur. Lymphangiomas are associated with a high rate of local recurrence and metastasis, even after aggressive surgical treatment. Race No racial predominance exists. Sex Most patients with Stewart-Treves syndrome are women with a history of breast cancer that has been treated with radical mastectomy, which causes chronic lymphedema. Age Stewart-Treves syndrome usually occurs in middle-aged or elderly women, a few years or many years after mastectomy. In 1981, Sordillo and associates reported a peak incidence in persons aged 65-70 years. In 1972, Woodward et al described a series of 23 patients in a review of 163 cases of Stewart-Treves syndrome from the literature. They recorded an average patient age of 68.8 years at the onset of lymphangiosarcoma; the youngest patient was aged 44 years and the oldest, 84 years. CLINICALSection 3 of 9 Authors and Editors Introduction Clinical Differentials Workup Treatment Follow-up Miscellaneous References History This tumor typically develops in patients many years after mastectomy, more commonly 5-15 years after surgery. In their original series, Stewart and Treves reported that the earliest angiosarcoma appeared 6 years after radical mastectomy, the longest interval being 24 years (average, 12.5 y). In 1988, Tomita and associates demonstrated that the most common interval between radical mastectomy and the onset of lymphangiosarcoma was 5-14 years. In 1981, Yap et al reported a series of 22 patients in whom the median interval from mastectomy to the onset of angiosarcoma was 11 years (range, 5-16 y). Physical As Stewart and Treves described, edema occurs first. Severe chronic edema of an upper extremity usually occurs in patients with Stewart-Treves syndrome. In patients who undergo radical mastectomy, edema first appears on the arm on the side operated on. The occurrence of edema is not associated with complications such as postoperative infection or thrombosis. The edematous area gradually extends from arm to forearm and dorsal aspect of the hand and fingers. Initially, pain is absent, although skin distention may produce local discomfort. In the areas of long-standing chronic edema, recurrent erysipelas may occur, just as they do in patients with congenital lymphedema. The skin tends to become atrophic and eventually pachydermatous, with prominent wrinkle lines. At times, hyperkeratoses and telangiectasias can be observed. After an interval of 1-30 years, a purplish patch appears that then develops into a plaque or nodule in the area of chronic lymphedema. Other initial lesions may include a palpable subcutaneous mass or a poorly healing eschar with recurrent bleeding and oozing. The lesions of Stewart-Treves syndrome typically appear as multiple reddish blue macules or nodules that may become polypoid. Around these nodules, small satellite areas can develop and become confluent, forming an enlarging lesion. Sometimes, a bullous component may be seen. As the angiosarcoma continues to grow and expand, the overlying atrophic epidermis may ulcerate, producing recurrent episodes of bleeding and infection. Necrosis may be evident in advanced cutaneous tumors. Ultimately, extensive cutaneous nodules and systemic metastases appear. These nodules most commonly occur in the lungs and cause the patient's death. Not every tumor in an area of lymphedema is an angiosarcoma. Causes The most important single causative agent in Stewart-Treves syndrome is prolonged chronic lymphedema. Although Stewart-Treves syndrome develops after radical mastectomy in most patients, lymphangiosarcoma also develops in other forms of acquired lymphedema and in congenital lymphedema. Causes for such secondary lymphedema may include trauma, surgical invasion of the groin for the treatment of penile or cervical cancer, filariasis, idiopathic acquired lymphedema, vascular stasis, and morbid obesity. Edema secondary to cardiac or renal disease is not associated with this malignancy. Thus, edema alone is not sufficient to cause lymphangiosarcoma. Perhaps additional factors such as a genetic predisposition are required. DIFFERENTIALSSection 4 of 9 Authors and Editors Introduction Clinical Differentials Workup Treatment Follow-up Miscellaneous References Angioedema, Acquired Angioedema, Hereditary Angioendotheliomatosis Angiolymphoid Hyperplasia with Eosinophilia Kaposi Sarcoma Lymphangiectasia Lymphangioma Lymphocytoma Cutis Malignant Melanoma Metastatic Carcinoma of the Skin Other Problems to be Considered Telangiectatic metastatic breast disease to the skin Hemangioendotheliomas Hemangiopericytomas WORKUPSection 5 of 9 Authors and Editors Introduction Clinical Differentials Workup Treatment Follow-up Miscellaneous References Lab Studies Although Stewart-Treves syndrome is also known as lymphangiosarcoma, ultrastructural and immunohistologic studies show that this malignancy arises from blood vessels rather than lymphatic vessels. The following immunohistologic and ultrastructural findings can be used to confirm that the tumor originates from blood vessels. Antibodies against factor VIII–related antigen are markers for endothelial cells. Although malignant endothelial cells may not always show positive staining with this marker, a more sensitive endothelial marker, lectin Ulex europaeus- I, is more likely to react with hemangiosarcoma tumor cells. However, the specificity of this marker is reduced in people with blood group O because normal epithelial cells and carcinomas also bind this lectin in these individuals. CD34 antigen is a marker of vascular endothelial cells and does not react with the lymphatic endothelium. Antikeratin antibodies show no evidence of keratin in this malignancy; this finding confirms that the tumor cells are nonepithelial in origin. Positive staining for laminin, CD31, collagen IV, and vimentin can aid in diagnosing the tumors as angiosarcomas. Imaging Studies MRI is recommended to evaluate the local extent of angiosarcomas. However, its true value is in question because of poor results in delineating the margin of the tumor. It may be low in signal intensity on T2-weighting and short- tau inversion recovery (STIR) imaging, reflecting the densely cellular, fibrous stroma and sparsely vascularized tumor histology (Schindera, 2005). Additional administration of intravenous contrast medium may reveal