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Idiopathic calcinosis circumscripta
Idiopathic GERALD
I.
Calcinosis PLITMAN,
Circumscripta*
M.D. and BENJAMIN
Memphis,
R.
GENDEL,
M.D.
Tennessee
C
ALCINOSIS, the deposition of calcium masses in the skin and soft tissues, is an unusual and interesting condition. In its broadest sense the term calcinosis may refer to calcification of skin or soft tissues from any of several causes. These causes may be divided into four categories, namely, (1) mineral disturbances mediated by metabolic or endocrinologic abnormality; (2) calcification of hematomas or of tissues damaged by trauma or infection; (3) calcification associated with a vascular disturbance as in Raynaud’s phenomenon or scleroderma and (4) calcification without obvious accompanying or preceding pathologic change. l In a stricter sense the term calcinosis refers to the latter two categories and the term idiopathic calcinosis to the lattermost category. It is to this group that the case herein presented belongs. The literature on this subject has been thoroughly reviewed at intervals in the past,2-5 and will not be completely discussed here. The etiology of this condition is unknown.‘jv7 The varied theories of causation have included first, disorders of calcium metabolism and secondly, predisposition by tissue injury and death. In regard to the former it may be pointed out that in these cases there is no history of vitamin D intoxication; the urinary findings reveal no renal basis; and normal serum calcium and phosphorus values do not indicate parathyroid hyperactivity. With regard to the latter theory, in the usual case there is no known antecedent trauma and the studies of Bauer, Marble and Bennett8 showed that, microscopically, early calcium deposition can be seen around normal-appearing fat tissue. Atkinson and Webe reported the frequent coexistence of calcinosis and vasospastic lesions but Ghormley3 found calcinosis to occur in only 2.5 per cent of a series of cases of vasospastic diseases studied at the Mayo Clinic.
Clinically the cases are divided into two groups: (1) calcinosis circumscripta in which the calcium deposits are of limited extent and confined to the skin and subcutaneous tissues, usually of the extremities; and (2) calcinosis universalis in which the calcification extensively involves the muscles and tendons as well. Although each type may occur at any time of life, calcinosis universalis is more common in childhood and youth while calcinosis circumscripta affects chiefly the older age groups. In each type the female sex is predominantly affected. zg The degree of involvement may vary from only slight involvement, as in the case herein reported, to massive involvement as in the case of Moore and Clarke.6 Symptoms vary according to site and degree of involvement and include the presence of nodules, pain in involved areas, limitation of motion of joints, general debility and sometimes the breakdown of superficial nodules to form sinuses which may discharge a cheesy, gritty material. Prognosis also depends upon the site and degree of involvement. The calcium deposits are, of course, readily demonstrable on x-ray. Pathologically there is deposition of calcium in non-encapsulated clumps with surrounding fibrosis and infiltration of chronic inflammatory cells. Foreign body giant cells are frequently seen. There is, as a rule, no evidence of active tissue necrosis. Chemically, the deposits consist chiefly of calcium phosphate and calcium carbonate. So varied have been the forms of attempted treatment that one gains the impression that no one method of therapy has been consistently successful. The relative rarity of the disease renders evaluation of a particular therapeutic regimen even more difficult. Moreover, the fact that spontaneous regressions have been reported makes any treatment even more difficult of
* From the General Medicine and Hematology Section of the Medical Service, Veterans Administration Medical Teaching Group, Kennedy Hospital, Memphis, Tenn. Reviewed in the Veterans Administration and published with the approval of the Chief Medical Director. The statements and conclusions published by the authors are the result of their own study and do not necessarily reflect the opinion and policy of the Veterans Administration. AUGUST,
1951
267
268
Idiopathic Calcinosis Circumscripta-Hitman,
FIG. 1. X-ray of the right arm showing multiple calcific densities.
