Drug causes of disease Flashcards
Which drugs cause drug-induced SLE?
Dopey Minnows Eat CCHIIPPPS and alfalfa sprouts
Methyl DOPA
Minocycline (can occur 2 years after starting, young females. Associated with P-ANCA).
Etanercept (Ant-TNF’s can induce ANA or unmask native anti-dsDNA disease, usually not Anti-histone+)
Carbamazepine
Chlorpromazine
Hydralazine esp slow acetylators
Isoniazid, IVIg
Phenytoin
Procainamide esp fast acetylators
Sulfonamides
+ Quinidine
Alfalfa sprouts (L-Canavanine) can induce SLE
Especially remember MyHyPIE Minocycline Hydralazine - high risk Procainamide - highest risk Isoniazid Etanercept/TNFalpha blockers
Which drugs cause a lichenoid drug eruption?
HANG (the) dopey PCT
Hydrocholthiazide + other diuretics (spironolactone, frusemide)
Antimalarials & quinidine
NSAIDS
Gold salts
Methyldopa
Penicillamine
Captopril and other ACE inhibitors + Beta blockers
TNFα inhibitors (ifliximab, etanercept, adalimumab)
Which drugs cause a pityriasiform drug eruption?
BIG MACO Bismuth, barbiturates, Beta blockers Immunization – BCG (isotretinoin reported but not confirmed) Gold, griseofulvin Metronidazole Arsenic, Allopurinol, Aspirin, Acetaminophen (paracetamol) Captopril (pos other ACE inhibitors) Omeprazole \+ HCZ
Which drugs and other factors can flare psoriasis?
BLAIN Ace Beta-blockers Lithium Antimalarials Interferons NSAIDs ACE inhibitors
Also; TNFα inhibitors can cause palmoplantar psoriasis withdrawal of steroids Irritants - tar, dithranol UV Low calcium Infection Emotional upset
Which drugs cause Exanthematous drug eruptions?
Funny(pheny) Gent with a Gold Pen eats Carbs at the Sulphur Cafe
Phenytoin Gentamicin Gold Penicillins Carbamazepine Sulphonides (eg sulphamethoxasole in Bactrim, thiazide diuretics) Cephalosporins
T/F
Minocycline causes PPDs
False
Minocycline can pigment existing PPD and cause ITP mimicking PPD but doesn’t cause PPD
Which drugs cause PPD?
How often is PPD due to a drug?
What else apart from drugs causes PPD?
PAN AM ABCD
Paracetamol
Aspirin
NSAIDs
Ampicillin
Meprobamate (anxiolytic-causes Schamberg-like purpura)
ACEI, Beta-blockers, Ca-channel blockers, Diuretics
Drugs cause up to 14% of cases
Also;
Tartrazine food colourant
Creatine supplements
Which drugs cause an Acneiform/Papulo-pustular/folliculitis drug eruption
E-SOLIDS EGFR inhibitors Steroids OCP (esp if androgen-like progestins) Lithium Iodides Danazol/androgens SSKI
Whic drugs cause fixed drug eruptions?
BARBwire PANTS (helps remember penis is comon site and it can be painful) Barbituates Phenolphthalein laxatives Aspirin NSAIDs inc ibuprofen Tetracyclines Sulphonamides esp TMP-SMX
What are the causes of pseudoporphyria?
Naproxen is number 1 cause
Can be any of same drugs as for phototoxic rcn
NODD – Naproxen, OCP, Doxy, Dapsone
TV FANS – Tetracyclines, VitB6 (pyridoxine), Frusemide, Amiodarone/Aspirin, NSAIDs, Sulphonylureas
Also; renal dialysis
What are the drug causes of erythema nodosum?
SHOPS IN Gold Mine Sulphur drugs; Sulphonamides, sulphonylurea, SMX-TMP Halides (Bromides, iodides) OCP Penicillin Salicylates Isotretinoin, IFN-gamma NSAIDs Gold, G-CSF Minocycline
Which drugs cause gingival hyperplasia?
Phenytoin (50%)
Nifedipine (25%)
Cyclosporin (25%)
Which drugs can trigger Bullous pemphigoid?
Fluid Sores Caused By Prescriptions Frusemide Spironolactone Ciprofloxacin Beta blockers Penicillin and Penicillamine, Pembrolizumab (keytruda)
Which drugs can cause livedo reticularis?
Heparin or warfarin (intravascular thrombosis)
Quinidine (+other cause sof drug-induced SLE)
Noradrenaline (vasosconstricts)
Amantadine (causes stasis)
Interferon
Levamisole (in cocaine cut in S. America) can cause retiform pupura
Which drugs can cause eruptive xanthomas?
