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Latitude gradient influences the age of onset of rheumatoid arthritis: a worldwide survey


The age of onset of rheumatoid arthritis (RA) is an important outcome predictor. Northern countries report an age of RA onset of around 50 years, but apparently, variability exists across different geographical regions. The objective of the present study is to assess whether the age of onset of RA varies across latitudes worldwide. In a proof-of-concept cross-sectional worldwide survey, rheumatologists from preselected cities interviewed 20 consecutive RA patients regarding the date of RA onset (RAO, when the patient first noted a swollen joint). Other studied variables included location of each city, rheumatologist settings, latitudes (10° increments, south to north), longitudes (three regions), intracountry consistency, and countries’ Inequality-adjusted Human Development Index (IHDI). Data from 2481 patients (82% females) were obtained from 126 rheumatologists in 77 cities of 41 countries. Worldwide mean age of RAO was 44 ± 14 years (95% CI 44–45). In 28% of patients, RA began before age 36 years and before age 46 years in 50% of patients. RAO was 8 years earlier around the Tropic of Cancer when compared with northern latitudes (p < 0.001, 95% CI 3.5–13). Multivariate analysis showed that females, western cities, and latitudes around the Tropic of Cancer are associated with younger age of RAO (R 2 0.045, p < 0.001). A positive correlation was found between the age of RAO and IHDI (r = 0.7, p < 0.01, R 2 0.5). RA often begins at an early age and onset varies across latitudes worldwide. We postulate that countries’ developmental status and their geographical and geomagnetic location influence the age of RAO.

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We thank Graciela S. Alarcon, M.P.H., for assistance with the preparation of an earlier version of the manuscript. We thank Maarten Boers, Ph.D., for providing data. We thank Leopoldo Mendoza-Garcia for artworks.

The members of the GEO-RA Group are as follows:

Universidad Autonoma de Guadalajara, Guadalajara, Mexico

Cesar Ramos-Remus

Unidad de Investigacion en Enfermedades Cronico-Degenerativas, Guadalajara, Mexico

Aldo Barajas-Ochoa

Andrea Ramirez-Gomez

Jose D. Castillo-Ortiz

Victor Brambila-Barba

Faculty of Medicine, Dentistry and Health University of Sheffield, Sheffield, UK

Adewale O. Adebajo

LSU Health Sciences Center, New Orleans, USA

Luis R. Espinoza

Hospital General Regional 46, Instituto Mexicano del Seguro Social, Guadalajara, Mexico

Francisco J. Aceves-Avila

Secretaria de Salud Jalisco, Guadalajara, Mexico

Jorge M. Sánchez-González

Dr. Benbadis University Hospital, Constantine, Algeria

Nadia Boudersa

University of Batna 2, Batna, Algeria

Samy Slimani

Ben Aknoun Hospital, University of Algiers, Algiers, Algeria

Aicha Ladjouze-Rezig

Centro Traumatológico Bariloche, Bariloche, Argentina

Mónica P. Diaz

Sanatorio San Carlos, Bariloche, Argentina

Karin I. Kirmayr

Hospital Alemán, Buenos Aires, Argentina

Cecilia A. Asnal

Hospital Italiano de Buenos Aires, Instituto Universitario, Escuela de Medicina Hospital Italiano de Buenos Aires y Fundación Dr. Pedro M. Catoggio para el Progreso de la Reumatología, Buenos Aires, Argentina

Luis J. Catoggio

Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina

Gustavo Citera

Hospital Militar Central, Buenos Aires, Argentina

Gustavo C. Casado

Hospital Penna, Buenos Aires, Argentina

Analia P. Alvarez

Departamento de Medicina Interna, CEMIC, Buenos Aires, Argentina

Cecilia N. Pisoni

Hospital Distrito Sanitario N 8: Eva Perón, Formosa, Argentina

Emilio Benavente

Centro Fleboestético del Sur, General Roca, Argentina

Adriana Lopez-Cabanillas

Hospital Zonal General Roca, General Roca, Argentina

Roberto M. Baez

Instituto Cardiovascular de Rosario, Rosario, Argentina

Bernardo A. Pons-Estel

Hospital Provincial de Rosario, Rosario, Argentina

Mónica P. Sacnún

Sección de Reumatologia y Enfermedades Autoimmunes, Hospital JB Iturraspe, Santa Fe, Argentina