small
evaluation. Acid salts, iodides, ketogenic x-ray therapy and parathyroidectomy been tried with varying success.4310
diet, have
CASE REPORT
A fifty-six year old white man was admitted to the hospital with a complaint of hard deposits in the subcutaneous tissues of both arms of four years’ duration. The appearance of these deposits was preceded in all instances by “burning and drawing” sensations but the masses themselves were asymptomatic except by virtue of their presence and progressive enlargement. In recent months the premonitory “burning and drawing” sensations had been noted in the right thigh posteriorly and in the right side of the face, but no hard masses had as yet appeared at those sites. There was no family history of this disorder and the patient gave no history of bone disease, renal stones or vitamin D ingestion. The past history was quite complex; the patient having
Gendel
had gonorrhea, syphilis, tuberculosis and influenza complicated by empyema many years before. He had had a number of operative procedures, chief among which were thoracotomy and construction of a perineal urethra following urinary extravasation due to urethral strictures. Physical examination revealed a well developed, well nourished, white man who appeared neither acutely nor chronically ill. Temperature and pulse were normal. Blood pressure was 180/100. All teeth were absent. The old thoracotomy scar was noted in the fifth intercostal space in the right axilla. The lung fields were essentially clear to percussion and auscultation. The heart was not remarkable except for a rough apical systolic murmur. No abnormalities were noted in the abdomen except an old suprapubic cystostomy scar. The left testis was atrophic. An artificial urethra was present in the middle of the perineum. In the right arm there were several large, hard, irregular masses which seemed to lie in the subcutaneous tissues and did not move with contraction and relaxation of the muscles; a similar single mass was present in the left arm. Except for the surgical scars and subcutaneous masses, the skin was entirely normal. There was no evidence of peripheral vascular disease. In the general laboratory work-up urinalysis and blood counts were within normal limits. Serologic test for syphilis was negative. Serum calcium level was 10.2 mg. per cent on each of two determinations; inorganic phosphorus was 3.6 and 3.0 mg. per cent on each of two occasions. Acid and alkaline phosphatases were 1.2 and 4.0 King-Armstrong units respectively. Urine concentration test revealed a maximum figure of 1.022; on a urea clearance test the patient showed 60 per cent of average normal clearance. Electrocardiog.am showed a right bundlebranch block. On chest x-ray the lungs were clear; there was, however, thickened pleura at both bases and an old resection of the right seventh rib. X-rays of the arms revealed numerous small, irregular, calcified densities varying in diameter from 0.1 to 0.3 cm. lying in the skin and subcutaneous tissues of both arms, (Fig. 1.) Similar calcifications were noted regional to the buttocks. X-rays of the long bones and spine showed no abnormalities except minimal osteoarthritic changes of the lumbar vertebrae. AMERICAN
JOURNAL
OF
MEDICINE
Idiopathic Calcinosis Circumscripta-Plitman, During the hospital stay calcium excretion studies were accomplished by measuring the patient’s twenty-four hour urinary calcium excretion while on a diet containing 137 mg. of calcium daily. The patient excreted 20, 40, 150 and 30 mg. of calcium on successive days during this time. During the first hospital week the patient had blood-streaked sputum. This, plus the history of tuberculosis, prompted the decision to have him bronchoscoped, including smears and cultures for acid-fast bacilli but all findings were normal. Biopsies were taken from the following sites: (1) a calcified area in the right arm; histologically this showed dense broad bands of collagen in the corium, throughout which lay oval masses of amorphous calcified material surrounded by dense, hyalinized fibrous tissue. Several areas of chronic inflammation containing vacuolated foreign body giant cells were noted. (2) A “precursor” site in the right thigh at which symptoms of “burning and drawing” had been present but no calcification had been apparent; this was histologically normal. (3) A presumably “normal” site far removed from the other sites; histologically this was normal. All biopsy sites healed well. Meanwhile, the patient had been receiving penile urethral dilatations by the GenitoUrinary Service with a view toward re-establishment of normal function. During the hospital course no specific therapy aimed at reducing the calcium masses was undertaken. Following completion of medical workup the patient was transferred to the Genito-Urinary Service where the urethrostomy was excised and function re-established in the penile urethra. COMMENTS
