Scleroderma (Crest Syndrome)

Scleroderma is a rare chronic autoimmune disease, the disease characterized by the replacement of normal tissues of the skin with thick fibrous tissue.

The immune system is a well-connected network system of the body that defends against diseases and infections.

However, in a sclerodermic situation, the immune system triggers other cells to produce a higher amount of a type of protein called collagen.

These increased levels of secreted collagens get deposited in the skin and organs, which causes the outer layer of the skin and organs to harden and thicken, very similar to the scarring process.  

 Scleroderma is simply a disease that causes hardening of the skin, and in more severe cases, other organs can be affected.

The medical term ‘scleroderma’ used to describe this rare autoimmune condition might have coined just not so long ago (around the 19th century), but the disease has a long history.

According to news-medical.com, its history dates back as early as 400BC. Scleroderma was formed Greek words, “sclera” meaning hard and “derma” meaning skin.

Hippocrates first described the disease as “thickened skin.” in the mid 16th century; it was first described in detail by an Italian doctor Carlo Curzio.

He described in a report about his first patient with the condition as presenting a symptom as hard, wood-like skin.

He further explained that the patient had tightened skin in many regions of her body, tightness around the mouth, and hardness on the neck.

In 1836, Giovambattista Fantonetti eventually used the term scleroderma. Fantonetti described one of his patients as having leathered skin with dark coloration and joint mobility problems due to tightening of the skin.

In present days, the prevalence of scleroderma varies throughout the world, and the disease has been observed to affect more women than men (4:1 ratio). Over the past few decades, statistics show that the number of individuals affected by scleroderma is rising.

However, the etiology is unknown. About 250 per million American adults are affected by the condition; it frequently develops between age 35 and 55. However, pediatric forms have also been recorded.

The skin is primarily involved in mild scleroderma cases but in its most severe form that may affect other body organs such as the kidneys, gastrointestinal tract, blood vessels, heart, muscles, and joints.

Scleroderma can be life-threatening.

Table of Contents

Risk Factors Scleroderma

Some risk factors that can cause a person developing scleroderma or increase the risk of developing the disease include:

  • Being a female
  • Being African American
  • Being Native American
  • Exposure to silica dust and organic solvents
  • Using certain chemotherapy drugs like Bleomycin

Types of Scleroderma

Scleroderma is sometimes also called systemic sclerosis (SS), progressive systemic sclerosis, or CREST syndrome. Typically, there are two forms of scleroderma: Systemic and localized forms of scleroderma.

Systemic scleroderma can be further divided into two main types: diffuse and limited systemic sclerodermas.

Localized Scleroderma

This type of scleroderma is the most common form of scleroderma. Localized scleroderma only affects an individual’s skin, usually in a few specific places.

This category often appears in the form of waxy patches and streaks on the skin, and it is a common trend for this mild form of scleroderma to fade away or stop progressing without treatment.

Systemic Scleroderma

A diffuse scleroderma is a form of systemic scleroderma that affects many parts of the body. Unlike a localized form of scleroderma, a diffused form of scleroderma affects the skin and many internal organs, resulting in the hindrance of digestive and respiratory functions, and may even cause kidney failure.

Most times, systemic scleroderma becomes severe and life-threatening.

Limited scleroderma is also referred to as CREST syndrome; each letter represents a feature of the disease:

  • alcinosis (increased calcium deposits in the skin)
  • aynaud’s phenomenon
  • sophageal dysmotility (difficulty in swallowing)
  • clerodactyly (skin tightening on the fingers)
  • elagectasias (red spots on the skin)

Skins thickening in patients with limited scleroderma is restricted to the hands, fingers, and forearms, but the feet and legs may be affected in some cases.

These patients with this form do not experience kidney problems. Gastrointestinal tract involvement is confined to the esophagus.

Patients with limited scleroderma may also develop later pulmonary hypertension complications (20% to 30% of cases), potentially serious. In a matter of pulmonary hypertension complication, the arteries from the heart to the lungs become narrow.

High pressure is generated on the right side of the heart resulting in right-side heart failure.

Causes of Scleroderma

The exact cause of scleroderma remains unclear, but scientists have narrowed it down to be a consequential interaction between genetic and environmental factors.

In a pathogenetic study of some cases (not all), mutations in the HLA (Human Leukocyte Antigen) genes seem to play a major role.

In a similar fashion, silica, aromatic, ketones, trichloroethylene, chlorinated solvents, welding fumes, and white spirit exposure seem to contribute to the condition in a small proportion of scleroderma patients. 

Pathophysiologically, scleroderma is characterized by increased collagen synthesis, leading to sclerosis, damages to small blood vessels, activation of T lymphocytes, and production of altered connective tissues.

Note: Scleroderma is not contagious.

