DOI: 10.1148/radiol.2421040423
(Radiology 2007;242:307-311.)
© RSNA, 2007
Case 104: Calcinosis in Juvenile Dermatomyositis1
Vikas Agarwal, MD, DM,
Atul Sachdev, MD, DM and
Ajay Kumar Dabra, MD
1 From the Departments of Medicine (V.A., A.S.) and Radiology (A.K.D.), Government Medical College and Hospital, Chandigarh, India. Received March 1, 2004; revision requested May 13; revision received June 8; accepted July 8; final version accepted September 29.
Correspondence: Address correspondence to V.A., Department of Clinical Immunology, SGPGIMS, Rae Bareli Road, Lucknow, India 226014 (e-mail: vikasagr{at}sgpgi.ac.in).
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HISTORY
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A 30-year-old woman presented with diffuse hard nodules of 10 years duration over her entire body (Fig 1) and dysphagia of 3 months duration. A physical examination revealed violaceous discoloration of the eyelids, grade 4 strength (ability to sustain movement against mild resistance) in proximal muscles, and diffuse numerous hard nodules in skin, subcutaneous, and muscular planes. She had experienced proximal muscle weakness since 6 years of age and had been taking prednisolone since then. She had no history of Raynaud phenomenon, skin thickening, or malar rash and no family history of muscle weakness or cutaneous nodules. Laboratory studies revealed a creatine phosphokinase level of 583 U/L (normal range, 60–170 U/L), a serum aspartate aminotransferase level of 93 U/L (normal range, 0–35 U/L), an aldolase level of 23 U/L (normal range, 0–6 U/L), a serum calcium level of 9.4 mg/dL (2.35 mmol/L) (normal range, 8.0–10.4 mg/dL [2.0–2.6 mmol/L]), a phosphorus level of 4.2 mg/dL (1.4 mmol/L) (normal range, 2.5–4.5 mg/dL [0.8–1.5 mmol/L]), an albumin level of 3.8 g/dL (normal range, 3.8–5.5 g/dL), and an alkaline phosphatase level of 208 U/mL (normal range, 60–306 U/mL). Parathyroid hormone and vitamin D levels were within normal limits, and the results of urine and renal function tests were normal. Abdominal ultrasonography did not reveal nephrocalcinosis. Electromyography revealed increased insertional activity, short duration of the action potential, and polyphasic potentials with low amplitude in the quadriceps and deltoid muscles. Results of an antinuclear antibody test were negative. Radiography and skeletal scintigraphy were performed at presentation.
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IMAGING FINDINGS
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Diffuse calcifications were seen in the skin and subcutaneous tissue (Fig 2); in the skin, subcutaneous, and deeper muscular planes and in the rib cage (Fig 3); along the skin, subcutaneous, and fascial planes of the muscles (Fig 4); and in the skin, subcutaneous, and deeper muscular planes (Fig 5). Figure 6 shows areas of increased soft-tissue uptake of technetium 99m (99mTc) medronate.
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DISCUSSION
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Soft-tissue calcifications may be caused by metastatic calcification (disturbance in calcium and phosphorus metabolism that leads to ectopic calcification in normal tissue), dystrophic calcification (deposit of calcium in damaged tissues without a generalized metabolic derangement), or calcinosis (deposit of calcium in soft tissue in the presence of normal calcium metabolism) (Table). The radiographic appearance of a soft-tissue calcification may not necessarily lead to a specific diagnosis; however, radiographic findings can be combined with clinical and biochemical findings to yield a diagnosis.
Metastatic calcification due to primary or secondary hyperparathyroidism results in calcification of the arteries, cartilage, and soft tissue. Large periarticular tumor-like calcifications are seen in patients with hyperparathyroidism secondary to renal failure who are undergoing hemodialysis (1). Biochemically, hyperparathyroidism is characterized by elevated levels of serum calcium and parathyroid hormone, with or without evidence of renal failure. Normal laboratory values of serum calcium, phosphate, parathyroid hormone, and renal function in this patient enabled us to rule out hyperparathyroidism (1).