The etiology and pathogenesis of idiopathic calcinosis is unknown. In view of the fact that this patient had certain premonitory symptoms of burning or drawing sensations prior to the deposition of calcium, it was thought that histologic study of such a “precursor site” might be informative. However, histologic study of the skin from such sites did not reveal any significant pathologic disorder. Some broadening of the collagen bands was noted but this did not differ from a similar variation in width of the collagen bands noted in sections of normal skin studied. In addition, no significant variations in the staining quality of the collagen could be detected. Study of our patient’s skin removed from a normal area likewise showed no changes. No AUGUST,
1951
Gendel
clue to the pathogenesis of this condition was afforded by a study of the many biopsies which this patient permitted. The etiology remains a mystery. Lansbury” mentions briefly the controversy which has existed as to whether or not calcinosis actually represents a distinct entity, citing its frequent occurrence in association with Raynaud’s phenomenon, scleroderma and dermatomyositis. He quotes Langmead12 as having suggested that all these syndromes were manifestations of a single disease. The findings in the case discussed here suggest a separate existence of calcinosis; there were no skin changes, clinically or histologically, to suggest pre-existing disease such as scleroderma or dermatomyositis, and the proximal locations of the calcinotic deposits were inconsistent with their having been secondary to Raynaud’s phenomenon. SUMMARY
A case of calcinosis circumscripta in a middlraged male is reported, and the pertinent features of the disease are reviewed briefly. The case herein described conformed to the rule in showing typical histologic changes and no demonstrable error of calcium metabolism. REFERENCES
1. PETERS,J. H., HORN, R. H. and GREENMAN,L. Idiopathic calcinosis universalis cutis without disability. Ann. Znt. Med., 32: 138, 1950. 2. ATKINSON,F. R. B. and PARKES-WEBER, F. Cutaneous and subcutaneous calcinosis. Rrit. 3. Dermot., 50: 267, 1938. 3. GHORMLEY,R. and MCCRARY, W. E. Multiple calcified bursae and calcified cysts in the soft tissues. Tr. West. S. A., 51: 292, 1942. 4. MORAN, F. T. Calcinosis: a brief review of the literatureand report of two cases. South. M. J., 40: 840, 1947. 5. ROTHSTEIN, J. L. and WELT, S. Calcinosisuniversalis and calcinosisin infancy and in childhood. Am. 3. Dis. Child., 52: 368, 1936. 6. MOORE, M., JR. and CLARKE, C. L. Extreme calcinosis intentitialis. South. M. J,, 43: 861, 1950. 7. F'USITZ, M. E., OWEN, A. K. and FINNEY, G. A. Calcinosis cutis. 3. A. M. A., 110: 360, 1938. 8. BAUER, W., MARBLE,A. and BENNETT, G. A. Further studies in a case of calcification of subcutaneous tissue. Am. 3. M. SC., 182: 237, 1931. 9. LUTZ, J. F. Calcinosis universalis. Ann. Int. Med., 14: 1270, 1941. 10. BARTELS, E. C. and CATTELL, R. B. Calcinosis treated by parathyroidectomy. Ann. Znt. Med., 17: 859, 1942. 11. LANSBURY, J. The Scleroderma Group of Collagen Diseases, in Arthritis and Allied Conditions, p. 687. J. L. HOLLANDER, Editor. Philadelphia, 1949. Lea & Febiger. 12. LANGMEAD,F. S. Quoted by Lansbury.”
I.
Calcinosis PLITMAN,
Circumscripta*
M.D. and BENJAMIN
Memphis,
R.
GENDEL,
M.D.
Tennessee
C
ALCINOSIS, the deposition of calcium masses in the skin and soft tissues, is an unusual and interesting condition. In its broadest sense the term calcinosis may refer to calcification of skin or soft tissues from any of several causes. These causes may be divided into four categories, namely, (1) mineral disturbances mediated by metabolic or endocrinologic abnormality; (2) calcification of hematomas or of tissues damaged by trauma or infection; (3) calcification associated with a vascular disturbance as in Raynaud’s phenomenon or scleroderma and (4) calcification without obvious accompanying or preceding pathologic change. l In a stricter sense the term calcinosis refers to the latter two categories and the term idiopathic calcinosis to the lattermost category. It is to this group that the case herein presented belongs. The literature on this subject has been thoroughly reviewed at intervals in the past,2-5 and will not be completely discussed here. The etiology of this condition is unknown.‘jv7 The varied theories of causation have included first, disorders of calcium metabolism and secondly, predisposition by tissue injury and death. In regard to the former it may be pointed out that in these cases there is no history of vitamin D intoxication; the urinary findings reveal no renal basis; and normal serum calcium and phosphorus values do not indicate parathyroid hyperactivity. With regard to the latter theory, in the usual case there is no known antecedent trauma and the studies of Bauer, Marble and Bennett8 showed that, microscopically, early calcium deposition can be seen around normal-appearing fat tissue. Atkinson and Webe reported the frequent coexistence of calcinosis and vasospastic lesions but Ghormley3 found calcinosis to occur in only 2.5 per cent of a series of cases of vasospastic diseases studied at the Mayo Clinic.