Javier A. Cavallasca

Centro Privado de Rehabilitación, Santa Rosa, Argentina

Raúl H. Paniego

Royal Adelaide Hospital and Discipline of Medicine, University of Adelaide, Adelaide, Australia

Susanna M. Proudman

The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Australia

Ranjeny Thomas

Bone & Joint Institute Royal New Castle Centre and University of Newcastle, Newcastle, Australia

Gabor Major

Georgetown Arthritis, Newcastle, Australia

David M. Mathers

Department of Rheumatology, Royal North Shore Hospital, Institute of Bone and Joint Research, Kolling Institute, Sydney, Australia

Leslie Schrieber

Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh

Nazrul Islam

Syed A. Haq

Rheumatology Division, University Hospital Brussels and Free University Brussels, Brussels, Belgium

Patrick H. Dessein

Rheuma Clinic and Brazilian Society of Autoimmunity, Porto Alegre, Brazil

Carlos A. von Muhlen

Postgraduate School-Pontifica Universidade Católica, and Rheumatology Department at Santa Casa da Misericórdia do Rio de Janeiro General Hospital, Rio de Janeiro, Brazil

Washington A. Bianchi

Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil

Geraldo da R. Castelar-Pinheiro

Escola Paulista de Medicina, Universidade Federal De Sao Paulo, Sao Paulo, Brazil

Daniel Feldman-Pollak

Rheumatology Division, School of Medicine of Jundiai, Sao Paulo, Brazil

Waldenise Cossermelli

Hospital das Clinicas-Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

Karina R. Bonfiglioli

Serviço de Reumatologia, Hospital do Servidor Público Estadual FranciscoMorato de Oliveira (HSPE-FMO), São Paulo, Brasil

Rina D. Giorgi

Centre Hospitalier Universitaire Yalgado Ouedraogo, University of Ouagadougou, Ouagadougou, Burkina Faso

Wendlassida J. Zabsonre-Tiendrebeogo

University of Alberta, Edmonton, Canada

Anthony S. Russell

Lilia Olaru

Ottawa Hospital, Ottawa, Canada

Jacob Karsh

University of Concepción, Concepción, Chile

Irene H. Castro-Esparza

Hospital Clínico San Borja Arriarán, Santiago, Chile

Carlos Fuentealba

Clínica Indisa, Universidad de Chile, Santiago, Chile

Sergio Aguilera

Pontificia Universidad Católica de Chile, Santiago, Chile

Paula I. Burgos

Hospital del Salvador, Facultad de Medicina Universidad de Chile, and Clínica Alemana, Facultad de Medicina Clínica Alemana-UDD, Santiago, Chile

Oscar Neira

Department of Rheumatology and Immunology, Beijing University Medical School People’s Hospital, Beijing, China

Zhan-guo Li

Department of Medicine & Therapeutics, the Chinese University of Hong Kong, Hong Kong, China

Lai-Shan Tam

Department of Biomedical Sciences, the City University of Hong Kong, Hong Kong, China

Mo Y. Mok

Universidad Nacional de Colombia, Bogotá, Colombia

Yimy F. Medina

Hospital Luis Vernaza, Guayaquil, Ecuador

Andrés E. Zúñiga-Vera

Mario J. Moreno-Alvarez

Universidad Católica de Guayaquil, Guayaquil, Ecuador

Claudia Vera

Hospital de Especialidades Eugenio Espejo, Quito, Ecuador

Ivonne Quezada

Clínica Santa Lucia, Quito, Ecuador

Iván M. Moreno

Centro de Atención Ambulatoria El Batán (IESS), Quito, Ecuador

Wendy Calapaqui

Rheumatology Unit, Cairo University Hospitals, Cairo, Egypt

Ghada El-Mardenly

Department of Medicine, Ain Shams University, Cairo, Egypt

M. Salah Salama

Rheumatology and Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt

Gaafar Ragab

Kamel Gado

Rheumatology Center, Cairo, Egypt

Tahsin Hadidi

Department of Rheumatology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

Marjatta Leirisalo-Repo

Riitta Tuompo

Kanta-Häme Hospital, Riihimäki, Finland

Riitta Koivuniemi

INSERM UMR-S938, Faculty of Medicine Pierre & Marie Curie Paris VI, Paris, France, and Department of Rheumatology, Saint-Antoine Hospital, AP-HP, Paris, France

