Case reports

An unusual case of calcinosis cutis Ronald J. Cochran, M.D. , and Jonathan K. Wilkin, M.D. Houston, 7X

A case of calcinosis cutis is presented in a patient with hypercalcemia of unknown etiology. The axillae and inguinal areas were involved and the clinical and histologic picture is compared with pseudoxanthoma elasticum, We propose that the similarities between the two diseases stem from a common origin in damaged elastic fibers. (J AM ACAD DERMATOL 8:103-106, 1983.)

Calcinosis cutis has been historically divided into two types: dystrophic form and metastatic form. z The more common dystrophic variety is found in patients with normal serum levels of cal- c ium and phosphorus and occurs in damaged skin. The metastatic variety occurs in normal-appearing skin in patients with elevated serum levels of cal- c ium or phosphorus or both. We recently saw a patient with idiopathic hypercalcemia who devel- oped metastatic calcinosis cutis in a distinctive, unusual pattern.

CASE R E P O R T

The patient was a 22-year-old man who developed acute lymphocytic leukemia (ALL) in February, 1981. He had a complete remission of his disease after three cycles of doxorubicin hydrochloride, vincristine sul- fate, cytosine arabinoside, and prednisone and was placed on maintenance therapy. He did well until April, 1981, when he was discovered to have a systemic Candida albicans infection. He was treated with ketoconazole, amphotericin B, and 5-fluorocytosine, and, in September, 1981, a splenectomy was per- formed to remove a possible Camlida tbcus. In July, 1981, he was found to have elevated serum calcium levels with normal serum phosphate levels. Accord- ingly, he was treated with oral phosphates and diuretic

From the Department of Dermatology, The University of Texas Med- ical School.

Reprint requests to: Dr. Jonathan K. Wilkin, Department of Der- matology, The University of Texas IVledical School, 6431 Fannin, Room 1.202, Houston, TX 77030.

0190-9622/83/010103 + 04500.40/0 © 1983 Am Acad Dermatol

therapy. During treatment calcium levels were high in- termittently.

On current admission in October, 1981, the patient complained of weakness, mental confusion, abdominal pain, and paresthesias in his lower extremities. The dermatology service was consulted for an evaluation of a rash present for 3 weeks in the crural and axillary areas. On examination of the skin, red-brown, woody- hard, indurated areas were seen on his upper inner thighs. Similar lesions were present in both axillary areas, but sparing the axillary vault (Figs. 1 and 2). The axillary involvement appeared reticulated, particularly at the edges, and resembled the chicken skin appear- ance seen in pseudoxanthoma elasticum. Examination of the eyes by the ophthalmology service revealed no funduscopie abnormalities. Laboratory data included a total serum calcium of 12.3 mg/dl (normal, 8.5-10.5), ionized calcium of 4.5 mg/dl, phosphorus, 5.4 mg/dl (normal, 4-7), hemoglobin, 9.3, white blood cell count, 27,700. A parathyroid hormone level was nor- real at 243 pg/ml. The remainder of his laboratory data was normal except for a Candida antigen of 1 : 1000.

A punch skin biopsy was performed on the indurated plaque on his left inner thigh. Hematoxylin-eosin- stained sections showed dense, clumped basophilic de- posits in the mid to upper dermis and around blood vessels (Fig. 3). yon Kossa staining confirmed the ma- terial as calcium. Calcified elastic fibers were also seen. A technetium 99m (Tc 99m) scan was performed for the evaluation of persistent leg pains, and, interest- ingly, the areas of the skin with calcinosis cutis took up the label (Fig. 4).

The areas of calcinosis curls have slowly improved

103

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:Fig. 1. Right axillary area showing the region of red-brown induration and sparing of the axillary vault. Fig. 2. Left axillary area illustrating chicken skin appearance of the disorder, Fig. 3. Skin biopsy from groin showing calcium deposited on elastic fibers in the mid and lower dennis. (Hematoxylin-eosin stain; x 50,)

with the normalization of his serum calcium, The cause of this patient's hypercalcemia remains unknown, but the endocrinologists favor hypercalcemia secondary to systemic candidiasis.

