Scleroderma

Forms of scleroderma

Two main forms of scleroderma can be distinguished.

Localized scleroderma (LS)
Localized scleroderma usually affects only the skin, although it can spread to the muscles, joints and bones. It does not affect internal organs. The three forms of local scleroderma are:
• Morphea. On the trunk, sometimes in the face and on the limbs, there are round to oval clearly defined often confluent skin lesions. The middle of the spots is ivory colored in the beginning and feels hardened. Later there is just dilution (atrophy). In the initial phase there is often a lilac-colored ring at the edge of the stain, later pigment shifts (light and dark areas) occur. There is also loss of hair and sweat glands on the spots. In the more elaborate form, several round, oval to erratic shaped areas mainly appear on the trunk.
• Linear scleroderma. In this form a line of hardened skin develops on your body. This line often starts on a knee, elbow or face and continues to the trunk. If the line runs over a joint, you can often move that joint less well.
• Scleroderma en coup de sabre. In this form the skin deviation is on one side of the forehead. The skin abnormality runs backwards, from the skin over the front hairline, through under the hair. The skin is indented in that area and seems to have been done with a saber. The affected scalp skin loses hair and causes a bald spot with pigment shifts.

Systemic scleroderma or systemic sclerosis (SSc)
The cause of this form of scleroderma is unknown. According to research, damage in the vascular wall of the capillaries and an overactive immune system play a role. The disease is not hereditary, but can be more common in the same family. There are two major forms: limited cutaneous systemic sclerosis (CREST syndrome) and diffuse cutaneous systemic scleroderma. Diffuse cutaneous systemic scleroderma is the most serious form of the disease and can affect the skin, muscles, joints, blood vessels, lungs, kidneys, heart and other organs.
• Limited cutaneous systemic sclerosis (CREST syndrome). Here the skin thickening and tightness is typically limited to the fingers and toes, but this form is also associated with pulmonary hypertension. Limited cutaneous scleroderma is typically associated with one or more symptoms that are known collectively as CREST syndrome. CREST syndrome symptoms include:
Calcinosis with formation of calcified nodules (calcium deposits) under the skin.
Raynaud phenomenon with episodes of decreased blood flow to fingers and toes, causing them to turn white, blue and red.
Esophageal dysfunction with difficulty swallowing, acid reflux, and heartburn.
Sclerodactyly with tight, thick, shiny skin on the hands and fingers. Sclerodactyly is a tightening and thickening of the skin of the fingers. It can cause the fingers to curl inward and the hands to form a clawed shape. Systemic scleroderma causes sclerodactyly, which is an autoimmune disease and a rare form of arthritis. Not everyone with scleroderma will get sclerodactyly.
Telangiectasia with dilated blood vessels in the skin and red spots on skin due to swollen capillaries.
There is a more gradual course with a late chance of complications of mainly the gastrointestinal tract, lungs or heart-lung circulation.
• Diffuse cutaneous systemic scleroderma. This form is very serious and affects larger parts of the skin of the limbs and trunk and affects your organs. The diffuse form has a faster increase in skin thickening and tightness that starts at the hands and feet, after which the trunk, arms and legs can become involved. The connective tissue in your internal organs increases, especially in the lungs, but also in the digestive tract, heart and kidneys. Connective tissue occurs throughout the body and includes protein threads, collagen and elastin. Elastin is a protein forming the main constituent of elastic connective tissue, found especially in the dermis of the skin. Collagen is a body substance and a protein that holds the connective tissue together, for example in your bones, blood vessels, but also in the skin. The dermis (the middle layer of your skin) consists of 30% of collagen. Collagen ensures that the skin remains firm and elastin provides elasticity. In scleroderma more collagen is formed than elastin. This makes the connective tissue tighter and less elastic. Inflammation occurs in the body and the capillaries become more and more blocked. This form of scleroderma more frequently involves internal organs, such as lungs, kidneys, or the gastrointestinal tract.

The above classification is made on the basis of the pattern of skin thickening.
This classification based on the skin pattern is relevant because the limited cutaneous systemic sclerosis (CREST syndrome) and diffuse cutaneous systemic scleroderma differ in disease course, involvement of the organs and the rate at which the disease progresses.

Complaints

Scleroderma starts with skin problems. In both types of scleroderma the skin problems are about the same. At certain spots on your body you first get whimsical, purple spots. The new connective tissue makes the skin thicker, hard, tight and dry. Skin folds disappear and the skin that develops resembles scar tissue. Your hair can disappear on your affected skin.
Almost all people with scleroderma experience fatigue and feel very tired. Sometimes there is a reason, for example there is anemia or a heart, lung or kidney function problem. Sometimes this is not the case and the reason is the disease itself, leading to fatigue.

Localized scleroderma
In localized scleroderma, the connective tissue of the skin becomes harder.
• Morphea. On the trunk, sometimes in the face and on the limbs, there are round to oval clearly defined often confluent skin lesions. The middle of the spots is ivory colored in the beginning and feels hardened. Later there is just dilution (atrophy). In the initial phase there is often a lilac-colored ring at the edge of the stain, later pigment shifts (light and dark areas) occur. There is also loss of hair and sweat glands on the spots. In the more elaborate form, several round, oval to erratic shaped areas mainly appear on the trunk.
• Linear scleroderma. The typical skin lesions are arranged in a band shape. This usually occurs on one leg or one arm, but also sometimes on one side of the chest, abdomen or buttocks. With an affected leg or arm, this can be locally swollen (edema). Sometimes bone and muscle tissue can also be affected, which can cause growth disturbances.
• Scleroderma en coup de sabre. In this form of localized scleroderma, the skin lesion is on one side of the forehead. The skin abnormality runs backwards, from the skin over the front hairline, through under the hair. The skin is indented in that area and this seems to have been done with a saber. The affected scalp skin loses hair and causes a bald spot with pigment shifts.

