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 is a rare severe complication of Stevens–Johnson syndrome and toxic epidermal necrolysis.

The article presents an observation of a fatal histologically confirmed bronchiolitis obliterans in a 16-year-old patient developed as a delayed complication of Stevens–Johnson syndrome after the use of lamotrigine and nonsteroidal anti-inflammatory drugs. The diagnosis of bronchiolitis obliterans was established based on the development of severe bronchoobstructive syndrome, confirmed by a study of the external respiratory function, chronic respiratory failure 2 months after Stevens–Johnson syndrome, characteristic computed tomography signs (foci of mosaic perfusion, bronchiectasis). Bronchiolitis obliterans 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-Stevens–Johnson syndrome/toxic epidermal necrolysis 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 Stevens–Johnson syndrome/toxic epidermal necrolysis were antibiotics (50 %) and nonsteroidal anti-inflammatory drugs (40 %), infection caused by Mycoplasma pneumoniae (12 %), and less often anticonvulsants. The average age of children with bronchiolitis obliterans was 7 years, and the average age of adults was 28 years. In 50 % of cases, the manifestation of bronchiolitis obliterans occurred 1–3 months after the start of Stevens–Johnson syndrome/toxic epidermal necrolysis. Most patients (35 %) had severe bronchoobstructive syndrome, and characteristic computed tomography signs included mosaic perfusion (75 %) and bronchiectasis (49 %). Systemic (77 %) and inhaled (35 %) glucocorticosteroids, bronchodilators (63 %), and macrolide antibiotics (26 %) formed the basis of bronchiolitis obliterans therapy. Mortality in the analyzed cases reached 30 %, complete recovery was observed in only 33 %, and 35 % of patients retained persistent bronchoobstructive syndrome.

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About the authors

Dmitriy Yu. Ovsyannikov

Peoples’ Friendship University of Russia; Morozov Children’s City Clinical Hospital

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

MD, Dr. Sci. (Medicine), Professor

Россия, Moscow; Moscow

Ilya A. Bykov

Russian Medical Academy of Continuous Professional Education

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

MD

Россия, Moscow

Shamil A. Gitinov

Peoples’ Friendship University of Russia; Morozov Children’s City Clinical Hospital

Email: dr.gitinov@mail.ru
ORCID iD: 0000-0001-6232-544X
SPIN-code: 7062-6008

MD

Россия, Moscow; Moscow

Suzanna P. Asatryan

Morozov Children’s City Clinical Hospital

Email: syzanna_pavlovna@mail.ru
ORCID iD: 0000-0003-1057-0536
SPIN-code: 3852-6705

MD

Россия, Moscow

Olga Yu. Brunova

Morozov Children’s City Clinical Hospital

Email: oubrunova@yandex.ru
ORCID iD: 0000-0003-2158-6672

MD

Россия, Moscow

Saniya I. Valieva

Morozov Children’s City Clinical Hospital; The Russian National Research Medical University named after N.I. Pirogov

Email: valieva.sania@yandex.ru
ORCID iD: 0009-0009-6241-9142
SPIN-code: 2902-2501

MD, Dr. Sci. (Medicine), Professor

Россия, Moscow; Moscow

Valeriy V. Gorev

Morozov Children’s City Clinical Hospital; Russian Medical Academy of Continuous Professional Education

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

MD, Cand. Sci. (Medicine)

Россия, Moscow; Moscow

Igor S. Davydov

Morozov Children’s City Clinical Hospital

Email: i@davidov41.ru
ORCID iD: 0000-0003-4019-3188
SPIN-code: 9402-2169

MD

Россия, Moscow

Evgeniya V. Deeva

Morozov Children’s City Clinical Hospital

Email: evgenia.v.deeva@gmail.com
ORCID iD: 0000-0002-0352-2563
SPIN-code: 9924-0270

MD, Cand. Sci. (Medicine)

Россия, Moscow

Sergey B. Zimin

Morozov Children’s City Clinical Hospital

Email: zimin-sb@rambler.ru
ORCID iD: 0000-0002-4514-8469
SPIN-code: 4363-1578

MD

Россия, Moscow

Aleksandr E. Kessel

Morozov Children’s City Clinical Hospital

Email: kesselae@yandex.ru
ORCID iD: 0000-0001-6012-250X
SPIN-code: 4748-1308

MD

Россия, Moscow

Oleg G. Malyshev

Peoples’ Friendship University of Russia; Morozov Children’s City Clinical Hospital

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

MD

Россия, Moscow; Moscow

Aleksandr N. Pampura

Russian Medical Academy of Continuous Professional Education

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

MD, Dr. Sci. (Medicine), Professor

Россия, Moscow

Aleksandr G. Talalaev

Morozov Children’s City Clinical Hospital

Email: talalaev@mail.ru
ORCID iD: 0000-0002-0348-1925
SPIN-code: 9938-7840

MD, Dr. Sci. (Medicine), Professor

Россия, Moscow

Zhanna G. Tigay

Peoples’ Friendship University of Russia

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

MD, Dr. Sci. (Medicine), Professor

Россия, Moscow

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Supplementary files

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2. Fig. 1. Erythematous-papular rash with a merging tendency of elements, which developed in patient K.

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3. Fig. 2. Results of computed tomography of the thoracic cavity of patient K., exhibiting bronchiectasis (red arrows), foci of mosaic perfusion and decreased pneumatization (yellow arrows).

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4. Fig. 3. Histological microslides of pulmonary parenchyma, obtained during autopsy of patient K. a – bronchiole with signs of obstruction (pinhole lumen), cross-section, proliferation of connective tissue on the periphery with lymphohistiocytic infiltration; hematoxylin-eosin stain; ×20; b – bronchiole with signs of obstruction (pinhole lumen), cross-section, connective tissue proliferation on the periphery (blue stain); Masson trichrome stain ×20.

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