TY - JOUR
T1 - Interleukin (IL)-1/IL-6-Inhibitor–Associated Drug Reaction With Eosinophilia and Systemic Symptoms (DReSS) in Systemic Inflammatory Illnesses
AU - CARRA Registry Investigators
AU - Saper, Vivian E.
AU - Tian, Lu
AU - Verstegen, Ruud H.J.
AU - Conrad, Carol K.
AU - Cidon, Michal
AU - Hopper, Rachel K.
AU - Kuo, Christin S.
AU - Osoegawa, Kazutoyo
AU - Baszis, Kevin
AU - Bingham, Catherine A.
AU - Ferguson, Ian
AU - Hahn, Timothy
AU - Horne, Annacarin
AU - Isupova, Eugenia A.
AU - Jones, Jordan T.
AU - Kasapcopur, Özgür
AU - Klein-Gitelman, Marisa S.
AU - Kostik, Mikhail M.
AU - Ozen, Seza
AU - Phadke, Omkar
AU - Prahalad, Sampath
AU - Randell, Rachel L.
AU - Sener, Seher
AU - Stingl, Cory
AU - Abdul-Aziz, Rabheh
AU - Akoghlanian, Shoghik
AU - Al Julandani, Dalila
AU - Alvarez, Marcela B.
AU - Bader-Meunier, Brigitte
AU - Balay-Dustrude, Erin E.
AU - Balboni, Imelda
AU - Baxter, Sarah K.
AU - Berard, Roberta A.
AU - Bhattad, Sagar
AU - Bolaria, Roxana
AU - Boneparth, Alexis
AU - Cassidy, Elaine A.
AU - Co, Dominic O.
AU - Collins, Kathleen P.
AU - Dancey, Paul
AU - Dickinson, Aileen M.
AU - Edelheit, Barbara S.
AU - Espada, Graciela
AU - Flanagan, Elaine R.
AU - Imundo, Lisa F.
AU - Jindal, Ankur K.
AU - Kim, Hyoun Ah
AU - Klaus, Günter
AU - Lake, Carol
AU - Lapin, W. Blaine
AU - Lawson, Erica F.
AU - Marmor, Itay
AU - Mombourquette, Joy
AU - Ogunjimi, Benson
AU - Olveda, Rebecca
AU - Ombrello, Michael J.
AU - Onel, Karen
AU - Poholek, Catherine
AU - Ramanan, Athimalaipet V.
AU - Ravelli, Angelo
AU - Reinhardt, Adam
AU - Robinson, Amanda D.
AU - Rouster-Stevens, Kelly
AU - Saad, Nadine
AU - Schneider, Rayfel
AU - Selmanovic, Velma
AU - Sefic Pasic, Irmina
AU - Shenoi, Susan
AU - Shilo, Natalie R.
AU - Soep, Jennifer B.
AU - Sura, Angeli
AU - Taber, Sarah F.
AU - Tesher, Melissa
AU - Tibaldi, Jessica
AU - Torok, Kathryn S.
AU - Tsin, Cathy Mei
AU - Vasquez-Canizares, Natalia
AU - Villacis Nunez, Diana S.
AU - Way, Emily E.
AU - Whitehead, Benjamin
AU - Zemel, Lawrence S.
AU - Sharma, Surbhi
AU - Fernández-Viña, Marcelo A.
AU - Mellins, Elizabeth D.
AU - Aamir, R.
AU - Abulaban, K.
AU - Adams, A.
AU - Lapsia, C. Aguiar
AU - Akinsete, A.
AU - Akoghlanian, S.
AU - Al Manaa, M.
AU - AlBijadi, A.
AU - Allenspach, E.
AU - Almutairi, A.
AU - Alperin, R.
AU - Amarilyo, G.
AU - Ambler, W.
AU - Amoruso, M.
AU - Angeles-Han, S.
AU - Ardoin, S.
AU - Armendariz, S.
AU - Asfaw, L.
AU - Aviran Dagan, N.
