Full case: Infant presents with an asymptomatic pearl-like nodule on the heel

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Infant is closely monitored at subsequent well visits and rechecked after 3 months, showed full resolution of the skin lesion over the heel area.

Figure 1

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Figure 1

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Figure 2

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Figure 2

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The case:

A healthy 12-month-old girl presented with one small skin lesion over the right heel (Figure 1) for one month. On examination, her right lateral heel showed a round white pearl like hard tiny lesion with smooth appearance without any redness, itching. Mother denied any pain, swelling, itching or fever. No significant travel, bites, heel stick injuries in the history. No systemic symptoms suggestive of any underlying systemic diseases. Infant is closely monitored at subsequent well visits and rechecked after 3 months, showed full resolution of the skin lesion over the heel area (Figure 2).

What’s your diagnosis?

Calcinosis cutis condition is a rarely described disease and poorly studied in children. These are a group of disorders characterized by calcium deposits in the skin. Virchow initially described Calcinosis cutis in 1855.1 This condition is broadly classified according to the etiology: dystrophic, metastatic, iatrogenic and idiopathic.1 Dystrophic calcification is associated with infection, inflammatory process, cutaneous neoplasm and connective tissue disorders.2 Idiopathic calcinosis cutis is cutaneous calcification of unknown cause with normal serum calcium. Subepidermal calcified nodule and tumor calcinosis are idiopathic forms of calcification. Iatrogenic calcinosis cutis refers to calcifications that develop inadvertently in response to medical therapy. They can be associated with the heel stick injuries, extravasation of IV calcium, Para amino salicylic acid use of saturated calcium chloride electrode paste, patients undergo liver transplants.3 In metastatic Calcinosis cutis, spontaneous deposition of calcium and phosphate in normal tissues is present due to increased serum calcium and or phosphate or both. Calcium treatment, hyperparathyroidism, hypervitaminosis D, renal failure, milk alkali syndrome, sarcoidosis, paraneoplastic hypercalcemia are associated with hypercalcemia and subsequent deposition of calcium in soft tissues (Table).

In all cases of calcinosis cutis, insoluble compounds of calcium (hydroxyapatite crystals or amorphous calcium phosphate) are deposited within the skin due to local or systemic factors. These elevated extracellular levels may result in increased intracellular levels, calcium phosphate nucleation, crystalline precipitation.4 Alternatively, damaged tissue may allow an influx of calcium ions leading to an elevated intracellular calcium level and subsequent crystalline precipitation. Tissue damage also may result in denatured proteins that preferentially bind phosphate. Calcium then reacts with bound phosphate ions leading to precipitation of calcium phosphate in the tissues.4 Calcified material may form palpable nodules which may induce muscle atrophy and predispose to contractures. Local inflammation may occur, leading to alteration and extrusion of calcified materials.

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Evaluation and work up

In this case, we made a clinical diagnosis of Milia like Idiopathic Calcinosis cutis, based on clinical features. In symptomatic cases and cases with diagnostic dilemmas, histological, clinical and laboratory findings may provide additional clues for diagnosis. Histological examination reveals a well circumscribed, round, basophilic substance, which is stained black with Von kossa stain, in the upper dermis, surrounded by thick collagen fibers and sometimes thyroid and multinucleated giant cells.6 Dermatoscopy may aid the diagnosis, it usually shows subtle metalloid appearance and central crust corresponding to the trance epidermal elimination of calcinosis may be important for the diagnosis of milk like idiopathic calcinosis cutis.7

Management

The management of these nodules is dependent upon underlying etiology and associated systemic diseases. If the nodule is an isolated one and not limiting child mobility, wait and watch will be the best option as spontaneous resolution in 5 to 6 months has been documented in children.8 If the lesion is large or multiple small lesions noted, then they can be treated with surgical excision, electrodessication, or CO2 LASER ablation. Recurrence following surgical excision is uncommon in children.9 Topical sodium thiosulfate has been recently used as an alternate treatment for dystrophic calcinosis cutis with no adverse effects. Intralesional injection may be effectively treated for a deeper lesion.10

Conclusion

Calcinosis cutis can be an isolated finding, or maybe a part of associated systemic diseases, iatrogenic etiology or associated with malignancies. Careful examination and laboratory work up are needed to rule out abnormalities of calcium and phosphorus metabolism, malignant processes, collagen vascular diseases, renal insufficiency, excessive milk ingestion, hypervitaminosis D, repeated heel stick injuries in NICU and extravasation of calcium containing fluids in hospitals. As spontaneous resolution is documented in children with Milia like Calcinosis cutis, differentiation of this benign lesion from molluscum, verruca, warts are needed to reassure parents and to avoid more invasive treatments such as -cryotherapy, cauterization, surgical excision, electrodessication, Co2 LASER therapy.

Final diagnosis:

Milia-like idiopathic calcinosis cutis.


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References:

  1. Reiter N, El-Shabrawi L, Leinweber B, Berghold A, Aberer E. Calcinosis cutis: part I. Diagnostic pathway. J Am Acad Dermatol. 2011;65(1):1-14. doi:10.1016/j.jaad.2010.08.038
  2. James WD, Berger T, Elston D. Andrew’s Diseases of the Skin : Clinical Dermatology. Elsevier Health Sciences; 2011.
  3. Walsh JS, Fairley JA. Calcifying disorders of the skin. J Am Acad Dermatol. 1995;33(5 Pt 1):693-710. doi:10.1016/0190-9622(95)91803-5
  4. Tristano AG, Villarroel JL, Rodríguez MA, Millan A. Calcinosis cutis universalis in a patient with systemic lupus erythematosus. Clin Rheumatol. 2006;25(1):70-74. doi:10.1007/s10067-005-1134-5
  5. Mansur AT, Küllü S. A solitary lesion of idiopathic calcinosis cutis in an infant: subepidermal nodular calcinosis or milia-like idiopathic calcinosis cutis?. Dermatol Online J. 2021;27(5):10.5070/D327553620. Published 2021 May 15. doi:10.5070/D327553620
  6. Jang EJ, Lee JY, Yoon TY. Milia-like Idiopathic Calcinosis Cutis Occurring in a Toddler Born as a Premature Baby. Ann Dermatol. 2011;23(4):490-492. doi:10.5021/ad.2011.23.4.490
  7. Kawaguchi M, Suzuki T. Dermoscopy is useful for the diagnosis of milia-like idiopathic calcinosis cutis. Australas J Dermatol. 2018;59(1):63-64. doi:10.1111/ajd.12675
  8. Randhawa MS, Varma TH, Dayal D. Benign calcinosis cutis. Turk Pediatri Ars. 2018;53(4):267-268. Published 2018 Dec 1. doi:10.5152/TurkPediatriArs.2018.6792
  9. Plott T, Wiss K, Raimer SS, Solomon AR. Recurrent subepidermal calcified nodule of the nose. Pediatr Dermatol. 1988;5(2):107-111. doi:10.1111/j.1525-1470.1988.tb01149.x
  10. Strazzula L, Nigwekar SU, Steele D, et al. Intralesional sodium thiosulfate for the treatment of calciphylaxis. JAMA Dermatol. 2013;149(8):946-949. doi:10.1001/jamadermatol.2013.4565
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