Progressive systemic sclerosis (scleroderma), carcinoma breast and valvular heart disease: an unusual combination.
MS Dewani, SR Qadri, MA Lone, KA Qureshi
Department of Medicine, Govt. Medical College and S. M. H. S. Hospital, Srinagar, Jammu & Kashmir, India., India
M S Dewani
Department of Medicine, Govt. Medical College and S. M. H. S. Hospital, Srinagar, Jammu & Kashmir, India.
Systemic sclerosis is a multi system disorder characterised by fibrosis of skin and internal organs. There are reports of relation between cancer and polymyositis/dermatomyositis, but no overall association with systemic sclerosis. Reports of the coexistence of cancer and systemic sclerosis, however, emphasise a close temporal relation in their occurrence. Cardiac involvement in the form of myocardial fibrosis and pericarditis occurs frequently in systemic sclerosis, while valvular involvement has been reported only sporadically. We report a patient, admitted for adenocarcinoma of left breast who was found to have features of systemic sclerosis, pulmonary hypertension, gangrene of toes, and stenotic mitral valve disease. The possible mechanisms of the coincidence of the three disorders are discussed.
|How to cite this article:|
Dewani M S, Qadri S R, Lone M A, Qureshi K A. Progressive systemic sclerosis (scleroderma), carcinoma breast and valvular heart disease: an unusual combination. J Postgrad Med 2000;46:181-3
|How to cite this URL:|
Dewani M S, Qadri S R, Lone M A, Qureshi K A. Progressive systemic sclerosis (scleroderma), carcinoma breast and valvular heart disease: an unusual combination. J Postgrad Med [serial online] 2000 [cited 2021 May 15 ];46:181-3
Available from: https://www.jpgmonline.com/text.asp?2000/46/3/181/283
The coincidence of cancer and progressive systemic sclerosis has been reported to range between 3 to7 percent, with breast cancer being second common after lung cancer in these patients. The close temporal association between the two, and the influence of treatment of one disease on the course of other suggests a pathogenic link between systemic sclerosis and cancer. The occurrence of valvular cardiac lesion in systemic sclerosis has been reported sporadically. We report a case with systemic sclerosis, carcinoma of breast and stenotic mitral valve disease and discuss the possible pathogenic links among the three.
A 55-year-old female, a housewife, menopausal, non-diabetic, normotensive with fine needle aspiration cytology proven ductal adenocarcinoma of left breast was referred for routine pre-surgical check-up. She gave history of non-progressive dysphagia to solid food, incapacitating difficulty in flexion of fingers, chalky white discharge from tip ulcers of hands and feet and Raynaud’s phenomenon over past 6 months. She also gave history of exertional breathlessness of three months’ duration. There was no history suggestive of rheumatic fever in the past. The family, occupational and drug histories were not significant. On examination, the patient had diffuse non-scarring alopecia, narrow palpebral fissures, mask like facies, pinched nose and microstomia. She had facial telangiectasias and had radial furrowing around her mouth. Sclerodactly and pitting ulcers over her fingertips were present [Figure:1]. The skin of feet was also thickened and there was dry gangrene of her right great toe with auto amputation of right little toe [Figure:2]. The skin involvement on the face, hands, and distal extremities as assessed by Rodnan total skin score (TSS) was severe (grade 3) with no skin involvement on the trunk and proximal extremities. Active arthritis was not present and no tendon friction rubs were palpable. Examination of left breast revealed a 7cm x 8cm, non-tender hard mass with indurated skin over it and greenish discharge from the nipple. Left axillary lymph nodes were enlarged and hard, non-tender but mobile. Except right dorsalis pedis all peripheral pulses were felt. She was normotensive. There were no features of congestive cardiac failure. Her chest examination revealed bilateral basal crepitations. Cardiovascular examination revealed findings suggestive of pulmonary hypertension in addition to loud first heart sound and mid diastolic murmur at apex. Abdominal and neurological examinations were normal.