IP HERO - X in xanthoma like Xmen superheroes Indomethacin Prednisone HAART (O)Estrogens Retinoids Olanzapine
Which drugs can cause pompholyx?
Aspirin
OCP
IVIg
Which drugs can cause linear IgA disease?
CAVE Captopril Ampicillin (+other beta lactams penicillins), Amioderone Vancomycin, Voltaren (diclofenac) Epileptics (phenytoin)
Which drugs can cause vasculitis?
Anti BHP – biotics, hypertensives and psychotics \+ NSAIDs, aspirin \+ Derm drugs; Retinoids Dapsone tetracyclines MTX, CsA, AZA, cyclophos Anti-TNFs
What are the Drug/toxin causes of PPK?
IV TALC, Flu vac BaCH
Iodine, Imatinib
Verapamil, Venlafaxine
TNFα inhibitors (can be palmoplantar psoriasis)
Arsenic
Lithium
Ca channel blockers
‘flu vaccination
BRAF inhibitors - vemurafenib, dabrafenib
Chronic hand-foot syndrome;
- 5-FU and Prodrugs; capecitabine, tegafur
Hyperkeratotic hand-foot syndrome reaction (HFSR);
- multikinase inhibitors; sorafenib>pazopanib
Which drugs can cause acquired icthyosis?
Fishy SNACcH (Ichthyosis means fish scales) Statins Nicotinamide Allopurinol Cimetidine Clofazamine Hydroxyurea
Which drugs can cause a widespread eruption resembling generalised pustular psoriasis
Halides
TNFα inhibitors
Photosensitizing drugs?
ie causes of phototoxic drug eruptions, pseudoporphyria or photo-onycholysis
Think of Adam and Eve in the sun - whats their twitter? AT FIG PANTS Amioderone Thiazides Frusemide Itraconazole Griseofulvin Psoralens, phenothiazine Acitretin, isotretinoin NSAID;esp proprionic acid derivative;naproxen, piroxicam Tetracyclines (doxy), topical calcineurin inhibitors Sulphonamides
Drugs causing pemphigus?
Thiols + ABC PIN Thiols – Captopril, Ramipril, Penicillamine, Gold, Piroxicam (Feldene, an NSAID) ACEI + ARIIB Beta lactams Chloroquine + HCQ Propanolol IFN Nifedpine
Drugs can induce or exacerbate pemphigus vulgaris or folliaceus or erythematosus or herpetiformis
Folliaceus most common drug-induced type
Onset is weeks-months after drug started
Half of pts with thiol-drug induced disease improve quickly after drug withdrawn
Only 15% of those caused by non-thiols do so
Drugs causing SJS/TEN?
SATAN
Sulphur drugs – co-trimoxazole, sulphonamides
Allopurinol – esp if dose >200mg/day or renal impairment
Tetracyclines
Anticonvulsants - barbiturates, phenytoin, lamotrigine, carbamazepine
NSAIDs (esp COX2 + oxicams), Nevirapine
Drugs causing SCLE?
GATCH Griseofulvin, terbinafine ACEI TNFα inhibitors Ca channel blockers HCZ - Thiazides
Also; NSAIDs Docetaxel, 5-FU + prodrugs IFN statins
Drugs which cause skin pigmentation?
Sumphasalazine turns skin yellow-orange The rest go shades of grey/brown/black/blue Amioderone Minocycline, doxycycline HCQ (antimalarials) Hydroxyurea clofazimine chlorpromazine, imipramine phenytoin Bismuth Silver (argyria), Gold Alkylating agents (cyclophosphamide etc) bleomycin, doxorubicin, danorubicin Antimetabolites - 5-fU, capecitabine, MTX, hydroxyurea OCP - melasma Iron injections - local hyperpigmentation or brown discolouration hydroquinone - ochronosis
Other chemo pigmentation rcns;
Serpentine supravenous hyperpigmentation - 5-FU, Doxorubicin, Docetaxel, Vinorelbine, alkylating agents
Mucosal hyperpigmenation – 5-FU, Busulfan, cyclophosphamide, hydroxyurea
Nail hyerpigmentation – 5-FU (can cause transverse melanoncyhia), cyclophosphamide, Hydroxyurea, Daunorubicin, Doxorubicin, MTX, Bleomycin
What drugs can flare/unmask native SLE?
BIG TOPS (TOP are most important) Beta blockers Itraconazole Griseofulvin TNFα inhibitors Oestrogens, testosterone Penicillamine Sulphonamides
Drug causes of AGEP?
