The Drug-Induced Respiratory Disease Website and App

Methotrexate

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 (interstitial lung disease/ILD)

I.b

Pneumonitis (ILD), acute and/or severe (may cause ARDS)

I.c

Eosinophilic pneumonia (pulmonary infiltrates and eosinophilia)

I.e

Organizing pneumonia pattern (an area or areas of consolidation on imaging)

I.g

Pulmonary fibrosis

I.i

Subclinical pulmonary infiltrates/ILD

I.l

Lung nodule or nodules

I.m

Diffuse alveolar damage (DAD) (see alsoo under IIb and XVf)

I.n

ILD with a granulomatous component

I.r

Pulmonary nodulosis

I.w

Abnormal lung function/pulmonary physiology (PFTs) without necessarily imaging or clinical evidence

I.x

Rapidly progressive ILD/pulmonary fibrosis (Hamman-Rich syndrome)

I.ab

Delayed ILD, -pneumonitis, -fibrosis

II - Pulmonary edema - Acute lung injury - ARDS

II.a

Pulmonary edema, noncardiogenic (NCPE)

II.e

ARDS - Acute lung injury

III - Pulmonary/alveolar./airway hemorrhage/bleeding

III.a

Alveolar hemorrhage (AH), diffuse AH (DAH)

IV - Airway involvement

IV.a

Bronchospasm - Wheezing - Asthma

IV.ab

Cough (lone)

V - Central-large-upper airway (incl. pharyngeal-nasal) involvement

V.a

Angioedema (may cause UAO, asphyxia and death)

V.ak

Endobronchial lymphoproliferative disorder

VI - Pleural and/or pericardial involvement

VI.a

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

VI.b

Eosinophilic pleural effusion

VI.e

Hemothorax - Serosanguineous pleural effusion

VI.i

Pleuritis (can cause chest pain)

VI.n

Hemopericardium - Bloody pericardial effusion

VI.t

Serositis - Polyserositis

VII - Pulmonary vasculopathy

VII.a

Pulmonary embolism - Venous thrombosis/thromboembolism

VIII - Mediastinal involvement

VIII.a

Lymphadenopathy (intrathoracic)

X - Systemic/Distant conditions, syndromes and reactions

X.a

DRES syndrome - DRESS-like reaction

X.f

Anaphylaxis-Anaphylactoid reaction (can be fatal)

X.m

Sarcoid-like granulomatosis (endo-/extrathoracic)

X.w

Multiple organ dysfunction/failure (MODS/MOF)

XI - Miscellaneous

XI.b

Chest pain (acute or subacute), lone or prominent

XI.c

Pleuritic chest pain

XII - Cardiovascular involvement / toxicity

XII.c

Pericardial effusion (w/wo tamponade)

XVI - Imaging

XVI.b

Imaging: Ground-glass opacities (GGO) / shadowing

XVI.k

Imaging: An area or areas of consolidation

XVI.w

Imaging: Lung nodule or nodules

XVI.be

Imaging: Intrathoracic lymph node enlargement

XVIII - Cytological, biochemical features of/in BAL, pleural fluid or FNA

XVIII.a

BAL: An excess proportion of lymphocytes

XVIII.b

BAL: An excess proportion of neutrophils

XVIII.c

BAL: An excess proportion of eosinophils

XIX - Pathology

XIX.a

Path: NSIP-cellular pattern (see also Ia, Ib)

XIX.d

Path: Organizing pneumonia (OP/BOOP) pattern (see also Id)

XIX.f

Path: ILD with a granulomatous component (see also Im)

XIX.o

Path: Diffuse alveolar damage (DAD-pattern) (see also IL)

XIX.q

Path: Pneumocyte atypia (reactive epithelial cells) (a.k.a. the "Napoleon Hat" sign)

XIX.t

Path: Pulmonary edema (see also II/IIa)

XIX.v

Path: NSIP-fibrotic pattern

XIX.ck

Path: Lymphoproliferative disease, endothoracic

XX - Infections & related conditions

XX.b

Opportunistic pulmonary/systemic infections

XX.d

Pneumocystis jiroveci pulmonary colonization

XX.e

Pneumocystis jiroveci pneumonia

XX.h

Nontuberculous pulmonary mycobacterial infection/superinfection

XX.q

Viral pneumonia

XXI - Neoplastic conditions

XXI.b

Lymphoproliferative disease (pulmonary, endobronchial, endothoracic)

XXI.g

Lymphomatoid granulomatosis (pulmonary, endothoracic)

XXI.k

Lymphoproliferative disease (extrathoracic)