Denosumab Therapy for Refractory Hypercalcemia Secondary to Squamous Cell Carcinoma of Skin in Epidermolysis Bullosa

Abstract

Hypercalcemia secondary to malignancy is rare in children and the majority is caused by tumor-produced parathyroid hormone-related protein (PTHrP). We report a case of hypercalcemia refractory to bisphosphonate and corticosteroid therapy, but responsive to denosumab. A 17-year-old boy with epidermolysis bullosa (EB) and advanced squamous cell carcinoma (SCC) of the left leg was referred with severe hypercalcemia (serum calcium, 4.2 mmol/L). The serum parathyroid hormone (PTH) was 0.7 pmol/L (1.1 - 6.9 pmol/L). The hypercalcemia was initially managed with hyperhydration, prednisolone and pamidronate. Following two infusions of pamidronate (1 mg/kg/dose), serum calcium fell to 2.87 mmol/L. However the hypercalcemia relapsed within a week (serum calcium, 3.61 mmol/L) needing aggressive management with intravenous fluids, prednisolone and two further doses of pamidronate. The serum calcium fell to 2.58 mmol/L over the first 4 days, but rose to 3.39 mmol/L 3 days later. As the hypercalcemia was refractory to bisphosphonate treatment, a trial dose of subcutaneous denosumab (60 mg) was administered following which the calcium fell to 2.86 mmol/L within 24 h and normocalcemia was sustained 4 days later. We report a case of refractory hypercalcemia secondary to malignant SCC, which responded well to denosumab therapy. To our knowledge, this is the first case of hypercalcemia of malignancy in an adolescent managed with denosumab.

Paraneoplastic Syndromes in Patients with Keratinocyte Skin Cancer

“…By evaluating the title/abstract information of the initially returned 831 papers we localized 53 articles with potentially relevant content for full-text search ( Figure 1 ). Of them, 15 were excluded (one was a duplicate publication, seven were cases of penile SCC, six were erroneously identified as reporting PNS in KSC and one reported no adequately personalized data) leaving to 39 papers reporting a total of 44 PNS cases associated with KSC [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. One paper ([ 47 ]) referred to five cases with relevant findings, however without any personalized data, and was excluded from this compilation, resulting in 38 papers reporting 39 relevant cases.…”

Successful Use of Denosumab for Life-Threatening Hypercalcemia in a Pediatric Patient with Primary Hyperparathyroidism

“…According to the literature, denosumab has been used off-label in adults with PHPT for the treatment of hypercalcemia prior to a parathyroidectomy [5, 6], long-term management of parathyroid carcinoma-mediated hypercalcemia [7-9], and medical treatment of osteoporosis in PHPT [10]. It has been used off-label in children with several skeletal diseases, for example, osteogenesis imperfecta [11-13], fibrous dysplasia [14], aneurysmal bone cysts [15-18], giant-cell tumors [19], Paget’s disease of bone [20], glucocorticoid-induced osteoporosis in Duchenne muscular dystrophy [21], osteoradionecrosis [22], cherubism [18, 23], as well as for hypercalcemia reduction after bone-marrow transplantation in osteopetrosis [24] and in squamous cell carcinoma [25]. To our knowledge, only 1 case of denosumab usage in a child with severe PHPT due to a parathyroid carcinoma and ineffectiveness of bisphosphonates has been reported to date [26].…”