Systemic scleroderma or systemic sclerosis (SSc)
There are two major forms: limited cutaneous systemic sclerosis (CREST syndrome) and diffuse cutaneous systemic scleroderma. Diffuse cutaneous systemic scleroderma is the most serious form of the disease and can affect the skin, muscles, joints, blood vessels, lungs, kidneys, heart and other organs.
• Limited cutaneous systemic sclerosis (CREST syndrome). Here the skin thickening and tightness is typically limited to the fingers and toes, but this form is also associated with pulmonary hypertension. Limited cutaneous scleroderma is typically associated with one or more symptoms that are known collectively as CREST syndrome. CREST syndrome symptoms include:
Calcinosis with formation of calcified nodules (calcium deposits) under the skin.
Raynaud phenomenon with episodes of decreased blood flow to fingers and toes, causing them to turn white, blue and red.
Esophageal dysfunction with difficulty swallowing, acid reflux, and heartburn.
Sclerodactyly with tight, thick, shiny skin on the hands and fingers.
Telangiectasia with dilated blood vessels in the skin and red spots on skin due to swollen capillaries.
There is a more gradual course with a late chance of complications of mainly the gastrointestinal tract, lungs or heart-lung circulation.
• Diffuse cutaneous systemic scleroderma. This form is very serious and affects larger parts of the skin of the limbs and trunk and affects your organs. The diffuse form has a faster increase in skin thickening and tightness that starts at the hands and feet, after which the trunk, arms and legs can become involved. This form of scleroderma more frequently involves internal organs, such as lungs, kidneys, or the gastrointestinal tract.
Problems may be:
•• Skin problems. Your fingers can swell and the skin harden due to the increase of connective tissue in your skin. The pigment of the skin can change at a later stage and often the sweat glands disappear and you can lose hair all over your body. Eventually your skin can tighten and harden further, which may cause it to itch or cause your joints to move less well.
•• Mouth problems. Your mouth opening will become smaller and wrinkled due to your tightened skin. It becomes more difficult to brush your teeth, so the chance of holes in your teeth and inflammation on your gums is greater. You may get wounds in your mouth when wearing dentures or putting in your dentures. If you produce less saliva, you may have a dry mouth and be more susceptible to fungal infections and other infections in your mouth. Deterioration of tooth enamel is possible when gastric acid is bubbled up. A possible hoarseness in your voice can occur due to more connective tissue at your vocal cords. Your tongue becomes less mobile. The skin of your lips and cheeks (increasingly) tightens.
•• Sclerodactyly. Sclerodactyly is a tightening and thickening of the skin of the fingers with movement limitations. It can cause the fingers to curl inward and the hands to form a clawed shape. Systemic scleroderma causes sclerodactyly, which is an autoimmune disease and a rare form of arthritis. Not everyone with scleroderma will get sclerodactyly. The fingertips are often pointed (pulp loss) and wounds or scars (digital pitting scars) may be present at the fingertips. Patients often also suffer from Raynaud’s phenomenon.
•• Telangiectasia. Telangiectasia are dilated blood vessels in the skin. They are finely branched small blood vessels in the skin, forming a kind of network pattern. Typical of these small red blood vessels is that they are ‘squeezable‘: by pressing the skin with a finger, the vessels become invisible and after the pressure is released the blood vessels fill up with blood again. Dilated blood vessels (telangiectasias) are common, are unavoidable and difficult to treat.
•• Calcinosis. In calcinosis there is formation of calcified nodules under the skin. Lime deposits under the skin can be painful and sometimes they cause wounds that heal badly.
•• Sores on your fingers and toes. Sores (digital ulcers) on your fingers and toes can start to ignite and then cause a lot of pain and loss of function. Sometimes wounds develop on bumps. These heal badly and give a lot of pain.
•• Joints become stiffer. In each joint connective tissue occurs and that gives the joint firmness. If the amount of connective tissue in the joint increases, the joint becomes stiffer. The skin around the joints can be pulled so tight that the joint ends up in an unnatural position. This causes you to move with difficulty and use the joint less well.
•• Esophageal problems. Too much connective tissue can interfere with the normal movements of your esophagus. Your food can get stuck behind your breastbone. Sores may develop in your esophagus. Maybe the sphincter of your esophagus does not work as well anymore. Then gastric acid flows back into your esophagus and starts to affect the mucous membrane, resulting in burning stomach acid or a burning pain behind your breastbone. Sometimes the stomach acid flows through your throat into the trachea, which then gets irritated, which causes coughing, swallowing or hoarseness. Because your esophagus stiffens, your body processes food less well. Food must be lowered by gravity or by a drink. The complaints can not be prevented and do not go away anymore.
•• Stomach problems. Your stomach contents can flow back to your mouth when you are sitting or lying, because the lid between stomach and esophagus is continuously open. Rising stomach acid can cause inflammation of the mucous membrane in your esophagus. You may experience a disturbed mobility of your stomach, so that the food stays in your stomach longer and you feel full for a longer time. A watermelon stomach is rare: blood vessels in the lower part of your stomach are turned off (the outside of your stomach therefore resembles that of a watermelon) and can start to bleed quickly.
•• Bowel problems. If more connective tissue develops in your intestines, this can lead to intestines that cannot contract properly anymore. Your food does not digest well, you can suffer from intestinal cramps, diarrhea and weight loss. Your intestinal flora will be affected and the relationship between the different bacterial species in your intestines will be disturbed. If your small intestine expands as a result of blockage and there are too many bacteria in the intestine, you will not absorb foods properly. Expelled blood vessels in the small intestine may bleed, causing you to get anemia. Due to the reduced mobility of the intestines you can also get intestinal blockages (constipation) in the large intestine. Very occasionally it happens that the sphincter muscle of the anus is insufficient and the stool cannot be held up (well) anymore.
•• Kidney problems. If the amount of connective tissue in your kidneys increases, the operation of your kidneys can suddenly deteriorate. If the blood vessels in your kidneys are affected, you may get a renal crisis: your blood pressure is seriously high and the kidneys lose their function. That almost always goes hand in hand with a sudden increase in blood pressure. Because of this increase in blood pressure you get a stabbing headache, you see blurred vision and you vomit vigorously. The risk of this is greatest if you have skin hardening above the elbows and knees during the first years of the disease.
•• Lung problems. You can suffer from pulmonary fibrosis and pulmonary hypertension. Pulmonary fibrosis. Tissue scars can develop because of inflamed lung tissue. The lung capacity reduces and your lungs absorb less oxygen. Your lungs will then become less elastic, allowing them to transport less oxygen to your blood and releasing with difficulty the waste product carbon dioxide to the blood. If the connective tissue increases in the membranes that surround your lungs, your endurance decreases and you get shortness of breath when you exercise. Pulmonary hypertension. This occurs when the blood pressure in your lungs becomes too high. Your condition will decrease and you may experience shortness of breath, chest pain, fainting and fluid retention in your legs. Pulmonary arterial hypertension is one of the forms of pulmonary hypertension. The cause of this may be unknown, may be hereditary and it occurs in rheumatic diseases and congenital heart defects. The condition is rare and the symptoms are not alarming at first. The diagnosis is therefore sometimes made late.
•• Heart problems. Due to the formation of scars in the heart muscle, your heart can no longer do its job properly. Your heart pumps blood through your body using rhythmic contractions. The contractions result from an electrical stimulus system: the heart rhythm. In this way all your cells get oxygen, nutrients and other substances that the body needs and waste products are removed. By forming extra connective tissue you can get various heart complaints: cardiac arrhythmias, in which the formation of more connective tissue in your heart can damage the stimulating system of your heart. Myocarditis, in which the pinching force of your heart decreases due to an inflamed heart muscle. Pericarditis, in which fluid can accumulate in your pericardium. Shortness of breath, in which an increase in connective tissue in the heart muscle can cause the pumping function of your heart to decrease, leading to shortness of breath during exertion and, especially in the evening, a problem with ankle swelling. Pain behind your sternum, in which the membrane that surrounds your heart may become inflamed and cause pain behind your sternum.

