Bronchiolitis obliterans is a fatal complication of Stevens-Johnson syndrome/toxic epidermal necrolysis in an adolescent with epilepsy treated with lamotrigine and nonsteroidal anti-inflammatory drugs: clinical and morphological comparisons



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Abstract

Bronchiolitis obliterans (OB) is a rare severe complication of Stevens—Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The article presents an observation of a fatal histologically confirmed OB in a 16-year-old patient who developed as a delayed complication of SJS after the use of lamotrigine and nonsteroidal anti-inflammatory drugs (NSAIDs). The diagnosis of OB was established based on the development of severe bronchoobstructive syndrome (BOS), confirmed by a study of the function of external respiration, chronic respiratory failure 2 months after SSD, characteristic CT signs (foci of mosaic perfusion, bronchiectasis). OB therapy, in addition to commonly used drugs, included the janus kinase inhibitor tofacitinib. To discuss clinical observation, a systematic review of the world literature over 45 years was conducted. 43 cases of post-SJS/TEN were selected from 187 publications with an analysis of the etiology, timing of onset, spirometric and radiological signs, features of therapy and course. According to the analysis, the main triggers of SSD/TEN were antibiotics (50%) and NSAIDs (40%), infection caused by Mycoplasma pneumoniae (12%), and less often anticonvulsants. The average age of children with OB was 7 years, and the average age of adults was 28 years. In 50% of cases, the manifestation of OB occurred 1-3 months after the start of SSD/TEN. Most patients (35%) had severe BOS, and characteristic CT signs included mosaic perfusion (75%) and bronchiectasis (49%). Systemic (77%) and inhaled (35%) glucocorticosteroids, bronchodilators (63%), and macrolide antibiotics (26%) formed the basis of OB therapy. Mortality in the analyzed cases reached 30%, complete recovery was observed in only 33%, and 35% of patients retained persistent BOS.

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About the authors

Dmitry Yu. Ovsyannikov

RUDN University, Moscow, Russian Federation;
Morozov Children's hospital, Moscow, Russian Federation;

Email: mdovsyannikov@yahoo.com
ORCID iD: 0000-0002-4961-384X
SPIN-code: 5249-5760

Professor, MD, DSc (Med), Head of the Department of Pediatrics, Medical Institute, Peoples’ Friendship University of Russia named after Patrice Lumumba (RUDN University);
Pediatric Pulmonologist, Morozov Children’s City Clinical Hospital

Россия, 6 Miklukho-Maklaya Street, Moscow, 117198, Russian Federation; 1/9 4th Dobryninsky Lane, Moscow, 119049, Russian Federation

Ilia A. Bykov

Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation

Email: svgkofein@yandex.ru
ORCID iD: 0000-0003-2375-4625
SPIN-code: 3077-6589

Senior Laboratory Assistant, Department of Allergology and Immunology, Russian Medical Academy of Continuous Professional Education

2/1 Barrikadnaya Street, Bldg. 1, Moscow, 125993, Russian Federation

Shamil A. Gitinov

RUDN University, Moscow, Russian Federation;
Morozov Children's hospital, Moscow, Russian Federation;

Email: mdgkb@zdrav.mos.ru
ORCID iD: 0000-0001-6232-544X
SPIN-code: 7062-6008

Assistant Professor, Department of Pediatrics, Medical Institute, RUDN University
Pediatric Pulmonologist, Morozov Children’s City Clinical Hospital

Россия, 6 Miklukho-Maklaya Street, Moscow, 117198, Russian Federation; 1/9 4th Dobryninsky Lane, Moscow, 119049, Russian Federation

Suzanna P. Asatryan

Morozov Children's hospital, Moscow, Russian Federation

Email: mdgkb@zdrav.mos.ru
ORCID iD: 0000-0003-1057-0536
SPIN-code: 3852-6705

Ophthalmologist, Department of Eye Microsurgery, Morozov Children’s City Clinical Hospital

Россия, 1/9 4th Dobryninsky Lane, Moscow, 119049, Russian Federation

Olga Yu. Brunova

Morozov Children's hospital, Moscow, Russian Federation

Email: mdgkb@zdrav.mos.ru
ORCID iD: 0000-0003-2158-6672

Head of the Department of Anesthesiology and Intensive Care, Anesthesiologist-Intensivist

