Target Organ Associations in Polyarteritis Nodosa (PAN): Results of a Worldwide Collaboration Study

Omer Karadag¹, Shunsuke Furuta ², Alojzija Hocevar ³, Ummugulsum Gazel ⁴, Andrea Hinojosa-Azaola ⁵, Serdal Ugurlu ⁶, Seerapani Gopaluni ⁷, Ertugrul Cagri Bolek ⁸, Berkan Armagan ⁹, Fatma Alibaz-Oner ¹⁰, Matija Tomšič ¹¹, Gizem Ayan ¹², Ayten Yazici ¹³, Eduardo Martin-Nares ¹⁴, Susy Marcela Sánchez-Cubías ⁵, Mehmet Nedim Tas ¹⁵, Ayşe Cefle ¹⁶, Kenan Aksu ¹⁷, Hajime Kono ¹⁸, Tamihiro Kawakami ¹⁹, Yoshiyuki Abe ²⁰, Timuçin Kaşifoğlu ²¹, Mehmet Engin Tezcan ²², Onay Gercik ²³, Sadettin Kilickap ²⁴, Haner Direskeneli ²⁵, Seza Ozen ²⁶, Ali İhsan Ertenli ⁸ and David Jayne ⁷, ¹Hacettepe University Vasculitis Centre, Ankara, Turkey / Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, University of Cambridge, UK, Ankara, Turkey, ²Department of Alergy and Immunology, Chiba University Hospital, Chiba, Japan, Chiba, Japan, ³Department of Rheumatology, University Medical Center Ljubljana, Slovenia, LJUBLJANA, Slovenia, ⁴Marmara University, Faculty of Medicine, Department of Rheumatology, Istanbul, Turkey, Istanbul, Turkey, ⁵Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Mexico City, Mexico, ⁶Istanbul University - Cerrahpasa, Cerrahpasa Medical Faculty, Department of Internal Medicine, Division of Rheumatology, istanbul, Turkey, ⁷Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, University of Cambridge, UK, Cambridge, United Kingdom, ⁸Hacettepe University Vasculitis Centre, Ankara, Turkey, ankara, Turkey, ⁹Department of Internal Medicine, Hacettepe University, Faculty of Medicine, Ankara, Turkey., Ankara, Turkey, ¹⁰Marmara University Faculty of Medicine,Department of Rheumatology,Istanbul,Turkey, Istanbul, Turkey, ¹¹Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia, LJUBLJANA, Slovenia, ¹²University of Ottawa Faculty of Medicine, Rheumatology, Ottawa, ON, Canada, ¹³Kocaeli University, Faculty of Medicine, Division of Rheumatology, Kocaeli, Kocaeli, Turkey, ¹⁴Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, ¹⁵Ege University, Faculty of Medicine, Department of Rheumatology, Izmir, Turkey, Izmir, Turkey, ¹⁶Division of Rheumatology, Kocaeli University School of Medicine, Kocaeli, Turkey, Kocaeli, Turkey, ¹⁷Ege University, Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, İzmir, Turkey, ¹⁸Teikyo University School of Medicine, Tokyo, Japan, ¹⁹Department of Dermatology, Tohoku Medical and Pharmaceutical University, Japan, Tohoku, Japan, ²⁰Department of Rheumatology, Juntendo University, Tokyo, Japan, Tokyo, Japan, ²¹Eskişehir Osmangazi University, Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Eskişehir, Turkey, ²²Department of Rheumatology, Kartal Dr. Lutfi Kirdar Training and Research Hospital , Istanbul, Turkey, Istanbul, Turkey, ²³Izmir Katip Celebi University, Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, İzmir, Turkey, ²⁴Hacettepe University, Faculty of Medicine, Department of Preventive Oncology, Ankara, Turkey, Ankara, Turkey, ²⁵Marmara University, School of Medicine, Division of Rheumatology, Istanbul, Turkey, ²⁶Hacettepe University Hospital, Ankara, Turkey

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: polyarteritis nodosa and vasculitis

Session Information

Date: Monday, November 11, 2019

Title: Vasculitis – Non-ANCA-Associated & Related Disorders Poster III: Behçet’s Disease & Other Vasculitides

Session Type: Poster Session (Monday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Polyarteritis nodosa (PAN) is a rare type of the systemic vasculitides with heterogeneous presentations.There is a paucity of information on the current phenotypes, ethnic and geographic differences of PAN. A global PAN study group has been working for clinical subphenotypes and GWAS studies.