significant enhancement of the tumorous lesions. Chest CT should be performed to rule out metastatic disease to the lungs before the patient undergoes extensive surgery. Chest radiography can help in identifying pulmonary metastases and pleural effusion. Procedures Analysis of a biopsy specimen is essential to the diagnosis of lymphangiosarcoma. Fine needle aspiration is inadequate for diagnosis. Histologic Findings Histologically, angiosarcomas in Stewart-Treves syndrome are indistinguishable from angiosarcomas in nonlymphedematous sites. Postlymphedema angiosarcomas are characterized by proliferating vascular channels, which dissect the dermal collagen and, often, the obliterate appendages. Tumor endothelial cells lining these channels show marked hyperchromatism and pleomorphism. Mitoses are commonly seen in these tumor cells. The vascular endothelial cells appear round or oval, and they are protuberant and often project into the lumen. Erythrocytes can be seen inside these vascular channels. The overlying epidermis may be hyperkeratotic and acanthotic, or it may be atrophic. Prominent proliferation of reticular fibers can be seen in association with this malignancy. At electron microscopic examination, lymphangiosarcoma cells are surrounded by a complete basal lamina. In some tumor cells, pinocytosis, intercellular junctions, and cytoplasmic intermediate filaments are observed. In addition, Weibel-Palade bodies and erythrophagocytosis are often present. These ultrastructural findings suggest a vascular endothelial origin rather than a lymphatic endothelial origin. Staging In 1959, McConnell and Haslam divided the course of development of lymphangiosarcoma into 3 stages. This staging system lacks universal application. Stage 1 - Prolonged lymphedema This stage is characterized by extensive edema that causes the degeneration of fat and collagen mainly in the deep part of the dermis. Edema separates the collagen bands, creating a misperception of an increased amount of fibrous tissue in the area. Stage 2 - Premalignant angiomatosis This stage involves multiple foci of small, proliferating channels in the dermis and subdermis. These vessels are lined by hyperplastic endothelial cells, as well as normal, flattened cells. The areas of angiomatosis vary in size, ranging from 100 µm to a couple of centimeters in diameter. Superficial areas can be seen as bruises or vesicles, whereas deeper areas are seen as areas of induration and hemorrhage. Early lesions show little evidence of malignancy, but more advanced lesions reveal early malignant transformation with an increased number of mitotic figures and pleomorphic cells. Stage 3 - Frankly malignant angiosarcoma These aggressive tumors develop from areas of premalignant angiomatosis. The histologic features of this malignancy are described above in stage 2. TREATMENTSection 6 of 9 Authors and Editors Introduction Clinical Differentials Workup Treatment Follow- up Miscellaneous References Medical Care Chemotherapy and irradiation continue to be evaluated as adjuvants to surgery. Currently, these treatment options offer little benefit. In 2000, Grobmyer and associates found no statistical significant difference in the survival rates of patients treated with chemotherapy compared with those treated with irradiation. Although long-term survivors after either radiation therapy or systemic chemotherapy have been reported, the overall results have been discouraging. As a result of these findings, these treatment options are reserved for patients with inoperable, advanced disease or those who refuse surgery. In 1994, Furue et al demonstrated that immunotherapy may be beneficial as palliative treatment for pleural effusions caused by metastatic angiosarcoma. Surgical Care Early amputation or wide local excision provides the best chance of long-term survival in patients with Stewart- Treves syndrome. Some authorities favor radical ablative surgery with an early diagnosis, in order to confer a reasonable prognosis with this rare but aggressive disease (Roy, 2005). A nihilistic approach is undesirable. The most common approach in patients with lymphangiosarcoma is amputation of the limb or forequarter rather than wide local surgical excision. Even in cases with early surgical treatment, the prognosis is disappointing, with a high rate of local recurrence and metastasis. Metastatic disease should exclude surgical treatment unless surgery is useful for symptomatic improvement. Chemotherapy, immunotherapy, and/or radiation therapy can be used as adjuvants to surgery (see Medical Care). FOLLOW-UPSection 7 of 9 Authors and Editors Introduction Clinical Differentials Workup Treatment Follow- up Miscellaneous References Further Inpatient Care Complications from metastatic disease, such as pleural effusions, may require hospitalization of the patient. The patient may need further inpatient care for pain control. Deterrence/Prevention The most efficient way to avoid this highly lethal disease is by preventing or treating long-standing lymphedema, which predisposes individuals to this lymphangiosarcoma years later. Other complications commonly associated with chronic lymphedema, such as erysipelas and deep venous thromboses, must be prevented by regularly examining these areas and then treating them. Early biopsy of any suggestive lesion should be performed because early diagnosis and surgical treatment offers the highest rate of long-term survival. Complications Patients can present with recurrent episodes of erysipelas and deep venous thromboses in areas of chronic lymphedema. Other complications include recurrent infections and malignancies. Prognosis The prognosis is dismal. The 5-year survival rate reported by Sordillo et al in 1981 is 13.6%, and it is 8.5% in the series by Woodward et al. In 1987, Hultberg found that patients with Stewart-Treves syndrome had a mean survival of 20 months after tumor onset. Untreated patients have an average survival of 5-8 months. Patient Education Patients should be informed about the significance of prolonged chronic lymphedema and about how to reduce and control it. Patients should be encouraged to seek early medical attention if they notice unexplained skin changes or unresolved lymphedema. Patients should be educated about complications, such as recurrent