Россия, 1/9 4th Dobryninsky Lane, Moscow, 119049, Russian Federation

Saniia I. Valieva

Morozov Children's hospital, Moscow, Russian Federation; Pirogov Russian National Research Medical University, Moscow, Russian Federation

Email: mdgkb@zdrav.mos.ru
SPIN-code: 2902-2501

DSc (Med), Deputy Chief Physician for Medical Affairs and Scientific-Educational Work, Morozov Children’s City Clinical Hospital;
Professor, Department of Pediatrics named after Academician M.Ya. Studenikin, Institute of Clinical Medicine, Pirogov Russian National Research Medical University

Россия, 1/9 4th Dobryninsky Lane, Moscow, 119049, Russian Federation; 1 Ostrovityanova Street, Moscow, 117997, Russian Federation

Valerii V. Gorev

Morozov Children's hospital, Moscow, Russian Federation;
Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation;

Email: mdgkb@zdrav.mos.ru
ORCID iD: 0000-0001-8272-3648
SPIN-code: 8944-9664

PhD (Med), Chief Physician, Morozov Children’s City Clinical Hospital;
Associate Professor, Department of Neonatology named after Professor V.V. Gavryushov, Russian Medical Academy of Continuous Professional Education

Россия, 1/9 4th Dobryninsky Lane, Moscow, 119049, Russian Federation; 1/9 4th Dobryninsky Lane, Moscow, 119049, Russian Federation

Igor S. Davydov

Morozov Children's hospital, Moscow, Russian Federation;

Email: mdgkb@zdrav.mos.ru
ORCID iD: 0000-0003-4019-3188
SPIN-code: 9402-2169

Pathologist, Department of Pathology, Morozov Children’s City Clinical Hospital

Россия, 1/9 4th Dobryninsky Lane, Moscow, 119049, Russian Federation

Evgeniia V. Deeva

Morozov Children's hospital, Moscow, Russian Federation;

Email: mdgkb@zdrav.mos.ru
ORCID iD: 0000-0002-0352-2563
SPIN-code: 9924-0270

PhD (Med), Head of the Department of Pulmonology, Morozov Children’s City Clinical Hospital;
Pediatric Pulmonologist

Россия, 1/9 4th Dobryninsky Lane, Moscow, 119049, Russian Federation

Sergei B. Zimin

Email: mdgkb@zdrav.mos.ru
ORCID iD: 0000-0002-4514-8469
SPIN-code: 4363-1578

Aleksander E. Kessel

Morozov Children's hospital, Moscow, Russian Federation;

Email: mdgkb@zdrav.mos.ru
ORCID iD: 0000-0001-6012-250X
SPIN-code: 4748-1308

Head of the Department of Neurology, Morozov Children’s City Clinical Hospital;
Pediatric Neurologist

Россия, 1/9 4th Dobryninsky Lane, Moscow, 119049, Russian Federation

Oleg G. Malyshev

RUDN University, Moscow, Russian Federation;

Email: omalyshev03@vk.com
ORCID iD: 0000-0003-1174-0736
SPIN-code: 9251-5267

Assistant Professor, Department of Pediatrics, Medical Institute, RUDN University

Россия, 6 Miklukho-Maklaya Street, Moscow, 117198, Russian Federation

Aleksander N. Pampura

Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation;

Email: apampura1@mail.ru
ORCID iD: 0000-0001-5039-8473
SPIN-code: 9722-7961

DSc (Med), Professor, Department of Pediatrics named after Academician G.N. Speransky, Russian Medical Academy of Continuous Professional Education

Россия, 2/1 Barrikadnaya Street, Bldg. 1, Moscow, 125993, Russian Federation

Aleksander G. Talalaev

Morozov Children's hospital, Moscow, Russian Federation;

Email: mdgkb@zdrav.mos.ru
ORCID iD: 0000-0002-0348-1925
SPIN-code: 9938-7840

DSc (Med), Professor, Pathologist, Department of Pathology, Morozov Children’s City Clinical Hospital

Россия, 1/9 4th Dobryninsky Lane, Moscow, 119049, Russian Federation

Zhanna G. Tigai

RUDN University, Moscow, Russian Federation;

Author for correspondence.
Email: shekz@mail.ru
ORCID iD: 0000-0003-4994-7193
SPIN-code: 6302-3406

DSc (Med), Professor, Director of the Accreditation and Simulation Center, Medical Institute, RUDN University

Россия, 6 Miklukho-Maklaya Street, Moscow, 117198, Russian Federation

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