Clinically the cases are divided into two groups: (1) calcinosis circumscripta in which the calcium deposits are of limited extent and confined to the skin and subcutaneous tissues, usually of the extremities; and (2) calcinosis universalis in which the calcification extensively involves the muscles and tendons as well. Although each type may occur at any time of life, calcinosis universalis is more common in childhood and youth while calcinosis circumscripta affects chiefly the older age groups. In each type the female sex is predominantly affected. zg The degree of involvement may vary from only slight involvement, as in the case herein reported, to massive involvement as in the case of Moore and Clarke.6 Symptoms vary according to site and degree of involvement and include the presence of nodules, pain in involved areas, limitation of motion of joints, general debility and sometimes the breakdown of superficial nodules to form sinuses which may discharge a cheesy, gritty material. Prognosis also depends upon the site and degree of involvement. The calcium deposits are, of course, readily demonstrable on x-ray. Pathologically there is deposition of calcium in non-encapsulated clumps with surrounding fibrosis and infiltration of chronic inflammatory cells. Foreign body giant cells are frequently seen. There is, as a rule, no evidence of active tissue necrosis. Chemically, the deposits consist chiefly of calcium phosphate and calcium carbonate. So varied have been the forms of attempted treatment that one gains the impression that no one method of therapy has been consistently successful. The relative rarity of the disease renders evaluation of a particular therapeutic regimen even more difficult. Moreover, the fact that spontaneous regressions have been reported makes any treatment even more difficult of
* From the General Medicine and Hematology Section of the Medical Service, Veterans Administration Medical Teaching Group, Kennedy Hospital, Memphis, Tenn. Reviewed in the Veterans Administration and published with the approval of the Chief Medical Director. The statements and conclusions published by the authors are the result of their own study and do not necessarily reflect the opinion and policy of the Veterans Administration. AUGUST,
1951
267
268
Idiopathic Calcinosis Circumscripta-Hitman,
FIG. 1. X-ray of the right arm showing multiple calcific densities.
small
evaluation. Acid salts, iodides, ketogenic x-ray therapy and parathyroidectomy been tried with varying success.4310
diet, have
CASE REPORT
A fifty-six year old white man was admitted to the hospital with a complaint of hard deposits in the subcutaneous tissues of both arms of four years’ duration. The appearance of these deposits was preceded in all instances by “burning and drawing” sensations but the masses themselves were asymptomatic except by virtue of their presence and progressive enlargement. In recent months the premonitory “burning and drawing” sensations had been noted in the right thigh posteriorly and in the right side of the face, but no hard masses had as yet appeared at those sites. There was no family history of this disorder and the patient gave no history of bone disease, renal stones or vitamin D ingestion. The past history was quite complex; the patient having
Gendel
had gonorrhea, syphilis, tuberculosis and influenza complicated by empyema many years before. He had had a number of operative procedures, chief among which were thoracotomy and construction of a perineal urethra following urinary extravasation due to urethral strictures. Physical examination revealed a well developed, well nourished, white man who appeared neither acutely nor chronically ill. Temperature and pulse were normal. Blood pressure was 180/100. All teeth were absent. The old thoracotomy scar was noted in the fifth intercostal space in the right axilla. The lung fields were essentially clear to percussion and auscultation. The heart was not remarkable except for a rough apical systolic murmur. No abnormalities were noted in the abdomen except an old suprapubic cystostomy scar. The left testis was atrophic. An artificial urethra was present in the middle of the perineum. In the right arm there were several large, hard, irregular masses which seemed to lie in the subcutaneous tissues and did not move with contraction and relaxation of the muscles; a similar single mass was present in the left arm. Except for the surgical scars and subcutaneous masses, the skin was entirely normal. There was no evidence of peripheral vascular disease. In the general laboratory work-up urinalysis and blood counts were within normal limits. Serologic test for syphilis was negative. Serum calcium level was 10.2 mg. per cent on each of two determinations; inorganic phosphorus was 3.6 and 3.0 mg. per cent on each of two occasions. Acid and alkaline phosphatases were 1.2 and 4.0 King-Armstrong units respectively. Urine concentration test revealed a maximum figure of 1.022; on a urea clearance test the patient showed 60 per cent of average normal clearance. Electrocardiog.am showed a right bundlebranch block. On chest x-ray the lungs were clear; there was, however, thickened pleura at both bases and an old resection of the right seventh rib. X-rays of the arms revealed numerous small, irregular, calcified densities varying in diameter from 0.1 to 0.3 cm. lying in the skin and subcutaneous tissues of both arms, (Fig. 1.) Similar calcifications were noted regional to the buttocks. X-rays of the long bones and spine showed no abnormalities except minimal osteoarthritic changes of the lumbar vertebrae. AMERICAN