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Diagnosis

Your doctor will base your diagnosis on a combination of the medical history, his findings and additional test results.

Anamneses
At the first visit, the doctor asks you a number of questions to get a good picture of your condition. You can think of the following questions:
– When did your complaints start?
– Can you describe your complaints?
– How are your working conditions?
– What medication do you use?
– Do rheumatic diseases occur in your family?
– What is your medical history?
– Are you under the treatment of other specialists and for what?

To make a diagnosis, a doctor will ask about the patient’s medical history, do a physical exam and possibly order lab tests and X-rays. Careful clinical evaluation is the primary method for monitoring scleroderma. X-rays and computerized tomography (CT) scans are used to look at bone abnormalities. Thermography can detect differences in skin temperature between the lesion and normal tissue. Ultrasound and magnetic resonance imaging (MRI) can aid soft tissue assessment.

If the suspicion exists of localized scleroderma, the physical examination in combination with a skin biopsy is usually sufficient to diagnose the localized scleroderma.

If there is a suspicion of limited cutaneous systemic sclerosis (CREST syndrome) or diffuse cutaneous systemic scleroderma, the presence of Raynaud’s phenomenon and skin thickening, swelling and tightening are the most common complaints in the early stages of the disease.
• Raynaud’s phenomenon. Raynaud’s can lead to finger swelling, color changes, numbness, pain, skin ulcers and gangrene on the fingers and toes. It occurs when the blood flow to the hands and fingers is temporarily reduced, often after exposure to cold temperatures. This is one of the earliest signs of the disease, because some 90% of patients with scleroderma have Raynaud’s. But people with other diseases can also have Raynaud’s and some people with Raynaud’s do not have any other disease.
• Skin thickening, swelling and tightening. This is the problem that leads to the name “scleroderma” (“Sclera” means hard and “derma” means skin). The skin may also become glossy or unusually dark or light in places. The disease can sometimes result in changes in personal appearance, especially in the face. When the skin becomes extremely tight, the function of the area affected can be reduced.

