Autoimmune hyperphosphatemic tumoral calcinosis in a patient with FGF23 autoantibodies.

Hyperphosphatemic familial tumoral calcinosis (HFTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is an autosomal recessive disorder of ectopic calcification due to deficiency of or resistance to intact fibroblast growth factor 23 (iFGF23). Inactivating mutations in FGF23, N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO (KL) have been reported as causing HFTC/HHS. We present what we believe is the first identified case of autoimmune hyperphosphatemic tumoral calcinosis in an 8-year-old boy. In addition to the classical clinical and biochemical features of hyperphosphatemic tumoral calcinosis, the patient exhibited markedly elevated intact and C-terminal FGF23 levels, suggestive of FGF23 resistance. However, no mutations in FGF23, KL, or FGF receptor 1 (FGFR1) were identified. He subsequently developed type 1 diabetes mellitus, which raised the possibility of an autoimmune cause for hyperphosphatemic tumoral calcinosis. Luciferase immunoprecipitation systems revealed markedly elevated FGF23 autoantibodies without detectable FGFR1 or Klotho autoantibodies. Using an in vitro FGF23 functional assay, we found that the FGF23 autoantibodies in the patient's plasma blocked downstream signaling via the MAPK/ERK signaling pathway in a dose-dependent manner. Thus, this report describes the first case, to our knowledge, of autoimmune hyperphosphatemic tumoral calcinosis with pathogenic autoantibodies targeting FGF23. Identification of this pathophysiology extends the etiologic spectrum of hyperphosphatemic tumoral calcinosis and suggests that immunomodulatory therapy may be an effective treatment.

Caffey disease with raised immunoglobulin levels and thrombocytosis.

Infantile cortical hyperostosis (Caffey disease) is characterized by radiological evidence of cortical hyperostosis, soft tissue swellings, fever and irritability. We report a case of Caffey disease highlighting its presentation with thrombocytosis and high serum immunoglobulin level to alert physicians to use steroids cautiously in view of the known thrombocythemic effect of the drug. Raised Immunoglobulin also suggests that this syndrome could be infectious in origin.

Infantile cortical hyperostosis (Caffey disease): ultrastructural and immunohistochemical characterization of the peritrabecular cells.

The ultrastructure and the immunohistochemical pattern of the cells which are responsible for the bone resorption in the cortical infantile hyperostosis were investigated. The osteoclasts present a great positivity to MB1 antigen and a low positivity to OKM5. Mononuclear cells with primary lysosomes, looking like osteoclast ones are present in high concentration in peritrabecular spaces. These cells show a high positivity to OKM5 antigen and a low positivity to MB1 antigen. The mononuclear granulated cells are positive to tartrate-resistent acid phosphatase. The possible common origin and their co-operation in bone resorption is discussed.

[Infantile cortical hyperostosis and fatal varicella (author's transl)]. / Hiperostosis cortical infantil y varicela fatal.

We report a male, prematurely born, affected by an Infantile Cortical Hyperostosis. He had very frequent infections in skin, ear, meninges, gastrointestinal and respiratory system. He died at 13 months during a varicella, and an immunological defect was suspected, but could not be proved. Our patient showed some remarkable peculiarities. He was premature, uncommon fact, and associated constant infections, undernutrition and fatal varicella. This case support the relationship between Infantile Cortical Hyperostosis and infection.

Infantile cortical hyperostosis with raised immunoglobulins.

Two cases of infantile cortical hyperostosis are reported. Both had raised immunoglobulins. Particularly remarkable were the IgA and IgM levels, a finding infrequently reported.

Infantile cortical hyperostosis with raised immumoglobulins

Two cases of infantile cortical hyperostosis are reported. Both had raised immunoglobulins. Particularly remarkable were the IgA and IgM levels, a finding infrequently reported (AU)