AU - Bacha, C.
AU - Balboni, I.
AU - Balevic, S.
AU - Ballinger, S.
AU - Baluta, S.
AU - Barillas-Arias, L.
AU - Basiaga, M.
AU - Baszis, K.
AU - Baxter, S.
AU - Becker, M.
AU - Begezda, A.
AU - Behrens, E.
AU - Beil, E.
AU - Benseler, S.
AU - Bermudez-Santiago, L.
AU - Bernal, W.
AU - Bigley, T.
AU - Bingham, C.
AU - Binstadt, B.
AU - Black, C.
AU - Blackmon, B.
AU - Blakley, M.
AU - Bohnsack, J.
AU - Boneparth, A.
AU - Bradfield, H.
AU - Bridges, J.
AU - Brooks, E.
AU - Brothers, M.
AU - Brunner, H.
AU - Buckley, L.
AU - Buckley, M.
AU - Bukulmez, H.
AU - Bullock, D.
AU - Canna, S.
AU - Cannon, L.
AU - Canny, S.
AU - Cartwright, V.
AU - Cassidy, E.
AU - Castro, D.
AU - Chalom, E.
AU - Chang, J.
AU - Chang, M.
AU - Chang-Hoftman, A.
AU - Chen, A.
AU - Chiraseveenuprapund, P.
AU - Ciaglia, K.
AU - Co, D.
AU - Cohen, E.
AU - Collinge, J.
AU - Conlon, H.
AU - Connor, R.
AU - Cook, K.
AU - Cooper, A.
AU - Cooper, J.
AU - Corbin, K.
AU - Correll, C.
AU - Cron, R.
AU - Curry, M.
AU - Dalrymple, A.
AU - Datyner, E.
AU - Davis, T.
AU - De Ranieri, D.
AU - Dean, J.
AU - DeCoste, C.
AU - Dedeoglu, F.
AU - DeGuzman, M.
AU - Delnay, N.
AU - DeSantis, E.
AU - Devine, R.
AU - Dhalla, M.
AU - Dhanrajani, A.
AU - Dissanayake, D.
AU - Dizon, B.
AU - Drapeau, N.
AU - Drew, J.
AU - Driest, K.
AU - Du, Q.
AU - Duncan, E.
AU - Dunnock, K.
AU - Durkee, D.
AU - Dvergsten, J.
AU - Eberhard, A.
AU - Ede, K.
AU - Edelheit, B.
AU - Edens, C.
AU - El Tal, T.
AU - Elder, M.
AU - Elzaki, Y.
AU - Fadrhonc, S.
AU - Failing, C.
AU - Fair, D.
AU - Favier, L.
AU - Fogel, L.
AU - Kitcharoensakkul, M.
AU - Schmitt, E.
AU - White, A.
AU - Yomogida, K.
N1 - Publisher Copyright:
© 2024 American Academy of Allergy, Asthma & Immunology
PY - 2024/11
Y1 - 2024/11
N2 - Background: After introducing IL-1/IL-6 inhibitors, some patients with Still and Still-like disease developed unusual, often fatal, pulmonary disease. This complication was associated with scoring as DReSS (drug reaction with eosinophilia and systemic symptoms) implicating these inhibitors, although DReSS can be difficult to recognize in the setting of systemic inflammatory disease. Objective: To facilitate recognition of IL-1/IL-6 inhibitor-DReSS in systemic inflammatory illnesses (Still/Still-like) by looking at timing and reaction-associated features. We evaluated outcomes of stopping or not stopping IL-1/IL-6 inhibitors after DReSS reaction began. Methods: In an international study collaborating primarily with pediatric specialists, we characterized features of 89 drug-reaction cases versus 773 drug-exposed controls and compared outcomes of 52 cases stopping IL-1/IL-6 inhibitors with 37 cases not stopping these drugs. Results: Before the reaction began, drug-reaction cases and controls were clinically comparable, except for younger disease-onset age for reaction cases with preexisting cardiothoracic comorbidities. After the reaction began, increased rates of pulmonary complications and macrophage activation syndrome differentiated drug-reaction cases from drug-tolerant controls (P = 4.7 × 10−35 and P = 1.1 × 10−24, respectively). The initial DReSS feature was typically reported 2 to 8 weeks after initiating IL-1/IL-6 inhibition. In drug-reaction cases stopping versus not stopping IL-1/IL-6–inhibitor treatment, reaction-related features were indistinguishable, including pulmonary complication rates (75% [39 of 52] vs 76% [28 of 37]). Those stopping subsequently required fewer medications for treatment of systemic inflammation, had decreased rates of macrophage activation syndrome, and improved survival (P = .005, multivariate regression). Resolution of pulmonary complications occurred in 67% (26 of 39) of drug-reaction cases who stopped and in none who continued inhibitors. Conclusions: In systemic inflammatory illnesses, recognition of IL-1/IL-6-inhibitor–associated reactions followed by avoidance of IL-1/IL-6 inhibitors significantly improved outcomes.