infections, deep venous thrombosis, and malignancies, that can occur with lymphedema. For excellent patient education resources, visit eMedicine's Women's Health Center and Cancer and Tumors Center. Also, see eMedicine's patient education articles Mastectomy and Breast Cancer. MISCELLANEOUSSection 8 of 9 Authors and Editors Introduction Clinical Differentials Workup Treatment Follow-up Miscellaneous References Medical/Legal Pitfalls Failure to perform biopsy to evaluate suspicious skin lesions in patients with long-standing lymphedema is a pitfall. REFERENCESSection 9 of 9 Authors and Editors Introduction Clinical Differentials Workup Treatment Follow- up Miscellaneous References Breidenbach M, Rein D, Schmidt T, et al. Intra-arterial mitoxantrone and paclitaxel in a patient with Stewart- Treves syndrome: selection of chemotherapy by an ex vivo ATP-based chemosensitivity assay. Anticancer Drugs. Apr 2000;11(4):269-73. [Medline]. Caldwell JB, Ryan MT, Benson PM, James WD. Cutaneous angiosarcoma arising in the radiation site of a congenital hemangioma. J Am Acad Dermatol. Nov 1995;33(5 Pt 2):865-70. [Medline]. Cozen W, Bernstein L, Wang F, et al. The risk of angiosarcoma following primary breast cancer. Br J Cancer. Oct 1999;81(3):532-6. [Medline]. Dürr HR, Pellengahr C, Nerlich A, et al. Stewart-Treves syndrome as a rare complication of a hereditary lymphedema. Vasa. Feb 2004;33(1):42-5. [Medline]. Furue M, Yamada N, Takahashi T, et al. Immunotherapy for Stewart-Treves syndrome. 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Am J Dermatopathol. Oct 1987;9(5):406-12. [Medline]. Krause KI, Hebert AA, Sanchez RL, Solomon AR Jr. Anterior abdominal wall angiosarcoma in a morbidly obese woman. J Am Acad Dermatol. Aug 1986;15(2 Pt 2):327-30. [Medline]. Laguerre B, Lefeuvre C, Kerbrat P, Hassel M. [Stewart-Treves syndrome arising in post-traumatic lymphedema]. Bull Cancer. Mar 1999;86(3):279-82. [Medline]. Lowenstein S. Der atiologische zusammenhang zwischen akutem ein-maligem trauma und sarkon. Beitr Z klin Clir. 1906;48:780. McConnell AH, Haslam P. Angiosarcoma in post-mastectomy lymphedema: report of five cases and review of the literature. Br J Surg. 1959;46:322-32. Muller R, Hajdu SI, Brennan MF. Lymphangiosarcoma associated with chronic filarial lymphedema. Cancer. Jan 1 1987;59(1):179-83. [Medline]. Nakazono T, Kudo S, Matsuo Y, et al. Angiosarcoma associated with chronic lymphedema (Stewart-Treves syndrome) of the leg: MR imaging. Skeletal Radiol. Jul 2000;29(7):413-6. [Medline]. Offori TW, Platt CC, Stephens M, Hopkinson GB. Angiosarcoma in congenital hereditary lymphoedema (Milroy''s disease)-- diagnostic beacons and a review of the literature. Clin Exp Dermatol. Mar 1993;18(2):174-7. [Medline]. Roy P, Clark MA, Thomas JM. Stewart-Treves syndrome--treatment and outcome in six patients from a single centre. Eur J Surg Oncol. Nov 2004;30(9):982-6. [Medline]. Ruocco V, Schwartz RA, Ruocco E. Lymphedema: an immunologically vulnerable site for development of neoplasms. J Am Acad Dermatol. Jul 2002;47(1):124-7. [Medline]. Schindera ST, Streit M, Kaelin U, et al. Stewart-Treves syndrome: MR imaging of a postmastectomy upper-limb chronic lymphedema with angiosarcoma. Skeletal Radiol. Mar 2005;34(3):156-60. [Medline]. Schirger A. Postoperative lymphedema: etiologic and diagnostic factors. Med Clin North Am. Jul 1962;46:1045- 50. [Medline]. Schreiber H, Barry FM, Russell WC, et al. Stewart-Treves syndrome. A lethal complication of postmastectomy lymphedema and regional immune deficiency. Arch Surg. Jan 1979;114(1):82-5. [Medline]. Schwartz RA, Kardashian JF, McNutt NS, et al. Cutaneous angiosarcoma resembling anaplastic Kaposi''s sarcoma in a homosexual man. Cancer. Feb 15 1983;51(4):721-6. [Medline]. Schwartz RA. Kaposi's sarcoma. In: Schwartz RA, ed. Skin Cancer: Recognition and Management. 1988:80-8. Sinclair SA, Sviland L, Natarajan S. Angiosarcoma arising in a chronically lymphoedematous leg. Br J Dermatol. Apr 1998;138(4):692-4. [Medline]. Sordillo PP, Chapman R, Hajdu SI, et al. Lymphangiosarcoma. Cancer. Oct 1 1981;48(7):1674-9. [Medline]. Stark RB, Dwyer EM, De Forest M. Effect of surgical ablation of regional lymph nodes on survival of homografts. Ann NY Acad Sci. 1960;87:140-148. Sternby NH, Gynning I, Hogeman KE. Postmastectomy angiosarcoma. Acta Chir Scand. 1961;121:420-432. Stewart FW, Treves N. Lymphangiosarcoma in postmastectomy lymphedema: A report of six cases in elephantiasis chirurgica. Cancer. 1948;1:64-81. Tomita K, Yokogawa A, Oda Y, Terahata S. Lymphangiosarcoma in postmastectomy lymphedema (Stewart- Treves syndrome): ultrastructural and immunohistologic characteristics. J Surg Oncol. Aug 1988;38(4):275-82. [Medline]. Woodward AH, Ivins JC, Soule EH. Lymphangiosarcoma arising in chronic lymphedematous extremities. Cancer. Aug 1972;30(2):562-72. [Medline]. Yap BS, Yap HY, McBride CM, Bodey GP. Chemotherapy for postmastectomy lymphangiosarcoma. Cancer. Mar 1 1981;47(5):853-6. [Medline]. Stewart-Treves Syndrome excerpt Article Last Updated: Mar 28, 2007 ------------------------------------ HYPERKERITOSIS In long standing lymphedemas hyperkeritosis can be a problem. This is an overabundant skin thickening with callous formation and possibly wart-like papillomas. It is gray-brown in color and can occur anywhere on the involved area. This is not often seen in upper extremity involvement. Sometimes hyperkeritosis can be mistaken for dried lymph fluid. Hyperkeritosis is a skin change, a scarring, and should never be removed through debridement. Surgical excision is the only treatment, however effective skin care treatment can substantially reduce the severity. FUNGAL INFECTIONS Fungal infections occur frequently in lower extremity lymphedema patients. The stagnant protein rich fluid is a breeding ground for bacteria and feet enclosed in a dark, moist environment are prime targets for infections. Fungal infections manifest themselves through itching between the toes, small blisters, a gray or whitish film on the skin, and foul odor. Sometimes the skin peels off between the toes. Initially only slight scale may be noted but soon it spreads and nail changes can take place. It can be a problem in only one foot or it can be bilateral. Patients with foot fungus need to be careful not to contaminate other household