• Other tests
If your doctor suspects that your internal organs are also involved in the disease, he can have a number of tests done.
•• Rodnan skin score (mRSS)
If you have skin abnormalities, your doctor usually measures the thickness and extent of skin abnormalities with a skin score test. The doctor assesses your skin at seventeen places in the skin score test. By feeling, he measures the thickness and stiffness of it. Each area gets a score between 0 (= normal) and 3 (= maximum thickened and stiff). In total this gives a score between 0 and 51 points. By doing this research at different times, the doctor can see how the disease develops. He can also measure whether the chosen treatment has an effect. Once the disease is under control, the skin score will no longer increase, usually the score decreases.
•• blood tests
• Sedimentation speed. Blood tests also measure the degree of inflammation through the sedimentation rate of the red blood cells. The erythrocyte sedimentation rate (ESR) is measured by a laboratory test. An erythrocyte sedimentation rate (ESR) test is also called a sedimentation rate test or sed rate test. The test measures the sedimentation rate of red blood cells (erythrocytes) through the speed at which the red blood cells settle, due to gravity, in an upright, narrow tube of blood. The upper part of the blood in the tube is the plasma, which becomes visible as a column of clear, yellowish liquid after the sedimentation of the red blood cells. The length of this column of plasma is measured after one hour and expressed in millimetres per hour (mm/hour). This blood test does not diagnose one specific condition. Instead, it helps your doctor to determine whether you are experiencing an inflammation. This can be the result of infections (bacteria, viruses), tumors and autoimmune diseases (such as arthritis).
• Blood gases. The measurement of blood gases is done to determine the ratio of oxygen (O2) and carbon dioxide (CO2) in the blood and to check the acid-base balance (the balance of the pH-value of the blood). This is done by taking a blood sample from the artery or vein. A disturbed oxygen-carbon dioxide balance or impaired acid-alkaline balance occurs in symptoms such as liver problems, oxygen deficiency, poor blood flow and problems with blood pressure.
• Hemoglobin level (Hb). The hemoglobin level (Hb) of the blood indicates whether there is sufficient production and filling of red blood cells. Hemoglobin is responsible for oxygen transport in the blood and a too low hemoglobin level leads to (severe) fatigue.
• Antibodies
– antinuclear antibodies (ANA), which respond positively to various autoimmune diseases and are present in approximately 95% of patients with scleroderma. The ANA test is one of the primary tests to diagnose a suspected autoimmune disease or to rule out other diseases with similar signs and symptoms. Antinuclear antibodies (ANA) are a group of autoantibodies produced by the immune system. The ANA test detects antinuclear antibodies (ANA) in your blood. Your immune system normally makes antibodies to help your cells fight infections. In contrast, the antinuclear antibodies often attack the body’s own cells, with the ANA specifically targeting substances found in the nucleus of a cell, hence the name ‘antinuclear’. ANA can cause damage to the tissue by reacting with nuclear substances when released by damaged or dying cells. They probably do not damage living cells because they can not reach their cores. In most cases, a positive ANA test indicates that your immune system has started a wrongly targeted attack on your own tissue, in other words, an autoimmune response. ANA reacts with components of the body’s own healthy cells and causes signs and symptoms such as tissue and organ inflammation, joint and muscle pain and fatigue. But some people have positive ANA tests, even if they are healthy.
– Scl-70 antibody (topoisomerase-1), which often reacts positively in 60 to 80% of people with SSc. This rarely occurs with localized scleroderma (morphea). The Scl-70 antibody is associated with an increased risk of pulmonary fibrosis (pulmonary fibrosis) in systemic scleroderma. Diffuse cutaneous systemic scleroderma (SSc) patients will test positive for antibodies against topoisomerase-1 in about 30% of the cases.
– anticentromere antibodies (ACA). About 60-80% of limited systemic scleroderma patients can test positive for anticentromere antibodies (ACA). ACA is found in only about 5% of patients with diffuse cutaneous systemic scleroderma. The anticentromere antibody (ACA) is an auto-antibody, a protein produced by the immune system that mistakenly targets the body’s own tissues. ACA is one of several antinuclear antibodies and targets the centromere, a component of the chromosomes found in all nucleated cells in our body, except red blood cells. The ACA test detects and measures the amount of anticentromere antibody found in blood to help diagnose a form of scleroderma.
But even if the antibodies are not detectable in the blood, you may have a form of scleroderma.
•• capillary microscopy to look at telangiectasias.
With a normal image of the capillaries (blood vessels) in the cuticle of your finger or toe,  these capillaries are placed neatly next to each other in the shape of a hairpin. The capillaries are slim and there is no bleeding to see. Often, abnormalities of your capillaries can be seen at an early stage of scleroderma. The abnormalities are often a first indication that you have systemic scleroderma (SSc) or (less often) another disease, such as systemic lupus erythematosus (SLE), poly- or dermatomyositis or mixed connective tissue disease (MCTD). The capillaries enlarge early in the disease process. The enlarged capillaries are very fragile and can easily bleed. Sometimes it can be seen with the naked eye. Later in the process, the vessel wall thickens and constricts the capillaries. Small clots develop, which means the blood can not flow through. As a result, fewer capillaries remain in the cuticles. If the disease is well advanced, oxygen deficiency arises and fewer new blood vessels are created, that are not next to each other and have a tree-like structure.
•• heart examination.
An electrocardiogram (ECG) can be made. With cardiac catheterization, the coronary arteries are visualized to see if there are constrictions. The doctor can also look at the heart valve functions, the pump function of the left ventricle and the pressure in the right and left half of the heart.
With a bicycle test it is examined what the effect is on your heart. It is thus possible to show whether your heart complaints are caused by oxygen deprivation. At rest, the circulation of the heart is often sufficient. In case of exercise, the blood flow sometimes cannot increase enough and then oxygen shortage occurs. It can also be determined if there is arrhythmia of the heart. Arrhythmia is a term for an irregular heartbeat. A person may feel dizzy or breathless or like their heart is racing or fluttering.
•• lung examination.
Often a lung function test is performed. In a lung function test, it is tested how much lung capacity you have and how quickly you can breathe in and out, breathe in deeply and blow out loud. The results give information about the airflow in the lungs, the oxygen uptake in the lungs and the volume of the lungs. Then you will be given a drug that widens the lungs and after 15 minutes the exercises will be repeated. The lung function analyst sees whether the contents of the lungs and the speed of inhalation and exhalation improve with the drug. In a bronchoscopy the inside of the lung is examined with the help of a bronchoscope. This is a flexible hose with a diameter of about 0.5 centimeters with a video camera at the end to inspect the lungs. Mucus or tissue from the wall of the lung can also be rinsed, brushed or removed (biopsy) by means of the bronchoscope. Using the X-rays of the CT scan, thin cross-sections can be made of your lungs to determine if there is lung fibrosis.
•• X-rays.
X-rays show possible formation of calcified nodules (calcium deposits) under the skin in the muscles and joints. Especially with the limited cutaneous systemic sclerosis (CREST syndrome) form of scleroderma you get calcium deposits at your fingertips and toes. These scale deposits can often only be seen on X-rays.
If you have problems with swallowing, X-rays of the esophagus can show if your esophagus is moving properly. Sometimes a gastroscopy (view of the esophagus and stomach) is also needed to assess the cause of the swallowing problems.