Methods: A retrospective survey of databases from centres was done for PAN patients fulfilling the EMEA Vasculitis Classification algorithm. Patients with typical angiographic and/or histopathologic findings consistent with PAN were enrolled. In addition to baseline clinical characteristics, treatment and outcome data was recorded.

Factor analysis was used to analyze target organ associations of these 229 patients. Four factors were identified by factor analysis of variables sex, ethnicity, disease onset age, pediatric-onset, monogenic disease relationship, HBV relationship, any cutaneous features, any musculoskeletal symptoms, any constitutional symptoms, any other involved areas (abdominal, renal, testicular, neurologic, ear nose and throat (ENT), cardiac, pulmonary), positive angiographic findings and relapses.

Results: PAN Cohorts from 5 different countries were investigated in this study. (Japan: n=39, Mexico: n=29, Slovenia: n=14, TUR: n=100, UK: n=47). Totally 229 (M/F: 130/99 and Caucasian 70.3%, Asian 17.0%, and Hispanic 12.7%) patients were included in the study. Four were HBV-related, and 21 of TR patients had a monogenic form of disease (Familial Mediterranean Fever association in 14, deficiency of adenosine deaminase 2-DADA2- in 7).

20.5% of patients were cutaneous-only PAN patients. 45.4% of patients had radiologic, and 69.4% had biopsy-proven PAN. Median age at disease onset was 38.5 (IQR 24.0-57.0) years. During a median 60 (16-130) months follow-up, 23 patients died.

Factor analysis revealed 4 factors that explained 60% of the original information on the matrix as follows: Factor 1,represented the association between any of gastrointestinal findings, renal involvement, and testicular involvement which are negatively associated with any of cutaneous involvement; Factor 2,the association between any of musculoskeletal findings, and any positive constitutional symptoms; Factor 3,any neurologic involvement was associated with ENT involvement, Factor 4,any monogenic relationship FMF or ADA itself. The eigenvalues of the 4 factors were 1.853, 1.297, 1.164, and 1.085, in decreasing order, i.e., the highest contribution to the overall variance in the matrix came from the togetherness of the 3 clinical manifestations that made up Factor 1. Factors, their relative contributions to the total variance and the communalities for each of the variables are shown in Table.

Conclusion: The target organ associations found in this study could support the hypothesis of subphenotypes in PAN. Factor 1-more organ involvement with less cutaneous features seems to be the most severe form. Patients with any monogenic genetic background (FMF or DADA2) have distinct target organ associations. Even though ENT involvement was rare, its association with neurologic involvement might define a different subphenotype- looks like a ANCA negative medium vessel vasculitis.

Table: Target organ associations in Polyarteritis Nodosa -PAN-

Disclosure: O. Karadag, None; S. Furuta, None; A. Hocevar, None; U. Gazel, None; A. Hinojosa-Azaola, None; S. Ugurlu, None; S. Gopaluni, None; E. Bolek, None; B. Armagan, None; F. Alibaz-Oner, None; M. Tomšič, None; G. Ayan, None; A. Yazici, None; E. Martin-Nares, None; S. Sánchez-Cubías, None; M. Nedim Tas, None; A. Cefle, None; K. Aksu, None; H. Kono, Celgene Corporation, 2; T. Kawakami, None; Y. Abe, None; T. Kaşifoğlu, None; M. Tezcan, None; O. Gercik, None; S. Kilickap, None; H. Direskeneli, None; S. Ozen, Enzyvant, 8; A. Ertenli, None; D. Jayne, Astra Zeneca, 5, Boehringer-Ingelheim, 5, Celgene, 5, ChemoCentryx, 2, 5, GSK, 2, 5, Infla-Rx, 5, InflaRx GmbH, 5, Insmed, 5, Roche Genetech, 2, Sanofi Genzyme, 2, Takeda, 5.

To cite this abstract in AMA style:

Karadag O, Furuta S, Hocevar A, Gazel U, Hinojosa-Azaola A, Ugurlu S, Gopaluni S, Bolek E, Armagan B, Alibaz-Oner F, Tomšič M, Ayan G, Yazici A, Martin-Nares E, Sánchez-Cubías S, Nedim Tas M, Cefle A, Aksu K, Kono H, Kawakami T, Abe Y, Kaşifoğlu T, Tezcan M, Gercik O, Kilickap S, Direskeneli H, Ozen S, Ertenli A, Jayne D. Target Organ Associations in Polyarteritis Nodosa (PAN): Results of a Worldwide Collaboration Study [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/target-organ-associations-in-polyarteritis-nodosa-pan-results-of-a-worldwide-collaboration-study/. Accessed .

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