What is scleroderma?

Scleroderma is typically described as a rheumatic disease of the connective tissues. It is a chronic, degenerative disorder accompanied by widespread vascular deterioration and tissue loss. Scleroderma can be disfiguring, debilitating and deadly. In the most serious cases, the disease causes severe damage and severe complications for the body’s digestive, respiratory and circulatory systems.

Pain, ranging in severity from uncomfortable to debilitating, is a common characteristic of the disease. Other common symptoms can include, but are not limited to the following:

  • General fatigue
  • Joint or bone aching
  • Stiffness of hands and feet
  • Skin discoloration
  • Swallowing difficulties
  • Skin thickening or tightness
  • Dry mucus membranes
  • Calcium deposits under the skin
  • Unexplained ulcers on fingers or toes
  • Raynaud’s phenomenon (described below)

Scleroderma is not a single disease, but a set of related disorders involving a similar set of symptoms. This makes a concise definition – and diagnosis – difficult. All forms of scleroderma do, however, share the basic characteristics of fibrosis (an excessive accumulation of tissue) and inflammation.

Recent research suggests that scleroderma is not only a rheumatic disease, but also has a blood vessel component. Inflammation in the body’s blood vessels leads to their narrowing. Further damage from the inflammation and impact of the increased blood pressure can lead to destruction of smaller arteries. As a result, or perhaps as a parallel disease process, fibrosis takes place. This process can have devastating implications and the heart and lungs can suffer a significant loss in efficiency. Pulmonary arterial hypertension (PAH) is the leading cause of death in scleroderma patients.

The first documented account of scleroderma was by Dr. Carlo Curzio of Naples in 1754, who described his patient as a 17-year-old Neapolitan woman afflicted by a disease of “extraordinary nature.” “Her complaint,” wrote Dr. Curzio, “was an excessive tension and hardness of her skin over all her body, by which she found herself so bound and straightened that she could hardly move her limbs.” Nor could she fully close her eyelids or open her mouth, due to “the firmness of the skin and membrane.”

The fibrosis witnessed by Dr. Curzio is the most noticeable feature of the disease. In fact, the word scleroderma is Greek for “hard skin,” although it is much more than that, often affecting the internal organs with life-threatening consequences.

Hundreds of thousands of people suffer from the various types of scleroderma, and as many as 10,000 patients die every year from the most serious form of the disease. Eighty percent of those afflicted with the disease are women, though scleroderma also strikes men and children across all ages and ethnic boundaries. Unfortunately, the disease typically strikes in the prime of patients’ lives, when they are 30-50 years old.

The cause of scleroderma is unknown. It is not contagious and it is rare for direct family members to manifest the disease. However, there is evidence of a genetic predisposition to scleroderma. Some scleroderma cases have been linked to environmental factors such as silica dust, organic solvents, and certain drugs, though the cause for most cases of scleroderma is still not known.

Significant progress has been made in managing the symptoms and some of the most serious complication of scleroderma, so that people with the disease are living longer, fuller lives. Still, no therapies yet exist to halt or reverse the disease process. Patients continue to experience pain, deterioration and debilitation – and many patients die.

The Scleroderma Research Foundation is devoting every possible resource to solving the mysteries of scleroderma. A collaborative approach to research is opening doors to therapeutic development and ultimately, a cure.

Types of scleroderma

There are two major types of scleroderma—localized and systemic. Localized scleroderma affects only the skin and is, generally, not as destructive or debilitating as systemic scleroderma, which is a multi-system disease often involving the skin, blood vessels, heart, lungs, kidneys and other major organs.

Localized sclerodermaSystemic scleroderma (systemic sclerosis)
Localized morphea Limited systemic sclerosis
Generalized morphea Diffuse systemic sclerosis
Linear scleroderma Sine sclerosis


Localized Scleroderma

The skin is typically the only organ involved in localized scleroderma. In extreme cases, however, the muscle below is also affected by a hardening of the tissues. Because internal organs are not affected by localized scleroderma, it is not a life-threatening illness and can be considered a less serious health threat than other forms of the disease. Symptoms of localized scleroderma will, in many cases, improve or go away on their own over time, but there is frequently permanent damage in the form of residual scar tissue. For some patients, localized scleroderma can be disfiguring and painful. In rare cases, it can be disabling. There are three major sub-types of localized scleroderma:

Localized Morphea

Morphea (mor-FEE-ah) is derived from the Greek word “morfi,” meaning shape or structure. With localized morphea, the body shows one or several patches of scleroderma. Symptoms include reddish patches of inflamed and discolored skin, usually on the chest or back, but sometimes on the face, arms and legs. These oval-shaped patches are limited to certain areas on the body and range in size from a half-inch to approximately 12 inches in diameter. Localized morphea is further pronounced by the absence of sweat glands and very little, if any, hair growth in affected areas.

