Philippe Camus, M.D.

Dijon, France

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The Drug-Induced Respiratory Disease Website and App

All-transretinoic acid (ATRA)

The PML-RAR inhibitor ATRA or tretinoin can cause the ATRA- or differentiation syndrome with dyspnea, fever, weight gain, hypotension, pulmonary infiltrates and hypoxemia, pulmonary edema, ARDS or DAH w/wo capillaritis. Imaging features at PMID 11804921

Frequency - Incidence

Incidence of respiratory adverse event(s) due to the specific drug as assessed by number of reported/published cases in the literature. Red digits in stars indicate: 0 = Very rare, questionable signal · 1 = < 10 cases · 2 = 10-50 cases · 3 = 50–100 cases · 4 = 100-200 cases · 5 = >200 cases

Evidence level/grade

Evidence level for respiratory adverse event(s) due to the specific drug as estimated using Hill’s (1965), Naranjo’s (1981), and Bégaud’s (1985) criteria applied to published cases. Blue digits in stars indicate: 0 = Questionable · 1 = Low · 2 = Moderate · 3 = Robust · 4 = Definite · 5 = Unquestionable, pathognomonic

I - Interstitial/parenchymal lung disease

I.a

Pneumonitis (ILD)
I.l

Lung nodule or nodules

II - Pulmonary edema - Acute lung injury - ARDS

II.a

Pulmonary edema, noncardiogenic (NCPE)
II.e

ARDS - Acute lung injury
II.h

Hypoxemia, low oxygen saturation (may occur in isolation)
II.l

Pulmonary edema/ARDS of the ATRA syndrome (see Xab)

III - Pulmonary/alveolar./airway hemorrhage/bleeding

III.a

Alveolar hemorrhage (AH), diffuse AH (DAH)

VI - Pleural and/or pericardial involvement

VI.a

Pleural effusion (uni- or bilateral) (can accompany DI-LDs)
VI.m

Pleuropericarditis - Pleuropericardial effusion (ANA unknown or negative)

VII - Pulmonary vasculopathy

VII.a

Pulmonary embolism - Venous thrombosis/thromboembolism
VII.d

Pulmonary vasculitis or capillaritis

X - Systemic/Distant conditions, syndromes and reactions

X.q

Neutrophilic dermatosis (Pyoderma, Sweet syndrome)
X.ad

The differentiation- or ATRA syndrome

XII - Cardiovascular involvement / toxicity

XII.c

Pericardial effusion (w/wo tamponade)