CREST Syndrome Clinical Presentation

Updated: Aug 07, 2018
  • Author: Jeanie C Yoon, MD; Chief Editor: Dirk M Elston, MD  more...
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Presentation

History

In the typical course of limited scleroderma, the patient first notices Raynaud phenomenon. Over time (usually years), fingers become puffy, then the skin thickens slowly. Internal organ manifestations are delayed for many years.

Calcinosis

Calcinosis is the pathologic calcification of soft tissues. 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.

Raynaud phenomenon

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. Less frequently, the feet 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 are often accompanied by symptoms that can include 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 from 1989, [43] 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.

In 1987, Zamost et al [44] correlated esophageal symptoms with anatomic and physiologic measurements in 53 patients with scleroderma. The prevalence of esophagitis and strictures (41%) in this patient population is higher than in otherwise healthy patients with gastroesophageal reflux disease. Abnormal motility was a significant predictor of erosive esophagitis; 70% of patients with dysmotility had gross or microscopic evidence of erosive esophagitis. No patients with normal motility had erosive esophagitis. Symptoms of heartburn and dysphagia were more common in patients with erosive esophagitis. Heartburn alone did not predict esophagitis; half the patients without this complication still experienced heartburn. Additionally, dysphagia did not predict the presence of stricture.

Barrett esophagitis, a complication of gastroesophageal reflux, has been found in scleroderma patients, perhaps at a higher rate (37% in patients with scleroderma vs 4-13% in patients without scleroderma). Esophageal adenocarcinoma, a malignant transformation of Barrett esophagitis, has also been documented in scleroderma patients.

Another potential complication of esophageal dysmotility and gastroesophageal reflux is occult aspiration and pulmonary disease. In 1989, Johnson et al [45] examined 13 patients with systemic sclerosis using endoscopy, laryngoscopy, esophageal manometry, 24-hour esophageal pH monitoring, pulmonary function testing, and aspiration scanning. All 13 patients had endoscopic evidence of reflux. Twelve patients had abnormal laryngeal examination findings suggestive of aspiration; however, in this group, 1 patient had no evidence of proximal reflux by pH monitoring and 2 patients had normal aspiration scan results. Nonetheless, an inverse relationship was found between diffusing capacity of lung for carbon dioxide and esophageal reflux scores, indicating that gastroesophageal reflux potentially contributes to diminished pulmonary function.

Sclerodactyly

Sclerodactyly means thickening of the skin of the digits of the hands and feet. Three phases of skin changes are seen in scleroderma: the edematous phase, indurative phase, and atrophic phase.

Patients with early scleroderma present with puffy edema in the fingers and may report morning stiffness or arthralgias. The edematous phase is usually short (ie, months, but occasionally years).

In the indurative phase, the skin becomes thickened. Patients may report 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.

Telangiectases

Telangiectases are lesions formed by collections of dilated blood vessels and may be highlighted by dermoscopy. [46]

In scleroderma patients, telangiectases occur on the face, upper trunk, and hands.

They also occur on mucosal surfaces (eg, lips) and throughout the GI tract and may be symptomatic. These were the most common cause of bleeding in a series of 144 patients with scleroderma (diffuse and limited disease). Telangiectases were associated with recurrent GI bleeding in 7 patients in this group. This bleeding can be chronic and cause anemia. [47]

Other manifestations

Arthralgias are common (90% of patients), but erosive arthritis is rare. Proximal muscle weakness can occur.

Pulmonary hypertension most often occurs in the absence of interstitial fibrosis in approximately 3-14% of CREST syndrome patients. It is a very late event and the prognosis is poor, with a mortality rate of 50% after 2 years. [48] Symptoms heralding this phenomenon include dyspnea on exertion and cough.

Myocardial involvement is rare in patients with limited scleroderma; however, patchy fibrosis in the myocardium can occur and typically is asymptomatic. Significant myocardial involvement manifests as dyspnea on exertion, fatigue, and palpitations. Arrhythmias and conduction abnormalities can occur. [49]

Primary biliary cirrhosis may be associated with CREST syndrome. [50, 51]

Renal crises rarely occur in persons with limited scleroderma (1%); they manifest accelerated hypertension, renal failure, and microangiopathic hemolytic anemia.

Entrapment neurologic syndromes (eg, carpal tunnel syndrome) occur. Autonomic dysfunction of the GI tract also occurs.

Sicca symptoms are present in approximately 35% of patients. Of patients with sicca symptoms, half have anti-Ro (SSA) or anti-La (SSB) antibodies.

Scleroderma is associated with an increased risk of cancer, in particular lung cancer. [52]

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Physical Examination

Calcinosis

In scleroderma, calcific deposits are found predominantly in the extremities, around joints, and around bony prominences. Osteonecrosis has also been reported. [53]

Deposits typically are found in the flexor surfaces of the hands and the extensor surfaces of the forearms and knees.

The deposits rest in the dermis but can be found in deeper periarticular tissues.

Calcinosis on dorsal forearm. Calcinosis on dorsal forearm.
Close-up view of calcinosis. Close-up view of calcinosis.

Raynaud phenomenon

Triphasic color changes of pallor, cyanosis, and erythema represent phases of vasoconstriction, slow blood flow, and reperfusion, respectively.

Color changes extend proximally from the tips of digits to various levels, with a well-demarcated border.

Raynaud phenomenon showing pallor of most of the f Raynaud phenomenon showing pallor of most of the finger tips with a violaceous discoloration (hyperemia) of the thumb tip.

Esophageal dysmotility

The earliest change in the distal esophagus (primarily smooth muscle) is an uncoordinated disorganized pattern of contractions resulting in low amplitude or absent peristalsis.

Lower esophageal sphincter (LES) pressure typically is lower than in healthy controls, and incomplete relaxation of the LES occurs. [29]

Sclerodactyly

The process typically begins in the distal fingers and advances proximally.

The process also may occur on the face, over the forehead, and around the mouth. Facial involvement can lead to a mauskopf (mouse head) appearance. Lips become thinner, and radial furrowing develops around the mouth. The oral aperture is reduced in size (microstomia). Wrinkles over the forehead diminish.

Sclerodactyly (also with Raynaud phenomenon). Sclerodactyly (also with Raynaud phenomenon).
Sclerodactyly. Sclerodactyly.

Telangiectases

These are flat and nonpulsatile and typically have a rectangular or elongated shape. The vessels are so close together that they appear as discrete mats.

Telangiectasia of the face. Telangiectasia of the face.
Telangiectasia of the lip. Telangiectasia of the lip.
Telangiectasia of the finger. Telangiectasia of the finger.
Close-up view of telangiectasia. Close-up view of telangiectasia.
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Complications

Limited disease is associated with better survival rates than diffuse disease (50% at 12 y compared to 15% for diffuse scleroderma).

Renal involvement is responsible for half the scleroderma-related deaths in patients with widespread skin changes, while patients with sclerodactyly alone do not tend to develop any renal disease.

Mortality in patients with limited skin involvement is a result of cardiac, pulmonary, and GI causes.

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