Periorbital Subcutaneous Calcifications Associated With Systemic Sclerosis
History
A 66-year-old African American female with an established diagnosis of diffuse systemic scleroderma, hypothyroidism, interstitial lung disease, and pulmonary arterial hypertension presented to the outpatient clinic for hypothyroidism and hypercalcemia. She had been undergoing home oxygen therapy with supplemental oxygen (2 L/min via nasal cannula). The laboratory findings showed a positive antinuclear antibody with a speckled pattern (1:1280) and anti-Scl-70 antibody was also positive. Of note is that the patient’s calcium and phosphorus levels were in the normal range.
PHYSICAL EXAMINATION
On physical examination, the patient exhibited the typical characteristics of systemic sclerosis, including sclerodactyly, narrow incisal opening, and tight, smooth facial skin with a “masklike” appearance. Upon further examination, the patient was noted to have a white, chalky-looking lesion of approximately 11 mm in diameter above the right eye due to loss of the overlying skin. In addition, on the contralateral side, there were 3 to 4 hardened nodules of varying size that were mobile on palpation (Figure). The patient denied any history of localized tenderness around the lesions, which had been progressing for the previous 16 to 18 months.
Figure. Periorbital subcutaneous calcification in a patient with diffuse systemic sclerosis.
ANSWER: Calcinosis cutis
Systemic sclerosis, or scleroderma, is an autoimmune connective tissue disease that causes skin thickening as well as a destruction of the microvasculature through immunologic and cytotoxic activity. It is thought that the generalized fibrotic destruction associated with systemic sclerosis is caused by the accumulation of scleroproteins in skin tissue and other involved organs.1 Systemic sclerosis can also manifest in a limited form that spares the internal organs, which is known as limited cutaneous systemic sclerosis or CREST (calcinosis, Raynaud’s syndrome, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome. One of the manifestations of systemic sclerosis is calcinosis cutis, also known as subcutaneous calcification, which may occur in all forms of systemic sclerosis but is most commonly seen in limited scleroderma.
CALCINOSIS CUTIS
Calcinosis cutis is an uncommon disorder characterized by deposition of calcium in the subcutaneous tissue. Cutaneous calcifications seen in systemic sclerosis are typically seen at sights of recurrent microtrauma—such as the distal phalanges, feet, elbows, and forearms.2-3 These calcifications can be localized or widespread, have been known to ulcerate, and, on occasion, may become infected.4 Even though cutaneous calcifications in systemic sclerosis have been well documented, facial subcutaneous calcifications are rare.5 It has been estimated that as many as 25% of all patients with systemic sclerosis will develop subcutaneous calcinosis, and the risk is even higher among patients who are positive for anticentromere antibodies.6
Calcinosis cutis can be seen in autoimmune connective tissue diseases, such as systemic sclerosis. Calcinosis cutis is classified into 4 subtypes: (i) metastatic, associated with chronic renal failure, hypervitaminosis D and neoplasms; (ii) dystrophic, encompassing collagen vascular diseases, Ehlers–Danlos syndrome, pseudoxanthoma elasticum, and pancreatic disease; (iii) idiopathic, which occurs in the scrotum, penis, vulva, and breast; and (iv) iatrogenic forms.7
Metastatic calcifications of the soft tissue involve elevation of the serum calcium-phosphorus metabolism, especially when the product level is more than 70 mg/dL.8 Dystrophic calcifications occur despite normal calcium and phosphorus levels and have been attributed to increased pH in damaged or devitalized tissue.9 The calcinosis seen in scleroderma is of the dystrophic type and may occur in both the limited and systemic forms. The pathophysiology of this type of calcification is thought to occur with aberrant tissue architecture as a result of chronic tissue damage or collagen synthesis in the setting of normal serum and calcium and phosphate levels.9 The calcifications in systemic sclerosis primarily occur in the areas of sclerodactyly (distal phalanges), but they may also been seen in the hip joint, shoulders, lower limbs, elbows, and forearms.10 Although cases of mandibular resorption and calcinosis have been reported, cases of periorbital tumoral calcifications have not.
Several treatments have been tried, with mixed results but no standard therapy is currently available. Medical therapies for calcinosis cutis include warfarin, colchicine, bisphosphonates, minocycline, and corticosteroid injection; the results remain equivocal. Symptoms do show some resolution after surgical excision, although this is not the primary treatment of choice, based on the site involved, number of lesions, and comorbid conditions.11 Extracorporeal shock wave lithotripsy and laser treatment using carbon dioxide or erbium-doped yttrium are new tools with some success and have future potential.12,13
Although subcutaneous calcinosis is a relatively common finding in patients with scleroderma, it is rarely observed around the facial region. Calcifications are commonly found in areas of microtrauma or in movable joints. These lesions can be extremely painful and may ulcerate, eventually leading to infection. The exact mechanism and pathophysiology is still unknown. Calcinosis in connective tissue disease should be promptly diagnosed and symptomatic patients should be managed with available therapies. ■
References
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