Do My Pits Pus Today? Diltiazem Macrolides Penicillins/beta lactams Plaquenil Terbinafine and azole antifungals
Drug causes of eosinophilic fasciitis
Phenytoin
Atorvatsatin
Simvastatin
Drug causes of pemphigus erythematosus
Mostly thiols - Captopril, Ramipril, Penicillamine, Gold, Piroxicam (Feldene, an NSAID)
gold penny ram cap
also propanolol
Which drugs can cause acute or chronic telogen effluvium?
ABCD ROME (from ASM, 2014) ACEi B-blockers anti-Coagulants anti-Depressants Retinoids (acitretin>isotretinoin) OCP/hormones Minoxidil anti-Epileptics
Drug causes of DLE
DING 5alpha Dapsone Isoniazid NSAIDs Griseofulvin, Voriconazole 5-FU + prodrugs TNFα inhibitors
Which drugs can cause all types of lupus? Unmask/flare native SLE Drug-induced SLE SCLE Chronic cutaneous LE (DLE)
Griseofulvin
TNFα inhibitors
Drug causes of (T cell) pseudolymphoma
‘Epileptic meds plus ABC’ Carbamazepine, Phenytoin, Sodium valproate ACEi, Allopurinol, Amitriptyline Beta-blockers, Benzodiazepines calcium channel blockers \+ many more in literature
Often single lesion
can cause exfoliative erythroderma
Drug-induced pseudolymphoma is almost always T cell predominant
Drug/toxin causes of anagen effluvium
3C's and T-BAG toxins Chemo – 5FU, high dose MTX, doxorubicin, bleomycin. Starts 2-4 wks into chemo Colchicine CsA Thallium Bismuth Arsenic Gold
T/F
AGEP has been triggered by Kentucky fried chicken
False
Lacquer chicken has triggered AGEP
What are the skin adverse effects of HRT?
melasma, spider naevi, pseudoporphyria, DLE, photosensitivity, pompholyx, acanthosis nigricans, urticaria, EM, contact derm to oestrogen creams or adhesive patches
Interstitial granulomatous drug eruption causes
common ABCD STAT ACEI – enalapril, lisinopril Beta blockers – atenolol, propanolol, labetolol, metoprolol Calcium channel blockers – verapamil, diltiazem, nifedepine Diuretics - Frusemide (+HCTZ) Statins – Simva, Prava, Lova TNFα blockers Antihistamines (H1 or H2), Anakinra Thalidomide, lenalidomide
Uncommon HCTZ Carbamazepine Diazepam Bupropion Ganciclovir Darifenacin Sennosides (senna) onset after months-years of taking the drug Can mimic Interstitial granulomatous dermatitis or Palisaded neutrophilic and granulomatous dermatitis clinically and histologically
Drug causes of dermatomyositis
PHD TO BOOST (the) CV
Penicillamine, Hydroxyurea, Diclofenac
Tamoxifen, TNFα blockers, Benzalkonium Chloride
Carbamazepine, cyclophosphamide, Vaccination (BCG)
- Statins sometimes included but really just cause myositis
Who is at increased risk of drug reactions?
Women
More prescribed meds
Older age
Immunosuppressed (esp immune mediated reactions – paradoxically)
Malignancy
AIDS
Connective tissue disease – Sjogrens, SLE, RA
What is a drug intolerance?
an expected drug reaction occurring to an exaggerated extent and at a lower dose than that expected to cause the reaction
What is a hapten?
A small molecule which can elicit an immune response but only when bound to a larger molecule esp a protein
What is an anaphylactoid reaction?
a reaction that involves histamine release and resembles anaphylaxis but is not caused by IgE-mediated type 1 hypersensitivity reaction
What is an idiosyncratic drug side effect?
unpredictable response not due to immunological mechanism. Can be due to a genetic variation in the metabolism pathway of the drug e.g DRESS TEN Drug-induced lupus Drug reactions in HIV pts
T/F
eskimos and Japanese are often slow acetylators
F
Fast acetylators
some Mediterranean jews are slow acetylators
T/F
Fast acetylators are at increased risk of procainamide-induced lupus-like syndrome
T
occurs due to an acetylation metabolite of procainamide
but slow acetylators more at risk or lupus-like syndrome overall
What drugs are more risky for slow acetylators?
Hydralazine – lupus like syndrome
Bactrim hypersensitivity in HIV pys
Isoniazid – pellagra-like syndrome and peripheral neuritis
Dapsone - haemolysis
Which immunological drug reactions are type 1?
– IgE mediated
– anaphylaxis, urticaria, angioedema
Which immunological drug reactions are type 2?
