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Sections CREST Syndrome
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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,^[44]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^[45]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^[46]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.^[47]

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.^[48]

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.^[49]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.^[50]

Primary biliary cirrhosis may be associated with CREST syndrome.^{[51, 52]}

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.^[53]

Calcinosis

In scleroderma, calcific deposits are found predominantly in the extremities, around joints, and around bony prominences. Osteonecrosis has also been reported.^[54]

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.

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Close-up view of calcinosis.

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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 finger tips with a violaceous discoloration (hyperemia) of the thumb tip.

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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.^[30]

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).

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Sclerodactyly.

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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.

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Telangiectasia of the lip.

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Telangiectasia of the finger.

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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.

Differential Diagnoses

Adigun R, Bhimji S. Systemic Sclerosis (CREST syndrome). 2017 Jun. [Medline]. [Full Text].
Adigun R, Goyal A, Bansal P, Hariz A. Systemic Sclerosis (CREST syndrome). StatPearls [Internet]. 2020 Jan. [Medline]. [Full Text].
Meyer O. [From Thibierge-Weissenbach syndrome (1910) to anti-centromere antibodies (1980). Clinical and biological features of scleroderma]. Ann Med Interne (Paris). 1999 Jan. 150(1):47-52. [Medline].
Winterbauer RH. Multiple telangiectasia, Raynaud's phenomenon, sclerodactyly, and subcutaneous calcinosis: A syndrome mimicking hereditary hemorrhagic telangiectasia. Bull Johns Hopkins Hosp. 1964 Jun. 114:361-83. [Medline].
Frayha RA, Scarola JA, Shulman LE. Calcinosis in scleroderma: A reevaluation of the CRST syndrome, abstracted. Arthritis Rheum. 1973. 16:542.
Velayos EE, Masi AT, Stevens MB, Shulman LE. The 'CREST' syndrome. Comparison with systemic sclerosis (scleroderma). Arch Intern Med. 1979 Nov. 139(11):1240-4. [Medline].
Rodnan GP, Jablonska S, Medsger TA. Classification and nomenclature of progressive systemic sclerosis (scleroderma). Clin Rheum Dis. 1979. 5:5-13.
Barnett AJ, Miller MH, Littlejohn GO. A survival study of patients with scleroderma diagnosed over 30 years (1953-1983): the value of a simple cutaneous classification in the early stages of the disease. J Rheumatol. 1988 Feb. 15(2):276-83. [Medline].
Tuffanelli DL, Winkelmann RK. Diffuse systemic scleroderma. A comparison with acrosclerosis. Ann Intern Med. 1962 Aug. 57:198-203. [Medline].
Ferri C, Valentini G, Cozzi F, Sebastiani M, Michelassi C, La Montagna G, et al. Systemic sclerosis: demographic, clinical, and serologic features and survival in 1,012 Italian patients. Medicine (Baltimore). 2002 Mar. 81(2):139-53. [Medline].
Scussel-Lonzetti L, Joyal F, Raynauld JP, Roussin A, Rich E, Goulet JR, et al. Predicting mortality in systemic sclerosis: analysis of a cohort of 309 French Canadian patients with emphasis on features at diagnosis as predictive factors for survival. Medicine (Baltimore). 2002 Mar. 81(2):154-67. [Medline].
LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA Jr, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988 Feb. 15(2):202-5. [Medline].
Mayes MD. Scleroderma epidemiology. Rheum Dis Clin North Am. 1996 Nov. 22(4):751-64. [Medline].