members. The infected patient can shed tiny fragments of skin and fungus. Similar sources of infection exist in discarded bandages or clothes on any surface. The tub or shower should be cleaned thoroughly immediately after use. Patients should not go barefoot in the bathroom but lay a towel down on the floor. That towel needs to be removed and placed in the wash immediately after use. All towels and washcloths should be used only once before washing. Going barefoot generally is not recommended unless the patient has been instructed to air feet at regular intervals. These patients should not go barefoot in the therapy clinic. Make sure you place a towel on the floor for the patient to step onto after removing shoes. Do not have the patient drop socks or stockings onto the floor. They should be placed inside the patient’s shoes. In the beginning stages of foot fungus, over the counter foot fungal medications can be used. Sometimes a prescription drug is required. Patients with repeated problems of foot fungus need to be followed by a physician. The therapist may chose to include treating the foot fungus as a part of the therapy session. Gloves should be worn.LYMPHATIC CYSTS These are abnormally widened initial lymph vessel visible as tiny vesicles or blisters. When they burst there is danger of infection. These need to be monitored daily. During manual lymph drainage be careful of over-pulling the skin around these areas. There should be no stimulation directly over the area itself. With increasing decongestion of the lymphedemetous area, the lymphatic cysts usually dry up. The skin needs to be kept supple and moist. Lymphedema is a very drying condition. Cracks in the skin, particularly on the feet and around the toe and fingernails, need to be avoided. A good low pH lotion or cream is recommended. Lotions or creams that have fragrances, dyes or lanolin should not be considered. There are many products on the market that advertise "low pH" or "pH balanced" and these are preferred. The best time to apply moisturizer is after bathing. It is not recommended it be applied just prior to donning medical compression garments. Lotions/creams can get "caught" up in the garment fabric. If the patient doesn’t wash the garment daily, this can hasten the deterioration of the garment fabric. Some patients can develop itching or a rash if applied prior to bandaging, particularly in the hot summer weather. Maintaining a good fluid intake will assist with skin moisturization. Sometimes patients mistakenly think if they limit the fluid intake, the swelling in the involved limb will be reduced. Good skin integrity can only be maintained if oral fluids are adequate Hyperkeratosis and Papillomatosis By Jenny Veitch, Lymphoedema Specialist Hyperkeratosis Papillomatosis What are hyperkeratosis and papillomatosis? These are changes which can take place within the skin and present as thickening and solidness (described as fibrosis*) of the tissues. The cause of these characteristic changes is the result of untreated lymphoedema and are generally found on lower limbs. How can they be recognised? Hyperkeratosis is a warty scaly change in the skin due to an increased production of keratin, a surface protein. Papillomatosis is a cobblestone change in the skin surface due to dilated surface lymphatic vessels or focal accumulations of lymph; they are non-compressible due to thickening and fibrosis of surrounding tissues. Warty hyperkeratosis and papillomatosis often coexist in which case the skin resembles elephant skin (known as elephantiasis). How can they be prevented? As already stated, these changes generally appear as a result of oedema being untreated. The fitting of good quality compression hosiery and meticulous daily skin care, including the use of moisturising cream, should help to prevent changes occurring within the skin and tissues. How can these changes be treated? It is important to moisturise the affected area twice daily with 50% white soft paraffin and 50% liquid paraffin mixed, until the skin improves. In more severe cases, salicylic acid 5% in an ointment base may be used, this will help to lift the scales from the skin surface. This must be discussed with the health care professional responsible for your care. When the skin condition has improved, daily application of aqueous cream can be applied at night in order to keep the skin well hydrated and supple. Appropriate class and size of compression hosiery must be worn daily to maintain the improved skin condition. If the limb is very swollen and distorted in shape it will be essential to receive an intensive course of treatment known as decongestive lymphatic therapy (DLT) from a qualified lymphoedema specialist. NB * Fibrosis is an increase in the thickness and amount of collagen in the skin. It conveys a harder consistency to the tissues concerned. Lymphorrhoea By LSN Trustee and Nursing Advisor, Denise Hardy Lymphorrhoea is the leakage, or weeping, of lymph fluid through the skin surface. Large beads of fluid appear on the skin and trickle from the affected areas. Causes of Lymphorrhoea May be the result of lacerations, abrasions, or trauma of the altered dry skin of longstanding oedema e.g. graze/cut It may result from the rupture (bursting) of lymphangiomas (described more fully below) It may also occur in a sudden or acute oedema (swelling) where the shiny, taut skin has stretched so rapidly that it splits, forming a leak. Lymphorrhoea - the problems it causes The skin feels very cold, wet and uncomfortable The fluid can soak through dressings which may need changing many times a day to cope with the large amounts of leakage The fluid can collect in shoes/slippers clothing and bed linen can become soaked and require frequent changes Lymphorroea will increase the risk of cellulitis - the break in the skin acts as an entry for bacteria. Infection will cause further problems (pain/inflammation/flu-like symptoms and increased amounts of fluid leakage) If left to leak and dressings are not regularly changed the lymph (being an excellent culture medium) may grow bacteria causing odour and discolouration Lymphorrhoea may cause social difficulties and embarassement. Lymphorrhoea not uncommonly affects the genital area and may be difficult to distinguish from urinary incontinence. Treatment