– Ab mediated
– petechiae in drug-induced thrombocytopenia e.g penicillins, quinine, sulphonamides
Which immunological drug reactions are type 3?
– immune complex mediated
– serum sickness, vasculitis, some urticarias
Which immunological drug reactions are type 4?
– delayed type hypersensitivty (cell mediated)
– exanthematous, lichenoid, FDE, ?SJS/TEN
T/F
Hypersensitivty means immune reaction to an drug or other exogenous agent
T
T/F
Exanthematous and urticarial are the 2 most common types of drug eruptions
T
Why should you monitor ANA + LFTs in any pt on minocycline for over 1 year?
risk of ANCA positive drug-induced lupus
check ANCA if symptomatic
What is Vancomycin red man syndrome?
specific vancomycin infusion reaction where there is flushing and may be angio-oedema AKA ‘red neck syndrome’
How long do hypersensitivity drug reactions take to appear after starting a drug?
1-3 weeks typically but can be longer
most often within 6 weeks
SJS/TEN is same time period
Serum-sickness like reaction is same time period
How long do anaphylactoid drug reactions take to appear after starting a drug?
Up to 3 weeks
contrast to mins-hrs after last dose for true urticarial and anaphylactic reactions
When do Fixed drug eruptions appear?
1st episode 1-2 wks after starting drug
subsequently 8hr - 24 hrs
T/F
An Exanthem is a widespread rash usually accompanied by fever + sometimes other systemic features
T
AKA Morbiliform or Maculopapular drug eruption
Most common type of drug eruption
pt usuallly has low grade fever
T/F
Exanthematous drug eruptions classically occur 4-14 days after starting drug
T
but can be up to 6 weeks
How is exanthematous drug eruption distinguished from viral exanthem?
often indistinguishable;
Drug eruption usually favoured in adults
Viral exanthem usually favoured in kids
Drug rcn more polymorphic;
– often confluent areas on trunk; macules, papules or urticarial lesions on limbs, can be purpuric lesions on lower legs/feet
- Can involve palms and soles, can be mainly flexural, often spares face
- Can be scarlatiniform on trunk
- Can be rubelliform
- Can be annular plaques or atypical targetoid lesions
Drug rcn more likely to be itchy
Eos in blood favours drug
- viral infcn may have high lymphocytes or sometimes neuts
Biopsy sometimes helps - in drug;
Mild superficial perivascular lymphocytic infiltrate
Eos in 30%
Lichenoid in 50%
Apart from viral exanthem what DDs should be considered in an exanthematous drug eruption?
Facial oedema and eosinophilia – think DRESS (however onset usually later; 14-40 days)
Mucosal involvement and dusky lesions – think early SJS/TEN – look for Nikolsky sign
Toxic erythemas – exclude on basis of Hx and clinical features
- Scarlet fever
- Toxic shock syndrome
- Acute GvHD
- Kawasaki disease
Still’s disease
T/F
you must always stop the presumed drug cause in an exanthematous drug eruption
F
If drug is very important and there is no substitute you can try to ‘treat through’
Be cautious in case it is in fact evolving TEN or DRESS
May progress to erythroderma if drug not stopped
What are drug and toxin causes of erythroderma?
All Bloody Scarlet + toxins Allopurinol, Ampicillin/penicillins Barbiturates, Carbamazepine, Phenytoin Sulphasalazine, Sulphonamides Arsenic, Gold, Mercury, Lithium \+ many more listed
T/F
Red man syndrome means erythroderma
F
2 specific meanings. Either;
vancomycin infusion reaction where there is flushing and may be angio-oedema
Or;
chronic erythroderma in old men of unknown aetiology often with palmoplantar keratoderma, dermatopathic LNs and high IgE ?actinic reticuloid/ chronic light reactors
T/F
Urticaria is most common type of acute cutaneous drug reaction
F
second most common after exanthematous
what are the 4 ways drugs can cause an acute urticarial eruption?
- Allergic/immunological (inc anaphylaxis) - type 1 response
- Non-allergic/non-immunological (inc anaphylactoid) – direct mast cell degranulators and other, unknown mechanisms (pseudoallergens)
- Serum-sickness like reaction w/ urticarial rash (type 3 immune rcn)
- Urticarial vasculitis (usually also type 3 immune rcn)
How can drugs cause or exacerbate chronic urticaria?
Chronic urticaria or angio-oedema e.g. ACE inhibitors
Exacerbation of chronic urticaria despite not being the original cause (esp pseudoallergens) e.g. Aspirin, NSAIDs
Which drugs are high risk for anaphylaxis?