Nadashkevich O, Davis P, Fritzler MJ. A proposal of criteria for the classification of systemic sclerosis. Med Sci Monit. 2004 Nov. 10(11):CR615-21. [Medline].
Maricq HR, Valter I. A working classification of scleroderma spectrum disorders: a proposal and the results of testing on a sample of patients. Clin Exp Rheumatol. 2004 Jan-Feb. 22(3 Suppl 33):S5-13. [Medline].
Wollheim FA. Classification of systemic sclerosis. Visions and reality. Rheumatology (Oxford). 2005 Oct. 44(10):1212-6. [Medline].
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. 2002 Jan. 29(1):94-101. [Medline].
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. 2000 Nov. 143(5):1098-100. [Medline].
Postiglione L, Ladogana P, Montagnani S, di Spigna G, Castaldo C, Turano M, et al. Effect of granulocyte macrophage-colony stimulating factor on extracellular matrix deposition by dermal fibroblasts from patients with scleroderma. J Rheumatol. 2005 Apr. 32(4):656-64. [Medline].
Kikuchi K, Kadono T, Furue M, Tamaki K. Tissue inhibitor of metalloproteinase 1 (TIMP-1) may be an autocrine growth factor in scleroderma fibroblasts. J Invest Dermatol. 1997 Mar. 108(3):281-4. [Medline].
de Oliveira JG, Guedes AC, Lanna CC, Coelho LF, Prados RZ, Feghali C, et al. Protease nexin-1 messenger RNA levels are not affected by serum or interferon beta in cultured systemic sclerosis fibroblasts. Arch Dermatol Res. 2002 Jan. 293(11):584-9. [Medline].
Helmbold P, Fiedler E, Fischer M, Marsch WCh. Hyperplasia of dermal microvascular pericytes in scleroderma. J Cutan Pathol. 2004 Jul. 31(6):431-40. [Medline].
LeRoy EC. Systemic sclerosis. A vascular perspective. Rheum Dis Clin North Am. 1996 Nov. 22(4):675-94. [Medline].
Klareskog L, Gustafsson R, Scheynius A, Hällgren R. Increased expression of platelet-derived growth factor type B receptors in the skin of patients with systemic sclerosis. Arthritis Rheum. 1990 Oct. 33(10):1534-41. [Medline].
Nelson JL. Microchimerism and the pathogenesis of systemic sclerosis. Curr Opin Rheumatol. 1998 Nov. 10(6):564-71. [Medline].
Gladman DD, Kung TN, Siannis F, Pellett F, Farewell VT, Lee P. HLA markers for susceptibility and expression in scleroderma. J Rheumatol. 2005 Aug. 32(8):1481-7. [Medline].
Bovenzi M, Barbone F, Pisa FE, Betta A, Romeo L, Tonello A, et al. A case-control study of occupational exposures and systemic sclerosis. Int Arch Occup Environ Health. 2004 Jan. 77(1):10-6. [Medline].
Maître A, Hours M, Bonneterre V, Arnaud J, Arslan MT, Carpentier P, et al. Systemic sclerosis and occupational risk factors: role of solvents and cleaning products. J Rheumatol. 2004 Dec. 31(12):2395-401. [Medline].
Mayes MD. Endothelin and endothelin receptor antagonists in systemic rheumatic disease. Arthritis Rheum. 2003 May. 48(5):1190-9. [Medline].
Sjogren RW. Gastrointestinal motility disorders in scleroderma. Arthritis Rheum. 1994 Sep. 37(9):1265-82. [Medline].
Anastasopoulos G, Marinis A, Konstantinidis C, Theodosopoulos T, Fragulidis G, Vassiliou I. Adenocarcinoma of the third portion of the duodenum in a man with CREST syndrome. World J Surg Oncol. 2008 Oct 1. 6:106. [Medline]. [Full Text].
Lauritano D, Bussolati A, Baldoni M, Leonida A. Scleroderma and CREST syndrome: a case report in dentistry. Minerva Stomatol. 2011 Sep. 60(9):443-66. [Medline].
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. 2003 Aug. 48(8):2246-55. [Medline].
Arnett FC, Howard RF, Tan F, Moulds JM, Bias WB, Durban E, et al. Increased prevalence of systemic sclerosis in a Native American tribe in Oklahoma. Association with an Amerindian HLA haplotype. Arthritis Rheum. 1996 Aug. 39(8):1362-70. [Medline].
Steen VD, Powell DL, Medsger TA Jr. Clinical correlations and prognosis based on serum autoantibodies in patients with systemic sclerosis. Arthritis Rheum. 1988 Feb. 31(2):196-203. [Medline].
Pakunpanya K, Verasertniyom O, Vanichapuntu M, Pisitkun P, Totemchokchyakarn K, Nantiruj K, et al. Incidence and clinical correlation of anticentromere antibody in Thai patients. Clin Rheumatol. 2006 May. 25(3):325-8. [Medline].
