CREST Syndrome
CREST Syndrome and Limited Scleroderma also fall under the umbrella
of being referred to as Systemic Sclerosis (scleroderma). These forms are believed to be
less progressive and a diagnosis of CREST or Limited is believed to place the person at a
less risk of involvement of life sustaining organs.
Doctors vary on the opinion concerning whether CREST Syndrome and
Limited Scleroderma are one and the same form of scleroderma or if they are two separate
conditions. Opinions by some physicians place Limited as a little more progressive then
CREST Syndrome therefore believing they are separate. However, in recent years more and
more doctors are categorizing CREST Syndrome as Limited Scleroderma.
CREST Syndrome is an acronym which stands for
C.....Calcinosis,
R.....Raynauds phenomenon
E.....Esophagus
S.....Sclerodactyly
T.....Telangiectasia
Diagnosis of CREST Syndrome
You may receive a diagnosis of CREST without presenting symptoms of
all the elements noted above. To receive a diagnosis of CREST the doctors only require
that a person meet at least two of these five elements. Some people can have CREST along
with overlaps of diffuse scleroderma or other connective tissue diseases such as lupus,
arthritis and polymyositis.
A diagnosis of CREST/Limited scleroderma may be made if a person
tests positive for the Anti-Centromere when checked by a blood test. Although a
positive ANA is not disease specific it may be found in persons with CREST/Limited as well
as diffuse scleroderma. In many cases people will not fit the laboratory profile when they
first seek a doctors care and in large part a diagnosis may be made through both
laboratory testing and clinical examination.
Some people who obtain a diagnosis of CREST or Limited Scleroderma
may have the early signs of skin involvement while others may not present visible signs of
the disease at all. In many instances a person will go to their doctor with complaints of
abnormal fatigue, repeated heartburn, stiff or swollen joints and some may become
sensitive to cool temperatures in their hands and some have been diagnosed with Raynaud's
Phenomenon.
When skin involvement is present it may play a major role in the
diagnosis a person receives. If it appears to remain limited to the hands, face and neck
over a time of assessment by your doctor you may be diagnosed with CREST Syndrome or
Limited scleroderma instead of diffuse.
A person with CREST may have digital ulcers which are very painful
sores or infections in the fingers, usually in the end of the finger or tip area. These
digital ulcers are believed to be due to the vascular aspects of scleroderma and/or
raynaud's phenomenon.
Internal Involvement is typically also limited in a person diagnosed
with CREST Syndrome or Limited Scleroderma. The gastrointestinal tract can be affected and
the severity varies from person to person but the majority of people suffer mostly
with esophageal dysfunction. However it is important to mention that intestinal problems
may occur in those with this form of scleroderma.
This form of the disease also presents some vascular aspects and can
result in persons having a condition known as raynaud's phenomenon. There are also some
cases where people see musculoskeletal (Muscle, Joint) Involvement.
The lungs can become involved in someone with CREST/Limited
scleroderma. It has been reported through several sources that approximately 10 percent of
people with this form of disease get serious lung involvement. Many people may show early
signs of lung involvement but never see it progress to a life threatening stage. Pulmonary
hypertension is the most prevalent lung involvement that occurs in people with
CREST/Limited but Pulmonary Fibrosis can happen to those with this form as well.
Organs such as the heart and kidneys are rarely affected in those
diagnosed with CREST Syndrome or Limited Scleroderma. These organs are more at risk of
being involved in those diagnosed with diffuse. However when a person has severe pulmonary
hypertension their heart can be affected by that situation. Your doctor is most
likely to request that you have further testing to analyze what internal organs if any may
be involved to assist in their diagnosis
More detatailed information about CREST Syndrome
Patients with CREST syndrome are a subset of patients with scleroderma. CREST is an
acronym for the cardinal clinical features of the syndrome in a given patient: calcinosis,
Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia. In 1964,
Winterbauer described a series of 8 patients with calcinosis cutis, Raynaud phenomenon,
sclerodactyly, and telangiectasia (CRST), and he noted the similarity of appearance and
distribution of the telangiectasia to that seen in hereditary hemorrhagic telangiectasia
(Osler-Weber-Rendu syndrome). Although Winterbauer noted esophageal dysmotility in 4 of 8
patients, he did not include this feature in his original description of CRST syndrome.