Francis Berenbaum

Rheumatology A Department, Cochin Hospital, Paris Descartes University, Paris, France

Yannick Allanore

Centre de Rhumatologie, Hôpital Purpan, and Université Paul Sabatier Toulouse III, Toulouse, France

Arnaud Constantin

Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin (CCM), Berlin, Germany

Frank Buttgereit

Division of Rheumatology and Clinical Immunology, Medizinische Klinik und Poliklinik IV, Ludwig Maximilians University, Munich, Germany

Hendrik Schulze-Koops

Myriam Liz

School of Medicine and Dentistry, University of Ghana, Accra, Ghana

Dzifa Dey

Instituto Hondureño de Seguridad Social, Tegucigalpa, Honduras

Carlos B. Santiago-Pastelín

Hugo D. Alonzo-Borjas

Víctor Cuéllar-Cruz

Institute of Rheumatology and Autoimmune Disorders, Sakra World Hospital, Bangalore, India

Balebail G. Dharmanand

P.D. Hinduja Hospital and Medical Research Centre, Mumbai, India

G.C. Yathish

Mumbai Arthritis Clinic, Mumbai, India

Shashank M. Akerkar

Department of Rheumatology, ISIC Superspeciality Hospital and ‘A&R Clinic for Arthritis & Rheumatism’, New Delhi, India

Anand N. Malaviya

Shahid Beheshti University of Medical Sciences, Tehran, Iran

Arman Ahmadzadeh

Central Clinic, Tokyo, Japan

Tomoko Hasunuma

Kenyatta National Hospital, Nairobi, Kenya

Benard O. Owino

Facultad de Medicina, Universidad Autónoma de Chihuahua, Chihuahua, Mexico

César Pacheco-Tena

Departamento de Medicina, Clínica Hospital ISSSTE, Gómez Palacio, Mexico

Aaron Frausto-Arenas

Universidad de Colima, Colima, Mexico

Adrián A. De la Madrid-Cernas

Centro Reumatológico de Querétaro, Querétaro, Mexico

Román Cardona-Cabrera

Instituto Mexicano del Seguro Social, Hermosillo, Mexico

Juan D. Centeno-Valadez

Unidad de Enfermedades Reumáticas y Crónico Degenerativas, Torreón, Mexico

Isaura M. Rodríguez-Torres

National Center for Rheumatic Diseases, Kathmandu, Nepal

Binit Vaidya

Kathmandu, Nepal

Arun K. Gupta

Department of Medicine, University of Otago Wellington, Wellington, New Zealand

Andrew A. Harrison

Department of Medicine and Department of Pathology and Molecular Medicine, University of Otago Wellington, Wellington, New Zealand

Rebecca Grainger

Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria

Henry M. Nwankwo

Department of Rheumatology, Hospital for Rheumatic Diseases, Haugesund, Haugesund, Norway

Andreas P. Diamantopoulos

Elisabeth Mæland

UiT the Arctic University of Norway and Finnmarkssykehuset i Kirkenes, Kirkenes, Norway

Emilio Besada

Hospital Santo Tomas, Panama, Panama

Luis Gorriz

Hospital de Clínicas, Universidad Nacional de Asunción, Asunción, Paraguay

Margarita Duarte

Sonia Cabrera-Villalba

Sanatorio Santa Clara, Asunción, Paraguay

Maria T. Romero-de Albrecht

Hospital Carlos Alcántara B, Lima, Peru

Augusto García-Poma

Hospital Nacional Edgardo Rebagliati Martins, EsSalud, Lima Peru, and Universidad Nacional Mayor de San Marcos, Lima, Peru