Silman AJ, Newman J. Epidemiology of systemic sclerosis. Curr Opin Rheumatol. 1996 Nov. 8(6):585-9. [Medline].
Alamanos Y, Tsifetaki N, Voulgari PV, Siozos C, Tsamandouraki K, Alexiou GA, et al. Epidemiology of systemic sclerosis in northwest Greece 1981 to 2002. Semin Arthritis Rheum. 2005 Apr. 34(5):714-20. [Medline].
Allcock RJ, Forrest I, Corris PA, Crook PR, Griffiths ID. A study of the prevalence of systemic sclerosis in northeast England. Rheumatology (Oxford). 2004 May. 43(5):596-602. [Medline].
Le Guern V, Mahr A, Mouthon L, Jeanneret D, Carzon M, Guillevin L. Prevalence of systemic sclerosis in a French multi-ethnic county. Rheumatology (Oxford). 2004 Sep. 43(9):1129-37. [Medline].
Englert H, Small-McMahon J, Davis K, O'Connor H, Chambers P, Brooks P. Systemic sclerosis prevalence and mortality in Sydney 1974-88. Aust N Z J Med. 1999 Feb. 29(1):42-50. [Medline].
Medsger TA. Systemic sclerosis (scleroderma): Clinical aspects. Koopman WJ, ed. Arthritis and Allied Conditions: A Textbook of Rheumatology. 13th ed. Williams and Wilkins; 1997. 1433-64.
Düzgün N. Cutaneous calcinosis in a patient with limited scleroderma: CREST Syndrome. Eur J Rheumatol. 2017 Dec. 4 (4):305-306. [Medline].
Akesson A, Wollheim FA. Organ manifestations in 100 patients with progressive systemic sclerosis: a comparison between the CREST syndrome and diffuse scleroderma. Br J Rheumatol. 1989 Aug. 28(4):281-6. [Medline].
Zamost BJ, Hirschberg J, Ippoliti AF, Furst DE, Clements PJ, Weinstein WM. Esophagitis in scleroderma. Prevalence and risk factors. Gastroenterology. 1987 Feb. 92(2):421-8. [Medline].
Johnson DA, Drane WE, Curran J, Cattau EL Jr, Ciarleglio C, Khan A, et al. Pulmonary disease in progressive systemic sclerosis. A complication of gastroesophageal reflux and occult aspiration?. Arch Intern Med. 1989 Mar. 149(3):589-93. [Medline].
Díaz-González JM, Vega-Memije ME, Mosqueda-Taylor A, García-Edgar VN, Cuevas-González JC. Dermoscopic patterns of filiform papillae of the tongue in patients with and without connective tissue autoimmune diseases. Int J Dermatol. 2018 Aug. 57 (8):938-942. [Medline].
Lachter J, Suissa A, Schiff E, Rosner I. Anemia in CREST syndrome. Isr Med Assoc J. 2003 Jun. 5(6):449. [Medline].
Meyer O. [Crest Syndrome]. Ann med Interne (Paris). 2002. 153(3):183-188. [Medline].
Mavrogeni S, Bratis C, Manoussakis M. Coronary artery abnormalities in CREST syndrome revealed by cardiovascular magnetic resonance imaging. Can J Cardiol. 2011 May-Jun. 27(3):390.e5-7. [Medline].
Kouraklis G, Glinavou A, Karatzas G. Primary biliary cirrhosis accompanied by CREST syndrome. South Med J. 2002 Sep. 95(9):1058-9. [Medline].
Tojo J, Ohira H, Suzuki T, Takeda I, Shoji I, Kojima T, et al. Clinicolaboratory characteristics of patients with primary biliary cirrhosis associated with CREST symptoms. Hepatol Res. 2002 Mar. 22(3):187-195. [Medline].
Hill CL, Nguyen AM, Roder D, Roberts-Thomson P. Risk of cancer in patients with scleroderma: a population based cohort study. Ann Rheum Dis. 2003 Aug. 62(8):728-31. [Medline].
Desai K, Mian NZ. Osteonecrosis of multiple joints in a patient with limited scleroderma/CREST syndrome. J Clin Rheumatol. 2015 Apr. 21 (3):169-70. [Medline].
van Paassen P, Damoiseaux J, Tervaert JW. Laboratory assessment in musculoskeletal disorders. Best Pract Res Clin Rheumatol. 2003 Jun. 17(3):475-94. [Medline].
Aeschlimann A, Meyer O, Bourgeois P, Haim T, Belmatoug N, Palazzo E, et al. Anti-Scl-70 antibodies detected by immunoblotting in progressive systemic sclerosis: specificity and clinical correlations. Ann Rheum Dis. 1989 Dec. 48(12):992-7. [Medline].
Oliva Menacho JE, Arroyo-Acevedo JL, Oliva-Candela JA, García-Hjarles MA, Domínguez-Huarcaya L. Staining of antinuclear antibodies and antibodies against removable nuclear antigens in connective tissue diseases. Allergol Immunopathol (Madr). 2020 Jan - Feb. 48 (1):18-25. [Medline].
Gonzalez R, Storr M, Bloching H, Seige M, Ott R, Allescher HD. Autoantibody profile in progressive systemic sclerosis as markers for esophageal involvement. J Clin Gastroenterol. 2001 Feb. 32(2):123-7. [Medline].