of Lymphorrhoea In order to stop the fluid leaking, a series of steps are essential. Your Lymphoedema nurse/therapist or other nurse involved in your care should be able to help you with these steps following a full assessment of the cause of the leakage: The area around the 'leak' needs to be cleaned carefully to ensure the risk of infection is reduced. An emollient (moisturising cream/lotion) should be applied to the skin to improve the condition and protect it (by acting as a barrier) against further skin breakdown. A non-adherent (non sticky), absorbent, (e.g. Allevyn/Cutinova/lyofoam) sterile dressing should be applied to the leaking area to prevent further trauma to the skin - and to absorb the leakage. Pressure should be applied. For example a limb should be supported with appropriate bandaging e.g. Multi Layer Lymphoedema Bandaging (MLLB) with short stretch compression bandages. This normally stops the flow of leakage within 24-48 hours. Bandages may have to be replaced frequently during this period of time to remove wet bandages/ dressings and to prevent further skin breakdown. MLLB should continue until the skin condition has improved enough to wear your stockings/sleeve again. At rest, the affected limb should be elevated to reduce the effects of gravity. Once the leakage has stopped, and the skin condition has improved, your usual compression garment should once again be applied. The garment will keep the swelling to a minimum and prevent any further 'leaks' appearing. Lymphangiomas Lymphangiomas are often referred to as 'lymph blisters'. They consist of enlarged, or bulging lymphatic vessels just under the surface of the skin, which give the appearance of a blister. Lymphangiomas can occur as a result of damage to the deep lymphatic vessels e.g. following radiotherapy, or surgery and they generally contain clear lymph fluid (though sometimes it can be blood stained). If Lymphangiomas burst, they result in wetness around the area or even profuse leakage which is a risk of potential infection. Treatment involves strict skin hygiene and the usual lymphoedema cornerstones of treatment - especially compression. If left untreated, the lymph blisters may become harder and firmer and begin to look like firm skin nodules. Lymphangiomas are not cancerous. Information updated on this page 1/08 by the Lymphland Editorial Board Please note that lymphedema specialists are those specifically trained. Information about Jenny Vietch is not known so treat her article as if it came from a non-professional view. --------------------------------- Incontinentia Pigmenti Article Last Updated: Feb 18, 2008 AUTHOR AND EDITOR INFORMATIONSection 1 of 11 Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Multimedia References Author: Kara N Shah, MD, PhD, Assistant Professor, Department of Pediatrics, Section of Dermatology, Children's Hospital of Philadelphia Kara N Shah is a member of the following medical societies: American Academy of Dermatology, American Academy of Pediatrics, and Society for Pediatric Dermatology Editors: Bernice R Krafchik, MBChB, FRCPC, Professor Emeritus, Department of Pediatrics, Section of Dermatology, University of Toronto; David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic; Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School; Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center Author and Editor Disclosure Synonyms and related keywords: IP, Bloch-Sulzberger syndrome, ectodermal dysplasia, neurocutaneous syndrome INTRODUCTIONSection 2 of 11 Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Multimedia References Background Incontinentia pigmenti (IP) is an X-linked dominant neurocutaneous syndrome with cutaneous, neurologic, ophthalmologic, and dental manifestations. Garrod reported the first probable case of IP in 1906 and described it as a peculiar pigmentation of the skin in an infant. Subsequently, Bloch and Sulzberger further defined the condition in 1926 and 1928, respectively, as a clinical syndrome with a constellation of unique features that includes typical cutaneous manifestations. Pathophysiology IP is an X-linked dominant genodermatosis characterized by abnormalities of the tissues and organs derived from the ectoderm and neuroectoderm and represents a type of ectodermal dysplasia. Involvement of the skin, hair, teeth, and nails is seen in conjunction with neurologic and ophthalmologic anomalies. In female IP patients, lyonization results in functional mosaicism of X-linked genes, which is manifested by the blaschkoid distribution of cutaneous lesions.1 Cells expressing the mutated X chromosomes selectively eliminate around the time of birth; therefore, females with IP have an extremely skewed X-inactivation pattern. Normal X chromosomes are active in unaffected skin, and mutated X chromosomes are active in skin affected with IP. Frequency United States No incidence or prevalence data are available on IP in the US population. International IP is an uncommon disease. Up until 1987, only 700 cases had been reported in the literature. The disease is probably underreported because many mild or uncomplicated cases are likely unrecognized. Mortality/Morbidity The prognosis depends on the presence and severity of associated extracutaneous manifestations. Morbidity and mortality primarily result from neurologic and ophthalmologic complications, including mental retardation, seizures, and vision loss. Race IP has a worldwide distribution. IP appears to be more common among white patients, but it has also been reported in blacks and Asians. Sex IP is an X-linked dominant, male lethal syndrome. More than 95% of reported cases of IP occur in females. IP may rarely occur in males with Klinefelter syndrome (XXY syndrome) or as a result of somatic mosaicism or hypomorphic (less deleterious) mutations in the NEMO gene.2, 3 Age Characteristic skin lesions compatible with the early, vesicular and/or verrucous stages of IP are present at birth or develop in the first few weeks of life in approximately 90% of patients. The cutaneous manifestations of the hyperpigmented stage develop during infancy and persist during childhood. The hyperpigmented lesions usually fade during adolescence. The cutaneous manifestations of the atrophic/hypopigmented stage develop during adolescence