WHAT IS SCLERODERMA?
Scleroderma is a rare, progressive and chronic autoimmune connective tissue disorder that causes excess collagen accumulation.
The word scleroderma literally means ‘hard skin’ and is derived from the Greek words “sclerosis” meaning hardness and “derma” meaning skin. It is this thickening of the skin that is the most characteristic feature of scleroderma. Less visible, but of major importance, are the vascular lesions that occur in small blood vessels and which may affect major organs. Normally collagen helps to keep tissues soft. In scleroderma however, the overproduction of collagen causes the opposite effect, resulting in a thickening, hardening and scarring of tissues. These affected tissues can be further compromised by reduced blood flow through the small blood vessels.
The course of the disease varies widely from individual to individual, ranging from minor nuisance symptoms to a severe multifaceted disease. Forms of the disease that primarily affect the skin without major organ involvement are referred to as linear scleroderma, and have a better long-term outlook. Systemic scleroderma affects the skin as well as the underlying tissues, and is typified by vascular lesions in blood vessels and major organs. Symptoms of systemic scleroderma tend to be more severe with less desirable long term outcomes.
Medications are available to help slow the progression of scleroderma and provide symptom relief, but as of yet, there is no cure. In the past two decades, multidisciplinary research has provided new clues to understanding the disease. This research is an important step toward prevention and cure, and has resulted in new treatments to better manage symptoms, prevent organ damage and improve the quality of life for people with scleroderma.
Scientific evidence shows that scleroderma is not contagious, not infectious, and not cancerous, while studies of twins also suggest that scleroderma is not inherited. It can affect men and women of all races and ethnic groups at any stage of life, from infancy to late adulthood.
Research has helped highlight some disease patterns across populations:
Scleroderma is more common in women than in men, with female patients outnumbering male patients about four to one.
The average age of disease onset is 40 years.
Localized scleroderma is more common in children.
Systemic scleroderma is more common in adults.
Ethnic background may play a role in the rate of incidence, age of onset and severity.
Individuals with familial history of rheumatic disease may have a slight predisposition to scleroderma.
There are two types of scleroderma: localized and systemic, both which can be further classified into sub-categories as shown in the image below.
Localized scleroderma is limited to the skin and surrounding tissues and does not affect internal organs, nor does it progress to the systemic form. Often, localized symptoms improve or go away on their own over time, however damage that occurs when the disease is active such as skin changes, may be permanent. Localized scleroderma presents either as Morphea or Linear, both of which have unique symptoms as detailed below.
Morphea: The first signs of morphea scleroderma are reddish patches of skin that thicken into firm, oval-shaped areas. These patches become ivory coloured with violet borders, sweat very little and have sparse hair growth. Patches most commonly appear on the chest, stomach and back, but can also be present on the face, arms and legs. Morphea can be either localized or generalized. Localized morphea limits itself to a single or a few patches ranging in size from 1-30cm in diameter, and sometimes appearing on areas of the body treated by radiation therapy. Generalized morphea is typified by dark, hard skin patches that have spread over larger areas of the body. Regardless of the type, morphea generally fades out in three to five years; however, people are often left with darkened skin patches and, in rare cases, muscle weakness.
Linear Scleroderma: As suggested by its name, linear scleroderma is characterized by a single line or band of thickened, unusually coloured skin. Typically, the line runs down an arm or leg, but in some people it runs down the forehead. Some people have both morphea and linear scleroderma.
Systemic Scleroderma (Systemic Sclerosis):
Systemic scleroderma affects the skin as well as the underlying tissues, and is characterized by vascular lesions in blood vessels and major organs. Systemic sclerosis is further sub-divided into three distinct forms: Limited Systemic Sclerosis, Diffuse Systemic Sclerosis and Sine Systemic Sclerosis.
Limited Systemic Sclerosis: Limited systemic scleroderma typically comes on gradually and affects restricted areas of the skin including fingers, hands, face, lower arms and legs. People with limited systemic scleroderma often have some if not all symptoms associated with CREST. CREST is an acronym for the following complications which are further defined below: Calcinosis, Raynaud’s Phenomenon, Esophageal dysfunction, Sclerodactyly and Telangiectasia. A sixth, but less common, symptom associated with CREST is Bowel Dysfunction.
Calcinosis: small white chalky lumps consisting of calcium form under the skin. Lumps occur around the fingers but can be present anywhere in the body, and can rupture through the skin thereby oozing chalky white material. Note that calcinosis is not caused by too much calcium in the diet.
Raynaud’s Phenomenon: a condition caused by the constriction of blood vessels in response to cold temperature or anxiety. Fingers and sometimes toes change colour, first turning white, then blue, and then finally returning to normal. Most people with limited systemic sclerosis present with Raynaud’s Phenomenon for years before skin thickening starts. Note that smoking will aggravate this condition.
