Systemic mastocytosis: a rare cause of osteoporosis

Abstract

A 61-year old female patient who was referred to the endocrine clinic for evaluation of an elevated alkaline phosphatase. She was originally referred to gastroenterology (GI), however no GI causes of elevated alkaline phosphatase was found. Upon fractionation, it was noted that she had elevation in bone specific alkaline phosphatase. Past history was significant for hypertension, atrial fibrillation and menopause 6 years ago. She was also noted to have multiple drug allergies manifesting as urticaria and flushing. Review of the past records revealed a persistently elevated alkaline phosphatase over the last two years. She had no history of falls or fractures. Computed tomography (CT) abdomen done to rule out biliary pathology, revealed osteosclerotic and osteolytic lesion in the pelvis concerning neoplastic disease. Bone marrow biopsy however, was negative for cancer but consistent with systemic mastocytosis (SM). Dual Energy X-ray absorbimetery (DEXA) scan revealed osteoporosis Serum tryptase levels were elevated; further genetic analysis showed a positive CKIT D816 mutation. She was started on bisphosphonates (initially alendronate and then ibandronate). Upon follow up at two years she had not experienced any fractures and her bone mineral density also had improved significantly.

Simultaneous diagnosis of papillary thyroid cancer and systemic mastocytosis

“…There is a wide spectrum of disease, but SM typically presents with nonspecific clinical symptoms including flushing, nausea/vomiting, headache, wheezing, allergic reactions, and in some cases anaphylaxis. [4][5][6] The nonspecific nature of these symptoms presents a diagnostic challenge in the absence of skin involvement such as maculopapular cutaneous mastocytosis/urticaria pigmentosa, which was not seen in our patient. 4 SM is diagnosed when patients have 1 major and ≥1 minor criterion or ≥3 minor criteria according to the World Health Organization (WHO) classification (Table 1).…”

“…Osseus metastases from thyroid cancer are more common with follicular or medullary thyroid cancer, whereas PTC represents 1.4%–7% of all osseus metastases from thyroid cancer 3 . Systemic mastocytosis (SM), a heterogenous disease caused by malignant proliferation of mast cells, will involve large osteolytic lesions in the axial skeleton in 50%–70% of cases 4–6 . Interestingly, SM is associated with an increased risk for solid cancers, particularly melanoma and non‐melanoma skin cancers 5 .…”

Mast Cells and Vitamin D Status: A Clinical and Biological Link in the Onset of Allergy and Bone Diseases

“…Moreover, histamine working via many different receptors is answerable for the allergic effects such as pruritus, and the consequences on bronchial and gastrointestinal smooth muscle cells. Therefore, bone changes are the overall product of the chymotryptic proteases, cytokines, RANKL, fibroblast growth factor family proteins, hormonal factors, and histamine [ 96 , 110 , 111 , 112 ].…”

“…The existence of MCs is a characteristic feature of different skin pathologies and tumors, and MCs can be involved in the onset and progression of tumors via the effects exerted on mitogenesis and angiogenesis, the effects on the extracellular matrix, and the effects on the immune response [ 117 , 118 ]. It has been theorized that MCs may have a different phenotype in several pathologic conditions and may present an immunosuppressive set-up in skin tumors, but a proinflammatory set-up in chronic skin inflammation [ 110 ]. However, the reason and the mechanisms able to cause a different phenotype are not well clarified.…”

Does Allergy Break Bones? Osteoporosis and Its Connection to Allergy

“…In mastocytosis, a disease with abnormal growth and the accumulation of mast cells and symptoms mostly related to released mediator effects, reduced bone mass has been described due to increased bone resorption and normal or decreased bone formation [64]. In 70% of patients with systemic mastocytosis, bone involvement has been observed with a high prevalence of osteoporotic fractures [85][86][87][88]. Osteoporosis is due to neoplastic infiltration of mast cells and the effects of the mediators that they release.…”