Patients with hypoparathyroidism, idiopathic hypoparathyroidism, pseudohypoparathyroidism, or pseudopseudohypoparathyroidism may have hypocalcemia, hyperphosphatemia, or calcifications in the cerebral basal ganglia, cerebellum, or soft tissue of the extremities (1,2). Patients with pseudohypoparathyroidism or pseudopseudohypoparathyroidism have characteristic skeletal abnormalities—such as Albright hereditary osteodystrophy phenotype, broad bones with coned epiphyses, brachydactyly, and short metacarpals, metatarsals, or both (1). In this patient, normal laboratory values for serum calcium, phosphate, and parathyroid hormone and the absence of the Albright hereditary osteodystrophy phenotype enabled us to exclude these diagnoses.
This patient's history did not include a chronic peptic ulcer or excessive intake of milk, absorbable antacids, or vitamin D; thus, we ruled out milk-alkali syndrome and hypervitaminosis D. Patients with sarcoidosis, which is a chronic granulomatous disease of unknown origin, may present with metastatic soft-tissue calcifications due to long-standing hypercalcemia (1). Glucocorticoid administration is known to cause serum calcium levels to decrease in these patients (2). The fact that our patient had been taking prednisolone for many years and had a normal serum calcium concentration enabled us to rule out the possibility of metastatic calcification due to sarcoidosis. A long-standing history of soft-tissue calcifications in combination with normal levels of serum calcium, phosphate, parathyroid hormone, and vitamin D and an absence of an evident primary tumor allowed us to rule out paraneoplastic hypercalcemia and destructive bone diseases as possible etiologies.
Soft-tissue tumors usually manifest with localized calcification. Diffuse calcifications of many years duration without associated soft-tissue masses or calcification along the fascial planes are unlikely to be caused by soft-tissue tumors.
Inherited disorders, such as Ehlers-Danlos syndrome or pseudoxanthoma elasticum, are characterized by hypermobility of the skin and joints, and patients with these disorders may experience calcification of the arteries, skin, tendons, ligaments, or periarticular structures (1). Age at presentation, absence of hypermobility of the skin and joints, and cutaneous xanthoma allowed us to rule out both of these disorders.
Parasitic infections are known to produce rice-grain or crescentic calcinosis scattered throughout muscle tissue (1,2). However, in this patient, the radiologic appearance of tumor-like calcification and calcification along the fascial planes did not support the possibility of parasitic infection. Under rare circumstances, patients with diffuse tophaceous gout may have calcified tophi (1,2). However, because this patient was a premenopausal woman who had never had arthritis and there were no typical punched-out lytic lesions in the bone underlying the tophi, the possibility of tophaceous gout was ruled out.
Idiopathic tumoral calcinosis may manifest with large tumor-like calcific deposits in soft tissue and muscles in the periarticular distribution in individuals in the 2nd or 3rd decade of life. Family history is positive for idiopathic tumoral calcinosis in 30%–40% cases. Idiopathic tumoral calcinosis is caused by an error in renal phosphate metabolism that results in hyperphosphatemia (3). Normal serum phosphate concentration enabled us to rule out idiopathic tumoral calcinosis in this case.
Calcinosis interstitialis universalis is a disease of unknown etiology that is characterized by diffuse calcifications in the subcutaneous and deeper muscular planes (2,4,5). Typically, calcium deposits are discrete conglomerations arranged in longitudinal bands on the limb (2). Calcinosis interstitialis universalis occurs in young individuals: It is frequently progressive and may lead to death. Connective tissue associated with muscles, nerves, tendons, and joints becomes calcified. However, this disease is not associated with systemic manifestations (5), and it is a diagnosis of exclusion. Serologic findings that were negative for antinuclear antibody and the absence of cutaneous, renal, and articular symptoms enabled us to rule out systemic lupus erythematosus. The absence of both Raynaud phenomenon and skin thickening allowed us to rule out scleroderma. In view of the long-standing history of proximal muscle weakness since childhood, the presence of a heliotrope rash over the eyelids, the increased muscle enzyme levels (creatine phosphokinase, serum aspartate aminotransferase, and aldolase), the myopathic pattern on the electromyogram, and the development of calcinosis 12–14 years after the onset of illness, the most likely diagnosis in this patient was extensive calcinosis in juvenile dermatomyositis (JDM).