Bar-Sever Z, Mukamel M, Harel L, Hardoff R. Scintigraphic evaluation of calcinosis in juvenile dermatomyositis with Tc-99m MDP. Clin Nucl Med. 2000 Dec. 25(12):1013-6. [Medline].
Strumia R. Videodermatoscopy: a useful tool for diagnosing cutaneous dystrophic calcifications. Dermatol Online J. 2005. 11(1):28. [Medline].
Ling TC, Johnston BT. Esophageal investigations in connective tissue disease: which tests are most appropriate?. J Clin Gastroenterol. 2001 Jan. 32(1):33-6. [Medline].
Joslin N. Early identification key to scleroderma treatment. Nurse Pract. 2004 Jul. 29(7):24-39; quiz 40-1. [Medline].
Rus V, White B. Systemic sclerosis: multiple therapies control morbidity. J Musculoskel Med. 2002. 19:110-121.
Samuelson UK, Ahlmen EM. Development and evaluation of a patient education program for persons with systemic sclerosis (scleroderma). Arthritis Care Res. 2000 Jun. 13(3):141-8. [Medline].
Legendre C, Allanore Y, Ferrand I, Kahan A. Evaluation of depression and anxiety in patients with systemic sclerosis. Joint Bone Spine. 2005 Oct. 72(5):408-11. [Medline].
Matsuura E, Ohta A, Kanegae F, Haruda Y, Ushiyama O, Koarada S, et al. Frequency and analysis of factors closely associated with the development of depressive symptoms in patients with scleroderma. J Rheumatol. 2003 Aug. 30(8):1782-7. [Medline].
Farge D, Passweg J, van Laar JM, Marjanovic Z, Besenthal C, Finke J, et al. Autologous stem cell transplantation in the treatment of systemic sclerosis: report from the EBMT/EULAR Registry. Ann Rheum Dis. 2004 Aug. 63(8):974-81. [Medline].
Thomas-Golbanov CK, Wilke WS, Fessler BJ, Hoffman GS. Open label trial of tamoxifen in scleroderma. Clin Exp Rheumatol. 2003 Jan-Feb. 21(1):99-102. [Medline].
Fink CW, Cook JD. Spontaneous resolution of calcinosis in childhood dermatomyositis. Arthritis Rheum. 1986. 29(suppl):S91.
Merlino G, Germano S, Carlucci S. Surgical management of digital calcinosis in CREST syndrome. Aesthetic Plast Surg. 2013 Dec. 37 (6):1214-9. [Medline].
Hazen PG, Walker AE, Carney JF, Stewart JJ. Cutaneous calcinosis of scleroderma. Successful treatment with intralesional adrenal steroids. Arch Dermatol. 1982 May. 118(5):366-7. [Medline].
Vayssairat M, Hidouche D, Abdoucheli-Baudot N, Gaitz JP. Clinical significance of subcutaneous calcinosis in patients with systemic sclerosis. Does diltiazem induce its regression?. Ann Rheum Dis. 1998 Apr. 57(4):252-4. [Medline].
Berger RG, Featherstone GL, Raasch RH, McCartney WH, Hadler NM. Treatment of calcinosis universalis with low-dose warfarin. Am J Med. 1987 Jul. 83(1):72-6. [Medline].
Cukierman T, Elinav E, Korem M, Chajek-Shaul T. Low dose warfarin treatment for calcinosis in patients with systemic sclerosis. Ann Rheum Dis. 2004 Oct. 63(10):1341-3. [Medline].
Lassoued K, Saiag P, Anglade MC, Roujeau JC, Touraine RL. Failure of warfarin in treatment of calcinosis universalis. Am J Med. 1988 Apr. 84(4):795-6. [Medline].
Boulman N, Slobodin G, Rozenbaum M, Rosner I. Calcinosis in rheumatic diseases. Semin Arthritis Rheum. 2005 Jun. 34(6):805-12. [Medline].
Rabens SF, Bethune JE. Disodium etidronate therapy for dystrophic cutaneous calcification. Arch Dermatol. 1975 Mar. 111(3):357-61. [Medline].
Metzger AL, Singer FR, Bluestone R, Pearson CM. Failure of disodium etidronate in calcinosis due to dermatomyositis and scleroderma. N Engl J Med. 1974 Dec 12. 291(24):1294-6. [Medline].
Ambler GR, Chaitow J, Rogers M, McDonald DW, Ouvrier RA. Rapid improvement of calcinosis in juvenile dermatomyositis with alendronate therapy. J Rheumatol. 2005 Sep. 32(9):1837-9. [Medline].
Robertson LP, Marshall RW, Hickling P. Treatment of cutaneous calcinosis in limited systemic sclerosis with minocycline. Ann Rheum Dis. 2003 Mar. 62(3):267-9. [Medline].
Taborn J, Bole GG, Thompson GR. Colchicine suppression of local and systemic inflammation due to calcinosis universalis in chronic dermatomyositis. Ann Intern Med. 1978 Nov. 89(5 Pt 1):648-9. [Medline].
Kalajian AH, Perryman JH, Callen JP. Intravenous immunoglobulin therapy for dystrophic calcinosis cutis: unreliable in our hands. Arch Dermatol. 2009 Mar. 145(3):334; author reply 335. [Medline].