Frayha noted the frequent occurrence of esophageal dysmotility and suggested that the
acronym CREST may be more appropriate. Velayos reviewed 13 patients with CREST and CRST
syndromes and found the syndromes equivalent.
Several classification schemes for scleroderma have been presented and remain in use.
The American College of Rheumatology (ACR; formerly, the American Rheumatology
Association) criteria for classification of scleroderma requires either 1 major criterion
(proximal cutaneous scleroderma) or 2 of 3 minor criteria (sclerodactyly, digital pitting
scars, bibasilar pulmonary fibrosis). Proximal cutaneous scleroderma is defined as
symmetric thickening, tightening, or induration of skin proximal to metacarpophalangeal or
metatarsophalangeal joints. Satisfaction of 1 major or 2 minor criteria offers a
sensitivity of 97% and a specificity of more than 98% compared to other patients with
connective tissue disease.
While useful for identifying patients for enrollment in clinical trials, the ACR
criteria are less useful in demonstrating correlations between clinical and laboratory
findings and in predicting the clinical course. Several authors (ie, Rodnan, Barnett, and
Tuffanelli and Winkelmann) recognized this limitation and responded by categorizing
patients with scleroderma syndromes into 2 groups: those with diffuse cutaneous
scleroderma and those with acrosclerosis, which we now recognize as a limited form of
scleroderma. Visceral involvement and prognosis differ in patients with diffuse cutaneous
versus limited cutaneous scleroderma.
Diffuse cutaneous scleroderma (defined as thickening of skin proximal to the elbows,
including upper arms and trunk) is associated with early visceral involvement, joint and
tendon involvement, late onset of Raynaud phenomenon, and the presence of serum
anti-Scl-70 antibodies. Limited cutaneous scleroderma is defined as a thickening of skin
distal to the elbows but may include the face. Limited disease is associated with slow
progression of the disease, late internal organ involvement, calcinosis, telangiectasia,
the presence of serum anticentromere antibodies, and early onset of Raynaud phenomenon.
Leroy et al and Mayes have reported that limited disease is associated with a better
survival rate than diffuse disease.
Other forms of scleroderma include overlap syndromes with sclerodermalike features and
localized scleroderma (eg, morphea, linear scleroderma). CREST syndrome is defined only by
the presence of calcinosis, Raynaud, esophageal dysmotility, sclerodactyly, and
telangiectasia. This constellation of findings can be found in patients with diffuse
cutaneous scleroderma. More often, CREST syndrome is found in patients with limited
cutaneous scleroderma.
Symoptoms and progression of Crest Syndrome
In the typical course of limited scleroderma, the patient first notices Raynaud
phenomenon. Over time (usually years), fingers become puffy, then skin thickens slowly.
Internal organ manifestations are delayed for many years.
Calcinosis is the pathologic calcification of soft tissues.
- Calcinosis can occur in, but is not limited to, patients with scleroderma and other
connective tissue diseases.
- The calcific deposits can be subclinical. When symptomatic, they can be tender and
painful. They can ulcerate, drain a white chalky substance, and become secondarily
infected. Inflammatory reactions intermittently occur at the site of calcinosis.
Paraspinal calcifications rarely occur, causing local pain, radiculopathy, and diffuse
weakness.
Maurice Raynaud defined Raynaud phenomenon in 1862. He observed episodes of pallor,
cyanosis, and/or rubor on the hands bilaterally in response to cold or emotional stress,
in the setting of normal proximal arterial pulsations, and without gangrene.
- Patients occasionally describe color changes proximally as far as the wrist. The feet
less frequently are involved. Rarely, the nose and ears can be affected.
- Involved skin is cool during the attack, but the proximal skin is warm.
- Color changes often are accompanied by symptoms including pain and paresthesias.
- The phenomenon lasts minutes to hours, and the patient is symptom free between episodes.
Esophageal dysmotility: While the entire intestine can be involved in scleroderma,
esophageal involvement is most common and most often clinically relevant. According to
Akesson and Wollheim, dysmotility is common (cine-esophagram and radionuclide transit time
studies demonstrate hypomotility in as many as 75-86% of patients with CREST syndrome).