JDM is a multisystem autoimmune disease of unknown etiology that results from inflammation of the small vessels of the muscles, skin, gastrointestinal tract, and other organs (6). It accounts for 85% of cases of pediatric inflammatory myopathy (7). JDM affects children with an incidence of two or three cases per million children per year. Clinical characteristics of JDM include symmetric proximal muscle weakness, inflammatory cutaneous lesions, and Gottron papules (erythematous scaly lesions over the metacarpophalangeal and/or interphalangeal joints), heliotrope (violaceous hue over the eyelids), periorbital edema, malar erythema, periungual telangiectasia, and erythematous scaly rashes over the neck, upper back, and extensor surfaces of the extremities. Besides these characteristic manifestations, arthritis, contracture of the joints, respiratory difficulty due to weakness of the diaphragmatic muscles, difficulty swallowing due to palatal muscle weakness with nasal regurgitation and nasal voice, esophageal dysfunction, pulmonary fibrosis, and visual loss due to optic atrophy have also been reported (8).
Calcinosis occurs in 30%–70% of children with JDM (9–11); it usually occurs late in the course of the disease (1–20 years after onset) but can sometimes begin within 6 months of onset. Calcinosis shows a predilection for sites of trauma (elbows, knees, flexor surfaces of fingers, or buttocks) and can feel like pebbles or small stones under the surface of the skin. Occasionally, skin ulcerations due to underlying calcified lesions may lead to nonhealing sores.
Imaging of soft-tissue calcifications typically begins with conventional radiography. Four different patterns of calcinosis have been described in patients with JDM: These patterns are superficial plaques or nodules confined to the skin or subcutaneous tissue, deep nodular deposits that extend to the muscles, deposits along fascial planes of the muscles and tendons, and an extensive hard calcium deposit that covers the entire surface of the body. In one large series (10), 33% of patients developed superficial plaques, 20% developed deep nodular deposits, 16% developed deposits along the muscles and fascial planes, 10% developed an extensive hard calcium deposit that covered the entire body surface, and 22% had a mixture of different patterns of calcinosis.
Computed tomography (CT) has been reported to be more specific and sensitive than conventional radiography in the detection of deeper soft-tissue calcifications (12). CT has the added advantage of depicting ossifying lesions and the exact plane of calcification. Edema or inflammation in the skin, subcutaneous tissue, and fascia seen on short inversion time inversion-recovery magnetic resonance (MR) images but not detected with other standard assessments may precede the development of calcinosis in patients with JDM (13). Hernandez et al (14) have reported the use of fat-suppressed MR imaging in the evaluation of inflammatory disorders in the muscles of children. Whole-body scintigraphy with 99mTc medronate has been used to assess and follow the degree of calcinosis in patients with JDM (15). It has been claimed that scintigraphy is more sensitive than radiography in the detection of early soft-tissue calcinosis (16) in patients with JDM. However, scintigraphy may not depict all calcinosis lesions, and thin-section CT has been reported to be more sensitive in the detection of early lesions (17).
Calcinosis is associated with a variable natural history and a number of sequelae in children with JDM. Over an unpredictable period of time, spontaneous regression through reabsorption or extrusion of the calcific material may occur (18). Calcinosis may be more likely to improve in subjects with inactive disease, those who engage in physical activity, those with superficial plaques or nodules rather than those with deeper or more extensive deposits, and those who undergo an aggressive therapeutic regimen for JDM. Marked regression, retardation, or progression of calcinosis after treatment for 2–10 months with hydroxychloroquin, intravenous immunoglobulin, cyclosporine, and infliximab has been reported in a limited number of cases (18).
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FOOTNOTES
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| Part one of this case appeared 4 months previously and may contain larger images.