Goodfield MJ, Hume A, Rowell NR. The effect of simple warming procedures on finger blood flow in systemic sclerosis. Br J Dermatol. 1988 May. 118(5):661-8. [Medline].
Freedman RR. Quantitative measurements of finger blood flow during behavioral treatments for Raynaud''s disease. Psychophysiology. 1989 Jul. 26(4):437-41. [Medline].
Karavidas MK, Tsai PS, Yucha C, McGrady A, Lehrer PM. Thermal biofeedback for primary Raynaud's phenomenon: a review of the literature. Appl Psychophysiol Biofeedback. 2006 Sep. 31(3):203-16. [Medline].
Meyrick Thomas RH, Rademaker M, Grimes SM, MacKay A, Kovacs IB, Cook ED, et al. Nifedipine in the treatment of Raynaud's phenomenon in patients with systemic sclerosis. Br J Dermatol. 1987 Aug. 117(2):237-41. [Medline].
Thompson AE, Pope JE. Calcium channel blockers for primary Raynaud's phenomenon: a meta-analysis. Rheumatology (Oxford). 2005 Feb. 44(2):145-50. [Medline].
Fischer M, Reinhold B, Falck H, Torok M, Alexander K. Topical nitroglycerin ointment in Raynaud's phenomenon. Z Kardiol. 1985 May. 74(5):298-302. [Medline].
Anderson ME, Moore TL, Hollis S, Jayson MI, King TA, Herrick AL. Digital vascular response to topical glyceryl trinitrate, as measured by laser Doppler imaging, in primary Raynaud's phenomenon and systemic sclerosis. Rheumatology (Oxford). 2002 Mar. 41(3):324-8. [Medline].
Teh LS, Manning J, Moore T, Tully MP, O'Reilly D, Jayson MI. Sustained-release transdermal glyceryl trinitrate patches as a treatment for primary and secondary Raynaud's phenomenon. Br J Rheumatol. 1995 Jul. 34(7):636-41. [Medline].
Cruz JE, Ward A, Anthony S, Chang S, Bae HB, Hermes-DeSantis ER. Evidence for the Use of Epoprostenol to Treat Raynaud's Phenomenon With or Without Digital Ulcers: A Review of the Literature. Ann Pharmacother. 2016 Jul 26. [Medline].
Torley HI, Madhok R, Capell HA, Brouwer RM, Maddison PJ, Black CM, et al. A double blind, randomised, multicentre comparison of two doses of intravenous iloprost in the treatment of Raynaud's phenomenon secondary to connective tissue diseases. Ann Rheum Dis. 1991 Nov. 50(11):800-4. [Medline].
Milio G, Corrado E, Genova C, Amato C, Raimondi F, Almasio PL, et al. Iloprost treatment in patients with Raynaud's phenomenon secondary to systemic sclerosis and the quality of life: a new therapeutic protocol. Rheumatology (Oxford). 2006 Aug. 45(8):999-1004. [Medline].
Kaminaga T, Takada K, Kutomi K, Imai E, Furui S. Improvement in cold-induced Raynaud's syndrome with administration of ticlopidine hydrochloride detected by Tc-99m DTPA human serum albumin scintigraphy. Clin Nucl Med. 2002 Feb. 27(2):131-2. [Medline].
Rajagopalan S, Pfenninger D, Somers E, Kehrer C, Chakrabarti A, Mukherjee D, et al. Effects of cilostazol in patients with Raynaud's syndrome. Am J Cardiol. 2003 Dec 1. 92(11):1310-5. [Medline].
Dean SM, Satiani B. Three cases of digital ischemia successfully treated with cilostazol. Vasc Med. 2001 Nov. 6(4):245-8. [Medline].
Bridges AJ, Spadone DP. Tissue plasminogen activator treatment of digital thrombosis in severe Raynaud's phenomenon--a case report. Angiology. 1993 Jul. 44(7):566-9. [Medline].
Denton CP, Howell K, Stratton RJ, Black CM. Long-term low molecular weight heparin therapy for severe Raynaud's phenomenon: a pilot study. Clin Exp Rheumatol. 2000 Jul-Aug. 18(4):499-502. [Medline].
Jacobs MJ, Jörning PJ, Van Rhede van der Kloot EJ, Kitslaar PJ, Lemmens HA, Slaaf DW, et al. Plasmapheresis in Raynaud's phenomenon in systemic sclerosis: a microcirculatory study. Int J Microcirc Clin Exp. 1991 Feb. 10(1):1-11. [Medline].
O'Reilly MJ, Talpos G, Roberts VC, White JM, Cotton LT. Controlled trial of plasma exchange in treatment of Raynaud's syndrome. Br Med J. 1979 Apr 28. 1(6171):1113-5. [Medline].
Koo AP. Therapeutic apheresis in autoimmune and rheumatic diseases. J Clin Apher. 2000. 15(1-2):18-27. [Medline].
Dziadzio M, Denton CP, Smith R, Howell K, Blann A, Bowers E, et al. Losartan therapy for Raynaud''s phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial. Arthritis Rheum. 1999 Dec. 42(12):2646-55. [Medline].