Mainly antibiotics; Penicillins, cephalosporins, sulphonamides, tetracyclines (esp mino)
biologics
radiocontrast media
T/F
RAST testing is dangerous if testing for cause of anaphylaxis
T
have resucitation equipment ready
Useful test but limited by availability of preparations
Which drugs are direct mast cell degranulators?
Vancomycin, opiates, atrocurarium, polymixin, dextran, Iodine radiocontrast dye
(alcohol and strawberries also release histamine)
Whic drugs act as pseudoallergens to cause urticaria?
Aspirin, NSAIDs, ciprofloxacin, phenylbutazone
T/F
Aspirin is classic cause of anaphylactoid reaction
T
Which drugs cause urticarial vasculitis?
UV Makes Noisy Fun in the CBD MTX NSAIDs Fluoxetine Cimetidine Biologics Diltiazem
what is serum-sickness-like reaction?
drug reaction of unclear aetiology. May involve immune-complex deposition similar to true serum-sickness
May think of as a more acute form of urticarial vasculitis
starts 1-3 weeks after exposure
urticarial (or sometimes morbilliform) rash w/ lesions which may last >24hrs and may be tender and resolve with bruising, fever, oral oedema, lymphadenopathy, symmetrical arthralgia, myalgias, mild proteinuria
What are the causes of serum-sickness-like reaction?
drugs; Penicillins (inc amoxicillin), Cephalosporins (esp cefclor), sulphonamides, tetracyclines, ciprofloxacin, NSAIDs, carbamazepine, phenytoin, propanolol, allopurinol, barbiturates, bupropion, thiouracil Radiocontrast media Infection (esp HepB or C) Vaccinations (Hep B and tetanus toxoid) rarely foods
What drug most commonly causes angio-oedema?
ACE inhibitors - 1-2 per 1000 pts prescribed ACEI
- can occur after first dose or after years
Other are;
ARIIBs
Penicillins - 2nd most common after ACEIs
NSAIDs
radiocontrast media
monoclonal Abs,
T/F
drugs can sometimes trigger/unmask angio-oedema due to another cause
T
always consider this before ascribing reaction to drug entirely
e.g. acquired C1q esterase inhibitor deficiency
T/F
drug induced angio-oedema is more common in asian pts
F
Higher risk if black or Hx of idiopathic angio-oedema
What drug is most often responsible for anaphylaxis?
penicillin
How are drug photosensitivty reactions classified?
Classification – systemic drugs
- Phototoxicity (most common for systemic agents)
- Photoallergy (rare for systemic agents)
- Drug-induced photosensitive dermatosis e.g. lupus, pellagra, porphyria
- Drug induced UV-recall eruption
Classification – topical drugs
- Phototoxic contact dermatitis (rare for topical agents)
- Photoallergic contact dermatitis (Most common for topical agents); includes Riehls melanosis
T/F
Photoallergic drug reactions cause an exaggerated sunburn like reaction
F
Phototoxic drug reactions cause an exaggerated sunburn like reaction
T/F
Pseudoporphyria and Photo-onycholysis are variants of Phototoxic drug reactions
T
T/F
Drugs causing phototoxic reactions are also known as photosensitizers
T
which drugs most commonly cause photo-onycholysis?
psoralens, OCP, tetracyclines and fluoroquinolones
What topical drugs cause phototoxicity?
Unusual for topicals - photallergy more common
True phototoxicity should be due to UVR-activation of drug e.g. coal tar also medical dyes such as fluorescin or methylene blue
Photosensitivity to topicals is often due to thinning and inflammation of skin e.g. efudix and topical retinoids
Most contact photosensitizers are foods and plants
T/F
changing to evening dosing may be enough to prevent phototoxicity
T
if drug has short half life
T/F
photoallergic drug reactions are usually lichenoid
F
clinical and histo usually more eczematous like allergic contact dermatitis and can be bullae or vesicles. Sometimes lichenoid = lichenoid photodrug allergy
T/F
most systemic agents which cause photoallergy also cause phototoxicity
T
remember same list of ‘photosensitizers’
esp sulpha drugs and thiazides
Topical drug photoallergic reactions are a kind of allergic contact dermatitis triggered by UV exposure
T
photoallergic contact dermatitis
T/F
berloque dermatitis is a kind of photoallergic contact dermatitis
T
Typically due to fragrances containing bergapten fragrance
Bergapten is 5-methoxypsoralen and is found in the fragrance Bergamot oil as well as other fruits and plants e.g. figs (Ficus carica), celery (Apium graveolens), lemon oil, Tromso palm (H laciniatum), Queen Anne’s lace (Ammi majus), and giant Russian hogweed (H mantegazzianum)
T/F
Topical steroids are the most common topical drug photoallergens
F
Oxybenzone (a benzaphone sunscreen) is most common topical photoallergen
which drugs can cause pellagra?