DISCUSSION

Metastatic calcification occurs in diseases with chronically elevated serum calcium or phosphorus levels such as hyperparathyroidism, milk alkali syndrome, chronic renal disease, hypervitamino- sis D, sarcoidosis, and destructive bone disease. All tissues may be affected, but skin involvement is rare. 2 Our case of metastatic calcinosis cutis showed red-brown indurated areas on the upper inner thighs and anteroposterior axillary folds symmetricaIly. Several other reports of metastatic

calcinosis cutis describe a similar distribution and morphology of lesions) -~

Our patient's axillary lesions looked similar to pseudoxanthoma elasticum (PXE). Also, calcium was found in the cutaneous biopsy specimen in close proximity to damaged elastic fibers, a prom- inent feature of PXE histologically. 6 Calcium crystals tend to form on damaged tissues, and perhaps the abnormal-appearing elastic fibers in these areas initiate the process by nidation.7

These areas of calcinosis cutis were visualized unexpectedly with the Tc 99m bone scan. The uptake of this radiolabel is generally attributed to its high affinity for the surface of hydroxyapatite crystals, s It is noteworthy that these same hy- droxyapatite crystals have been found by electron

Volume 8 Number 1 January, 1983

Calcinosis cutis 105

Fig. 4. Technetium 99 m bone scan showing areas of uptake in the axillary and inguinal areas (arrows).

microscopy and diffraction analysis to be de- posited in elastic fibers of patients with pseu- doxanthoma elastieum. 9

Pseudoxanthoma elasticum classically has an- gioid streaks observable on retinal examination. This is thought to reflect crazing of Bruch's membrane, which has become brittle because of calcium deposition. Paget 's disease of the bone also has a high incidence of angioid streaks, and several reports call attention to pseudoxanthoma elasticum-like changes in the skin. Pinnell and McKusick 1° suggested these may be the result of

damage to elastic fibers from metastatic calcifica- tion. Christensen 1~ reported an exogenous variety of PXE that occurred in farmers exposed to Norwegian hydrous saltpeter, a fertilizer rich in calcium. This eruption was also localized to the antecubital fossae, and Christensen suggested that the calcium penetrated the skin and was deposited in damaged elastic fibers. Calcification in the aorta is also known to start in elastic fibers. 1

In summary, we believe the unusual pattern of metastatic calcinosis cutis to areas of the axillae and groin is the result of deposition of calcium

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crystals, probably as hydroxyapati te, on damaged

elastic fibers in these intertriginous areas. The

elastic fibers in these ,areas may be subject to more damage by friction by wearing apparel and by

stretching f rom b o d y and ann movements (shear-

ing stress and translatory deformation strain). The

similarities in clinical and histologic appearance

between calcinosis cutis and pseudoxanthoma

elast icum emerge f rom a common origin in dam-

aged elastic fibers,

REFERENCES

1. Miller LM, Krane SM: In Fitzpatrick TB, editor: Derma- tology in general medicine. New York, 1979, McGraw- Hill Book Co., pp. 1137-1142.

2. Moschella SL: Dermatology. Philadelphia, 1976, W. B. Saunders Co,, pp. 1291-i294.

3. Kolton B, Pederson J: Calcinosis cutis and renal failure. Arch Dermatol 110:256-257, 1974.

4. Posey RE, Ritchie EB: Metastatic calcinosis cutis with renal hyperparathyroidism. Arch Dermatol 95:505-508, i967.

5. Smeenk G, Vink R: Calcinosis cutis metastatica in a patient with primary hyperoxaluria. Dermatologica 134: 356-363, 1966.

6. McKee PH, Cameron CHS, Archer DB, Logan WG: A study of four cases of pseudoxanthoma elasticum. J Cutan Pathol 4:146-153, 1977.

7. Hass GM: Pathological calcification, in Bourne GH: The biochemistry and physiology of bone. New York, 1956, Academic Press Inc., pp. 767-77 i.

8. Krane SM, Gluicher MJ: Transphorylation from nucleo- side di- and tri-phosphates by apatite crystals. J Biol Chem 237:2991-2998, 1962.

9. Otkjaer-Nielson A, Johnson E, Hentzer B, Danielsen L, Carlsen F: Apatite crystals in pseudoxanthoma elas- ticum: A combined study using electron microscopy and selected area diffraction analysis. J Invest Dermatol 69:376-378, 1977.

10. Pinnell SR, McKusick VA: Heritable disorders of con- nective tissue with skin changes, in Fitzpatrick TB, editor: Dermatology in general medicine. New York, 1979, McGraw-Hill Book Co., pp. 1151-1154.

11. Christensen OB: An exogenous variety of pseudoxan- thoma elasticum in old farmers. Acta Dermatol 58:319- 321, 1978.