title: Recurrent chronic histiocytic intervillositis with intrauterine growth restriction, osteopenia, and fractures.
abstract: Chronic histiocytic intervillositis (CHI) is characterized by the presence of histiocytes within the intervillous space of the placenta. The pathogenesis is unclear but available evidence supports an alloimmune mechanism on the basis of the presence in maternal blood of HLA antibodies directed against paternal HLA antigens. CHI has a high risk of recurrence and of abnormal perinatal outcomes. Little is known about the effects of CHI on the developing fetus, in particular on the growth and development of the skeleton. We have studied a woman whose third pregnancy was terminated after ultrasonography showed severe intrauterine growth restriction, raising the possibility of a lethal skeletal dysplasia. Postmortem radiographs showed multiple fractures and other signs of osteogenesis imperfecta (OI). However, bone histology was not typical of OI and no abnormalities were identified by sequencing OI genes. The subsequent pregnancy was also severely growth restricted and was terminated. The placenta showed chronic histiocytic intervillositis, which, on retrospective review, had also been present in her second and third pregnancies. Her fifth pregnancy was again associated with intrauterine growth restriction and CHI but resulted in a premature birth. CHI can be associated with radiographic features that mimic OI and should be considered when fetal fractures occur in the context of recurrent miscarriage, fetal death in utero, and intrauterine growth restriction. The correct diagnosis can be made by histopathology of the placenta, supported by bone histology and normal results of molecular studies for OI. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Surgical Pathology, SA Pathology (at Women's and Children's Hospital), Adelaide, South Australia, Australia.
authors.forename: April
authors.initials: A
authors.lastname: Crawford
authors.affiliation: Department of Surgical Pathology, SA Pathology (at Women's and Children's Hospital), Adelaide, South Australia, Australia.|School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Lynette
authors.initials: L
authors.lastname: Moore
authors.affiliation: Australian Red Cross Blood Service, National Transplant Services, Adelaide, South Australia, Australia.
authors.forename: Gregory
authors.initials: G
authors.lastname: Bennett
authors.affiliation: Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Ravi
authors.initials: R
authors.lastname: Savarirayan
authors.affiliation: Department of Surgical Pathology, SA Pathology (at Women's and Children's Hospital), Adelaide, South Australia, Australia.|School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Manton
authors.affiliation: Department of Surgical Pathology, SA Pathology (at Women's and Children's Hospital), Adelaide, South Australia, Australia.|School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Yee
authors.initials: Y
authors.lastname: Khong
authors.affiliation: School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.|Paediatric & Reproductive Genetics, South Australian Clinical Genetics Service, SA Pathology (at Women's and Children's Hospital), Adelaide, South Australia, Australia.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Barnett
authors.affiliation: School of Medicine, University of Adelaide, Adelaide, South Australia, Australia. eric.haan@sa.gov.au.|Paediatric & Reproductive Genetics, South Australian Clinical Genetics Service, SA Pathology (at Women's and Children's Hospital), Adelaide, South Australia, Australia. eric.haan@sa.gov.au.
authors.forename: Eric
authors.initials: E
authors.lastname: Haan
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers; D001851:Bone Diseases, Metabolic / Q000175:diagnosis*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D002908:Chronic Disease; D005260:Female; D005317:Fetal Growth Retardation / Q000175:diagnosis*; D050723:Fractures, Bone / Q000175:diagnosis*; D006644:Histiocytes / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D010920:Placenta / Q000473:pathology*; D011247:Pregnancy; D011859:Radiography; D012008:Recurrence; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: bone dysplasia; chronic histiocytic intervillositis (CHI); fetal development; intrauterine growth restriction; osteogenesis imperfecta; placental pathology