The journal of Dermatology Vol. 18: 616-618, 1991
Milialike Idiopathic Calcinosis Cutis and Syringoma in Down's Syndrome Tamotsu Kanzaki and Masaru Nakajima Abstract
A 6-year-old girl with Down's syndrome presented milialike whitish small papules on her hands and feet and periorbital syringoma. Histopathological examination of the hand lesion revealed small localized calcium deposits and syringoma in the adjacent upper dermis. This is a very rare but typical case of calcinosis cutis with syringoma in a patient with Down's syndrome.
Key words: Down's syndrome; calcinosis cutis; syringoma
Introduction Several skin disorders, such as syringoma (1) and alopecia areata (2), are well known to be associated with Down's syndrome. We herein report a very rare case, a patient with Down's syndrome associated with both idiopathic cutaneous calcinosis and syringoma.
Case Report A 6-year-old girl with Down's syndrome visited our clinic in April, 1991 for treatment of whitish "pustules" on her hands and feet. One year earlier, the eruption was first noted on the hands and later involved the feet. Her mother stated that some of the "pustules" had "ruptured" and disappeared. The patient showed no evidence of trauma, bums, or photosensitivity. She had had a congenital heart problem, patent ductus arteriosus. The family history was noncontributory. Examination of the skin revealed many discrete, whitish, I to 2 mm, dome shaped, round, firm papules and flesh-colored pinpoint papules over the dorsal and lateral aspects of hands, fingers (Fig. 1), wrists, and feet. There was no inflammation nor Received june 18, 1991; accepted for publication July 31,1991. Department of Dermatology, Nagoya City University Medical School, I-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467,japan. Reprint requests to: Tamotsu Kanzaki, M.D., Ph.D., Department of Dermatology, Nagoya City University Medical School, l-Kawasumi, Mizuho-cho, Mizuho-ku. Nagoya 467,Japan.
Fig. 1. Hand showing milialike whitish papules (arrowheads).
Fig. 2. Syringoma on eyelids (arrowheads).
cyanosis of the skin. In addition, many flesh-colored small papules; less than I mm in size, were present on the upper and lower eyelids (Fig. 2). A dissolving strawberry hemangioma was also present on the right lower eyelid (Fig. 2).
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Calcinosis in Down's Syndrome
Fig. 3. Histopathology of a milialike lesion showing a calcium deposit (arrowheads) and syringoma (an arrowhead). Note the packed hyperkeratosis of the horny layer on the calcium deposit. x50, H.E. stain.
Fig. 4. Von Kossa staining showing calcium. x25. between the focus of the calcium deposit and syringoma or acrosyringium. Skin biopsy of the periorbital papules was not performed, but they were presumably syringoma.
Discussion
Fig. 5. A higher magnification of Figure 3 showing two syringomas. x120, H.E. stain. Laboratory findings were unremarkable, and serum calcium and calcitonin levels were normal. Histopathological examination of the skin from the right hand revealed thickened orthokeratosis and a small nodular focus of homogeneously stained, purplish, cracked material surrounded by epithelial cells and foreign body giant cells within the papillary dermis by RE. stain (Fig. 3). This material was shown to be calcium by von Kossa staining (Fig. 4). Adjacent to this calcium deposit, syringoma was present in the upper dermis (Figs. 3 and 5). Histological examination did not confirm transepidermal elimination of the calcium deposits. Serial sectioning did not show any relationship