Investigations revealed haemoglobin of 11.5 gm/dl with normal cell counts. Erythrocyte sedimentation rate was 40 mm in first hour. Urine showed albumin of 1 +, but no casts. Blood sugar, blood urea, serum creatinine, liver function tests, serum calcium and serum phosphorus were normal. Chest radiograph showed borderline cardiomegaly with evidence of pulmonary arterial hypertension. Ultrasonography of abdomen was normal. Pulmonary function tests were suggestive of restrictive lung disease. Barium swallow showed marked dilatation of lower two-thirds of oesophagus. Radiograph of hands and feet revealed resorption of terminal phalanges and few areas of punctate subcutaneous calcification suggestive of calcinosis. Antinuclear antibody, Rheumatoid factor and L.E. cell tests were negative. Anti-streptolysin-O (ASO) titre was not elevated. Skin biopsy showed perivascular fibrosis. Electrocardiograph revealed evidence of right atrial, left atrial and right ventricular enlargement in addition to sinus tachycardia. Echocardiography revealed that both atria were enlarged and left ventricular ejection fraction was 56 percent. Mitral valve area was 2.3 cm2 and it was suggestive of rheumatic in aetiology, with pulmonary gradient of 15 mm Hg and mitral gradient of 8 mm Hg. Aortic valve was normal. There was mild tricuspid regurgitation with right ventricular systolic pressure of 80 mm Hg. Patient was given symptomatic treatment for dysphagia and Raynaud’s phenomenon. She was considered high risk for surgery and radiotherapy and was referred for chemotherapy.
Progressive systemic sclerosis is a multisystem disorder of uncertain cause characterised by fibrosis of skin, blood vessels, visceral organs including gastrointestinal tract, heart and kidneys. A close temporal relationship between systemic sclerosis and cancer has been observed.,, The regression of scleroderma in two patients treated for malignancy of breast and bladder, and deterioration of scleroderma in a patient with breast carcinoma who developed metastatic disease suggests a pathogenic link between the two diseases.
Although no pathogenic links between cancer and systemic sclerosis have been confirmed, the increased occurrence of lung cancer in the absence of cigarette smoking has been attributed to the presence of chronic pulmonary fibrosis. The postulated explanations for this coincidence include a sustained increase in mitotic activity in cells involved in the inflammatory component of the disease, and those involved in tissue repair; and impaired clearance of carcinogens in tissues with disorganised architecture. The patients of progressive systemic sclerosis have high titres of antinuclear antibodies including anti-centromere antibody. A protein or autoantibody which induces sclerodermatous changes, could also act as a carcinogen or it could be a substance produced by tumour cell that induces sclerodermatous changes. Thus, progressive systemic sclerosis could be a paraneoplastic syndrome. For example, a metabolite in carcinoid syndrome (5 Hydroxy-tryptamine) may induce sclerodermatous skin changes but not systemic disease. Other possible mechanism of the association between the two could be a common pathogenesis. A common genetic susceptibility has been considered by Forbes. It has been postulated that impaired immune regulation leading to uncontrolled lymphoid proliferation may predispose to the development of malignant lymphoma in patients with connective tissue disease. Systemic sclerosis is known to occur in patients with graft vs. host disease.
The concurrence of progressive systemic sclerosis and breast cancer may also have implications on the treatment of breast cancer. There are case reports of severe fibrosis and exacerbation of the skin lesions in patients of progressive systemic sclerosis following radiation therapy, and collagen vascular diseases especially progressive systemic sclerosis and systemic lupus erythematosous are considered to be contraindications to radiation therapy. Any patient who is diagnosed to have systemic sclerosis should be screened for cancer and regular breast examination and mammography should be recommended for first five years after the onset of disease in females.
