Severe Pulmonary Fibrosis as the First Manifestation of Interferonopathy (TMEM173 Mutation).
We report three cases of pulmonary disease suggesting fibrosis in two familial and one sporadic case. Pulmonary symptoms were associated with various clinical features of systemic inflammation and vasculitis involving the skin, and appeared at different ages. A strong interferon signature was found in all three cases. Disease was not responsive to corticosteroids, and lung transplantation was considered for all three subjects at an early age. One of them underwent double-lung transplantation, but she immediately experienced a primary graft dysfunction and died soon after. Recognized causes of familial interstitial lung disease were all excluded. All three subjects had a mutation in the previously described autoinflammatory disease called SAVI (stimulator of interferon genes [STING]-associated vasculopathy with onset in infancy). These cases emphasize the need to consider this possibility in children and young adults with lung fibrosis after common causes have been ruled out.
Department of Pathology, Hôpital Femme-Mère-Enfant, Hospices civils de Lyon, Claude Bernard Lyon 1 University, Lyon, France; Inserm U1111, Lyon, France.
Cécile
C
Picard
Pediatric Pulmonology Department, Assistance publique-Hôpitaux de Paris, Hôpital Armand Trousseau, Paris, France; Inserm U938, Hôpital Saint-Antoine, Paris, France.
Guillaume
G
Thouvenin
Department of Genetic, Assistance publique-Hôpitaux de Paris, Hôpital Bichat, Université Paris Diderot, Paris, France.
Caroline
C
Kannengiesser
Pediatric Pulmonology Department, Assistance publique-Hôpitaux de Marseille, Hôpital de la Timone, Marseille, France.
Jean-Christophe
JC
Dubus
Institut Imagine, Hôpital Necker, Paris, France.
Nadia
N
Jeremiah
Institut Imagine, Hôpital Necker, Paris, France.
Frédéric
F
Rieux-Laucat
Inserm U1152, Université de Paris Diderot, Paris, France.
Bruno
B
Crestani
Inserm U1111, Lyon, France; Pediatric Rheumatology, Nephrology and Dermatology Department, Hôpital Femme-Mère-Enfant, Hospices civils de Lyon, Lyon, France.
Alexandre
A
Belot
Department of Pathology, Hôpital Femme-Mère-Enfant, Hospices civils de Lyon, Claude Bernard Lyon 1 University, Lyon, France.
Françoise
F
Thivolet-Béjui
Department of Pathology, Assistance publique-Hôpitaux de Marseille, Hôpital de la Timone, Marseille, France.
Véronique
V
Secq
Pediatric Pulmonology Department, Assistance publique-Hôpitaux de Paris, Hôpital Armand Trousseau, Paris, France.
Christelle
C
Ménard
Pulmonology Department, CHU Nord, Assistance publique-Hôpitaux de Marseille, Université de la Méditerranée, Marseille, France.
Martine
M
Reynaud-Gaubert
Pediatric Pulmonology Department, Hôpital Femme-Mère-Enfant, Hospices civils de Lyon, UMR5558, Lyon, France. Electronic address: philippe.reix@chu-lyon.fr.
Philippe
P
Reix
D000328:Adult; D001327:Autoimmune Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002647:Chilblains / Q000276:immunology; D002648:Child; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000000981:diagnostic imaging / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D011658:Pulmonary Fibrosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed; D000099197:STING Protein
D008565:Membrane Proteins; C532857:STING1 protein, human; D000099197:STING Protein
TMEM173; autoinflammatory disease; pulmonary fibrosis; vasculopathy