title: Granulomatous inflammation in cartilage-hair hypoplasia: risks and benefits of anti-TNF-α mAbs.
abstract: BACKGROUND
  Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disorder characterized by short-limbed skeletal dysplasia. Some patients also have defects in cell-mediated immunity and antibody production. Granulomatous inflammation has been described in patients with various forms of primary immunodeficiencies but has not been reported in patients with CHH.
  
  
  OBJECTIVE
  We sought to describe granulomatous inflammation as a novel feature in patients with CHH, assess associated immunodeficiency, and evaluate treatment options.
  
  
  METHODS
  In a retrospective observational study we collected clinical data on 21 patients with CHH to identify and further characterize patients with granulomatous inflammation.
  
  
  RESULTS
  Four unrelated patients with CHH (with variable degrees of combined immunodeficiency) had epithelioid cell granulomatous inflammation in the skin and visceral organs. Anti-TNF-α mAb therapy in 3 of these patients led to significant regression of granulomas. However, 1 treated patient had fatal progressive multifocal leukoencephalopathy caused by the JC polyomavirus. In 2 patients immune reconstitution after allogeneic hematopoietic stem cell transplantation led to the complete disappearance of granulomas.
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first report of granulomatous inflammation in patients with CHH. Although TNF-α antagonists can effectively suppress granulomas, the risk of severe infectious complications limits their use in immunodeficient patients.
authors.affiliation: Department of Pediatric Immunology and Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France. despina.moshous@nck.aphp.fr
authors.forename: Despina
authors.initials: D
authors.lastname: Moshous
authors.forename: Isabelle
authors.initials: I
authors.lastname: Meyts
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fraitag
authors.forename: Carl E I
authors.initials: CE
authors.lastname: Janssen
authors.forename: Marianne
authors.initials: M
authors.lastname: Debré
authors.forename: Felipe
authors.initials: F
authors.lastname: Suarez
authors.forename: Jaan
authors.initials: J
authors.lastname: Toelen
authors.forename: Kris
authors.initials: K
authors.lastname: De Boeck
authors.forename: Tania
authors.initials: T
authors.lastname: Roskams
authors.forename: Antoine
authors.initials: A
authors.lastname: Deschildre
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Christine
authors.initials: C
authors.lastname: Bodemer
authors.forename: Carine
authors.initials: C
authors.lastname: Wouters
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003872:Dermatitis / Q000276:immunology / Q000473:pathology / Q000628:therapy; D005260:Female; D006099:Granuloma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006197:Hair / Q000002:abnormalities / Q000276:immunology / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006627:Hirschsprung Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology / Q000473:pathology / Q000628:therapy; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000628:therapy; D007968:Leukoencephalopathy, Progressive Multifocal / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008297:Male; D010009:Osteochondrodysplasias / Q000151:congenital* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D000081207:Primary Immunodeficiency Diseases; D012189:Retrospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha