Tumoral calcinosis presenting as adhesive capsulitiscase report and literature review.код для вставкиСкачать
455 BRIEF REPORT TUMORAL CALCINOSIS PRESENTING AS ADHESIVE CAPSULITIS: CASE REPORT AND LITERATURE REVIEW ALAN D. CROOCK and RICHARD M. SILVER Tumoral calcinosis (TC) is an uncommon disorder characterized by large calcific soft tissue deposits, usually adjacent to large joints. In the past, the etiology was unclear, but recently, TC has been considered to be an inherited metabolic disorder, characterized by elevated serum phosphorus and 1,25-dihydroxyvitamin D levels, normocalcemia, and calcific deposits. However, these features have been shown to vary widely, with formes frustes of TC now being recognized. We report an unusual case of TC, which presented as an adhesive capsulitis, in an elderly North American black woman. The patient’s nationality, late age of presentation, aad multiple sites of involvement are uncommon features of TC. The clinicopathologic features and possible etiologies of this rare condition are briefly reviewed. Case report. The patient, a 76-year-old North American black woman, presented with a 3-month history of left shoulder and arm pain of insidious onset. No previous shoulder or neck trauma was reported. The pain involved the entire shoulder and upper arm circumference, was constant, and caused increased restriction of all shoulder movement to the point that the patient required assistance in dressing and bathing. Nonsteroidal antiinflammatory drug therapy, prescribed by a family physician who had diagFrom the Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston. Alan D. Croock, MBBCh, FCP(SA); Richard M. Silver, MD, FACP. Address reprint requests to Alan D. Croock, MD, Medical University of South Carolina, Division of Rheumatology, 171 Ashley Avenue, Charleston, SC 29425. Submitted for publication August 1 1 , 1986; accepted September 15, 1986. Arthritis and Rheumatism, Vol. 30, No. 4 (April 1987) nosed severe bursitis, was unsuccessful. There were no symptoms of cervical spondylosis, brachial plexus abnormalities, or cardiothoracic, pulmonary, endocrine, or autoimmune disease. Of note, there was no history of excessive milk or vitamin D intake or of recent or past renal disease. The patient also reported vague pain in the left hip and thigh regions, of 2 months duration, unrelated to trauma. There had been no previous symptoms suggestive of an inflammatory polyarthropathy. Family history was noncontributory . Physical examination revealed an obese, afebrile,edentulous female with a blood pressure of 160/80 mm Hg, normal pulses, and no evidence of systemic disease. Of note, there was no lymphadenopathy, intrathoracic disease, abdominal visceromegaly , generalized myopathy, or neuropathy. Examination of the left shoulder revealed features of an adhesive capsulitis, with minimal mobility in all ranges of motion tested. Deep palpation around the left shoulder and left thigh, circumferentially, elicited tenderness. There were no abnormalities of the other joints of the arms, nor was there evidence of bicipital tendinitis or carpal tunnel syndrome. Mobility of both hip joints was normal, and straight-leg raising was not limited. The trochanteric bursae were not tender. The provisional clinical diagnosis was adhesive capsulitis of the left shoulder and nonspecific left thigh pain. Laboratory investigations revealed a normal hemoglobin level (13.7 g d d l ) , white blood cell count (5,000/mm3), and platelet count (216,000/mm3). The Westergren erythrocyte sedimentation rate was normal (35 mdhour). Calcium and inorganic phosphorus levels were normal (9.4 mg/dl and 3.8 mg/dl, respectively), thereby excluding overt parathyroid disease 456 and milk-alkali syndrome. Serum alkaline phosphatase was elevated (231 unitsfliter; normal 30-1 15). Alkaline phosphatase isoenzyme studies revealed a moderately elevated bone fraction. Levels of serum 5’-nucleotidase, uric acid, urea nitrogen, creatinine, albumin, bilirubin, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, T3, T4, and thyroid-stimulating hormone were all normal. Rheumatoid factor and antinuclear antibody were absent. The serum 