Treatment

While some treatments are effective in treating some aspects of the different forms of scleroderma, there is no drug that has been clearly proven to stop, or reverse, the key symptom of skin thickening and hardening. Drugs that have proven helpful in treating other auto-immune diseases, such as rheumatoid arthritis and lupus erythematosus, usually do not work for people with scleroderma.

Drug treatment
Drugs without a prescription
• For the pain you can get a simple painkiller with the active ingredient paracetamol without a prescription. Paracetamol helps against pain and fever, does not cause stomach problems, usually does not cause side effects and can be easily combined with other medications.
• An NSAID, an anti-inflammatory analgesic in a lower dose. The abbreviation NSAID stands for Non-Steroidal Anti-Inflammatory Drugs, such as diclofenac, naproxen and ibuprofen. These painkillers inhibit inflammation.

Do you have physical complaints? Always go to your doctor or specialist for a proper diagnosis and proper treatment.

Drugs on prescription
This is provided by your doctor or rheumatologist or internist.
Some drugs or treatments, mentioned below, may reduce your symptoms and slow down the disease.
• An NSAID, an anti-inflammatory analgesic, such as naproxen, ibuprofen, meloxicam or indomethacin. These are drugs that are effective against inflammation, swelling, pain, stiffness and fever, but do not prevent joint damage. They do not contain corticosteroids (steroids). There is no proof that any one NSAID is better than others. Your doctor will prescribe these prescription drugs with a higher dose of the active substance. The exact effective dose varies from patient to patient. High doses of short‐acting NSAIDs give the fastest relief of symptoms. Given in the correct dose and duration, these drugs give great relief for most patients. The NSAIDs may cause stomach upset, gastrointestinal (GI) bleeding, ulcers or diarrhea, but they are well tolerated by most people when used for the short term. Some people cannot take NSAIDs because of health conditions such as ulcer disease, impaired kidney function or the use of blood thinners. NSAIDs can also be used to counter the tendency to thrombosis. In a low dose, these agents (especially acetylsalicylic acid) can have an inhibitory effect on blood clotting. This may be beneficial for people who develop blood clots quickly or with sores on the fingers. In the case of the forms of systemic sclerosis (SSc), inflammation is common in the skin, muscles, joints and the organs (lungs, heart, kidneys). That is why patients often get prescribed medicines that inhibit inflammation.
• A conventional synthetic DMARD (Disease-Modifying Anti Rheumatic Drug). In scleroderma methotrexate, azathioprine or mycophenolate mofetil are prescribed. A DMARD has different mechanisms of action and suppresses joint inflammations in a number of forms of arthritis. When using a DMARD at an early stage of your condition, your joints will be less damaged by the inflammations. These drugs not only relieve symptoms but also slow down progression of the joint damage. Because of the medication, the body sometimes makes less connective tissue. In addition to the DMARD, the specialist can also prescribe an NSAID or a corticosteroid or a low dose of prednisone or a combination of the rheumatic inhibitors to directly combat the pain and to tackle the inflammation more effectively.
• Immunosuppressant drugs. In systemic sclerosis (SSc), inflammation is common in the skin, muscles, joints and the organs (lungs, heart, kidneys). That is why patients often get prescribed medicines that inhibit inflammation. If these drugs have insufficient effect, the doctor may prescribe medication that suppresses the immune system. Immunosuppressant drugs are used to treat autoimmune diseases. With an autoimmune disease, the immune system attacks the body’s own tissue. Because immunosuppressant drugs weaken the immune system, they suppress this reaction. This helps reduce the impact of the autoimmune disease on the body. Under the influence of these substances, the inflammation decreases and the disease becomes calmer, causing the symptoms to disappear or diminish. There are many different immunosuppressant drugs. In the treatment of scleroderma, use is mainly made of the agents azathioprine (DMARD), cyclophosphamide and mycophenolic acid. These drugs are only prescribed for severe inflammations, for example, of the lungs or kidneys.
•• A biologic DMARD (TNF alpha inhibitors, Interleukin inhibitors, B cell inhibitors and T cell inhibitors). A biologic response modifier is a drug that can affect your immune system. If you are healthy, the immune system itself produces enough antibodies to defend itself against pathogens (viruses and bacteria). This balance is disrupted in people with chronic inflammatory disease. A biologic response modifier can restore that balance. The drugs can block the immune system chemical signals that lead to inflammation and joint/tissue damage. Most often, patients take these drugs with methotrexate, as the mix of medicines is more helpful.
•• Immunomodulators are chemical agents (as methotrexate or azathioprine), that are used to modify the immune response or the functioning of the immune system (as by the stimulation of antibody formation or the inhibition of white blood cell activity).
•• Cytostatics are drugs that suppress the immune system by inhibiting cell division. These drugs are also used in the treatment of cancer. Cyclophosphamide is sometimes prescribed if you have a form of scleroderma in which organs are also affected by the disease. Cyclophosphamide is a drug that works on a rapidly dividing cell division and has an oppressive effect on inflammation. The dosage of cyclophosphamide varies per disease and depends on the symptoms you have of your illness. Normally, the immune system ensures that foreign cells are repelled. But in an autoimmune disease, this defense mechanism is disrupted. The immune system therefore no longer recognizes and attacks the body’s own cells and substances. Treatment with cyclophosphamide can prevent this process. The dose of cyclophosphamide in cancer treatment is different than in the treatment of auto-immune diseases.
