CREST - an acronym for Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly and Telangiectasia. It is also known as Acrosclerosis. It is considered as a milder form of scleroderma, thus called Limited Cutaneus Scleroderma but can have life threatening complications. The presentation provides a guide to Etiopathogenesis, Clinical features, Oral manifestations, Diagnosis, Histopathological features, Radiographical features, its managemnt both general and dental and its prognosis. Presentation by - Dr. Harsimran Singh Kapoor.

1. CREST Syndrome
(ACROSCLEROSIS, LIMITED SCLERODERMA)
- Harsimran Singh Kapoor

2. INTRODUCTION
It is an uncommon condition that may be considered a
relatively mild variant of systemic sclerosis.
●
CREST syndrome, also known as the limited cutaneous
form of systemic sclerosis (lcSSc), is a multisystem
connective tissue disorder.
The symptoms involved in CREST syndrome are associated
with the generalized form of the disease Systemic sclerosis
(scleroderma).

3. CREST is an acronym for the clinical features that are seen in a
patient with this disease.
The "C" stands for Calcinosis, where calcium deposits form under
the skin on the fingers or other areas of the body.
The "R", stands for Raynaud's phenomenon, spasm of blood vessels
in the fingers or toes in response to cold or stress.
The "E" represents Esophageal dysmotility, which can cause
difficulty in swallowing.
The "S" is for Sclerodactyly, tightening of the skin causing the
fingers to bend.
The letter "T" is for Telangiectasia, dilated vessels on the skin of the
fingers, face, or inside of the mouth.

4. Scleroderma, derived from the Greek words for hard and skin, is
used to describe a group of clinical disorders characterized by
thickening and fibrosis of the skin.
There are two main forms, progressive systemic sclerosis (PSS)
and localized sclerodema.
PSS is further divided into limited cutaneous scleroderma (also
called CREST syndrome) and diffuse cutaneous scleroderma.
●
Patients with limited scleroderma often have a long history of
Raynaud’s phenomenon before the appearance of other
symptoms.
●
They have skin thickening limited to the hands and frequently
have problems with digital ulcers and esophageal dysmotility.

5. ETIOPATHOGENSIS
The etiology is unclear, but the pathogenesis is characterized
by vascular damage and an accumulation of collagen and
other extracellular matrix components at involved sites.
●
Biopsies of the skin in early stages demonstrate bundles of
collagen in the lower dermis and upper subcutaneum in
association with perivascular and interstitial mononuclear
cell infiltrates.
●
The inflammatory process precedes the deposition of
collagen.

6. ●
Once in the tissue, T cells drive processes through
secretion of cytokines such as IL-4 and IL-13 that result
in vasculopathy and fibrosis.
●
These cytokines induce fibroblast production of
transforming growth factor b1, which is the main
profibrotic cytokine in PSS.
●
As the disease progresses, the rete pegs are lost and
the epidermis thins.
●
Unregulated collagen deposition is a hallmark of this
disease. Cultured fibroblasts from patients synthesize
more collagen in vitro that is structurally normal,
although collagen degradation pathways appear to be
normal.

7. ●
The excess collagen narrows small arteries and changes
the microvasculature in early stages of the disease,
causing eventual pulmonary hypertension, renal disease,
myocardial dysfunction and digital gangrene.
●
There appears to be a small genetic predisposition to
PSS.
●
●
Environmental exposure to pesticides, benzene
derivatives, and silica has been linked to the
development of scleroderma-like conditions in miners
and stonemasons.
●
Viral triggers, such as parvovirus B19, are proposed.

8. CLINICAL MANIFESTATIONS
The characteristic signs may not appear synchronously but
instead may develop over a period of months to years.
1. Calcinosis cutis -
●
It occurs in the form of movable, nontender,
subcutaneous nodules, 0.5 to 2.0 cm in size,
which are usually multiple.
●
Larger, more numerous or superficial
calcifications may occasionally become
bothersome and require removal.

9. 2. Raynaud’s phenomenon -
It may be observed when a person’s hands
or feet are exposed to cold temperatures.
●
The initial clinical sign is a dramatic
blanching of the digits, which appear dead-
white in color as a result of severe
vasospasm.
●
A few minutes later, the affected extremity
takes on a bluish color because of venous
stasis.

10. ●
After warming, increased blood flow results in a dusky-
red hue with the return of hyperemic blood flow.
●
This may be accompanied by varying degrees of
throbbing pain.
●
When extreme and frequent, this phenomenon can lead
to digital ulcerations, gangrene, or amputation. Ulceration
can predispose to chronic infections of the involved site.

11. 3. Esophageal dysfunction -
It is caused by abnormal collagen deposition in the esophageal
submucosa, may not be noticeable in the early phases of CREST
syndrome.
It may present as a sensation of food getting stuck (dysphagia) in
the mid- or lower esophagus, atypical chest pain, or cough.
●
People often state they must drink liquids to swallow solid food.
This motility problem results from atrophy of the gastrointestinal
tract wall smooth muscle.
●
This change may occur with or without pathologic evidence of
significant tissue fibrosis.
●
Often the subtle initial signs of this problem must be
demonstrated by barium swallow radiologic studies.