25-hydroxyvitamin D level was 5 ng/ml (normal 6-11 in young adult blacks), and the serum 1,25- dihydroxyvitamin D level was 49 pg/ml (normal 3040 in young adult blacks). The serum immunoreactive parathyroid hormone (PTH) level was 89 pg/ml (normal <90, mid-molecule radioimmunoassay). Radiographs of the shoulders and hips revealed lobulated, circumferential, soft tissue calcification around the left shoulder, proximal ends of both femoral shafts, and subtrochanteric regions (Figures lA, B, and C). The shoulder and hip joints per se were nomial. These soft tissue radiologic findings were considered to be typical of tumoral calcinosis, particularly in the absence of renal or systemic disease. The patient refused to undergo surgical exploration or any biopsy procedure. Physical therapy, including local heat and ultrasound, and oral nonsteroidal agents produced minimal improvement of her symptoms. Discussion. Tumoral calcinosis (TC) is a distinct entity in which deposits of calcified material are formed. They are typically large and lobulated in appearance, and occur adjacent to large joints. Although previously considered to be a rare condition, TC has been reported with increasing frequency in the black populations of southern, central, and eastern Africa. It is rare in Europe and North America (1). The earliest report of a TC-type condition was by Giard, who, in 1898,described 2 affected members in 1 family (2). By 1965,only 23 additional cases had been reported in the literature. In 1966, Palmer (2) reported 50 new cases of TC; the majority of these were seen at 1 hospital in the southern African nation of Rhodesia, now Zimbabwe. Numerous case reports have followed. In 1982, McKee et a1 reported on 56 Malawi subjects who presented with TC during a 10-year period (1970-1979) (1). The term tumoral calcinosis was first used by Inclan in 1943 (3). The disease has also been called tumoral lipocalcinosis and lipocalcinogranulomatosis (1). In New Guinea, it is known as “hip-stone’’ (4). In addition to the cases reported in Malawi and southern Africa (1,2), the condition has been seen in Sudan, BRIEF REPORTS Kenya, Uganda, Nigeria, New Guinea, Europe, India, and Iran (4-9). The majority of the patients are black, but there are occasional occurrences in Arabs, Indians, and whites (1). It affects a wide age spectrum, but particularly people under 30. In the review of 56 patients by McKee and coworkers, 41% were under 21 years old, and the fema1e:male ratio was 2:l (1). Palmer found a similar age distribution (6-25 years), but a male predominance (2). Veress et a1 found a ma1e:female ratio of 2:1 among Sudanese patients (5). The lesions may be observed incidentally on radiography, but they do not cause clinical symptoms until they reach a significant size; the disease generally presents as an isolated large swelling in close proximity to a joint. There is usually minimal or no impairment of joint mobility, although our patient had a typical frozen shoulder on presentation. The predominantly involved areas are the hip, elbow, and scapula. The condition is often misdiagnosed as a tumor, calcified bursa, tuberculosis, cyst, metastatic calcification, or onchdcerciasis. There is a typical radiographic appearance, which consists of dense, lobulated calcific nodules, often massive, in the soft tissues adjacent to one of the joints mentioned above. The joint itself and the bones appear normal. The lesions usually involve the soft tissues or skeletal muscle, but occasionally may be much more superficial, presenting as skin “tumors.” In 17 of the 56 cases reported by McKee et al, the reticular dermis was predominantly involved (1). Macroscopically, the lesions consist of multiple cysts surrounded by dense, fibrous tissue. When sectioned, they are seen to contain either a white granular fluid, likened to procainepenicillin (6), or a more densely calcified material. Histologically, the lesions can be divided into early and late stages. The former consists of collagen necrobiosis which results in cyst formation and a foreign body granulomatous response. After further collagen degradation, calcification occurs, first of a granular type, then followed