• A corticosteroid (an artificial adrenal cortex hormone) is an anti-inflammatory drug that resembles the natural hormone that the body produces in the adrenal cortex. Corticosteroids mimic the effects of hormones your body produces naturally in your adrenal glands, which sit on top of your kidneys. When prescribed in doses that exceed your body’s usual levels, corticosteroids suppress inflammation. This can reduce the signs and symptoms of inflammatory conditions, such as arthritis. Corticosteroids also suppress your immune system, which can help control conditions in which your immune system mistakenly attacks its own tissues. A corticosteroid drug can be quickly effective for a joint swelling that is localized (not widespread) by an injection or shot into the effected joint or tendon sheath (the membrane around a tendon). Very inflamed joints may benefit from corticosteroid injections (cortisone shots). Examples are prednisone or prednisolone.
• The most commonly used drugs are calcium channel blockers for Raynaud’s phenomenon. The vasodilating agents ensure that muscle cells in the walls of the blood vessels relax, so that the blood vessels become wider. This allows the blood to flow better and the blood pressure goes down. A better flow of blood ensures that wounds heal faster.
In severe forms of Raynaud’s, with wounds on the fingertips (digital ulcers), other drugs may be available such as a prostacyclin, which acts as a vasodilator and inhibits the aggregation of platelets.
You can also get prescribed blood vessel dilators that are used in other conditions (high blood pressure, heart failure, kidney disease). These are blood pressure medications called “angiotensin converting enzyme inhibitors” (ACE inhibitors), which inhibit a substance that causes the blood vessels to constrict.
Raynaud’s phenomenon can also be treated with drugs called PDE-5 inhibitors, which open up narrowed blood vessels and improve circulation of the blood flow, such as sildenafil (Viagra), tadalafil (Cialis). 
• Antacid drugs, especially proton-pump inhibitors. Heartburn in stomach and esophagus (acid reflux) can be treated with antacid drugs, especially proton-pump inhibitors (omeprazole and others). These drugs ease gastro-esophageal reflux disease (GERD). Because these drugs are usually well tolerated, you can use them for a longer period of time. This also ensures that less stomach acid flows back to your esophagus.
• Drugs with heart problems. If your heart does not pump well anymore, you can get drugs that stimulate heart muscle cells. Myocarditis, an inflamed heart muscle, reduces the pinching force of your heart. This is a dangerous complication. You will be prescribed immunosuppressant drugs such as azathioprine, cyclophosphamide, prednisone or mycophenolate mofetil.
• ACE inhibitors with kidney problems. Scleroderma kidney disease can be treated with blood pressure drugs called “angiotensin converting enzyme inhibitors” (ACE inhibitors). The blood pressure decreases due to the vasodilating action of ACE inhibitors. These drugs inhibit a substance that causes the blood vessels to constrict. The heart therefore needs less force to pump the blood around. This makes them suitable for the treatment of severe kidney problems, heart failure and increased blood pressure. In scleroderma, loss of kidney function is often associated with increased blood pressure. Your blood pressure should be closely monitored. These drugs can often effectively control kidney damage if started early and use of these drugs has been a major advance for treating scleroderma. Usually your kidney function will partially recover, but sometimes your kidney is so damaged that kidney dialysis is necessary. You will be prescribed antidepressant drugs such as azathioprine, cyclophosphamide, prednisone or mycophenolate mofetil.
• Drugs with lung problems. There are two types of lung disease that patients with scleroderma may develop. The first type is called interstitial lung disease (pulmonary fibrosis), which causes scarring of the lung tissue. There is evidence that drugs, such as cyclophosphamide and mycophenolate mofetil, are somewhat effective in treating the interstitial lung disease in scleroderma. The second type of lung disease seen in scleroderma is pulmonary arterial hypertension (high blood pressure in the arteries in the lungs). A number of drugs have become available to treat this condition, which work by opening up the blood vessels in the lungs to improve blood flow. Drugs used for treatment of pulmonary hypertension are usually managed by specialists in the condition and include prostacyclin-like drugs (epoprostenol, treprostinol, iloprost), the endothelin receptor antagonists (bosentan, ambrisentan) and PDE-5 inhibitors (sildenafil, vardenafil, tadalafil).
• Oxygen problems. If the lungs can absorb much less oxygen through connective tissue formation and you become short of breath, it can help if you get extra oxygen from an oxygen tank. If the blood pressure in your small bloodstream (collecting oxygen, removing waste) is too high, your doctor may prescribe a drug that dilates your blood vessels and thus lowers blood pressure.
• Skin complaints. In the case of severe skin abnormalities, your doctor can give you an ointment with corticosteroids, sometimes in combination with immunosuppressant drugs such as prednisone and azathioprine. In localized scleroderma, UVA light therapy can have a positive effect on your skin. In case of itching you can use oily cream and possibly antihistamines. Histamine is released in an allergic reaction and is a substance that causes itching and causes the small blood vessels in the skin to expand, causing the skin to turn red and develop itchy bumps (edema). Antihistamines can be used to combat the effects of histamine. Itching can also be caused by an iron deficiency. Your doctor may rule out an iron deficiency with a blood test.
• Drugs to combat high fever. Your doctor can prescribe prednisone and/or a DMARD in case of sudden high fever.
• Drugs for severe fatigue. Severe fatigue can mean that the disease has become more active. Hydroxychloroquine or prednisone can reduce severe fatigue.
• Muscle pain and weakness can be treated with anti-inflammatory drugs such as glucocorticoids (prednisone), intravenous immunoglobin (IVIg) and/or immunosuppressant drugs. Inflammation of your muscles can reduce your muscle strength. If your large skeletal muscles ignite, we call that polymyositis. This can be treated with drugs such as prednisone or methotrexate. The joints are sensitive to inflammation (especially the hands and knees). For this you can get anti-inflammatory painkillers or prednisone. Inflammation can develop in your tendon sheath or connective tissue, causing you to feel pain or crack your tendons. For this you can get anti-inflammatory painkillers or prednisone.
• Stem cell transplantation may be a potential treatment in some patients with very severe systemic scleroderma. Sometimes systemic scleroderma progresses so severely that only perhaps a stem cell transplant may stop the disease. Stem cell transplantation is a very heavy treatment.

