The Drug-Induced Respiratory Disease Website and App

Pembrolizumab

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), acute and/or severe (may produce the ARDS pattern)

I.b

Pneumonitis (interstitial lung disease/ILD)

I.c

Eosinophilic pneumonia (pulmonary infiltrates and eosinophilia)

I.d

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

I.f

Acute fibrinous organizing pneumonia (AFOP)

I.m

ILD with a granulomatous component

I.o

Focal/localized area of pneumonitis/fibrosis

I.y

Progression, acceleration or exacerbation of preexisting ILD/fibrosis

I.ad

Radiation recall pneumonitis

II - Pulmonary edema - Acute lung injury - ARDS

II.b

ARDS - Acute lung injury

III - Pulmonary/alveolar/airway hemorrhage/bleeding

III.h

Major/massive hemoptysis

III.l

Alveolar hemorrhage, localized (e.g. lobar)

IV - Airway involvement

IV.a

Bronchospasm - Wheezing - Asthma

IV.c

Obliterative bronchiolitis (a pattern consistent with) (see also IVn, XVx)

IV.d

Cough (lone)

IV.j

Bronchiolitis (a clinical-imaging pattern suggestive of)

IV.k

Bronchiectasis

IV.n

Obstructive airway dysfunction (see also IVc, XVx)

IV.t

Sptutum production - Bronchorrhea - 'Bronchitis'

IV.y

Eosinophilic airway disease (asthma, bronchitis, bronchiolitis)

IV.ab

Exacerbation or deterioration of preexisting COPD

IV.ac

Exacerbation or deterioration of preexisting asthma

IV.ad

Large airway inflammation - Tracheitis (w/wo tissue eosinophilia)

IV.al

Sputum production - Bonchorrhea - ‘Bronchitis’

V - Pleural and/or pericardial involvement

V.m

Pleuropericarditis - Pleuropericardial effusion (ANA unknown or negative)

VI - Pulmonary vasculopathy

VI.a

Pulmonary embolism - Venous thrombosis/thromboembolism

VI.b

Pulmonary arterial hypertension

VII - Mediastinal involvement

VII.a

Lymphadenopathy (intrathoracic)

VII.e

Granulomatous mediastinal lymphadenopathy

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

VIII.q

Tongue involvement (edema, glossitis, hematoma)

VIII.t

Vocal cord paresis/paralysis

IX - Neuromuscular / CNS involvement - Disordered breathing (during sleep)

IX.r

Myasthenia gravis - Myasthenic-like syndrome

X - Systemic/Distant conditions, syndromes and reactions

X.b

Antiphospholipid antibodies w/wo the APL syndrome

X.c

Capillary leak syndrome (CLS)

X.d

Lupus - Lupus syndrome (see also Vd)

X.f

Anaphylaxis-Anaphylactoid reaction (can be fatal)

X.g

Hypersensitivity reaction (may manifest with fever and/or skin, throat or airway involvement)

X.j

Myopathy-Myositis-Polymyositis (see also under Xba)

X.k

Sarcoid-like granulomatosis (endo-/extrathoracic)

X.m

Vascultis (pulmonary, extrathoracic or systemic)-ANCA status unknown or negative)

X.s

Vasculitis, pulmonary (w/wo AH), extrapulmonary, systemic: ANCA-positive

X.ah

Granulomatosis with polyangiitis (typically ANCA pos.) - GPA flare

X.an

Cytokine release syndrome - Cytokine storm

X.aw

Connective tissue disease

X.ax

Scleroderma

X.ay

Polymyalgia rheumatica

X.bi

Temporal arteritis (Horton’s)

XI - Miscellaneous

XI.d

Metabolic acidosis (incl. lactic acidosis/-gap). May cause hyperpnea/dyspnea

XI.n

Neutropenia, agranulocytosis (w/wo infection/sepsis)

XII - Cardiovascular involvement / toxicity

XII.a

Left or biventricular dysfunction/failure

XII.c

Pericardial effusion (w/wo tamponade)

XII.d

Myocarditis (can be fulminant)

XII.r

Heart failure (biventricular, congestive)

XII.s

Heart block (bundle branch- or AV-)

XV - Pathology

XV.a

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

XV.b

Path: Eosinophilic pneumonia (subacute or acute) (see also Ic)

XV.c

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

XV.d

Path: Acute fibrinous organizing pneumonia (AFOP-pattern) (see also pattern If)

XV.e

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

XV.f

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

XV.x

Path: Acute/subacute bronchiolitis (see also IVc, IVi)

XV.bb

Path: Airway inflammation

XV.ca

Path: Myocarditis

XV.cw

Path: Myocardial vasculitis

XVI - Imaging

XVI.b

Imaging: Ground-glass opacities (GGO) / shadowing

XVI.e

Imaging: Pulmonary opacities with a subpleural distribution

XVI.k

Imaging: An area or areas of consolidation

XVI.v

Imaging: Centrilobular micronodules (can be diffuse)

XVI.z

Imaging: A large nodule or a mass

XVI.ai

Imaging: A 'tree-in-bud' pattern

XVII - Infections & related conditions

XVII.c

Aspergillosis, pulmonary (invasive, allergic [ABPA], or mycetoma)

XVII.g

Tuberculosis (pulmonary, pulmonary, extrapulmonary or disseminated). Reactivation or de novo

XVII.o

Nocardia pulmonary/systemic infection

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

XIX.a

BAL: An excess proportion of lymphocytes

XIX.b

BAL: An excess proportion of neutrophils