by dense deposits which, rarely, may undergo metaplasia (1). The etiology of TC is still unknown. Early hypotheses included calcifying endothelioma, calcified bursa, aberrant synovial tissue, and a clinical form of “calciphylaxis” (5). Other theories have been presented in the more recent literature. One is that TC is a form of dystrophic calcification related to mechanical trauma or injury. The main evidence in favor of this thesis is the distribution of lesions characterized by deposits related to pressure areas, with possible focal ischemia resulting in collagen damage (1,5). A low- C B Figure 1. Radiographs of the patient’s left shoulder (A) and both upper thighs (B and C), illustrating dense, lobulated, calcific soft tissue deposits typical of tumoral calcinosis. 457 BRIEF REPORTS grade vasculitis has been documented in some cases (5). Foreign body reaction is also considered to be a possible etiology, since most patients have single-site involvement. Another hypothesis relates TC to an abnormality of calcium and phosphorus metabolism, particularly in the setting of renal failure (10,ll). TC has been reported in 2 patients who were receiving 1-ahydroxycholecalciferol therapy, and the authors of the report suggested that vitamin D therapy in patients with renal failure stimulates the progression of metastatic calcification to tumoral calcinosis (12). Results of studies of calcium and phosphorus levels in patients with TC have varied. Some authors have found elevated serum phosphorus levels, while others have found normal values (1). In view of the former findings, a possible recessive inborn error of phosphorus metabolism has been suggested. Some patients have shown clinical and radiologic improvement on treatment with phosphorus deprivation and phosphorusbinding antacids (13). Such therapy was not considered for our patient, who had normal values of serum calcium, phosphorus, and FTH. Lyles et a1 (14), in a study of 14 of 27 subjects in a kindred, concluded that TC is an autosomal dominant disorder with variable clinical expression. They found a dental lesion in 3 members of the kindred. This previously unreported lesion, consisting of short bulbous roots, pulp stones, and radicular dentin deposited in swirls, is apparently specific to TC. Lyles et a1 also noted that serum 1,254ihydroxyvitamin D levels were elevated in all affected subjects, even those with no other clinical markers of the disorder (14). No firstdegree relatives of our patient were available for examination. Under normal circumstances, PTH is a major regulator of serum 1,254ihydroxyvitamin D. Serum levels are elevated in primary hyperparathyroidism. In addition, hypophosphatemia stimulates increased production of 1,254ihydroxyvitamin D. Lyles et a1 reported on 11 affected patients from 2 kindreds, who were all found to have elevated 1,254ihydroxyvitamin D levels and normocalcemia (15). PTH levels were found to vary inversely with the serum phosphorus (P) concentrations, as well as with the renal TmP/GFR ratios (TmP = tubular maximum for P; GFR = glomerular filtration rate). The authors concluded that the serum PTH may continuously regulate the serum phosphorus concentration, and that depression of the latter by PTH may protect affected subjects from developing the calcific tumors characteristically asso- ciated with TC. However, the finding of a normal serum PTH value and normophosphatemia in our patient, who had multiple tumor deposits, is not consistent with this theory. The serum 1,254ihydroxyvitamin D level was 49 pglml in our patient. This may represent an elevated value in an elderly black subject. Low serum 1,25-hydroxyvitamin D levels are characteristic of blacks and are attributed to impaired dermal production of previtamin D3, because of skin pigment (16). It is of interest that the vast majority of cases reported from Africa had singly localized deposits of TC. This would negate the theory that a generalized biochemical disorder is etiologically related. In McKee and colleagues’ series (l), only 2 patients had multiple lesions; 1 of these patients had a recurrent lesion. The duration was known in 14 cases; it ranged from 6-24 months. The