and early adulthood and persist indefinitely. Hair, nail, and dental anomalies often first manifest during infancy and are permanent. Late-onset IP is occasionally reported in older infants. Neurologic and ophthalmologic sequelae often manifest during early infancy. CLINICALSection 3 of 11 Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Multimedia References History In most patients, cutaneous manifestations are present at birth or occur within the first 2 weeks of life. The cutaneous manifestations usually appear in a characteristic, chronologic sequence. Other systemic manifestations, including ocular defects, CNS abnormalities, and dental abnormalities, may not be recognized until infancy or early childhood. A family history of IP in the mother is reported to occur in 28% of patients. In most patients (62%), the syndrome occurs sporadically. Germline mutations inherited from the father have been reported in over 80% of cases of sporadic IP. Male patients with IP generally appear to have a sporadic form. The development of postzygotic mutation and resulting somatic mosaicism is the likely mechanism in most male patients. In a study of 42 boys with IP, only 5 had evidence of NEMO gene mutation. The male phenotype is similar to that of the female phenotype, although unilateral presentation is a more common occurrence in boys (15%). The proposed diagnostic criteria for IP are as follows: In the absence of a family history, the presence of at least 1 major criterion is necessary. The presence of minor criteria supports the diagnosis of IP. Major criteria Typical neonatal vesicular rash with eosinophilia Typical blaschkoid hyperpigmentation on the trunk, fading in adolescence Linear, atrophic hairless lesions Minor criteria Dental anomalies Alopecia Wooly hair Abnormal nails With a definitive family history, the presence of any major criterion strongly supports the diagnosis of IP. Other characteristic features include the following: Suggestive history or evidence of typical rash, hyperpigmentation, or atrophic hairless lesions Vertex alopecia Dental anomalies Retinal disease Multiple male miscarriages Physical Significant clinical heterogeneity exists in IP with regard to ectodermal, ophthalmologic, and neurologic abnormalities, even within families. The cutaneous findings generally progress through 4 distinct characteristic stages, although some stages may overlap temporally and some may not occur at all in individual patients. Affected males often have limited involvement of 1 or 2 limbs. Ectodermal changes Skin features occur in 4 stages. Stage 1 (vesicular) is characterized by the development of red papules and vesicles on an erythematous base that follow Blaschko lines. Lesions are seen predominantly on the extremities but may also occur on the trunk or on the head and neck. The vesicular stage has been reported to occur in 90-95% of patients. In most patients (>90%), lesions are present at birth or develop within the first 2 weeks of life. They resolve within several months. Rarely, self-limiting episodes of recrudescence of vesicular lesions have been reported to occur in older infants and children with IP in association with an intercurrent febrile illness. Stage 2 (verrucous) is characterized by thickened, warty-appearing linear and whorled plaques on an erythematous base that follow Blaschko lines. In general, lesions develop on the extremities and trunk but may also be seen on the head and neck. Verrucous lesions have been reported to occur in 70-80% of IP patients. In most patients, verrucous lesions develop in the first few weeks to months of life and subsequently resolve over weeks to months. Stage 3 (hyperpigmented) is characterized by the development of streaks and whorls of brown or slate-gray pigmentation along Blaschko lines; this occurs in 90-98% of IP patients. Hyperpigmented lesions usually involve the trunk but may also involve the extremities, the skin folds, or the head and neck. The location of the hyperpigmented lesions does not appear to correlate with areas of prior skin involvement during the earlier vesicular and verrucous stages. Hyperpigmented lesions generally develop within the first few months of life and resolve slowly by adolescence. Stage 4 (atrophic/hypopigmented) is characterized by hypopigmented, atrophic, and reticulate or linear patches observed on the lower extremities, usually involving the calves. Atrophic lesions usually develop during adolescence and persist into adulthood. Atrophic lesions have been reported to occur in 30-75% of IP patients. Abnormal dermatoglyphic patterns have also been reported. Hair changes include scarring alopecia and are seen in 28-38% of patients. An absence or hypoplasia of the eyebrows and eyelashes has also been reported. Finally, hair is sparse in early childhood; later, it has a lusterless, wiry, and coarse appearance. Nail features4 include nail dystrophy, which ranges from mild pitting or ridging of the nail plate to hyperkeratosis and onycholysis. This is observed in 7-40% of IP patients, and usually multiple fingernails and toenails are affected. Nail dystrophy may improve with age. Subungual and periungual keratotic tumors associated with pain, bony deformities, and lytic lesions involving the underlying phalanges also may be seen, usually in older children and adults.5, 6, 7 The fingers are most commonly affected. Dental abnormalities8, 9 are seen in 80% of patients and can involve both deciduous and permanent teeth. Dental anomalies are permanent and thus serve as a very useful diagnostic finding in older patients. Delayed dentition, partial anodontia, and conical or pegged teeth are the most common dental findings. Poor enamel quality leading to an increased incidence of dental caries has been reported historically, but this association has been questioned. Ophthalmologic findings10, 11 Ophthalmologic findings occur in 20-35% of patients, and asymmetric involvement is common. Loss of visual acuity and blindness are significant complications. Blindness has been reported to develop in 7% of IP patients. Ophthalmologic manifestations may become evident within the first few weeks to months of life and may progress rapidly to permanent visual deficits. Retinal vaso-occlusive events with resultant ischemia are believed to be the primary