Symptoms of Scleroderma

 Other symptoms in addition to the primary symptom of scleroderma (thickening of the skin) include:

  • Increased calcium deposition in the skin
  • Swelling of hands and feet
  • Red spots on the skin (telangiectasias)
  • Joint contractures (rigidity)
  • Tight, mask-like facial skin
  • Fingers and toes ulcerations.
  • Pain and stiff joints
  • Chronic cough
  • Shortness of breath
  • Acid reflux (heartburn)
  • Difficulty swallowing
  • Digestive and gastrointestinal complications
  • Constipation
  • Weight loss
  • Fatigue
  • Hair loss
  • Sjögren’s syndrome manifested by dry eyes and mouth. This dryness is from lack of tears and saliva secretion due to immune damage and destruction of the body’s moisture-producing glands. It is seen in about 20% of scleroderma patients.

Approximately 85% to 95% of scleroderma patients experience Raynaud’s phenomenon. However, Raynaud’s phenomenon is common and often self-occurring without any underlying connective tissue disorder.

Only about 10% of persons with Raynaud’s phenomenon will develop. 

Diagnosis of Scleroderma

Typically, it is not easy to diagnose scleroderma since it can affect other vital parts of the body, such as the joints, and doctors might initially mistake this for lupus or rheumatoid arthritis.

First, in scleroderma diagnosis, the doctor will perform a physical examination of symptoms presented, especially the primary symptom of skin thickening or hardening around the extremities (finger and toes) and skin discoloration.

If a scleroderma case is suspected, other tests are conducted to confirm a diagnosis. These tests include:

Blood tests

Blood tests are conducted to observe for increased levels of immune factors, known as antinuclear antibodies. These levels are elevated in about 95% of patients with scleroderma.

However, this cannot confirm scleroderma as these antibodies are also elevated in other autoimmune diseases such as lupus. A blood test helps assist with an accurate diagnosis in potential scleroderma patients.

Pulmonary function tests (PFTs)

PFTs are conducted to measure how well the lungs are functioning. If scleroderma is present and requires confirmation, it is necessary to verify if it has spread to the lungs or not, resulting in scar tissue formation.

CT (computed tomography) scan and X-ray can be used to check for any lung damage.

Electrocardiogram

Also, scleroderma can result in scarring of the heart’s tissues, leading to congestive heart failure and the defective electrical activity of the heart. This test is conducted to evaluate if scleroderma has affected the heart.

Echocardiogram

This test is an ultrasonogram of the heart, and it is recommended once every 6 to 12 months to evaluate for complications like pulmonary hypertension and congestive heart failure.

Kidney function

In a case where sclerodermaaffects the kidney(s), the result can be elevated blood pressure and proteinuria (the leakage of protein into the urine).

In the most serious form, called a scleroderma-renal crisis, a rapid increase in blood pressure might occur, leading to kidney failure. Blood tests can assist in assessing kidney function.

Gastrointestinal or Digestive tests

Muscles of the esophagus and intestinal walls can be affected by scleroderma. It results in heartburns and difficulty in swallowing and can also affect food movement through the intestines, subsequently affecting the absorption of nutrients.

An endoscopy can be performed to observe the esophagus and the intestines, and a test known as manometry can be conducted to measure the strength of the esophageal muscles.

Differential Diagnosis

Some conditions that are often presenting similar symptoms as scleroderma include:

  • Eosinophilia (a medical condition of increased levels of eosinophils, which is a type of white blood cells that fights parasites in the blood).
  • Graft-versus-host disease (a case of an autoimmune condition where immune cells from a transplanted bone marrow begin to attack the host’s body).
  • Mycosis fungoides
  • Eosinophilic fascilitis (a condition where connective tissues surrounding skeletal muscles, bones, nerves, and blood vessels in the arms and legs are affected).
  • Primary biliary cirrhosis
  • Complex regional pain syndrome
  • Nephrogenic systemic fibrosis

Treatment of Scleroderma

 There are no typical treatments for scleroderma; approaches are to help reduce the severity of the symptoms and slow disease progression.

Treatment approaches are based on a patient’s symptoms and the need to avert complications.

Treatment generally recommended for common symptoms include:

  • Corticosteroids
  • NSAIDs (non-steroidal anti-inflammatory drugs)
  • Immuosuppressants, such as cytoxan, azathioprine, and methtrxate.

Depending on the presented symptoms, other treatments may include:

  • Breathing aid medications
  • Blood pressure medications
  • Heartburn medications
  • Antibiotics
  • Physical therapy
  • Exercise
  • More fiber and fluid in diet
  • Stress management
  • Phototherapy
  • Nitroglycerin ointment to treat localized areas of skin tightening.
  • In case of severely damaged organ, a transplant may be recommended.

Complications of Scleroderma

Potential conditions that may arise as a result of scleroderma symptoms progression. Complications such as:

  • Heart failure
  • Hypertension
  • Cancer
  • Kidney failure
  • Infection
  • Cyanosis in fingers and toes
  • Lung scarring

Summary

Scleroderma is a rare condition and treatments have drastically increased in the last few decades. However, there is still no cure for this hard-skin condition. Medications correctly and regularly taken can assist manage symptoms, preferable treatment approaches can be carefully selected by a physician.

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