Esophageal dysfunction: difficulty in swallowing resulting from tissue changes in the esophagus. Normally, food is carried down from the mouth to the stomach by the rhythmic muscle action in the esophagus. During esophageal dysfunction, the esophageal muscle is damaged by scar tissue and becomes less mobile, thus diminishing muscle action. Over time the dynamic muscular esophagus begins to resemble a static open pipe, resulting in difficulty swallowing. Heartburn can occur as acid from the stomach floods upwards into the esophagus where it causes burning. There may also be a feeling of bloating when eating and a desire to vomit after eating.
Sclerodactyly: thickening of the skin in the fingers and toes. The term comes from the Greek “skleros” meaning hard, and “daktylos” meaning digits. The skin of the digits becomes dry and coarse, with a textured woody feeling. Hair vanishes, creases disappear, and the affected area looks shiny. Fingers tend to flex or tighten into a bent position and there is accompanying difficulty in movement.
Telangiectasia: damage to small blood vessels results in the formation of compact red spots that appear on the fingers, palms, face, lips and tongue.
Bowel Dysfunction: tissue damage in the intestine reduces motility and leads to complications including an inability to absorb nutrients from food, an overgrowth of bacteria in the bowel, weight loss and diarrhea or constipation.
Diffuse Systemic Sclerosis: Diffuse systemic sclerosis typically comes on suddenly. Skin thickening begins in the hands and spreads quickly and over much of the body, affecting the hands, face, upper arms, upper legs, chest and stomach in a symmetrical fashion. Some people may have more area of their skin affected than others. Internally, this condition can damage to key organs such as the intestines, lungs, heart, and kidneys.
People with diffuse disease are often tired, lose appetite and weight, and have joint swelling or pain. Skin changes can cause the skin to swell, appear shiny, and feel tight and itchy. The damage of diffuse scleroderma typically occurs over a few years. After the first three to five years, people with diffuse disease often enter a stable phase lasting for varying lengths of time. During this stable phase, symptoms subside: joint pain eases, fatigue lessens, and appetite returns, while progressive skin thickening and organ damage decrease. The skin may begin to soften gradually, usually occurring in reverse order of the thickening process so that the last areas thickened are the first to begin softening. Some patients’ skin returns to a somewhat normal state, while other patients are left with thin, fragile skin lacking hair or sweat glands. Serious new damage to the heart, lungs, or kidneys is unlikely to occur, although patients are left with whatever damage they have in specific organs.
The most serious long-term outlook for diffuse systemic scleroderma patients is if severe kidney, lung, digestive, or heart problems have developed. Fortunately, less than one-third of patients with diffuse disease develop these severe problems. Early diagnosis and continual and careful medical monitoring are important in order to help manage symptoms and prevent health complications.
Sine Systemic Sclerosis: The term ‘sine’ has Latin origins and means “without”. Sine sclerosis a form of systemic sclerosis where patients do not have any overt skin thickening, but do have other manifestations of systemic sclerosis which may involve the blood vessels and major organs.
The cause of scleroderma is unknown, however a great deal is understood about the biological processes involved. In localized scleroderma, the underlying problem is fibrosis, while in systemic sclerosis, fibrosis, vascular disease and autoimmunity, are all involved.
Fibrosis is the abnormal accumulation of collagen, which
results in the scarring and thickened skin so typical of scleroderma.
Fibroblasts are the most common cells in our connective tissues and are responsible for making collagen, which is the basic component of scar tissue. Under normal circumstances,
fibroblasts are activated by the immune system after injury or infection to produce collagen during the final stage of the healing process. On the skin’s surface, the resulting outcome is what we know as a scar.
In scleroderma patients, fibroblasts are activated to make more collagen and the delicate balance of collagen formation and breakdown is altered, resulting in collagen overproduction. Localized scleroderma confines the abnormal accumulation to some areas of the skin, while in systemic sclerosis, the excess collagen can cause fibrosis in the heart, lungs and the muscles that line the gastrointestinal tract.
In systemic sclerosis the small blood vessels are damaged and become narrowed. It is this process that causes Raynaud’s Phenomenon and the painful ulcers that can occur on the fingers. Vascular damage also occurs in the internal organs and is responsible for scleroderma renal crisis and pulmonary hypertension. Small arteries are normally capable of constricting or dilating to adjust blood flow as required by the body. In systemic sclerosis however, the damaged blood vessels lose their ability to dilate thus becoming prone to episodes of vasospasm, which is a contraction of the muscle wall that closes the vessel. The vessels become overly sensitive to cold temperatures and other stimuli like emotional stress, which result in symptoms like Raynaud’s attacks.
Systemic sclerosis immune system dysfunction results in an attack on the body’s own tissues and leads to inflammation. One way to detect activation of the immune system is to find antibodies in the blood that target the body’s own tissues. Antibodies are proteins made by immune cells, and are the foundation of our immune system. The term ‘autoantibody’ is used when describing antibodies that target the body’s own tissues.
A very specific set of autoantibodies is found in scleroderma, however it is not yet clear what role they play in damaging blood vessels or stimulating collagen overproduction. The autoantibodies found in systemic sclerosis patients can be thought of as footprints of the scleroderma disease process because they are only made under the very specific conditions typical of scleroderma.