mechanism underlying ocular pathology. Retinal manifestations include retinal detachment, proliferative retinopathy, fibrovascular retrolental membranes, foveal hypoplasia, vitreous hemorrhages, and atrophy of the ciliary body. Nonretinal manifestations include strabismus, optic nerve atrophy, conjunctival pigmentation, microphthalmia, keratitis, cataracts, iris hypoplasia, nystagmus, and uveitis. Neurologic abnormalities Neurologic complications occur in 30% of IP patients and often manifest within the neonatal period. Seizures are the most common neurologic complication and usually develop within the first few weeks of life. Neurologic complications may result in part from microvascular vaso-occlusive ischemic events involving the CNS. Involvement of the cerebral hemispheres, cerebellum, and corpus callosum may occur.12 Progressive periventricular hemorrhagic infarcts have been reported. Other neurodevelopmental manifestations include developmental delay, mental retardation, ataxia, spastic paralysis, microcephaly, cerebral atrophy, porencephaly, hypoplasia of the corpus callosum, and periventricular cerebral edema. Other anomalies that have been reported to occur with increased frequency in patients with IP include supernumerary nipples, nipple hypoplasia, and breast hypoplasia. Causes IP is caused by mutations in the NEMO/IKK-gamma gene, which is located on chromosome Xq28. NEMO/IKK- gamma is the regulatory subunit of the inhibitor kappa kinase (IKK) complex and is required for the activation of the transcription factor NF-kappaB (NF-kB). NF-kB is central to many immune, inflammatory, and apoptotic pathways. Activation of NF-kB prevents apoptosis in response to the tumor necrosis factor family of cytokines. NF-kB activity is normally regulated via the inhibitor kB protein. Tumor necrosis factor receptor activation results in phosphorylation and inactivation of inhibitor kB by IKK, thus resulting in activation of NF-kB. Loss of IKK activity results in deficient NF-kB activity and increased susceptibility to apoptosis. Cells that retain IKK activity may produce additional cytokines that trigger apoptosis in neighboring IKK-deficient cells, thus creating an amplification loop that eventually results in the death of all of the IKK-deficient cells. This mechanism is believed to produce the cutaneous manifestations of the vesicular stage of IP. The proliferation of surviving IKK-positive cells may result in the production of the verrucous lesions seen in stage 2 of IP. The pathophysiology of the hyperpigmented cutaneous findings seen in stage 3 and the atrophic/hypopigmented manifestations of stage 4 remains unknown. Inflammation and subsequent postinflammatory changes may play a role. The peripheral eosinophilia seen in the early stages of IP may result from the production of eotaxin, an eosinophil- selective cytokine, during the inflammatory cascade that results from a loss of NEMO/IKK-gamma activity. Activation of eosinophils with subsequent release of cellular proteases may trigger the development of the vesicular stage of IP.13 The pathophysiology underlying the CNS manifestations in IP are unknown, but inflammation resulting from loss of NEMO/IKK-gamma activity may contribute to the development of vascular occlusive events. Females with hypomorphic mutations in NEMO/IKK-gamma may have few clinical manifestations of IP. A single mutation in NEMO/IKK-gamma involving the deletion of exons 4 through 10 accounts for most (80%) IP mutations. Hypomorphic mutations in the zinc-finger domain of NEMO/IKK-gamma result in X-linked recessive ectodermal dysplasia and immunodeficiency. A family history of IP may be elicited. Such mutations result in decreased but not absent IKK activity and thus allow for low-level NF-kB activation. Hypomorphic mutations in the stop codon of NEMO/IKK-gamma result in the X-linked dominant ectodermal dysplasia osteopetrosis lymphedema syndrome. Confirmation of NEMO/IKK-gamma mutations in males is difficult due to the high rate of post-zygotic mosaicism. NEMO/IKK-gamma knockout mice manifest a cutaneous phenotype similar to female IP patients and develop neurologic sequelae, although they do not develop dental or ocular abnormalities. They also develop diffuse apoptosis of splenic and thymic lymphocytes, which does not occur in human IP patients.14, 15 Genetic testing for NEMO/IKK-gamma mutations is available through the Baylor College of Medicine Medical Genetics Laboratories. DIFFERENTIALSSection 4 of 11 Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Multimedia References Acropustulosis of Infancy Bullous Pemphigoid Dermatopathia Pigmentosa Reticularis Epidermolysis Bullosa Focal Dermal Hypoplasia Syndrome Herpes Simplex Herpes Zoster Hypomelanosis of Ito Impetigo Insect Bites Langerhans Cell Histiocytosis Lichen Striatus Mastocytosis Milia Miliaria Naegeli-Franceschetti-Jadassohn Syndrome Other Problems to be Considered Stage 1 - Vesicular Bullous impetigo Herpes simplex Varicella (herpes) zoster Epidermolysis bullosa Bullous mastocytosis Bullous congenital ichthyosiform erythroderma (epidermolytic hyperkeratosis) Congenital bullous pemphigoid Linear IgA bullous disease of childhood Langerhans cell histiocytosis Erythema toxicum Miliaria Acropustulosis of infancy Arthropod assault Stage 2 - Verrucous Linear epidermal nevus Lichen striatus X-linked dominant chondrodysplasia punctata Verruca vulgaris Stage 3 - Pigmented Linear and whorled nevoid hypermelanosis Pigmentary mosaicism Dermatopathia pigmentosa reticularis Naegeli-Franceschetti-Jadassohn syndrome X-linked dominant chondrodysplasia punctata Stage 4 - Depigmented Hypomelanosis of Ito (IP achromians) Focal dermal hypoplasia syndrome (Goltz syndrome) X-linked dominant chondrodysplasia punctata WORKUPSection 5 of 11 Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Multimedia References Lab Studies Leukocytosis and eosinophilia may be noted. When acute inflammatory skin changes are present, eosinophilia (=80%) may be seen in the peripheral blood. Evidence of neutrophil dysfunction (defects in chemotaxis), lymphocyte dysfunction (decreased proliferation in response to mitogen stimulation), and altered immunologic reactivity has been reported in some patients. Quantitative immunoglobulin levels and lymphocyte subpopulation counts are normal. Imaging Studies Head CT scanning and brain MRI16 may demonstrate cerebral edema, hydrocephalus, structural brain abnormalities, cerebral infarctions, and hypointense areas or hypoattenuation. Magnetic resonance spectroscopy and angiography have demonstrated reduced cerebral blood flow and elevated cerebrospinal fluid lactate levels, consistent with cerebral ischemia secondary to cerebrovascular occlusive events. 