Generalized Morphea

Generalized morphea is a more severe, although less common, condition than localized morphea. Large dark patches of thick, tight skin form on the trunk, arms and legs, and can be so extensive that they merge into one another. These widespread plaques closely resemble oversized patches of localized morphea, but are usually ivory-colored and sometimes have a distinct violet-colored border. Patients with generalized morphea do not suffer from the internal life-threatening features of systemic sclerosis, but the disease can result in severe scars and physical disability.

Generalized morphea has been known to appear on areas of the skin treated by radiation therapy.

In many cases, both localized and generalized morphea improve spontaneously over time (typically 3 through 5 years); however, patients are often left with patches of darkened or discolored skin and, in rare cases, muscle damage.

Linear Scleroderma

Linear scleroderma, also known as bilateral scleroderma, is characterized by a highly visible band or bands of thick, tight skin on the arms, legs, chest, stomach, back, buttocks or face. It is often considered a pediatric disease as it usually manifests itself within the first 10 years of life.

When affecting a limb, linear scleroderma can cause arms and legs to develop at noticeably different rates. It is not uncommon for the disease to extend down to the bones and muscles underneath it, thus damaging their structure, limiting motion of affected joints, and interfering with normal growth.

When linear scleroderma occurs on the face, it is often referred to as en coup de saber (en-KOO-de-sob), a French term for “a strike of the sword,” due to its appearance. Linear scleroderma may be disfiguring, but is not life threatening and rarely progresses to systemic scleroderma.

Systemic Scleroderma (Systemic Sclerosis)

Systemic scleroderma, also known as systemic sclerosis, is a multi-system disease with numerous manifestations that can affect not only the skin, but also underlying blood vessels, muscles and joints, as well as the gastrointestinal tract, kidneys, lungs and heart. There are two subsets of systemic scleroderma, limited and diffuse – both are characterized by vascular injury, as well as severe inflammation and fibrosis.

Systemic scleroderma causes a loss of circulation that can result in painful skin ulcers occurring on fingers, toes and other extremities. Joint pain caused by inflammation and swelling can be chronic. Loss of flexibility in the hands and severe skin tightening can impair the use of fingers and toes. The skin of the face may also tighten and harden, especially around the mouth, making eating and drinking difficult.

Systemic scleroderma (both limited and diffuse) is the most dangerous form of the disease and the primary focus of research funded by the Scleroderma Research Foundation.

It is estimated that approximately 90% of systemic scleroderma patients experience Raynaud’s (ray-NOHZ) phenomenon as a primary symptom. Named after the French physician who discovered it more than a century ago, Raynaud’s is a condition in which the small blood vessels of the hands and, sometimes, feet contract in response to cold or stress. The process makes the hands/feet extremely sensitive to cold and causes their pigmentation to blanch from white to blue. As blood flow returns, they become red. With scleroderma patients, tissues in fingertips, especially the capillaries, may suffer damage. This damage can lead to ulcers, scars, or, in severe cases, gangrene.

It should be noted that Raynaud’s phenomenon is quite common, affecting approximately 1 of every 20 people in the United States. Research suggests that only 5 – 20% of people with Raynaud’s phenomenon will go on to develop a form of systemic scleroderma.

Limited Scleroderma

Systemic limited scleroderma affects approximately two-thirds of the systemic population. Although the progression is typically more slow-moving, the disease can still be life-threatening. It is imperative to treat these symptoms and carefully monitor for end-organ damage. Chronic pain, loss of mobility and disfigurement are possible. There is also the potential for serious complications related to the esophagus and other parts of the gastrointestinal tract, as well as pulmonary complications leading in some cases to dangerously high blood pressure. Systemic-limited scleroderma is often referred to as CREST, an acronym for several of the most prominent symptoms:

Calcinosis Hard, painful calcium deposits in the skin
Raynaud’s phenomenon Blanching of feet and hands from white, to blue to red in response to cold or stress
Esophageal dysfunction Problems with swallowing caused by internal scarring. The scarring is caused by the collagen build-up.
Sclerodactyly Tightening of the skin on the fingers and toes, progressing to the hands and face, and sometimes the neck and feet
Telangiecstasia Small red spots on the fingers, palms, forearms, face and lips


Diffuse Scleroderma

Diffuse scleroderma is typically characterized by an early internal inflammatory phase. Also, unlike limited scleroderma, the onset of symptoms that significantly impact quality of life can be rapid and severe. In most cases of diffuse scleroderma, there is extensive skin fibrosis covering large parts of the body and extremities. Even cases without significant skin involvement can be life-threatening, depending on the type and magnitude of organ damage.

