5. Rare adverse effects detected by separate adverse event search.

Intervention	Rare severe adverse effects
PUVA	transient lymphomatoid papulosis (Aronsson 1982) basal cell carcinoma/squamous cell carcinoma (Herrmann 1995) squamous cell carcinoma (Molin 1981) cataract (Rupoli 2005)
extracorporeal photopheresis	sarcoma (Korpusik 2007)
imiquimod	no reported SAEs found
electron beam	total epilation (Braverman 1987, Desai 1988), nail dystrophy/oedema of hands and feet/bullae dorsum and feet/conjunctivitis/hospitalisation due to skin ulcers (Desai 1988) diffuse permanent telangiectasia/linear sclerosis/Ischaemic ulceration of finger tips (Micaily 1983)
cyclophosphamide, doxorubicin, etoposide, vincristine	haematological toxicity: febrile neutropenia/staphylococcal bacteraemia/disseminated herpes infection/pneumocystis carinii pneumonia/neurologic toxicity grade 3/decreased left ventricular ejection fraction (Akpek 1999) pulmonary embolism and death due to drug‐related cardiac infarction reported for doxorubicin monotherapy (Dummer 2012) nephrotic syndrome (Kairouani 2012) acute nonlymphocytic leukaemia reported for combination of CHOP with TSEBT (Kaye 1989) reticulated generalised skin pigmentation reported for combination of cyclophosphamide with prednisone (Youssef 2013)
active transfer factor	no reported SAEs found
methotrexate	severe oedematous erythroderma/denudation on the trunk and extremities/Interstitial pulmonary fibrosis (Zackheim 1996) epidermal necrosis (Mna 2016)
interferon‐alpha	acrocyanosis (Campo‐Voegeli 1998) oropharyngeal lichen planus (Kütting 1997) seizures (Legroux‐Crespel 2003) fatal neutropenia and sepsis (Vegna 1990) liver toxicity (Rupoli 2005, Simoni 1987, Vegna 1990) generalised urticaria in association with angio‐oedema (Hüsken 2012)
bexarotene	neutropenia/non‐ST‐elevation myocardial infarction/elevated liver enzymes (Abbott 2009) lethal sepsis (Bohmeyer 2003) pancreatitis (Duvic 2001b) bleeding gastric ulcer (Sokolowska‐Wojdylo 2016)
peldesine (BCX‐34)	no reported SAEs found
denileukin diftitox (ONTAK)	capillary leak syndrome (Duvic 2002 and Duvic 2013, Talpur 2012) lethal vascular leak syndrome with rhabdomyolysis (Avarbock 2008) grade 4 infusion event (Foss 2001) visual changes (McCann 2012)
nitrogen mustard	urticaria and anaphylactoid reaction (Daughters 1973, Grunnet 1976, Sanchez 1977) local bullous reaction (Goday 1990) perforating follicular mucinosis (Guilhou 1980) Stevens‐Johnson‐Syndrome (Newman 1997) cutaneous squamous/basal cell carcinoma (Hoppe 1987)
brentuximab vedotin	peripheral neuropathy (Duvic 2015, Corbin 2017) unstable angina or myocardial infarction, pulmonary embolism (Duvic 2015) progressive multifocal leukoencephalopathy (Carson 2014) acute renal failure (Kim 2015)
lenalidomide	thrombocytopenia, pneumonitis, fatigue, dyspnoea, cognitive disturbance, respiratory failure, seizure (Dueck 2010a) anaemia, lymphopenia, neutropenia, cardiac ischaemia/infarction‐acute myocardial infarction, hypoxia‐respiratory failure, rash, supraventricular arrhythmia (Toumishey 2015) pneumonitis, fatigue, cognitive disturbance, dyspnoea (Dueck 2010a, Toumishey 2015)