AB - Background: After introducing IL-1/IL-6 inhibitors, some patients with Still and Still-like disease developed unusual, often fatal, pulmonary disease. This complication was associated with scoring as DReSS (drug reaction with eosinophilia and systemic symptoms) implicating these inhibitors, although DReSS can be difficult to recognize in the setting of systemic inflammatory disease. Objective: To facilitate recognition of IL-1/IL-6 inhibitor-DReSS in systemic inflammatory illnesses (Still/Still-like) by looking at timing and reaction-associated features. We evaluated outcomes of stopping or not stopping IL-1/IL-6 inhibitors after DReSS reaction began. Methods: In an international study collaborating primarily with pediatric specialists, we characterized features of 89 drug-reaction cases versus 773 drug-exposed controls and compared outcomes of 52 cases stopping IL-1/IL-6 inhibitors with 37 cases not stopping these drugs. Results: Before the reaction began, drug-reaction cases and controls were clinically comparable, except for younger disease-onset age for reaction cases with preexisting cardiothoracic comorbidities. After the reaction began, increased rates of pulmonary complications and macrophage activation syndrome differentiated drug-reaction cases from drug-tolerant controls (P = 4.7 × 10−35 and P = 1.1 × 10−24, respectively). The initial DReSS feature was typically reported 2 to 8 weeks after initiating IL-1/IL-6 inhibition. In drug-reaction cases stopping versus not stopping IL-1/IL-6–inhibitor treatment, reaction-related features were indistinguishable, including pulmonary complication rates (75% [39 of 52] vs 76% [28 of 37]). Those stopping subsequently required fewer medications for treatment of systemic inflammation, had decreased rates of macrophage activation syndrome, and improved survival (P = .005, multivariate regression). Resolution of pulmonary complications occurred in 67% (26 of 39) of drug-reaction cases who stopped and in none who continued inhibitors. Conclusions: In systemic inflammatory illnesses, recognition of IL-1/IL-6-inhibitor–associated reactions followed by avoidance of IL-1/IL-6 inhibitors significantly improved outcomes.
KW - Biologic therapy
KW - Drug reaction with eosinophilia and systemic symptoms
KW - Drug-induced lung disease
KW - Hemophagocytic lymphohistiocytosis
KW - Macrophage activation syndrome
KW - Pulmonary hypertension
KW - Still disease
KW - Systemic inflammatory illnesses
UR - http://www.scopus.com/inward/record.url?scp=85201511504&partnerID=8YFLogxK
U2 - 10.1016/j.jaip.2024.07.002
DO - 10.1016/j.jaip.2024.07.002
M3 - Article
C2 - 39002722
AN - SCOPUS:85201511504
SN - 2213-2198
VL - 12
SP - 2996-3013.e7
JO - Journal of Allergy and Clinical Immunology: In Practice
JF - Journal of Allergy and Clinical Immunology: In Practice
IS - 11
ER -