lesions were located in the area of the hip (69% of all patients), elbow (9%), scapula (9%), sacrum (6%), ankle (3%), and scalp (1%). Our patient was atypical in that she had 3 sites of involvement: 1 shoulder and both hips. Her case was also unusual with respect to the late age of presentation. The majority of patients present with the disease in the second or third decade of life. The significance of the finding of a moderately elevated level of serum alkaline phosphatase of bone origin in our patient is unclear. Surgery is the only recognized treatment for TC. Recurrences may occur, however, since complete excision is often difficult. In fact, a saw has frequently been required by pathologists to cut through tissue specimens (1) ! Spontaneous regression of a tumor mass has not been known to occur. Hyperphosphatemic patients may be treated with phosphorus deprivation and phosphorus-binding antacids (13). In summary, we have reported an unusual case of tumoral calcinosis in an elderly North American black woman. The patient’s nationality, late age of presentation, and multiple-site involvement are particularly noteworthy. Acknowledgments. We express our gratitude to Dr. Norman H. Bell and associates (Veterans Administration Medical Center, Charleston and Departments of Medicine and Rheumatology , Medical University of South Carolina) for performing the vitamin D assays, Dr. Betty Roof (Division of Endocrinology, Medical University of South Carolina) for performing the parathyroid hormone assay, and Dr. E. Carwile LeRoy (Division of Rheumatology and Immunology, Medical University of South Carolina) for reviewing the manuscript. We also thank Judy Anderson for typing the manuscript. BRIEF REPORTS 459 REFERENCES 1. McKee PH, Liomba NG, Hutt MSR: Tumoral calcinosis: a pathological study of fifty-six cases. Br J Dermatol 107:669-674, 1982 2. Palmer PES: Tumoural calcinosis. Br J Radio1 39518525, 1966 3. Inclan A: Tumoral calcinosis. JAMA 121:490-495, 1943 4. Berg D: Tumoral calcinosis. Br J Surg 59570-571, 1972 5. Veress B, Malik MOA, El Hassan AM: Tumoral lipocalcinosis: a clinicopathological study of 20 cases. J Pathol 119:113-118, 1976 6. McClatchie S, Bremner AD: Tumoral calcinosis, an unrecognized disease. Br Med J 1:153-155, 1969 7. Owor R: Tumoral calcinosis in Uganda. Trop Geogr Med 24:39-43, 1972 8. Reddy CRRM, Rao BS: Tumoral calcinosis. J Indian Med Assoc 43:336-337, 1964 9. Wilson AL, Chatter EH: Tumoral calcinosis: an obscure disease. J Irish Med Assoc 69:6143, 1976 10. Barton DL, Reeves RJ: Tumoral calcinosis: report of 3 cases and review of the literature. AJR 86:351-358, 1961 11. Levin RT, Genovesse PD: Report of a case of longstand- ing renal insufficiency with extensive metastatic calcification (renal osteitis fibrosa cystica). AJR 64:423429, 1950 12. Walker GS, Davison AM, Peacock M, McLachlan MSF: Tumoral calcinosis: a manifestation of extreme metastatic calcification occumng with l-a-hydroxycholecalciferol therapy. Postgrad Med J 53570-573, 1977 13. Mozzaferrian G, LaEerty FW, Pearson OH: Treatment of tumoral calcinosis with phosphorus deprivation. Ann Intern Med 77:741-745, 1972 14. Lyles KW, Burkes EJ, Ellis GJ, Lucas KJ, Dolan EA, Drezner MK: Genetic transmission of tumoral calcinosis: autosornal dominant with variable clinical expressivity. J Clin Endocrinol Metab 60:1093-1096, 1985 15. Lyles KW, Halsey DL, Friedman NE, Drezner MK, Lobaugh B: Modulation of serum phosphorus levels and expression of calcific tumors (abstract). Seventh Annual ScientificMeeting of the American Society for Bone and Mineral Research, Washington, DC, June 15-18, 1985 16. Bell NH, Greene A, Epstein S, Oexmann MJ, Shaw S, Shary J: Evidence for alteration of the vitamin Dendocrine system in blacks. J Clin Invest 76:470473, 1985 Erratum In the article entitled "Sulfasalazine in Rheumatoid Arthritis: A Double-Blind, Placebo-Controlled Trial" by Pinals et al in the December 1986 issue of Arthritis and Rheumatism, four words were inadvertently omitted from the third line of the second column on page 1428. The line should read, ". . . involvement of previously inactive joints in a number fewer than 10% of initially active joints."