12. 4. Sclerodactyly -
Sclerodactyly of CREST syndrome is rather remarkable. The
fingers become stiff and the skintakes on a smooth, shiny
appearance.
Often the fingers undergo permanent flexure, resulting in a
characteristic “claw” deformity.
●
Though it is the most easily recognizable manifestation, it is
not prominent in all patients.
●
Thickening generally only involves the skin of the fingers
distal to the metacarpophalangeal joints in CREST.

13. ●
Early in the course of disease, the skin may appear edematous and
inflamed. Eventually, dermal fibroblasts overproduce extracellular
matrix leading to increased tissue collagen deposition in the skin.
●
Collagen cross-linking then causes a progressive skin tightening.
●
Digital ischemic ulcers commonly form on the distal fingers in 30-
50% of patients.
●
As with systemic sclerosis, this change is due to abnormal
deposition of collagen within the dermis in these areas.

14. 5. Telangiectasias -
Telangiectasis in this syndrome are similar
to those seen in hereditary hemorrhagic
telangiectasia (HHT).
●
As with that condition, significant
bleeding from the superficial dilated
capillaries may occur.
●
The facial skin and the vermilion zone of
the lips are commonly affected.

15. ●
Marked telengiectasis (dilated capillaries) occur on the skin
of the face, the palmar surface of the hands, and the
mucous membranes.
●
Telangiectasias tend to be more numerous in people with
other scleroderma related vascular disease (i.e., pulmonary
arterial hypertension). The number of telangiectasias and
the sites involved tend to increase over time.

16. Other symptoms of CREST syndrome can be.....
- exhaustion,
- weakness,
- difficulties with breathing,
- pain in hands and feet,
- dizziness and
- badly healing wounds.
Patients with syndrome commonly induce pulmonary artery
hypertension which may result in cor pulmonale (heart
failure due to increased pulmonary artery pressure).

17. ORAL MANIFESTATIONS
The clinical signs of scleroderma of the mouth and jaws
are consistent with findings elsewhere in the body.
- The lips become rigid and the oral aperture narrows
considerably.
- Skin folds are lost around the mouth, giving a mask like
appearance to the face.
- The tongue can also become hard and rigid, making
speaking and swallowing difficult. Involvement of the
esophagus may cause dysphagia.

18. ●
Oral telangiectasia is most commonly observed on the hard
palate and the lips.
●
When fibrosis involves the muscles of mastication, mandibular
resorption can occur either the angle of the mandible, the
condylar heads, the coronoid process, or the digastric region.
●
Mandibular movement may be restricted by muscular fibrosis.

19. DIAGNOSIS
CREST is not easily diagnosed as it closely mimics symptoms
of other connective tissue and autoimmune diseases.
Diagnosis is usually given when a patient presents two or
more of the five major clinical symptoms.
●
In these cases, laboratory studies directed at identifying
anticentromere (ACA) ; antitopoisomerase I (anti-topo I);
anti–ribonucleic acid (RNA) polymerase I/III; and anti-Th/To
antibodies may be useful, because these tests are relatively
specific for CREST syndrome.

20. ●
Circulating ANAs are present in >90% of the patients.
●
Other non specific autoantibodies which can be detected
in serum, include anti-PM-Scl, anti- U3RNP, and anti-
U1RNP.
●
Autoantibodies appear to have prognostic value for
patients. ACAs are strongly associated with slowly
progressive, limited disease, whereas anti-topo I and anti-
RNA polymerase I/III are found more frequently in patients
with progressive and diffuse disease.
●
Additionally, skin biopsies can be given to help confirm a
diagnosis.

21. ●
Other abnormal laboratory findings include anemia, an
elevated erythrocyte sedimentation rate, and
hypergammaglobulinemia.
●
The diagnosis is made from the presence of
characteristic cutaneous skin thickening in association
with Raynaud’s phenomena.
●
Proximal sclerodermatous skin changes (proximal to the
metacarpophalangeal joints) in the presence of two minor
criteria (sclerodactyly, digital pitting scars of fingertips or
loss of the distal finger pad, or bibasilar pulmonary
fibrosis).

22. RADIOGRAPHICAL FINDINGS

23. ●
Classic dental radiographic findings such as extreme widening
of the periodontal ligament, two to four times normal thickness.
●
Bone resorption of the angle of the mandibular ramus (usually
bilaterally), Partial or complete resorption of condyles and/or
coronoid processes of the mandible has been reported.
●
Other characteristic radiographic findings include calcinosis of
the soft tissues around the jaws.