17 Single-photon emission CT scanning may show decreased cerebral blood flow.18 EEG is helpful for localizing CNS lesions and epileptogenic foci in patients with seizures. Other Tests Karyotype analysis is recommended in male infants with IP in order to detect Klinefelter syndrome (XXY syndrome). Genetic testing for NEMO/IKK-gamma mutations is available through the Baylor College of Medicine Medical Genetics Laboratories. Procedures Skin biopsy may be diagnostic if performed during the early vesicular and verrucous stages of IP (stages 1-2). Histologic Findings Stage 1 (vesicular) Spongiotic dermatitis with eosinophil-filled intraepidermal vesicles and an eosinophilic epidermal and dermal infiltrate are seen. The epidermis often contains dyskeratotic cells, either singly or in small clusters. Stage 2 (verrucous) Acanthosis, papillomatosis, and hyperkeratosis with increased numbers of dyskeratotic cells, which sometimes form whorled collections,19 are seen. Basal cells show vacuolization and a decrease in melanin content. Eosinophils can persist in the epidermis and dermis, and melanophages are often present in the papillary dermis. Stage 3 (hyperpigmented) Melanin deposition in melanophages within a thickened papillary dermis is seen. Colloid bodies in the papillary dermis, dyskeratotic cells in the epidermis, and basal cell layer vacuolar changes may be seen. The histologic findings are often suggestive of IP but are not specific. Stage 4 atrophic/hypopigmented) Atrophic epidermis with loss of the normal rete ridge pattern and dermal eccrine structures with a reduction in basal melanocytes are seen. Colloid bodies may be seen. The histologic findings are nonspecific. TREATMENTSection 6 of 11 Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Multimedia References Medical Care Treatment is not usually required for the cutaneous lesions. The vesicles of the inflammatory stage should be left intact, and the skin should be monitored for the development of secondary bacterial infections. Emollients and topical antibiotics may be used as needed. Oral hygiene and regular dental care is necessary, and dental restoration may be indicated. Seizures should be treated with anticonvulsants. Routine neurodevelopmental assessments should be made, with referral to occupational and physical therapists as warranted. Frequent ophthalmologic evaluations are required, especially during the first year of life, in order to diagnose and treat potential ophthalmologic complications. Surgical Care Abnormal retinal fibrovascular proliferation can be treated with xenon laser photocoagulation or cryosurgery.20 Retinal detachments may be treated using vitreoretinal surgery. Consultations Dermatologists may help in the initial evaluation and can perform a skin biopsy to aid in diagnosis. Ophthalmologists can perform regular ophthalmologic examinations and manage any ophthalmologic sequelae. Neurologists can perform a complete initial neurologic examination (including imaging studies and EEG), initiate and monitor anticonvulsant therapy in patients with seizures, and facilitate neurodevelopmental evaluation and intervention. General dentists can provide regular dental care, screening for dental complications, and restorative dental care. Geneticists can provide appropriate genetic counseling and genetic testing for the patient and his or her family. MEDICATIONSection 7 of 11 Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Multimedia References In patients with seizures, anticonvulsant drugs are used. These agents have central and peripheral anticholinergic effects and sedative effects. They also block the active reuptake of norepinephrine and serotonin. A variety of anticonvulsants are available, and they should be selected at the discretion of the neurologist. FOLLOW-UPSection 8 of 11 Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Multimedia References Further Outpatient Care The presence of variable disease expression in an affected family makes monitoring for potential complications important. Regular follow-up with a neurologist, ophthalmologist, dentist, and dermatologist should be coordinated as needed. Complications Secondary bacterial infection can develop during the vesicular stage, but this is rare. Seizures and mental retardation are common in patients with structural brain malformations or evidence of ischemic brain injury. Ophthalmologic complications can lead to reduced visual acuity and blindness. Prognosis The prognosis of IP is generally good. Morbidity and mortality are related to neurologic and ophthalmologic sequelae, including seizures, visual impairment, and mental retardation. Patients with structural brain abnormalities and neonatal seizures are at greater risk for motor and intellectual impairment. Patient Education Inform parents that delayed eruption of both deciduous and permanent teeth is common. Reassure parents that if no evidence of CNS involvement or seizures is seen in their infant, the neurodevelopmental prognosis is excellent. Genetic counseling should be offered to the family. Counsel parents on the expected course of cutaneous manifestations. MISCELLANEOUSSection 9 of 11 Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Multimedia References Medical/Legal Pitfalls Failure to make a correct diagnosis based on cutaneous findings and ocular, CNS, and dental abnormalities Failure to perform skin biopsy of vesicular or verrucous lesions to confirm a diagnosis of IP Failure to refer patients to neurologists and ophthalmologists for evaluation and treatment Failure to provide appropriate genetic counseling Special Concerns Examine the mother and all female relatives of a child with IP for clinical features of IP. Carefully look for dental abnormalities and stage 4 cutaneous changes (eg, atrophic/hypopigmented lesions involving the lower legs). 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