Emergent high fatality lung disease in systemic juvenile arthritis
treatment; inflammation; adult onset still's disease; DMARDs (biologic); juvenile idiopathic arthritis
OBJECTIVE: To investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA). METHODS: In a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data. RESULTS: LD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features. CONCLUSIONS: A rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.
Saper Vivian E; Chen Guangbo; Deutsch Gail H; Guillerman R Paul; Birgmeier Johannes; Jagadeesh Karthik; Canna Scott; Schulert Grant; Deterding Robin; Xu Jianpeng; Leung Ann N; Bouzoubaa Layla; Abulaban Khalid; Baszis Kevin; Behrens Edward M; Birmingham James; Casey Alicia; Cidon Michal; Cron Randy Q; De Aliva; De Benedetti Fabrizio; Ferguson Ian; Fishman Martha P; Goodman Steven I; Graham T Brent; Grom Alexei A; Haines Kathleen; Hazen Melissa; Henderson Lauren A; Ho Assunta; Ibarra Maria; Inman Christi J; Jerath Rita; Khawaja Khulood; Kingsbury Daniel J; Klein-Gitelman Marisa; Lai Khanh; Lapidus Sivia; Lin Clara; Lin Jenny; Liptzin Deborah R; Milojevic Diana; Mombourquette Joy; Onel Karen; Ozen Seza; Perez Maria; Phillippi Kathryn; Prahalad Sampath; Radhakrishna Suhas; Reinhardt Adam; Riskalla Mona; Rosenwasser Natalie; Roth Johannes; Schneider Rayfel; Schonenberg-Meinema Dieneke; Shenoi Susan; Smith Judith A; Sönmez Hafize Emine; Stoll Matthew L; Towe Christopher; Vargas Sara O; Vehe Richard K; Young Lisa R; Yang Jacqueline; Desai Tushar; Balise Raymond; Lu Ying; Tian Lu; Bejerano Gill; Davis Mark M; Khatri Purvesh; Mellins Elizabeth D; Childhood Arthritis and Rheumatology Research Alliance Registry Investigators
Annals Of The Rheumatic Diseases
2019
2019-12
Journal Article
<a href="http://doi.org/10.1136/annrheumdis-2019-216040" target="_blank" rel="noreferrer noopener">10.1136/annrheumdis-2019-216040</a>
PMID: 31562126
Microrna Expression Profile In Patients With Spondyloarthritis- A Pilot Study
Rheumatology
Magrey M N; Haqqi T; Haseeb A
Annals of the Rheumatic Diseases
2013
2013-06
Journal Article or Conference Abstract Publication
n/a
ZCCHC6 DELETION DOWNREGULATES IL-6 AND REDUCES THE SEVERITY OF EXPERIMENTAL OSTEOARTHRITIS IN MICE
Rheumatology
Ansari M Y; Khan M N; Ahmad I; Haqqi T M
Annals of the Rheumatic Diseases
2018
2018-06
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1136/annrheumdis-2018-eular.2071" target="_blank" rel="noreferrer noopener">10.1136/annrheumdis-2018-eular.2071</a>
Whale of a tale
arthritis; Rheumatology; spondyloarthropathy
Rothschild B; Naples V
Annals of the Rheumatic Diseases
2005
2005-09
Journal Article
<a href="http://doi.org/10.1136/ard.2004.033423" target="_blank" rel="noreferrer noopener">10.1136/ard.2004.033423</a>
Osteoarthritis as a complication of artificial environment: the Cavia (guinea pig) story
knee; Rheumatology
Rothschild B M
Annals of the Rheumatic Diseases
2003
2003-10
Journal Article
<a href="http://doi.org/10.1136/ard.62.10.1022" target="_blank" rel="noreferrer noopener">10.1136/ard.62.10.1022</a>
Commented glossary for rheumatic spinal diseases
ankylosing spondylitis; defleshed bones; erosive arthritis; Rheumatology; spondyloarthropathy
Rothschild B M
Annals of the Rheumatic Diseases
1996
1996-01
Journal Article
<a href="http://doi.org/10.1136/ard.55.1.76-b" target="_blank" rel="noreferrer noopener">10.1136/ard.55.1.76-b</a>
WNT-BETA CATENIN PATHWAY MAY BE UPREGULATED IN ANKYLOSING SPONDYLITIS
Rheumatology
Magrey M; Haqqi T; Singer N; Breitman M; Haghiac M
Annals of the Rheumatic Diseases
2019
2019-06
<a href="http://doi.org/10.1136/annrheumdis-2019-eular.5173" target="_blank" rel="noreferrer noopener">10.1136/annrheumdis-2019-eular.5173</a>
The often overlooked digital tuft: clues to diagnosis and pathophysiology of neuropathic disease and spondyloarthropathy.
*Foot Bones/pathology; Adult; Alcoholism/complications; Arthropathy; Bone/etiology; Diabetes Mellitus/pathology; Diagnosis; Diaphyses/pathology; Differential; Female; Fractures; Humans; Leprosy/diagnosis/pathology; Male; Middle Aged; Neurogenic/*diagnosis/etiology/pathology; Neurosyphilis/diagnosis/pathology; Scleroderma; Spondylarthropathies/*diagnosis/pathology; Stroke/complications; Systemic/diagnosis
OBJECTIVE: To assess diagnostic implications of abnormalities of the pedal digital tufts and to identify features to facilitate distinguishing of spondyloarthropathy and leprosy. BACKGROUND: Better criteria for distinguishing between these disorders are necessary if their character, natural history, and evolution are to be understood. METHODS: Pedal x rays of 91 consecutive patients with diabetes, 21 alcoholic patients, 100 with spondyloarthropathy, 8 with scleroderma, and 137 with leprosy, and 188 defleshed skeletons of individuals with alcoholism, syphilis, cerebrovascular disease, and paraplegia from the Terry and Hamman-Todd collections were examined for evidence of osseous and articular pathologies. Digital tuft abnormalities were divided into irregularity, divot, flattening, resorption, whittling, and fragmentation. RESULTS: Tuft divots were more common in alcoholics than in diabetic, and were more common in both than in the other groups studied. Tuft flattening was limited to alcoholic and neurosyphilis groups. Tuft whittling was especially prominent among individuals with spondyloarthropathy, contrasted with leprosy and diabetes. Aligned fractures were more common in diabetics than individuals with leprosy. Misaligned fractures were limited to individuals with leprosy and neurosyphilis. Leprosy and spondyloarthropathy were complicated by phalangeal and metatarsal whittling more commonly than other diseases studied. Background pedal abnormalities, derived from individuals with cardiovascular syphilis, cerebrovascular accidents, and paraplegia, was limited to abnormal divots only. CONCLUSIONS: Pedal digital tufts undergo a variety of pathological alterations useful in the recognition of disorders traditionally considered neuropathic in aetiology and in distinguishing differential considerations. Tuft flattening appears specific for alcoholism and neurosyphilis, and misaligned fractures seem specific for neurosyphilis and leprosy, providing differential assistance related to spondyloarthropathy. Conversely, periosteal reaction distinguishes spondyloarthropathy from leprosy.
Rothschild B M; Behnam S
Annals of the rheumatic diseases
2005
2005-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1136/ard.2004.021303" target="_blank" rel="noreferrer noopener">10.1136/ard.2004.021303</a>