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References
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- Davis AM. Imaging of soft tissues. In: Grainger RG, Allison D, Adam A, Dixon AK, eds. Diagnostic radiology. London, England: Churchill Livingstone, 2001; 2075–2095.
- Greenfield GB, ed. The soft tissues. In: Radiology of bone diseases. Philadelphia, Pa: Lippincott, 1990; 733–801.
- Stewart VL, Herling P, Dalinka MK. Calcifications in soft tissue. JAMA 1983;250:78–81.[CrossRef][Medline]
- Homma W, Rutt A. Familial interstitial calcinosis (a 20-year follow-up study) [in German]. Z Orthop Ihre Grenzgeb 1982;120:774–779.[Medline]
- Haher TR, Devlin VJ, Haher JN, Freeman B, Smith AG. A case report of calcinosis universalis. J Hand Surg [Am] 1984;9:243–245.[Medline]
- Ramanan AV, Feldman BM. Clinical outcomes in juvenile dermatomyositis. Curr Opin Rheumatol 2002;14:658–662.[CrossRef][Medline]
- Pachman LM. Juvenile dermatomyositis: immunogenetics, pathophysiology, and disease expression. Rheum Dis Clin North Am 2002;28:579–602.[CrossRef][Medline]
- Chari G, Laude TA. Juvenile dermatomyositis: a review. Int Pediatr 2000;15:21–25.
- Pachman LM, Friedman JM, Maryjowski-Sweeney ML, et al. Immunogenetic studies of juvenile dermatomyositis. III. Study of antibody to organ-specific and nuclear antigens. Arthritis Rheum 1985;28:151–157.
- Bowyer SL, Clark RA, Ragsdale CG, et al. Juvenile dermatomyositis: histologic findings and pathogenetic hypothesis for the associated skin changes. J Rheumatol 1986;13:753–759.[Medline]
- Walton J. The inflammatory myopathies. J R Soc Med 1983;76:998–1010.[Medline]
- Fishel B, Diamant S, Papo I, Yaron M. CT assessment of calcinosis in a patient with dermatomyositis. Clin Rheumatol 1986;5:242–244.[CrossRef][Medline]
- Kimball AB, Summers RM, Turner M, et al. Magnetic resonance imaging detection of occult skin and subcutaneous abnormalities in juvenile dermatomyositis: implications for diagnosis and therapy. Arthritis Rheum 2000;43:1866–1873.[CrossRef][Medline]
- Hernandez RJ, Keim DR, Chenevert TL, Sullivan DB, Aisen AM. Fat-suppressed MR imaging of myositis. Radiology 1992;182:217–219.[Abstract/Free Full Text]
- Bar-Sever Z, Mukamel M, Harel L, Hardoff R. Scintigraphic evaluation of calcinosis in juvenile dermatomyositis with Tc-99m MDP. Clin Nucl Med 2000;25:1013–1016.[CrossRef][Medline]
- Berger RG, Featherstone GL, McCartney WH, Hadler NM. Treatment of calcinosis universalis with low dose warfarin. Am J Med 1987;83:72–76.[Medline]
- Randle HW, Sander HM, Howard K. Early diagnosis of calcinosis cutis in childhood dermatomyositis using computed tomography. JAMA 1986;256:1137–1138.[CrossRef][Medline]
- Rider LG. Calcinosis in juvenile dermatomyositis: pathogenesis and current therapies. Pediatric Rheumatology Online Journal 2003; 1(2):119-133. http://www.pedrheumonlinejournal.org/April/calinosis.html. Accessed January 18, 2004.
