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Limited Cutaneous Systemic Scleroderma

CREST Syndrome

CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome is a form of scleroderma.


Presentation

Symptoms may gradually appear through time and may start with the progressive tightening of the skin of the face and the lower arm and leg area. Studies have concurred that both limited and system sclerosis predominantly present with perineural inflammations and lichen like fibrosis [8].

Raynaud phenomenon presents as white cold fingers or toes due to abrupt flow of blood to the extremities. The chronic disruption of the distal blood supply to the fingers may induce a necrotizing vasculitis that may damage the peripheral nerves and cause polyneuropathy in patients [9]. Blood vessels may swell in the surface of the skin of the hands and face presenting as painless red spots or lines known as “spider angioma” or telangiectasia.

Small deposition of calcium (calcinosis) under the skin may present as bumps in the fingers, elbows and knees. The scarring of the esophagus can present with acid reflux signs that may impair proper digestion.

Raynaud Phenomenon
  • Raynaud phenomenon presents as white cold fingers or toes due to abrupt flow of blood to the extremities.[symptoma.com]
  • The patient was found to have unusually severe calcinosis cutis in both legs extending from the knees to the ankles bilaterally, as well as Raynaud's phenomenon, sclerodactyly, and telangiectasias.[ncbi.nlm.nih.gov]
  • Raynaud's phenomenon [ edit ] Raynaud's phenomenon is frequently the first manifestation of CREST/lcSSc, preceding other symptoms by years.[en.wikipedia.org]
Coarctation of the Aorta
  • Cardiovascular lesions in these syndromes include coarctation of the aorta, persistent truncus arteriosus, patent ductus arteriosus, and coronary artery disease, and cerebrovascular lesions include agenesis and stenosis/occlusion of the internal carotid[ncbi.nlm.nih.gov]
Acrocyanosis
  • Extra-oral examination underlined taut, thickened and rigid skin, pallid-red irregular maculae all over the face, telangiectasias and acrocyanosis.[ncbi.nlm.nih.gov]
Macula
  • Extra-oral examination underlined taut, thickened and rigid skin, pallid-red irregular maculae all over the face, telangiectasias and acrocyanosis.[ncbi.nlm.nih.gov]
Piebaldism
  • The similarities between piebaldism and the Waardenburg syndromes are discussed.[ncbi.nlm.nih.gov]
Mask-like Facies
  • Sclerodactyly Red-blue discoloration of the fingers Edema and fibrosis with waxy appearance of the skin and limited range of motion Atrophy and necrotic spots Lesions on the proximal nail fold Multiple, painful ischemic digital ulcers Face Loss of expression ( mask-like[amboss.com]
Foot Drop
  • A 66-year-old woman with a history of longstanding limited cutaneous systemic sclerosis of the CREST syndrome variant presented with a sudden left foot drop and rapidly progressive renal insufficiency associated with mild proteinuria, a nephritic urine[ncbi.nlm.nih.gov]

Workup

The diagnosis of CREST Syndrome is mainly based on the clinical history and clinical symptomatology of the disease. Like most autoimmune diseases, definitive diagnosis is often times difficult because it may co-exist with other autoimmune disorders like Lupus erythematosus and Rheumatoid Arthritis.
Blood studies may reveal auto antibodies in the serum and other inflammatory markers. Skin biopsy may reveal fibrotic changes with scleroderma under the microscope.

Esophageal Motility Disorder
  • We report the case of a patient with PLCNA and CREST (calcinosis, Raynaud phenomenon, esophageal motility disorders, sclerodactyly, and telangiectasia) syndrome.[ncbi.nlm.nih.gov]
  • Its features include symptoms of CALCINOSIS; RAYNAUD DISEASE; ESOPHAGEAL MOTILITY DISORDERS; sclerodactyly, and TELANGIECTASIS. When the defect in esophageal function is not prominent, it is known as CRST syndrome.[definitions.net]
Trichophyton Mentagrophytes
  • We report an extensive case of tinea incognita caused by the zoophilic dermatophyte Trichophyton mentagrophytes (var. granulosa) in a 49-year-old female patient with CREST (Calcinosis; Raynaud phenomenon; Esophageal involvement; Sclerodactyly; Teleangiectasia[ncbi.nlm.nih.gov]
HLA-Cw6
  • HLA-Cw6 were associated with CREST-PBC overlap syndrome (p CONCLUSION: It was suggested that there was a genetic difference between CREST syndrome alone and CREST-PBC overlap syndrome and there were differences (the positivity of AMA and the severity[ncbi.nlm.nih.gov]