Use of drugs and adherence

• It is important that you take the drugs as prescribed. In order to get your illness under control, it is very important that you take your drugs on a regular basis every day. If you do not, there is no good concentration of the drug in your blood and therefore the drug will work less well.
• Do you have trouble remembering when and how many of your drugs you should take on a daily basis and at what time of the day? Then buy a drug dispenser, in which you can sort your drugs per day.
• Do you have difficulty or objection to taking the drug prescribed to you, for example because of possible side-effects? Then that can lead to you no longer taking the drug regularly. Discuss this with your doctor!

Deterioration of your illness and/or complications
The doctor will look at:
• The dosage and amount of drugs you use.
• Switching to another drug in the same type or a completely new type of drug.
• Combining different drugs at the same time.

Your doctor can tell you
• whether the drug can work for you.
• how you can best use the drug.
• how much and how often you can use the drug.
• how you can best reduce the drug.

You should always tell your doctor or specialist
• if you use other drugs (bought or prescribed by another doctor).
• if you have another medical condition.
• whether you will be operated on soon.
• if you have previously been prescribed an anti-inflammatory analgesic that has caused side-effects.
• whether you want to become pregnant or are pregnant.
• if you are breast-feeding.
This is important because your doctor or specialist has to make a careful choice between different drugs.

Side-effects
• All medications may have side-effects when used, so ask your doctor or pharmacist what side-effects you can expect or read the leaflet.

Reduce or stop
• If you stop using a drug yourself or reduce the number of drugs yourself, your symptoms may worsen. Always consult your doctor or specialist first if you want to use less drugs or want to stop.

Alternative treatments

There are many types of alternative treatments. This refers to all treatments that fall outside normal scientific medical care. No scientific evidence has been provided for the operation of these treatments. The alternative treatments are also called ‘complementary‘ because they can supplement the regular medical treatment by your doctor.
Many people choose an alternative treatment in addition to their regular medical treatment. They hope that this helps extra against their complaints or better helps to deal with the complaints.

Can an alternative treatment be a replacement for your regular medical treatment?
No, if you opt for an alternative treatment method, it is always a supplement to your regular medical treatment. You should not stop your regular treatment, because otherwise you run unnecessary health risks. Always consult your attending doctor before you start an alternative treatment.

What alternative treatments are there for example?
There are many different alternative treatment methods available, which can also be combined. Some examples are:
• Chinese medicine (acupuncture, pressure point massage, nutrition and tai chi).
• homeopathy (products made from plants and minerals).
• Bowen therapy.
• Ayurveda.
• Bach flower treatment.
• shiatsu, foot-sole and classic massage.
• Touch for Health.
• Reiki.
• dietary supplements.

What do you have to pay attention to?
• Many alternative treatments have not shown that they actually work. If you choose to try alternative treatment, make sure that your complaints do not increase. Stop an alternative treatment as soon as your symptoms increase.
• Always consider first why you want to follow an alternative treatment.
• Prepare yourself by looking up and reading information about the alternative treatment. Consult with your attending doctor, because certain complaints may be reduced by some alternative treatment methods.
• Determine yourself in which alternative method you trust for the relief of your complaints and whether you want to start.

What can you do best when choosing an alternative treatment?
• Always consult your doctor about the alternative treatment method you want to follow.
• Consult with your attending doctor and with the alternative therapist if they want to discuss your treatment with each other.
• Choose an alternative therapist who has followed a recognized vocational training and is affiliated to a professional organization.
• Ask your alternative therapist in advance about the purpose, duration, costs and risks of the treatment. How much money you spend depends on which treatment you choose and how long it takes.
• Do not stop your regular medical treatment, as this may worsen your symptoms.
• Weigh during treatment whether you want to continue or stop if your symptoms get worse, if you do not notice any effect of the alternative treatment or if you get side-effects.

Why is your food important?

• Healthy nutrition is important to get the vitamins and minerals and other nutrients that your body needs.
• Obesity creates risks for your health and disease progression. In the case of arthritis and obesity, for example, obesity plays an important role in overburdening and osteoarthritis in the knees, hips and ankles. The pressure on your joints is then simply too great. Healthy eating and exercise (exercising a sport and active in the home and outdoors) can help to reduce or prevent excess weight.
• A healthy diet is always important and the dietitian can support you with the right dietary advice.

What is a healthy diet?
With a healthy diet your body gets the right amount of good nutrients, which it needs. You eat the quantities that your body needs. The dietitian can support you with the right nutritional advice.
The 5 courses to choose from are:
• Vegetables and fruit
• Bread, cereal products and potatoes
• Fish, legumes, meat, egg, nuts and dairy
• Lubrication and preparation fats
• Drinks.

Where can you get advice for a healthy diet?
• You can request advice from your doctor or a dietitian. The doctor can refer you to a dietitian. Some diets may possibly help against your symptoms. Consult with your doctor or dietitian if you want to try a certain diet. And make sure that you do not omit important foods from your daily diet.