Pancera P, Sansone S, Secchi S, Covi G, Lechi A. The effects of thromboxane A2 inhibition (picotamide) and angiotensin II receptor blockade (losartan) in primary Raynaud's phenomenon. J Intern Med. 1997 Nov. 242(5):373-6. [Medline].
Wood HM, Ernst ME. Renin-angiotensin system mediators and Raynaud's phenomenon. Ann Pharmacother. 2006 Nov. 40(11):1998-2002. [Medline].
Baumhaekel M, Scheffler P, Boehm M. Use of tadalafil in a patient with a secondary Raynaud's phenomenon not responding to sildenafil. Microvasc Res. 2005 May. 69(3):178-9. [Medline].
Gore J, Silver R. Oral sildenafil for the treatment of Raynaud's phenomenon and digital ulcers secondary to systemic sclerosis. Ann Rheum Dis. 2005 Sep. 64(9):1387. [Medline].
Caglayan E, Huntgeburth M, Karasch T, Weihrauch J, Hunzelmann N, Krieg T, et al. Phosphodiesterase type 5 inhibition is a novel therapeutic option in Raynaud disease. Arch Intern Med. 2006 Jan 23. 166(2):231-3. [Medline].
Wise RA, Wigley FM, White B, Leatherman G, Zhong J, Krasa H, et al. Efficacy and tolerability of a selective alpha(2C)-adrenergic receptor blocker in recovery from cold-induced vasospasm in scleroderma patients: a single-center, double-blind, placebo-controlled, randomized crossover study. Arthritis Rheum. 2004 Dec. 50(12):3994-4001. [Medline].
Johnson S, Iazzetta J, Dewar C. Severe Raynaud's phenomenon with yohimbine therapy for erectile dysfunction. J Rheumatol. 2003 Nov. 30(11):2503-5. [Medline].
Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM, Keogh A, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002 Mar 21. 346(12):896-903. [Medline].
Coleiro B, Marshall SE, Denton CP, Howell K, Blann A, Welsh KI, et al. Treatment of Raynaud's phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology (Oxford). 2001 Sep. 40(9):1038-43. [Medline].
Garcia-Porrua C, Margarinos CC, Gonzalez-Gay MA. Raynaud's phenomenon and serotonin reuptake inhibitors. J Rheumatol. 2004 Oct. 31(10):2090; author reply 2090-1. [Medline].
Herrick AL. Treatment of Raynaud's phenomenon: new insights and developments. Curr Rheumatol Rep. 2003 Apr. 5(2):168-74. [Medline].
Wang SJ, La JL, Chen DY, Chen YH, Hsieh TY, Lin WY. Effects of cisapride on oesophageal transit of solids in patients with progressive systemic sclerosis. Clin Rheumatol. 2002 Feb. 21(1):43-5. [Medline].
Hulshof MM, Bouwes Bavinck JN, Bergman W, Masclee AA, Heickendorff L, Breedveld FC, et al. Double-blind, placebo-controlled study of oral calcitriol for the treatment of localized and systemic scleroderma. J Am Acad Dermatol. 2000 Dec. 43(6):1017-23. [Medline].
Clements PJ, Furst DE, Wong WK, Mayes M, White B, Wigley F, et al. High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis: analysis of a two-year, double-blind, randomized, controlled clinical trial. Arthritis Rheum. 1999 Jun. 42(6):1194-203. [Medline].
Alam M, Dover JS, Arndt KA. Treatment of facial telangiectasia with variable-pulse high-fluence pulsed-dye laser: comparison of efficacy with fluences immediately above and below the purpura threshold. Dermatol Surg. 2003 Jul. 29(7):681-4; discussion 685. [Medline].
Saddic N, Miller JJ, Miller OF 3rd, Clarke JT. Surgical debridement of painful fingertip calcinosis cutis in CREST syndrome. Arch Dermatol. 2009 Feb. 145(2):212-3. [Medline].
Melone CP Jr, McLoughlin JC, Beldner S. Surgical management of the hand in scleroderma. Curr Opin Rheumatol. 1999 Nov. 11(6):514-20. [Medline].
Chamberlain AJ, Walker NP. Successful palliation and significant remission of cutaneous calcinosis in CREST syndrome with carbon dioxide laser. Dermatol Surg. 2003 Sep. 29(9):968-70. [Medline].
Bottomley WW, Goodfield MJ, Sheehan-Dare RA. Digital calcification in systemic sclerosis: effective treatment with good tissue preservation using the carbon dioxide laser. Br J Dermatol. 1996 Aug. 135(2):302-4. [Medline].
Husain MQ, Alsheikh O. Complications in Placement of a Glaucoma Drainage Device in a Patient With CREST Syndrome. J Glaucoma. 2017 Feb. 26 (2):e82-e83. [Medline].