Problems of the digestive tract can make eating, nutrient absorption and elimination difficult. The most serious complications of diffuse scleroderma involve the kidneys, lungs and heart and may include renal failure, pulmonary arterial hypertension (PAH) and the potential for heart failure. PAH is the leading cause of death among scleroderma patients.

People with diffuse scleroderma are often chronically tired, have a diminished appetite, show weight loss, and suffer from joint swelling and pain. Changes in the skin can include swelling, tightening and chronic itchiness.

It is not uncommon for people with diffuse scleroderma to enter a phase where disease progression stabilizes for varying lengths of time. This stabilizing phase often begins within three to five years after onset and can last for varying amounts of time.

As will all forms of the disease, there is no cure for diffuse scleroderma. Although the disease may continue to lie dormant for several years, there can be no certainty as to whether symptoms will improve, remain stagnate or worsen.

Early diagnosis, symptomatic treatment and frequent visits to a physician for monitoring are critically important for diffuse scleroderma patients.

Sine Sclerosis

Sine (SEEN-ay) sclerosis is a term used by many physicians to describe systemic scleroderma without the characteristic skin involvement. In fact, the word “sine” is Latin for “without.” Patients with sine sclerosis may have symptoms of either limited or diffuse scleroderma, causing damage to the internal organs. Because there are no external manifestations of the disease, it can be difficult to diagnose. As with other forms of systemic sclerosis, however, the presence of Raynaud’s phenomenon and positive autoantibodies can be useful indicators. Complications of the internal organ systems can be serious and often life threatening.

 
 

Research News

Cardiac troponin testing in idiopathic inflammatory myopathies and systemic sclerosis-spectrum disorders: biomarkers to distinguish between primary cardiac involvement and low-grade skeletal muscle disease activity

Author: Michael Hughes, James B Lilleker, Ariane L Herrick, Hector Chinoy
Date Published: March-2015
Source: Annals of the Rheumatic Diseases

Primary cardiac involvement, an under-recognised manifestation of the idiopathic inflammatory myopathies (IIM) and systemic sclerosis (SSc)-spectrum disorders, is associated with significant mortality. Within these two conditions, traditional skeletal muscle enzyme testing may not effectively distinguish between skeletal and cardiac muscle involvement, especially in patients with subclinical cardiac disease.

Adipocyte–myofibroblast transition: linking intradermal fat loss to skin fibrosis in SSc

Author: Sarah Onuora
Date Published: January-2015
Source: Nature Reviews Rheumatology

Myofibroblasts are considered the primary fibrogenic effector cells in systemic sclerosis (SSc), but the origin of these cells within fibrotic lesions is a matter of debate. A new study published in Arthritis & Rheumatology shows that the majority of dermal myofibroblasts in fibrotic skin arise from adiponectin-positive progenitors resident in the…

Review: Cancer-Induced Autoimmunity in the Rheumatic Diseases

Author: Ami A. Shah, Livia Casciola-Rosen and Antony Rosen
Date Published: January-2015
Source: Arthritis & Rheumatology

Tantalizing connections between autoimmune rheumatic diseases and cancer have become increasingly evident over the past several decades. These connections are complex, with different relationships in frequency, timing, and types of cancers observed in different diseases or disease subgroups. Several recent advances from disparate fields have begun to illuminate the dynamic and bidirectional interactions occurring at the cancer–immune system interface which may be relevant to understanding the origins of autoimmunity ([1]). These interactions include the existence of potent anticancer immune responses that limit tumor growth, as well as multiple immune and inflammatory pathways that can contribute to tumor growth and robustness. The striking ability of immune checkpoint inhibitors to reveal powerful anticancer immune responses in patients with cancer highlights the fact that natural immune responses to cancers occur, and may regulate the emergence of cancer ([2]).