Congratulations to the 62 individuals and two resident groups that submitted the most likely diagnosis (calcinosis in juvenile dermatomyositis) for Diagnosis Please, Case 104. Both calcinosis and dermatomyositis had to be mentioned for a correct response. The names and locations of the individuals and resident groups, as submitted, are as follows:
Individual responses
- Gholamali Afshang, MD, Tinley Park, Ill
- Erhan Akpinar, Ankara, Turkey
- Albert J. Alter, Madison, Wis
- Alexandra Araújo, Lisbon, Portugal
- Jason Brandon Ashley, MD, London, Ontario, Canada
- Murray J. Bartlett, MBBS, Melbourne, Australia
- Eric L. Bressler, MD, Minnetonka, Minn
- Douglas C. Brown, MD, Virginia Beach, Va
- Alan Dong Shing Chan, MD, West Sacramento, Calif
- Govind Chavhan, MD, Toronto, Ontario, Canada
- Yves-Sebastien Cordoliani, MD, Paris, France
- Marc G. de Baets, MD, Lugano, Switzerland
- Johannes F. K. de Villiers, MBChB, MMed, Gisborne, New Zealand
- Jacques F. Demers, MD, La Pocatière, Quebec, Canada
- Mustafa Kemal Demir, MD, Ataköy, Istanbul, Turkey
- Thaworn Dendumrongsup, MD, Hat Yai, Songkla, Thailand
- Bart D'herde, Hasselt, Belgium
- Seyed Emamian, MD, PhD, Rockville, Md
- Juliet H. Fallah, MD, Chicago, Ill
- Francis Flaherty, MD, Ridgefield, Conn
- Ángeles Franco, Madrid, Spain
- Akira Fujikawa, MD, Tokyo, Japan
- Rajneesh Galwa, Jaipur, India
- Ram Prakash Galwa, Chandigarh, India
- Francisco Jose Gonzalez, MD, Cantabria, Spain
- Sadashiv Gowda, Jr, MD, Davangere, Karnataka, India
- Flavius Guglielmo, MD, Basking Ridge, NJ
- Ferris M. Hall, MD, Boston, Mass
- Marc Heinrich, Erlangen, Germany
- Rajapandian Ilangovan, MD, FRCR, London, United Kingdom
- Mary Ann Johnson, MD, Edmonton, Alberta, Canada
- Kiriakos Kalampoukas, MD, Athens, Greece
- Takuji Kiryu, MD, PhD, Gifu, Japan
- Dr Martin Lecompte, Ottawa, Ontario, Canada
- David A. Lisle, Brisbane, Australia
- Edward Lubat, MD, Englewood, NJ
- Naganathan B. S. Mani, MD, Nassau, Bahamas
- Alberto Antonio Marangoni, MD, Córdoba, Argentina
- Franklin Marden, MD, Fairfax, Va
- Michael B. Martin, MD, Austin, Tex
- Rogério Melo, Belo Horizonte, Brazil
- Manabu Minami, MD, Tsukuba, Ibaraki, Japan
- Sankar R. Mondal, MD, Nassau, Bahamas
- Sugoto Mukherjee, MBBS, Charlottesville, Va
- Hiroshi Nobusawa, MD, Tokyo, Japan
- Marcos Nogueira Chagas, MD, Brasilia, Brazil
- Patrick Augustine O'Keeffe, MBBCh, Boston, Mass
- Sanford M. Ornstein, MD, Phoenix, Ariz
- Narendrakumar P. Patel, MD, Newburgh, NY
- Ivan Pilate, MD, Mechelen, Belgium
- Ryan Paul Rebello, MD, Dundas, Ontario, Canada
- Marcio Bustamante Sa Rodrigues, MD, Rio de Janeiro, Brazil
- Todd Christopher Schirmang, MD, Providence, RI
- Steven M. Schultz, MD, Fort Worth, Tex
- Mustafa Secil, MD, Izmir, Turkey
- Taro Shimono, MD, Sakai, Osaka, Japan
- Rogério Teles de Melo, Belo Horizonte, Brazil
- Dr Özgür Tosun, Bilkent, Ankara, Turkey
- Hiroyuki Ueda, MD, Kyoto, Japan
- Silvio Alejandro Vollmer, MD, Cipolleti, Rio Negro, Argentina
- Sanjay Ramaswamy Vydianath, MRCP, FRCR, Wolverhampton, United Kingdom
- Joe Yut, Olathe, Kan
Resident group responses
- Trakya University School of Medicine Radiology Residents, Edirne, Turkey
- Prince of Songkla University Radiology Residents, Hat Yai, Songlka, Thailand
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HISTORY
IMAGING FINDINGS