PIP
Pellagra – isoniazid, phenytoin
which drugs can cause UV-recall (photorecall) rcns?
MTX
piperacillin, tobramycin, vancomycin, ciprofloxacin
Docetaxel with or without cyclophopshamide, paclitaxel, etoposide, suramin, sorafenib
Which drugs caise ANCA positive cutaneous vasculitis?
‘wear ANKLE chains in Her Majesties Prison’
Hydralazine
Minocycline
Propylthiouracil
+ cocaine - causes ANCApos (in >80%) vasculitis that mimics WG and can have facial midline destructive lesions
List some drug causes of purpura (other than drug-induced vasculitis)
Cytotoxic drugs – BM suppression induced purpura
Bleomycin – thrombocytopenia
Aspirin – platelet inhibition
Heparin – see later re HITTs
Warfarin – increased INR
tPA assoc w/ painful purpura
TMP-SMX (bactrim) can cause an acral purpuric eruption similar to the papular-purpuric glove and socks syndrome
Numerous other drugs can cause thrombocytopenia or altered coagulation causing purpura
T/F
eosinophilia is seen in drug-induced systemic vasculitis
T
in 80%
also seen in 25% of non-drug vasculitis
What is ‘granulomatous lichenoid dermatitis’ ?
Variant of lichenoid drug eruption
Red-purple papules and plaques
Histo shows lichenoid drug eruption with granulomatous histiocytic infiltrate with multinucleated giant cells.
Usually but not always a drug induced reaction pattern esp to antibiotics, ACE inhibitors, beta blockers, statins and NSAIDs.
what is the latent period for lichenoid drug eruptions?
1 month to 3 years after starting drug
T/F
lichenoid drug eruptions resolve in 3-6 months after stopping drug
F
usually 1-4 months
but up to 2 years if due to gold
How does lichenoid drug differ clinically from LP?
older ave age of onset - 65 for drug, M=F
Generalized distribution; often spares classic LP sites
often photodistributed
mucosa usually spared
Not typical LP appearance; Can look more eczematous/psoriasiform/pityriasiform
usually no Wickham’s striae
hyperpigmentation very uncommon in drug rcn
How does lichenoid drug differ histologically from LP?
Lichenoid Drug;
Lichenoid infiltrate w/ Civatte bodies high up in epidermis
May have eos and/or plasma cells
May extend to deep vascular plexus
May be parakeratosis
May be some spongiosis
LP;
Lichenoid reaction
Mild inflammation confined to papillary dermis
w/out parakeratosis
rarely eos or plasma cells (but presence of eos doesn’t=drug)
T/F
chelation therapy is of no use in Gold drug reactions
F
Can use EDTA or dimercaprol (=BAL-British Anti-Lewisite)
- used for gold, arsenic, mercury and lead poisoning and Wilsons disease
T/F
Photoallergic drug eruptions are caused by a delayed type hypersensitivity response (Cell mediated) to a UVR-induced metabolite of the drug which acts a hapten
T
What drug is classic cause of widespread eczematous eruption which can involve flexures resembling atopic dermatitis
Carbamazepine
T/F
Eczematous drug eruptions are an exogenous eczema
F
Classified as endogenous as not due to something contacting the skin
What is systemic contact-type dermatitis medicamentosa’?
An eczematous reaction to an oral drug due to prior contact sensitization to the drug or to a cross reacting chemical
Often first or most severely affects site of prior ACD
Often symmetrical
E.g;
phenothiazines (parabens ACD)
Gentamicin (neomycin ACD)
Disulfiram (thiuram ACD)
Can be Baboon syndrome e.g. mercury, nickel, penicillins
T/F
Inhalation of tincture of benzoin (Friar’s Balsam) can cause reaction in pts sensitized to balsam of Peru
T
Kind of systemic contact-type dermatitis medicamentosa
What is ‘Endogenic contact eczema’?
ACD occurring to a substance in topical form after initial sensitization to the drug taken orally
E.g.
penicillin, methyldopa, allopurinol, indomethacin, sulphonamides, gold, quinine, clonidine, chloramphenicol, bleomycin
Which drug eruptions are neutrophilic?
