Skin and bones: systemic mastocytosis and bone

Abstract

Summary We report the case of a 69-year-old female with systemic mastocytosis, diagnosed based on widespread pigmented papules and macules, elevated serum tryptase levels and confirmatory skin and bone marrow biopsy, on a background of osteoporosis. A CT demonstrated multiple sclerotic lesions within lumbar vertebral bodies, sacrum and ileum, with surrounding osteolysis but no obvious compression fractures. She was treated with the RANK-L inhibitor denosumab, resulting in significant bone mineral density gain over the following 5 years. However, her serum tryptase levels gradually increased during this period despite treatment with the multikinase inhibitor, midostaurin. It is thus conceivable that her rapid increase in bone mineral density may be partly contributed by a predominance of pro-osteoblastic mediators released by abnormal mast cells, suggestive of more advanced disease. This case highlights the complexities of systemic mastocytosis-related bone disease and the interplay of numerous mediators contributing to a phenotype of both increased bone resorption and formation. Learning points Systemic mastocytosis is a neoplastic disease of mast cells characterized by abnormal proliferation and accumulation in the skin and other organs. It is most frequently associated with the somatic gain-of-function KIT D816V mutation. Systemic mastocytosis should be suspected in patients presenting with not only cutaneous symptoms suggestive of mast cell degranulation such as anaphylaxis, flushing or urticaria but also unexplained osteoporosis and gastrointestinal and constitutional symptoms. The prevalence of osteoporosis in systemic mastocytosis is high. Mast cell activation leads to the secretion of numerous chemical mediators which either promote or inhibit osteoclastic and/or osteoblastic activity, with the balance usually in favour of increased bone resorption. However, in advanced diseases with high mast cell burden, mast-cell-derived cytokines and mediators may promote osteoblastic activity, leading to osteosclerosis and apparent increases in bone mineral density. Treatment of osteoporosis in systemic mastocytosis involves antiresorptive therapy with bisphosphonates and more recently, denosumab. There are limited data on the role of osteoanabolic agents.

Simultaneous diagnosis of papillary thyroid cancer and systemic mastocytosis

“…The prevalence of bone involvement in SM is high and can manifest as focal lytic or sclerotic lesions, bony pain from marrow infiltration, or osteoporosis. Mast cells secrete many mediators that promote osteoclastic and inhibit osteoblastic function, such as histamine, heparin, tumor necrosis factor, and interleukin‐6 9 . Vertebral fractures can occur in 20% of patients with SM 10 .…”

“…Vertebral fractures can occur in 20% of patients with SM 10 . Antiresorptive therapy with bisphosphonates or denosumab is the current treatment of choice 9 …”

“…Mast cells secrete many mediators that promote osteoclastic and inhibit osteoblastic function, such as histamine, heparin, tumor necrosis factor, and interleukin-6. 9 Vertebral fractures can occur in 20% of patients with SM. 10 Antiresorptive therapy with bisphosphonates or denosumab is the current treatment of choice.…”

“…10 Antiresorptive therapy with bisphosphonates or denosumab is the current treatment of choice. 9 It is well established that patients with SM are at increased risk of developing solid cancers (Table 2). The mechanism is poorly understood but is thought to involve tumorigenic effects of mast cells.…”

Systemic mastocytosis - a common diagnosis for allergists and hematologists

“…těžká difuzní osteoporóza mohou být příčinou patologických fraktur. Osteosklerotická ložiska s okolními ložisky osteolýzy jsou typická pro pokročilé formy(9).Obr. 1.…”