Treatment

Treatment of CREST Syndrome is only limited in the alleviation of the signs and symptoms and the prevention of the complications of the disease. Topical emollients moisturizes the skin of scleroderma while topical antibiotics combats the infections in finger and toe ulcers caused by Raynaud phenomenon.

Proton-pump inhibitors and antacids may smoothen the esophageal reflux symptoms. Calcinosis can be controlled with oral intake of colchicine, minocycline, ditiazem, and topical sodium thiosulfate [10]. Immunosuppressant drugs controls excessive fibrosis of the lungs.

Prognosis

The constellation of symptoms from early to late stage is still compatible with life. Disfiguring changes may be delayed with pharmacologic agents if diagnosed early.

Patients with pulmonary hypertension carry a poor prognosis due to its relatively high mortality rate [6]. Quality of life is affected especially with gastrointestinal dysfunction that may cause long term weight loss and malnutrition.

Complications

The chronic fibrosis in CREST Syndrome may cause a perennial drying of mouth, throat and eyes in patients. Dental problems occur with gingival thickening and the acid reflux seen in esophageal dysfunction directly damages the enamel of the teeth. The esophageal involvement can cause frequent acid reflux symptoms and intestinal disturbances like constipation and diarrhea.

Malnutrition may ensue with the chronic intestinal fibrotic changes. Systemic fibrosis may affect the heart and cause dysrhythmia. Imaging studies in CREST patients reveal ectatic coronary vessels that adversely affects the heart’s hemodynamics [7].

Pulmonary vessels become less efficient with vascular fibrosis leading to lung failure. Raynaud phenomenon in the fingers and toes can cause ulcers and gangrene due to the disruption of the blood flow towards them.

Etiology

It has been postulated that CREST syndrome is an autoimmune disease, where the body tends to produce excessive collagen. The overproduction of collagen leads to the thickening of the connective tissue causing the pathologic scarring, thereby compromising normal function.

Epidemiology

CREST syndrome appears to occur sparingly at approximately 2.7-19.3 new cases per one million adults, and prevalence rate of 253-286 cases per million population in the United States [1].

The progressive increase of cases through the years is attributable to the advances in diagnostic modalities and the advancement in therapy that increases life expectancy of the patients. It is believed that CREST Syndrome represents 22-25% of all scleroderma cases [2]. United States has the highest prevalence rate compared to other countries.

Sex distribution
Age distribution

Pathophysiology

The main pathophysiology of CREST syndrome is the accumulation of collagen and fibrosis in limited areas of the body causing dysfunction. Small arteries in the digits will accrue heavy deposits of collagen, fibronectin, glycosaminoglycan and proteoglycan in the interstitium and intima layer of the blood vessel [3].

Skin fibrosis is systemically uninhibited causing localized scarring of tissues. Mononuclear infiltrates and CD4 lymphocytes abounds vessel undergoing severe fibrosis connoting an earlier immune response before the onset of fibrosis. The role of collagen stimulator, Transforming Growth Factor – Beta (TGF-B) has been implicated to initiate the symptomatology of calcinosis in CREST Syndrome [4].

Pericytes (vascular mural cells) produce excess matrix materials and trigger cytokine activities in blood vessels has been identified to architect the vascular pathologies found in scleroderma [5]. The autoimmune or the “against self” response explains all the pathogenesis that occurs in CREST Syndrome.

Prevention

Patients must wear protective gloves during cold season to prevent gangrene of the fingers when Raynaud phenomenon take its tool. Extra caution should be in effect when manipulating the snow or freezer with bare hands to prevent frost bites. Regular exercise makes your body more flexible to combat the limiting effects of local scleroderma.