Autologous Fat Grafting in the Treatment of Fibrotic Perioral Changes in Patients With Systemic Sclerosis

Author: Del Papa, Nicoletta; Caviggioli, Fabio; Sambataro, Domenico; et al
Date Published: January-2015
Source: Cell Transplantation

Autologous fat tissue grafting (AFTG) has been successfully used in the treatment of different sclerotic conditions, including localized scleroderma. Patients with advanced systemic sclerosis (SSc)-related perioral thickening and mouth opening limitation are candidates for this therapeutic approach. AFTG of the lips was performed to improve mouth opening in patients with SSc. We enrolled in the study 20 female patients with diffuse SSc (median age 35 ± 15 years and 11 ± 10 years of disease duration). Two-milliliter fractions of autologous fat drawn from trochanteric or periumbilical areas were injected in eight different sites around the mouth.

Impaired BMPRII Signalling in a TGFβ Dependent Mouse Model of Pulmonary Hypertension and in Systemic Sclerosis.

Author: A. Gilbane, E. Derrett-Smith, S. Trinder, R. Good, A. Pearce , C. Denton , and A. Holmes
Date Published: January-2015
Source: American Journal of Respiratory and Critical Care Medicine

Rationale: Up to 10 percent of systemic sclerosis (SSc) patients develop pulmonary arterial hypertension (PAH). This risk persists throughout the disease and is time-dependent, suggesting that SSc is a susceptibility factor. Outcome for SSc-PAH is poor compared with heritable (hPAH) or idiopathic (iPAH) forms, despite clinical and pathological similarities. Whereas susceptibility in hPAH and iPAH is strongly associated with gene mutations leading to reduced expression of bone morphogenetic protein type II receptor (BMPRII), these mutations have not been observed in SSc-PAH.

News for Patients

Actemra Looks Promising in Scleroderma

Author: Nancy Walsh
Date Published: April-2015
Source: MedPage Today

Encouraging results were seen for tocilizumab (Actemra) in the treatment of diffuse systemic sclerosis (SSc) in a proof-of-concept study, an investigator reported here. At 24 weeks, a numerically favorable response was seen on modified Rodnan skin scores among patients randomized to tocilizumab compared with those receiving placebo, with changes of -3.9 units versus -1.2 units, for a difference of -2.70 (95% CI -5.85 to 0.45, P=0.09), according to Christopher P. Denton, MBBS, of University College London.

Systemic Sclerosis Patients Are More Prone to Atherosclerosis

Author: Patricia Silva
Date Published: April-2015
Source: Scleroderma News

In a new study entitled “Subclinical atherosclerosis and peripheral vascular disease in systemic sclerosis patients: Relation to potential risk factors,” authors suggest that patients with Systemic sclerosis may have increased risk of developing subclinical atherosclerotic macro vascular disease. The team highlights that further research is necessary to tackle both the cause for increased risk of atherosclerosis and the vessel damage in the SSc patient population. The study was published in the journal The Egyptian Rheumatologist.

Researchers Find New Small Molecule Capable of Triggering the Immune System

Author: Patricia Silva
Date Published: April-2015
Source: Scleroderma News

Researchers at the University of Colorado Boulder and Tsinghua University in China recently published in the journal Science Advances that a specific small molecule is capable of triggering an immune response, having potential biomedical applications for treating diseases such as Scleroderma. The study is entitled “Specific activation of the TLR1-TLR2 heterodimer by small-molecule agonists.”

7 Things You Should Know About Autoimmune Diseases

Author: Sarah Klein
Date Published: February-2015
Source: Huffington Post

As if living with chronic illness wasn't challenging enough, living with an autoimmune disease can be even more difficult. Still highly misunderstood by medical professionals and the public alike, autoimmune diseases are characterized by nebulous symptoms that can make diagnoses difficult to come by. Treatments vary, and in some cases rely entirely on behavior changes. In an effort to making living with -- or loving someone with -- an autoimmune disease just a little bit easier, here are seven important things to know about these health conditions.

Autoantibodies May Explain Link Between Cancer and Scleroderma Onset

Author: Patricia Silva
Date Published: February-2015
Source: Scleroderma News

Researchers at Johns Hopkins University School of Medicine in Baltimore investigated the association between autoantibodies, the risk of developing cancer and the possible link between cancer and scleroderma. The study is entitled “Examination of autoantibody status and clinical features that associate with cancer risk and cancer-associated scleroderma,” and is published in the journal Arthritis & Rheumatology.

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