Media Gallery

Calcinosis on dorsal forearm.
Close-up view of calcinosis.
Raynaud phenomenon showing pallor of most of the finger tips with a violaceous discoloration (hyperemia) of the thumb tip.
Sclerodactyly (also with Raynaud phenomenon).
Sclerodactyly.
Telangiectasia of the face.
Telangiectasia of the lip.
Telangiectasia of the finger.
Close-up view of telangiectasia.

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Author

Jeanie C Yoon, MD Clinical Instructor, Department of General Internal Medicine, University of Washington School of Medicine

Jeanie C Yoon, MD is a member of the following medical societies: American College of Physicians, Society of Hospital Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American College of Rheumatology

Disclosure: Received honoraria from UpToDate for author/editor; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for i inherited these trust accounts; I serve on a safety monitoring committee for Principia Biopharma for: Allergen; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen; Gilead.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Gregory J Raugi, MD, PhD Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle School of Medicine; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle

Gregory J Raugi, MD, PhD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference wish to thank Dr. Bruce Gilliland for assistance in reviewing the manuscript and Dr. Jan V. Hirschmann and Dr. Netayna Sandler for their images.

The authors and editors of Medscape Reference also gratefully acknowledge the contributions of previous authors, Mary A. Wemple, MD, and Kyle L. Horner, MD, MS, to the development and writing of this article.