Various cutaneous changes associated with Down's syndrome have been reported. These include dry skin, atopic dermatitis, seborrheic dermatitis, elastosis perforans serpiginosa, alopecia areata, and syringoma (1-3). The Down's syndrome patient presented here showed both calcinosis cutis and syringoma. The strawberry hemangioma was probably coincidental. Calcinosis cutis associated with syringoma in Down's syndrome was first reported by Sano et al. (4) in 1978. Subsequently, Shibuya et al. reported a similar case (5) in 1985. These were published inJapanese. Smith et al. (6) and Maroon et al. (7) recently reported two such cases in English language journals. All 5 cases, including ours, are very similar: children with Down's syndrome with milialike white papules on hands and feet, which were revealed to be calcium deposits in the upper dermis. Among the four cases reported, the case of Maroon et al. was, surprisingly, almost identical to ours. They report a 12-year-old boy with Down's syndrome with periorbital syringoma as well as milialike carcinosis cutis on hands and feet. Histopathological examination revealed small syringomas adjacent to calcium deposits and transepiderrnal elimination of calcium. We also observed syringomas adjacent
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Kanzaki and Nakajima
to the calcium deposit in the hands. The syringomas were initially not clinically noticeable, because they were so small. Transepidermal elimination of calcium was not confirmed histologically in our case, but it possibly had occurred; the patient's mother stated that some "pustules" had disappeared after a "rupture". Although Maroon et al. suggested that the primary site of calcium deposition would be in the acrosyringium, we did not observe any close relationship between the deposit and the sweat gland apparatus. The calcium seemed to have deposited primarily in dermal components such as fibroblasts or connective tissues. In fact, fibroblasts from Down's syndrome have been reported to contain higher calcium levels in culture than those from normal subjects (8). Neural tissue (basal ganglia) calcification has been reported with increased frequency (15 of 33 cases) in this disease (9). Certainly, such calcium deposition does not indicate metastatic calcinosis or dystrophic calcinosis since none of the reported cases, including ours, had abnormal calcium metabolism nor precedent skin diseases. Calcinosis cutis in Down's syndrome may mimic subepidermal calcified nodules clinically and histologically. The latter, however, are usually solitary and often appear on the face. Histopathologically, the calcium is present largely as closely aggregated globules (l0). Thus, it is reasonable to assume that calcinosis in Down's syndrome is idiopathic. If physicians are made aware that this unusual skin condition can
afflict certain patients with Down's syndrome, a correct diagnosis can be made at the outset and such cases will be reported more often. References 1) Butterworth T, Strean LP, Beerman H, Gray Wood M: Syringoma and Mongolism, Arch Dermatol, 90: 483487, 1964. 2) Carter DM,jegasothy BV: Alopecia areata and Down Syndrome, ArchDermatol, 112: 1397-1399,1976. 3) Rasmussen jE: Disseminated elastosis perforans serpiginosa in four Mongoloids, BrJ Dermatol, 86: 2-13, 1972. 4) Sano T, Tate S, Ishikawa C: A case of Down's syndrome associated with syringoma, milia, and subepidermal calcified nodule, Jpn J Dermatol, 88: 740 (abstract), 1978. (in japanese) 5) Shibuya M, Iizuka H, Ohkawara A, Kishiyama K: A case of calcinosis cutis in Down's syndrome, Hifurinsho, 27: 1218-1219,1985. (in japanese) 6) Smith ML, Golitz LE, Morelli lG, Weston WL, Markewich G: Milialike idiopathic calcinosis cutis in Down's syndrome, Arch Dermatol, 125: 1586-1587, 1989. 7) Maroon M, Tyler W, Marks ~: Calcinosis cutis associated with syringomas: A transepidennal elimination disorder in a patient with Down syndrome, JAm Acad Dermatol, 23: 372-375, 1990. 8) Ceder 0, Roomas GM, Hosli P: Increased calcium content in cultured fibroblast from trisomy patients: . Comparison with cystic fibroblasts, Scan Electron Microsc, II: 723-730, 1982. 9) Takashima S, Becker LE: Basal ganglia calcification in Down's syndrome,] NeurolNeurosurg Psychiatr, 48: 61-64,1985. 10) Walter FL, Schaumberg-Lever G: Calcinosis cutis, in Lever WF, Schaumberg-Lever G: Histopathology of the Skin (7th eds),jB Lippincott Co., Philadelphia, 1990, pp 466-469.