JOURNAL
OF
MEDICINE
Idiopathic Calcinosis Circumscripta-Plitman, During the hospital stay calcium excretion studies were accomplished by measuring the patient’s twenty-four hour urinary calcium excretion while on a diet containing 137 mg. of calcium daily. The patient excreted 20, 40, 150 and 30 mg. of calcium on successive days during this time. During the first hospital week the patient had blood-streaked sputum. This, plus the history of tuberculosis, prompted the decision to have him bronchoscoped, including smears and cultures for acid-fast bacilli but all findings were normal. Biopsies were taken from the following sites: (1) a calcified area in the right arm; histologically this showed dense broad bands of collagen in the corium, throughout which lay oval masses of amorphous calcified material surrounded by dense, hyalinized fibrous tissue. Several areas of chronic inflammation containing vacuolated foreign body giant cells were noted. (2) A “precursor” site in the right thigh at which symptoms of “burning and drawing” had been present but no calcification had been apparent; this was histologically normal. (3) A presumably “normal” site far removed from the other sites; histologically this was normal. All biopsy sites healed well. Meanwhile, the patient had been receiving penile urethral dilatations by the GenitoUrinary Service with a view toward re-establishment of normal function. During the hospital course no specific therapy aimed at reducing the calcium masses was undertaken. Following completion of medical workup the patient was transferred to the Genito-Urinary Service where the urethrostomy was excised and function re-established in the penile urethra. COMMENTS
The etiology and pathogenesis of idiopathic calcinosis is unknown. In view of the fact that this patient had certain premonitory symptoms of burning or drawing sensations prior to the deposition of calcium, it was thought that histologic study of such a “precursor site” might be informative. However, histologic study of the skin from such sites did not reveal any significant pathologic disorder. Some broadening of the collagen bands was noted but this did not differ from a similar variation in width of the collagen bands noted in sections of normal skin studied. In addition, no significant variations in the staining quality of the collagen could be detected. Study of our patient’s skin removed from a normal area likewise showed no changes. No AUGUST,
1951
Gendel
clue to the pathogenesis of this condition was afforded by a study of the many biopsies which this patient permitted. The etiology remains a mystery. Lansbury” mentions briefly the controversy which has existed as to whether or not calcinosis actually represents a distinct entity, citing its frequent occurrence in association with Raynaud’s phenomenon, scleroderma and dermatomyositis. He quotes Langmead12 as having suggested that all these syndromes were manifestations of a single disease. The findings in the case discussed here suggest a separate existence of calcinosis; there were no skin changes, clinically or histologically, to suggest pre-existing disease such as scleroderma or dermatomyositis, and the proximal locations of the calcinotic deposits were inconsistent with their having been secondary to Raynaud’s phenomenon. SUMMARY
A case of calcinosis circumscripta in a middlraged male is reported, and the pertinent features of the disease are reviewed briefly. The case herein described conformed to the rule in showing typical histologic changes and no demonstrable error of calcium metabolism. REFERENCES
1. PETERS,J. H., HORN, R. H. and GREENMAN,L. Idiopathic calcinosis universalis cutis without disability. Ann. Znt. Med., 32: 138, 1950. 2. ATKINSON,F. R. B. and PARKES-WEBER, F. Cutaneous and subcutaneous calcinosis. Rrit. 3. Dermot., 50: 267, 1938. 3. GHORMLEY,R. and MCCRARY, W. E. Multiple calcified bursae and calcified cysts in the soft tissues. Tr. West. S. A., 51: 292, 1942. 4. MORAN, F. T. Calcinosis: a brief review of the literatureand report of two cases. South. M. J., 40: 840, 1947. 5. ROTHSTEIN, J. L. and WELT, S. Calcinosisuniversalis and calcinosisin infancy and in childhood. Am. 3. Dis. Child., 52: 368, 1936. 6. MOORE, M., JR. and CLARKE, C. L. Extreme calcinosis intentitialis. South. M. J,, 43: 861, 1950. 7. F'USITZ, M. E., OWEN, A. K. and FINNEY, G. A. Calcinosis cutis. 3. A. M. A., 110: 360, 1938. 8. BAUER, W., MARBLE,A. and BENNETT, G. A. Further studies in a case of calcification of subcutaneous tissue. Am. 3. M. SC., 182: 237, 1931. 9. LUTZ, J. F. Calcinosis universalis. Ann. Int. Med., 14: 1270, 1941. 10. BARTELS, E. C. and CATTELL, R. B. Calcinosis treated by parathyroidectomy. Ann. Znt. Med., 17: 859, 1942. 11. LANSBURY, J. The Scleroderma Group of Collagen Diseases, in Arthritis and Allied Conditions, p. 687. J. L. HOLLANDER, Editor. Philadelphia, 1949. Lea & Febiger. 12. LANGMEAD,F. S. Quoted by Lansbury.”