Our patient also had mitral stenosis in addition to decreased left ventricular ejection fraction and pulmonary artery hypertension. Myocardial lesions (fibrosis), conduction abnormalities and pericarditis occurs frequently in patients with progressive systemic sclerosis. Involvement of cardiac valves in systemic sclerosis has been reported sporadically. Oram et al recorded valvular lesions in five out of twenty eight cases of scleroderma culled from the literature. Jones found valvular disease in four of thirty-four patients with systemic sclerosis three of whom had previous history of acute rheumatic fever. D’Angelo et al in an autopsy study of 58 patients of systemic sclerosis found the prevalence of mitral valvular abnormalities to be 38 percent, but this was matched by a 42 percent prevalence of such abnormalities in the control group. Moreover, there was no difference in the type or severity of the lesions in the two groups. In no patient, either in the sclerodermatous or the control group were the lesions significant.
Our patient had clinically evident mitral stenosis, which was confirmed by echocardiography. Although the echocardiographic findings suggested that the mitral valve was rheumatic, but keeping in view the negative past history and normal ASO titre, we feel that valve involvement could well be due to systemic sclerosis. In systemic sclerosis, as reported by D’Angelo thickening of valves especially of free edges of mitral valve cusps along with shortening of chordae tendinae can occur which can be confused with rheumatic changes on autopsy or echocardiography. The pulmonary arterial hypertension present in our patient could be due to mitral stenosis or it could be due to lung parenchymal involvement, which was present in our patient as evidenced by clinical examination and lung function tests.
Duncan SC, Winkelman RK. Cancer and Scleroderma. Arch Dermatol 1979; 115:950-955.|
|2||Roumm AD, Medsger TA Jr. Cancer and Systemic sclerosis. An epidemiological study. Arthritis Rheum 1985; 28:1336-1340.|
|3||Lee P, Alderdice C, Wilkinson S, Keystone EC, Urowitz MB, Gladman DD. Malignancy in progressive systemic sclerosis. Association with breast carcinoma. J Rheumatol 1983; 10:665-666.|
|4||Peter-Golden M, Wise RA, Hochberg MC, Stevens MB, Wigley FM. Incidence of lung carcinoma in systemic sclerosis. J Rheumatol 1985; 12:1136-1139.|
|5||Fries JF, Landgren JA, Bull JM. Scleroderma like lesions and the carcinoid syndrome. Arch Intern Med 1973; 131:550-553.|
|6||Forbes A, Woodrow JC, Verbo JL, Graham RM. Carcinoma of the breast and scleroderma. Four further cases and a literature review. Br J Rheumatol 1989; 28:65-69.|
|7||McLeish KR, Smith MR, Golara AF. Non Hodgkin’s lymphoma and membranous nephropathy in mixed connective tissue disease. Am J Med Sci 1985; 240:152-154.|
|8||Furst DE, Clements PJ, Grase P, Gale R, Roberts N. A syndrome resembling progressive systemic sclerosis after bone marrow transplantation. A model for scleroderma? Arthritis Rheum 1979; 22:904-910. |
|9||Aref I, Cross P, Nair B. Case report: Severe fibrosis in a patient with scleroderma and previous radiotherapy,a case report and literature review; Br J Radiol 1996; 69:1055-1056.|
|10||Breast radiotherapy after breast conservation surgery: The Steering Committee on Clinical Practice Guidelines for Treatment of Breast Cancer; Canadian Association of Radiation Oncologists. Cand Med Assoc J 1998; 158 (suppl 3):S35-S42.|
|11||Oram S, Stokes W; The heart in scleroderma. Br Heart J 1961; 23:243.|
|12||Jones EW. Valvular disease of heart in systemic scleroderma. Br J Dermatol 1962; 74:183|
|13||D’Angelo WA, Fries JF, Masi AT, Shulman LE. Pathological observations in systemic sclerosis (scleroderma). A study of fifty-eight cases and fifty-eight matched controls. Am J Med 1969; 46:428-440.