Milialike Idiopathic Calcinosis Cutis and Syringoma in Down's Syndrome Tamotsu Kanzaki and Masaru Nakajima Abstract
A 6-year-old girl with Down's syndrome presented milialike whitish small papules on her hands and feet and periorbital syringoma. Histopathological examination of the hand lesion revealed small localized calcium deposits and syringoma in the adjacent upper dermis. This is a very rare but typical case of calcinosis cutis with syringoma in a patient with Down's syndrome.
Key words: Down's syndrome; calcinosis cutis; syringoma
Introduction Several skin disorders, such as syringoma (1) and alopecia areata (2), are well known to be associated with Down's syndrome. We herein report a very rare case, a patient with Down's syndrome associated with both idiopathic cutaneous calcinosis and syringoma.
Case Report A 6-year-old girl with Down's syndrome visited our clinic in April, 1991 for treatment of whitish "pustules" on her hands and feet. One year earlier, the eruption was first noted on the hands and later involved the feet. Her mother stated that some of the "pustules" had "ruptured" and disappeared. The patient showed no evidence of trauma, bums, or photosensitivity. She had had a congenital heart problem, patent ductus arteriosus. The family history was noncontributory. Examination of the skin revealed many discrete, whitish, I to 2 mm, dome shaped, round, firm papules and flesh-colored pinpoint papules over the dorsal and lateral aspects of hands, fingers (Fig. 1), wrists, and feet. There was no inflammation nor Received june 18, 1991; accepted for publication July 31,1991. Department of Dermatology, Nagoya City University Medical School, I-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467,japan. Reprint requests to: Tamotsu Kanzaki, M.D., Ph.D., Department of Dermatology, Nagoya City University Medical School, l-Kawasumi, Mizuho-cho, Mizuho-ku. Nagoya 467,Japan.
Fig. 1. Hand showing milialike whitish papules (arrowheads).
Fig. 2. Syringoma on eyelids (arrowheads).
cyanosis of the skin. In addition, many flesh-colored small papules; less than I mm in size, were present on the upper and lower eyelids (Fig. 2). A dissolving strawberry hemangioma was also present on the right lower eyelid (Fig. 2).
617
Calcinosis in Down's Syndrome
Fig. 3. Histopathology of a milialike lesion showing a calcium deposit (arrowheads) and syringoma (an arrowhead). Note the packed hyperkeratosis of the horny layer on the calcium deposit. x50, H.E. stain.
Fig. 4. Von Kossa staining showing calcium. x25. between the focus of the calcium deposit and syringoma or acrosyringium. Skin biopsy of the periorbital papules was not performed, but they were presumably syringoma.
Discussion
Fig. 5. A higher magnification of Figure 3 showing two syringomas. x120, H.E. stain. Laboratory findings were unremarkable, and serum calcium and calcitonin levels were normal. Histopathological examination of the skin from the right hand revealed thickened orthokeratosis and a small nodular focus of homogeneously stained, purplish, cracked material surrounded by epithelial cells and foreign body giant cells within the papillary dermis by RE. stain (Fig. 3). This material was shown to be calcium by von Kossa staining (Fig. 4). Adjacent to this calcium deposit, syringoma was present in the upper dermis (Figs. 3 and 5). Histological examination did not confirm transepidermal elimination of the calcium deposits. Serial sectioning did not show any relationship