Neutrophilic eccrine hidradenitis + PASH PG AGEP Sweets Halogenodermas (bromoderma, iododerma, fluoroderma)
T/F
drugs are a major cause of pyoderma gangrenosum
F v rare G-CSF or GM-CSF most common Can be Isotretinoin Possibly; MTX AZA hydralazine
T/F
Neutrophilia on blood often absent in drug-induced cases Sweets
T
may be because many due to G-CSF in neutropenic chemo patients (given to try to reverse the neutropenia)
What systemic features may be seen in AGEP?
Fever - classical feature
AKI - next most common
Liver - cholestatic or hepatitic picture, can be hepatomegally or steatosis
Lungs – hypoxia w/ bilat effusions
Rare multiorgan dysfunction–can be DIC and death
T/F
Neutrophilic eccrine hidradenitis is a neutrophilic inflammation of eccrine sweat glands triggered by drugs or rarely by infection
T
Which drugs most typically trigger Neutrophilic eccrine hidradenitis?
Chemo drugs Typically follows chemo esp cytarabine for AML – onset 1-2 weeks after chemo MTX, cyclophosphamide, anthracyclines, 5FU, bleomycin, vinca alkaloids, imatinib sites of bleomycin injection Rare causes; G-CSF (esp in HIV), paracetamol In Behcets strep, staph, gram neg bacilli, HIV
what does Neutrophilic eccrine hidradenitis look like
Erythematous papules and plaques on trunk and extremeties and face
Can be linear, annular, targetoid or polymorphic, can be purpuric and pustular
What are the histo findings of Neutrophilic eccrine hidradenitis?
Eccrine glands show vacuolar degeneration in secretory and ductal cells sparing acrosyringium
Neutrophilic infiltrate
May see some eccrine squamous syringometaplasia (squamous metaplasia of cuboidal epithelial cells of eccrine ducts)
what is treatment of Neutrophilic eccrine hidradenitis?
stop drug if drug cause
resolves in days-weeks
steroids orally if severe
dapsone
T/F
aromatic anticonvulsants; phenytoin, carbamazepine and phenobarbitol cross react in 40-80% of cases
T
Non-aromatics usually don’t; sodium valproate, topiramate, Gabapentin, levetiracetam, ethosuximide, tiagabine
T/F
fixed drug eruptions are due to humoral immunity mechanisms?
F
cell-mediated
what are most common sites for FDE?
face, lips, hands, feet, genitals
can be intraoral
trunk rare
In FDE rechallenge always results in return of rash at same site
F
Usually at exactly same site and sometimes at additional sites
but may be a refractory period when readministration doesn’t cause a reaction
T/F
generalized FDE is a morbiliform rash rather than a macule
F
means many typical lesions of FDE
which drugs high risk for FDE?
SCANT Sulphonamides esp TMP-SMX Cacium channel blockers Aspirin NSAIDs inc ibuprofen Tetracyclines
T/F
histo can differentiate drug-induced linear IgA disease from sporadic form
F
clinical and histo the same
always think of drugs as many reported drug causes
e.g.
CAAVVE – Captopril, Ampicillin, Amioderone, Vanc, Voltaren, Epileptics
Resolves in 2-5 wks after stopping drug
T/F
drug induced types account for 20% of all pemphigus
F
up to 10% of pemphigus cases in developed countries
T/F
direct and indirect may be negative in drug-induced pemphigus
T
esp if penicillamine cause;
perilesional direct IF negative in up to 10% of penicillamine induced pemphigus
Sometimes indirect IF also negative – 30% of penicillamine cases but is more often posiitve the same frequency as sporadic forms
T/F
thiols account for 80% of drug induced pemphigus cases
T
captopril, Ramipril, penicillamine, gold, Piroxicam (Feldene, an NSAID)
T/F
drug-induced BP affects younger pts than sporadic BP
T
what is Symmetrical Drug-Related Intertriginous and Flexural Exanthem (SDRIFE)
A drug allergy rash without systemic symptoms which may be called baboon syndrome.
Most often due to antibiotics or contrast media
Criteria are ;
Exposure to a systemic drug but not chemo agent – can occur after initial or repeated dose
Sharply demarcated area of gluteal/perianal area and/or V-shaped erythema of genital/ inguinal area
At least one other flexural site involved
Symmetrical
No systemic signs or symptoms
what are DDs of SDRIFE?
Systemic contact type dermatitis Baboon syndrome
Toxic erythema of chemotherapy
T/F
Pseudolymphomatous drug hypersensitivity syndrome is a drug eruption which simulates lymphoma clinically and histologically
T
which drugs cause Pseudolymphomatous drug hypersensitivity syndrome?
what is the natural history?