María I. Segami

Hospital Nacional Edgardo Rebagliati Martins, EsSalud, Lima, Peru

María P. Ramos

Wilkerson Pérez-Medina

Dr. Pablo O. Torre Memorial Hospital, Manila, Philippines

Maria L. Dianongco

St Luke’s Medical Center, Manila, Philippines

Juan J. Lichauco

St. Luke’s Medical Center BGC; Manila Doctors Hospital; University of the Philippines-Philippine General Hospital, Manila, Philippines

Geraldine Z. Racaza

University of Santo Tomas Hospital, Manila, Philippines

Sandra V. Navarra

Tito P. Torralba

University of the Philippines-Philippine General Hospital, Manila, Philippines

Bernadette H. Manapat-Reyes

Ester G. Penserga

Hamad Medical Corporation, Doha, Qatar

Mohammed Hammoudeh

Samar Al-Emadi

Privat out-patients’ clinic “Agat”, Egorievsk, Russia

Anna G. Botchkova

Department of Medicine, Rheumatology Unit, King Fahd Hospital, Jeddah, Saudi Arabia

Sabri H. AlSaeedi

Alzaidi Chair of Research in Rheumatic Diseases-Umm Alqura University, Makkah, Saudi Arabia, and Department of Medicine, Dr. Soliman Fakeeh Hospital, Jeddah, Saudi Arabia

Hani Almoallim

King Saud University, Riyadh, Saudi Arabia

Hussein F. Al-Arfaj

Koh Wei Howe Arthritis & Rheumatism Medical Clinic, Singapore, Singapore

Wei H. Koh

Department of Rheumatology & Immunology, Singapore General Hospital, and Duke-NUS Graduate Medical School, Singapore, Singapore

Ying Y. Leung

Tygerberg Hospital and Stellenbosch University, Bellville, South Africa

David A. Whitelaw

Department of Medicine, Division of Rheumatology, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa

Bridget Hodkinson

Hospital Universitari Sagrat Cor, Barcelona, Spain

Javier García-Miguel

Rheumatology Unit. IDC-Salud, Clínica del Pilar, Barcelona, Spain

Juan C. Duro

Department of Rheumatology, Hospital Universitario La Paz, Madrid, Spain

Emilio Martin-Mola

Hospital Central de la Defensa Gómez Ulla, Madrid, Spain

María Ahijón-Lana

Hospital Universitario Puerta de Hierro, Majadahonda, Spain

José L. Andreu

University Hospitals of Geneva, Geneva, Switzerland

Axel Finckh

Deshiré Alpízar-Rodríguez

Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

Manathip Osiri

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

Nuntana Kasitanon

Worawit Louthrenoo

Amsterdam Rheumatology and Immunology Center (ARC), Amsterdam, The Netherlands

Ronald F. van Vollenhoven

Amsterdam Rheumatology and Immunology Center (ARC), Department of Clinical Immunology & Rheumatology, Academic Medical Center, Amsterdam, The Netherlands

Niek de Vries

Amsterdam Rheumatology and Immunology Center (ARC), Reade Institute, Amsterdam, The Netherlands

Christiaan van Denderen

Martjin Gerritsen

VieCuri Medical Centre, Venlo, and Scientific Institute for Quality of Healthcare, Radboud University Medical Center, Nijmegen, The Netherlands

Tim L. Jansen

Department of Rheumatology, Bernhoven, Uden, The Netherlands

Piet van Riel

Universidad Centroccidental Lisandro Alvarado, Clínica Razetti de Barquisimeto, Barquisimeto, Venezuela

Concepción M. Núñez-Sotelo

Servicio de Reumatología, Hospital Vargas, Caracas, Venezuela

Sol Villegas-Morales

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GEO-RA Group. Latitude gradient influences the age of onset of rheumatoid arthritis: a worldwide survey. Clin Rheumatol 36, 485–497 (2017).

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  • Age of onset
  • Environmental
  • Geoepidemiology
  • Inequality
  • Pollution
  • Rheumatoid arthritis