Various cutaneous changes associated with Down's syndrome have been reported. These include dry skin, atopic dermatitis, seborrheic dermatitis, elastosis perforans serpiginosa, alopecia areata, and syringoma (1-3). The Down's syndrome patient presented here showed both calcinosis cutis and syringoma. The strawberry hemangioma was probably coincidental. Calcinosis cutis associated with syringoma in Down's syndrome was first reported by Sano et al. (4) in 1978. Subsequently, Shibuya et al. reported a similar case (5) in 1985. These were published inJapanese. Smith et al. (6) and Maroon et al. (7) recently reported two such cases in English language journals. All 5 cases, including ours, are very similar: children with Down's syndrome with milialike white papules on hands and feet, which were revealed to be calcium deposits in the upper dermis. Among the four cases reported, the case of Maroon et al. was, surprisingly, almost identical to ours. They report a 12-year-old boy with Down's syndrome with periorbital syringoma as well as milialike carcinosis cutis on hands and feet. Histopathological examination revealed small syringomas adjacent to calcium deposits and transepiderrnal elimination of calcium. We also observed syringomas adjacent
618
Kanzaki and Nakajima
to the calcium deposit in the hands. The syringomas were initially not clinically noticeable, because they were so small. Transepidermal elimination of calcium was not confirmed histologically in our case, but it possibly had occurred; the patient's mother stated that some "pustules" had disappeared after a "rupture". Although Maroon et al. suggested that the primary site of calcium deposition would be in the acrosyringium, we did not observe any close relationship between the deposit and the sweat gland apparatus. The calcium seemed to have deposited primarily in dermal components such as fibroblasts or connective tissues. In fact, fibroblasts from Down's syndrome have been reported to contain higher calcium levels in culture than those from normal subjects (8). Neural tissue (basal ganglia) calcification has been reported with increased frequency (15 of 33 cases) in this disease (9). Certainly, such calcium deposition does not indicate metastatic calcinosis or dystrophic calcinosis since none of the reported cases, including ours, had abnormal calcium metabolism nor precedent skin diseases. Calcinosis cutis in Down's syndrome may mimic subepidermal calcified nodules clinically and histologically. The latter, however, are usually solitary and often appear on the face. Histopathologically, the calcium is present largely as closely aggregated globules (l0). Thus, it is reasonable to assume that calcinosis in Down's syndrome is idiopathic. If physicians are made aware that this unusual skin condition can
afflict certain patients with Down's syndrome, a correct diagnosis can be made at the outset and such cases will be reported more often. References 1) Butterworth T, Strean LP, Beerman H, Gray Wood M: Syringoma and Mongolism, Arch Dermatol, 90: 483487, 1964. 2) Carter DM,jegasothy BV: Alopecia areata and Down Syndrome, ArchDermatol, 112: 1397-1399,1976. 3) Rasmussen jE: Disseminated elastosis perforans serpiginosa in four Mongoloids, BrJ Dermatol, 86: 2-13, 1972. 4) Sano T, Tate S, Ishikawa C: A case of Down's syndrome associated with syringoma, milia, and subepidermal calcified nodule, Jpn J Dermatol, 88: 740 (abstract), 1978. (in japanese) 5) Shibuya M, Iizuka H, Ohkawara A, Kishiyama K: A case of calcinosis cutis in Down's syndrome, Hifurinsho, 27: 1218-1219,1985. (in japanese) 6) Smith ML, Golitz LE, Morelli lG, Weston WL, Markewich G: Milialike idiopathic calcinosis cutis in Down's syndrome, Arch Dermatol, 125: 1586-1587, 1989. 7) Maroon M, Tyler W, Marks ~: Calcinosis cutis associated with syringomas: A transepidennal elimination disorder in a patient with Down syndrome, JAm Acad Dermatol, 23: 372-375, 1990. 8) Ceder 0, Roomas GM, Hosli P: Increased calcium content in cultured fibroblast from trisomy patients: . Comparison with cystic fibroblasts, Scan Electron Microsc, II: 723-730, 1982. 9) Takashima S, Becker LE: Basal ganglia calcification in Down's syndrome,] NeurolNeurosurg Psychiatr, 48: 61-64,1985. 10) Walter FL, Schaumberg-Lever G: Calcinosis cutis, in Lever WF, Schaumberg-Lever G: Histopathology of the Skin (7th eds),jB Lippincott Co., Philadelphia, 1990, pp 466-469.