What can you do with a painful or dry mouth?
Sometimes you can suffer from a dry or painful mouth for various reasons, also due to your illness. Tips:
• by chewing (for example piece of cucumber, sugar-free candy or chewing gum) and sucking (ice cube) the salivary glands are stimulated to produce saliva.
• good oral care is important: good tooth brushing, flossing and the use of mouthwash.
• rinse your mouth regularly, drink small amounts of water and use a mouth sprayer if necessary.
• let hot drinks cool down first.
• use ice or cold dishes, because the cold numbs the pain.
• do not use sharp herbs and spices, fruit juice, carbonated soft drinks, alcoholic beverages, very salty foods and sour food.
• food with hard crusts, nuts, bones and bones can cause injuries.
• use soup, gravy or sauce with the hot meal to make the food smoother.
• spreadable cheese, spreadable paté or salad, jam or honey on bread, porridge, drinking breakfast and custard, for example, swallows easier than dry spreads.
• if you need to use ground or liquid food, you can use a mixer to grind your meal with some extra moisture.

In some forms of arthritis or use of certain drugs intestinal complaints can occur. The intestinal complaints can arise from the influence of certain drugs on food intake. Conversely, the food you eat can have an effect on the way your drugs work.

Dietary supplements, fish fatty acids, glucosamine and vitamin D?
• Dietary supplements are available as pills, powders, drops, capsules or drinks and are intended as a supplement to inadequate daily nutrition. They contain vitamins, minerals or bio-active substances. These synthetic or isolated vitamins, minerals or bio-active substances have the same effect as the vitamins and minerals that are already naturally in your food and drink.
Many people choose an additional supplement, in addition to their daily diet. The users of dietary supplements indicate that they experience positive effects of the use of certain herbs, vitamins and minerals. The body absorbs the nutrients in pills more easily than the nutrients in food. But if you eat healthy and varied, you do not need additional nutritional supplements, because you already get enough nutrients, minerals and vitamins. Always report to your doctor and pharmacist that you are using dietary supplements.
• Fish fatty acids appear to have a mild anti-inflammatory effect with a high intake. Research has been done especially in rheumatoid arthritis. The advice is to eat oily fish twice a week.
• Glucosamine can act as a mild painkiller for osteoarthritis in the knee, but does not stop arthritis.
• Our body naturally makes vitamin D under the influence of outdoor sunlight. Vitamin D may have a beneficial effect in inflammatory arthritis, but that has not yet been proven sufficiently. People with Lupus erythematosus get vitamin D prescribed as they are not often outside, because sun exposure can lead to lupus flares and skin problems. Vitamine D is given with calcium tablets to ensure a good intake in the body, when you have osteoporosis or osteoarthritis.

Living with scleroderma

Living with scleroderma is quite challenging. Patients must deal with the psychological setbacks that come from living with a disease that is chronic and currently incurable. Problems can range from digestion (often having to eat several small meals rather than fewer large meals), stiffness (keeping the skin well-moisturized to lessen this and exercise), finger injuries (to be avoided in activities such as gardening, cooking and so on) to coldness (to keep the body warm, patients should dress in layers and avoid very cold rooms). Significant changes in appearance can affect a patient’s self-esteem and self-image and support of family and friends is needed to maintain a good quality of life.

Advice
• For skin complaints you can use a moisturizing lotion for a (very) sensitive skin and place a humidifier in the house and possibly at work.
• If you have mouth problems, it is important to clean and care for your mouth and teeth properly to prevent dental problems. You can do mouth exercises to keep your mouth opening as smooth as possible. You should have a dental prosthesis checked regularly, because if it does not fit well, it will regularly cause irritation and/or damage to your mucous membranes. Smoking deteriorates the condition of your gums.
• When tired, it helps to move regularly. People with a chronic condition appear to suffer less from their fatigue if they exercise regularly. Also try to distribute your energy and divide your activities throughout the day.
• In case of an irritated painful esophagus, the stomach valve sometimes does not function properly. As a result acid stomach contents flow back into the esophagus. The heartburn can cause inflammation of your esophagus and damage your teeth. Because of the irritated painful esophagus, swallowing can hurt or food may not sink properly into your esophagus. Adjust your diet accordingly, it is important to eat slowly and chew well, use small portions throughout the day, not use sharp herbs in the food and drink water, coffee and tea without sugar and milk while eating. The food becomes softer as a result of a drink when eating. Then you can probably swallow more easily.
• For painful and stiff joints, you can keep the functionality and mobility of your joints and a good blood flow as long as possible by moving your joints every day. Regular exercise is good because it prevents bone decalcification, lowers your cholesterol, makes muscles stronger, is good for your condition, strengthens the heart and lungs, reduces the fat percentage and keeps the joints supple.
Heat helps well with stiffness. Warm clothing in layers keeps your body on temperature. Do you have painful fingers and toes because of Raynaud’s phenomenon? Heat provides a good blood supply to the hands and feet and use gloves, hat ans socks. Take a hot shower if you suffer from stiff joints and make sure your house is evenly heated. Avoid cold water and cold environments.
• Avoid stress and ensure a good night’s sleep.
• Stop smoking. Smoking narrows the blood vessels and increases the risk of cardiovascular disease, while in scleroderma this risk is already increased. The complaints also increase due to Raynaud’s phenomenon. Smoking also increases the risk of thrombosis (formation of blood clots in the blood vessels) in people with scleroderma.

Videos sources

Demystifying Medicine I An Overview of Scleroderma Part 1 I Breaking it down I https://youtu.be/h6ti1eVo-9s
Demystifying Medicine I An Overview of Scleroderma Part 2 I Treatment and management I https://youtu.be/6KLeGkeREkM
Demystifying Medicine I An Overview of Scleroderma Part 3 I Nutrition for Patients I https://youtu.be/ePBlZPXO7Ko
Demystifying Medicine: Relationship between Scleroderma and Pulmonary Fibrosis I https://youtu.be/jq7A-ImuBJY
Demystifying Medicine: Unmasking the causes of Scleroderma I https://youtu.be/euoTTOD33QI
Copyright Demystifying Medicine I McMaster University 2016
Scleroderma Foundation Tri-State I Living with Scleroderma I https://youtu.be/Gl66qO8uxSM

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