24. HISTOPATHOLOGICAL FINDINGS
The histopathologic findings in CREST syndrome are similar,
although milder, to those seen in systemic sclerosis.
Microscopic examination of tissue involved shows diffuse
deposition of dense collagen within and around the normal
structures. This abnormal collagen replaces and destroys the
normal tissue, causing the loss of normal tissue function.
Superficial dilated capillaries are
observed if a telangiectatic
vessel is included in the biopsy
specimen.

25. ●
thickening and hyalinization of
the collagen fibers in the skin,
●
loss of dermal appendages,
particularly the sweat glands,
●
atrophy of the epithelium with
loss of rete pegs and increased
melanin pigmentation.
●
Subcutaneous fat disappears
and the walls of the blood
vessels become sclerotic.
It is characterized microscopically by -

26. ●
There is an increase in PAS-positive, diastase-resistant
material present in the areas of the homogeneous collagen.
●
Mucous membrane changes are similar to those occurring in
the skin.
The microscopic changes in the periodontal ligament consist of a
widening due to an increase of collagen and oxytalan fibers as
well as an appearance of hyalinization and sclerosis of collagen
with a diminution in the number of connective tissue cells usually
found.

27. MANAGEMENT
The treatment of patients with CREST syndrome is
essentially the same as that of those with systemic
sclerosis. Because CREST syndrome usually is not as
severe, so the treatment does not have to be as
aggressive.
Unfortunately, many of the recommended treatments have
not been examined in controlled trials, and the natural
waxing and waning course of the disease makes it difficult
to assess the effectiveness of a given treatment in an open-
label trial.

28. ●
Systemic medications such as penicillamine, are
prescribed in an attempt to inhibit collagen production.
●
A recent double-blind study, however, showed no
difference in measured patient outcomes with high-dose
versus low-dose penicillamine, suggesting that perhaps
this medication has limited efficacy.
●
Surprisingly, corticosteroids are of a little benefit.
●
Extracorporeal photochemotherapy has shown some
beneficial effect on the skin lesions; however, no
improvement of the pulmonary function tests is observed.

29. ●
Other management strategies directed at controlling
symptoms. Such as esophageal dilation to temporarily
correct dysfunction and dysphagia.
●
Calcium channel blocking agents help to increase
peripheral blood flow and lessen the symptoms of
Raynaud’s phenomenon, but many patients can reduce
episodes by keeping warm (especially their hands and
feet) or by stopping cigarette smoking.
●
Angiotensin-converting enzyme (ACE) inhibitors often
effectively control hypertension if kidney involvement is
prominent.

30. ●
Physical therapy - Stretching exercises are
important to help prevent loss of mobility in stiff &
painful joints. Facial exercises can help keep your
face and mouth flexible. It helps to maintain
flexibility and strength.
Surgery may be needed for certain problems, such as:
●
Calcium deposits - Large or painful calcium deposits
are sometimes surgically removed.
●
Red spots or lines - Laser surgery can reduce the
appearance of red spots or lines caused by swollen
blood vessels near the surface of the skin.

31. DENTAL MANGEMENT
The most common problem in the dental treatment of
patients is the physical limitation caused by the narrowing
of the oral aperture and rigidity of the tongue.
Procedures such as molar endodontics, prosthetics and
restorative procedures in the posterior portions of the
mouth become difficult and the dental treatment plan may
sometimes need to be altered because of the physical
problem of access.

32. ●
The oral opening may be increased an average of 5
mm by stretching exercises.
●
One particularly effective technique is the use of an
increasing number of tongue blades between the
posterior teeth to stretch the facial tissues.
●
Mechanical stretching devices are available. If these
approaches are insufficient, a bilateral
commissurotomy may be necessary.
●
Collapsible dental appliances with special hinges have
been made to facilitate the insertion and removal of
dentures.

33. ●
Microstomia and inelastic soft tissue also hamper the
maintenance of good oral hygiene.
●
Patients have a decreased ability to manipulate a
toothbrush as a result of sclerotic changes in the
fingers and hands.
●
Caries and plaque were associated with decreasing
dexterity and strength.
●
Customized toothbrush handles should be provided
for patients who cannot grip an ordinary toothbrush.

34. ●
Surgical correction of open bite associated with
condylar resorption has been described.
●
Patients with extensive resorption of the angle of the
mandible are at risk of developing pathologic fractures
from minor trauma, including dental extractions.
When treating a patient, the extent of the heart, lung, or
kidney involvement should be considered, and
appropriate alterations should be made before, during
and after treatment.

35. PROGNOSIS
Although the prognosis for this condition is much better than that for
systemic sclerosis, patients should be monitored for an increased
risk of developing pulmonary hypertension or primary biliary
cirrhosis, generally more than 10 years after the initial diagnosis.
If the heart is affected, then the prognosis is particularly poor, most
patients die because of pulmonary involvement.
Overall survival figures are difficult to calculate because of a variety
of factors, including the rarity of the disease, the inherent variability
of its natural course and the variation in treatments provided at
medical centers around the world.

36. THANK YOU !