Food should be consumed in small and moist parcel for easier digestion. Avoidance of alcohol, fatty foods, caffeine and chocolate should be implemented to prevent chronic esophageal reflux disease. The use of skin lotions with moisturizers will allay the discomforts in sclerodactyly. Harsh soaps and detergents should be avoided to prevent the aggravation of fibrotic symptoms.

Summary

CREST Syndrome stands for the acronym Calcinosis (calcium deposits in the fingers), Raynaud phenomenon (cold hands or feet), Esophageal dysfunction (difficulty in swallowing because of scarring in the esophagus), Sclerodactyly (thickening of finger or toe skin), and Telangiectasias (spider angioma of the hand or face).

CREST Syndrome is sometimes referred to as limited scleroderma as it only occurs in limited portions of the hand, feet or esophagus. This autoimmune disease has no known cure, and control of complications and alleviation of symptoms are the only medical approach available.

Patient Information

CREST Syndrome stands for the acronym Calcinosis (calcium deposits in the skin), Raynaud phenomenon (cold hands or feet), Esophageal dysfunction (difficulty in swallowing because of scarring in the esophagus), Sclerodactyly (thickening of skin), and Telangiectasias (spider angioma of the hand or face). It is a multisystem connective tissue disorder.

It is best to cease smoking when one is diagnosed with CREST Syndrome. Nicotine in cigarettes worsens the vasoconstriction in Raynaud phenomenon, worsens the gum and teeth conditions, and relaxes the stomach acid causing chronic reflux symptoms.

Sclerodactyly can be effectively managed by the occupational therapist. One should consider joining a CREST Syndrome support group to learn useful tips and overcome depression.

References

Article

  1. Mayes MD, Lacey JV Jr, Beebe-Dimmer J, Gillespie BW, Cooper B, Laing TJ, et al. Prevalence, incidence, survival, and disease characteristics of systemic sclerosis in a large US population. Arthritis Rheum. Aug 2003;48(8):2246-55
  2. Steen VD, Powell DL, Medsger TA Jr. Clinical correlations and prognosis based on serum autoantibodies in patients with systemic sclerosis. Arthritis Rheum. Feb 1988;31(2):196-203.
  3. Postiglione L, Montagnani S, Riccio A, Montuori N, Sciorio S, Ladogana P, et al. Enhanced expression of the receptor for granulocyte macrophage colony stimulating factor on dermal fibroblasts from scleroderma patients. J Rheumatol. Jan 2002;29(1):94-101.
  4. Kawakami T, Soma Y, Mizoguchi M, Saito R. Immunohistochemical expression of transforming growth factor beta3 in calcinosis in a patient with systemic sclerosis and CREST syndrome. Br J Dermatol. Nov 2000;143(5):1098-100
  5. Helmbold P, Fiedler E, Fischer M, Marsch WCh. Hyperplasia of dermal microvascular pericytes in scleroderma. J Cutan Pathol. Jul 2004;31(6):431-40
  6. Carneiro AC, Barbosa IP, Chaves FC. CREST syndrome and pulmonary hypertension: a dark prognosis. Acta Med Port. 2004; 17(5):409-14 (ISSN: 1646-0758)
  7. Mavrogeni S, Bratis C, Manoussakis M. Coronary artery abnormalities in CREST syndrome revealed by cardiovascular magnetic resonance imaging. Can J Cardiol. 2011; 27(3):390.e5-7 (ISSN: 1916-7075)
  8. Succaria F, Kurban M, Kibbi AG, Abbas O. Clinicopathological study of 81 cases of localized and systemic scleroderma. J Eur Acad Dermatol Venereol. 2013; 27(2):e191-6 (ISSN: 1468-3083)
  9. Andreadou E, Zouvelou V, Karandreas N, Kilidireas C. Anti-myelin-associated glycoprotein polyneuropathy coexistent with CREST syndrome. J Postgrad Med. 2012; 58(1):57-9 (ISSN: 0022-3859)
  10. Gutierrez A, Wetter DA. Calcinosis cutis in autoimmune connective tissue diseases. Dermatol Ther. 2012; 25(2):195-206 (ISSN: 1529-8019).

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Last updated: 2019-07-11 22:05