All patients have normal motility of the proximal esophagus, which primarily is striated
muscle.
Barrett esophagitis, a complication of gastroesophageal reflux, has been found in
scleroderma patients, and perhaps at a higher rate (37% in patients with scleroderma
versus 4-13% in patients without scleroderma). Esophageal adenocarcinoma, a malignant
transformation of Barrett esophagitis, has been documented in scleroderma patients as
well.
Another potential complication of esophageal dysmotility and gastroesophageal reflux is
occult aspiration and pulmonary disease. Johnson et al examined 13 patients with systemic
sclerosis using endoscopy, laryngoscopy, esophageal manometry, 24-hour esophageal pH
monitoring, pulmonary function testing, and aspiration scan. All 13 patients had
esophageal endoscopic evidence of reflux. Twelve patients had abnormal laryngeal
examinations suggestive of aspiration; however, in this group, 1 patient had no evidence
of proximal reflux by pH monitoring, and 2 patients had normal aspiration scans.
Nonetheless, an inverse relationship was found between diffusing capacity of lung for
carbon dioxide (DLCO) and esophageal reflux scores, indicating that gastroesophageal
reflux potentially contributes to diminished pulmonary function.
Sclerodactyly means thickening of the skin affecting the digits of the hands and feet.
Three phases of skin changes are seen in scleroderma, edematous phase, indurative phase,
and atrophic phase.
- Patients with early scleroderma present with puffy edema in the fingers and may complain
of morning stiffness or arthralgias. The edematous phase usually is short (ie, months, but
occasionally years).
- In the indurative phase, the skin becomes thickened. Patients may complain of pruritus.
The skin appears shiny and tight. Skin creases are lost. Erythema may be present. In
limited scleroderma, this process continues slowly for many years.
- Late in the course of scleroderma, the skin becomes fragile and lax as it enters the
atrophic phase.
- Patients with limited scleroderma find that the advancement of skin disease occurs
slowly, over many years. By definition, skin involvement remains distal to the elbows and
knees, although it can involve the face and neck.
Telangiectasia (a singular lesion is termed telangiectasis) is a collection of dilated
blood vessels.
- In scleroderma, telangiectases occur on the face, upper trunk, and hands.
- Telangiectases also can occur on mucosal surfaces (eg, lips) and throughout the GI tract
and may be symptomatic. Mucosal telangiectases were the most common cause of bleeding in a
series of 144 patients with scleroderma (diffuse and limited disease). Telangiectases
prompted recurrent GI bleeding in 7 patients in this group.
Other manifestations
- Musculoskeletal: Arthralgias are common (90% of patients), but erosive arthritis is
rare. Proximal muscle weakness can occur.
- Pulmonary: Pulmonary hypertension occurs in approximately 25% of patients with limited
scleroderma. These patients typically have long-standing disease. Pulmonary hypertension
most often occurs in the absence of interstitial fibrosis. Symptoms heralding this
phenomenon include dyspnea on exertion and cough.
- Cardiac: Myocardial involvement rarely is found in patients with limited scleroderma;
however, patchy fibrosis in the myocardium can occur and typically is asymptomatic.
Significant myocardial involvement presents as dyspnea on exertion, fatigue, and
palpitations. Arrhythmias and conduction abnormalities can occur.
- Renal: Renal crisis rarely occurs in limited scleroderma (1%) and presents as
accelerated hypertension, renal failure, and microangiopathic hemolytic anemia.
- Neurologic: Entrapment neurologic syndromes occur (eg, carpal tunnel syndrome).
Autonomic dysfunction of the GI tract occurs.
- Sicca symptoms are present in approximately 35% of patients. Of patients with sicca
symptoms, one half have anti-Ro (SSA) or anti-La (SSB) antibodies.
Causes of Crest Syndrome
The cause of limited scleroderma is yet to be determined. Studies of genetic factors
show only rare occasions of multicase families. Human leukocyte antigen associations are
present but are not strong.
The predominance of cases occurring in women after their childbearing years and the
similar clinical presentation of scleroderma to graft-versus-host disease has suggested
the importance of fetal/maternal microchimerism in the etiology of scleroderma.
Environmental factors also are likely important. Some similarities in clinical
presentation occur with silica, L-tryptophan, and rapeseed oil exposure. |