Anticonvulsants – phenytoin, carbamazepine, phenobarbital, mephenytoin, valproate, trimethadione
Antipsychotics – chlorpromazine, promethazine
ACEIs and ARIIBs
Allopurinol
Imatinib
Ibuprofen/NSAIDs
Starts weeks – years after starting drug; mostly in first 7 weeks
Completely resolves within weeks of stopping drug, sometimes takes months
what are clinical features of Pseudolymphomatous drug hypersensitivity syndrome?
Lesions on skin are solitary or multiple and can be localized or widespread
Red-violet papules, plaques or nodules
Can present as erythroderma – looks like Sezary syndrome
Often lymphadenopathy
What is histo of Pseudolymphomatous drug hypersensitivity syndrome?
What features help distinguish from true lymphoma?
Histo
Dense lymphocytic infiltrate in dermis mimics lymphoma
Can be band-like and mimic MF
Mainly T cells, usually polyclonal
Nuclei may look atypical with cerebriform outline
Can be epidermotropism and Pautrier-like microabscesses
Features which help distinguish from true lymphoma;
spongiosis, apoptotic keratinocytes, papillary dermal oedema, eos in epi, RBCs
T/F
Interstitial granulomatous drug reaction is easily distinguished from Interstitial granulomatous dermatitis or Palisaded neutrophilic and granulomatous dermatitis clinically and histologically
F
clinical and histo mimics these - always consider drug and try to stop meds
What is the cause of Warfarin (coumarin/coumadin) skin necrosis?
who is at risk?
whta are clinical features and management?
Due to reduced protein C function causing coagulation and ischaemic infarcts
inc risk if hereditary protein C deficiency (protein C and S are vit K-dependent and are inhibited by warfarin more quickly than the anticoagulant effect esp protein C as short half life)
1 in 10,000 warfarin pts
Esp pts in 50s-60s
F:M = >4:1
Usually starts 2-5 days after starting drug
Starts as pain then red, painful plaques esp breast, thighs, buttocks
Turn into haemorrhagic blisters and necrotic ulcers or eschar
Stop warfarin
Reverse with vitamin K
Give heparin to anticoagulate (as still need anticoagulation)
Can give intravenous protein C concentrates or activated protein C
T/F
Warfarin blue toe syndrome is due to Coumadin necrosis
F
Due to cholesterol emboli due to anticoagulation – not limited to warfarin alone
T/F
Heparin Induced Thrombocytopenia (+ Thrombosis) Syndrome is a cell mediated reaction
F
antibody mediated;
binding of antibodies to heparin and platelet factor 4 to form PF4/heparin complexes (HIT complexes) which stimulate platelet aggregation and consumption
5-30% of pts who develop HIT-IgG Abs will develop clinical HIT(T)S
T/F
HITS/HITTS is only cuased by unfractionated heparin
F
can be UFH or Lmolwt Heparin
T/F
It is safe for pts with HITS/HITTS to be given warfarin
F
Don’t use warfarin/Coumadin as can precipitate limb gangrene due to initial prothrombotic effects
can give dabigatran, danaparoid, lepirudin, argatroban
T/F
Pts who had HITS/HITTS more than 100 days ago may not get it again if rechallenged
T
but high risk if less than 100 days ago
T/F
In HITS/HITTS Drop in platelet count but may not be apparent unless there is a pre-treatment baseline
and a drop of >50% should lead to suspicion of HIT
T
T/F HITT syndrome (the thrombotic variant) causes cutaneous necrosis which occurs at injection sites and at distant sites including internal organs e.g. CNS (stroke), MI, PE
T
skin lesions are macular purpura with central necrosis and retiform extensions at the margins
which drugs can cause isolated mucosal ulceration?
Nicorandil, penicillamine, gold, phenylbutazone, captopril, phenindione, piroxicam, phenobarbitol and topical bleach (sodium hypochlorite)
Foscarnet can cause penile urethra ulceration by contact toxicity as excreted
T/F
chemo drugs usually cause hair loss by triggering telogen effluvium
F
most often anagen effluvium, rarely TE
e.g. Antimetabolites, vinca alkaloids, alkylating agents, topoisomerase inhibitors
also arsenic, gold, bismuth
NB - most non-chemo drug alopecia is due to acute or chronic telogen effluvium
Bisulfan causes characterisitic irrevrsible hairloss
T/F
anabolic steroids are the main drug cause of hirsuitism
T also; Combing Cheeks Makes Pam Angry • Corticosteroids • Cyclosporin • Minoxidil • Phenytoin • Androgens
Which drugs cause hypertrichosis?
cyclosporine, phenytoin, minoxidil, diazoxide, corticosteroids, androgens, penicillamine, psoralens, streptomycin
Also Bimatoprost (lumigan, latisse) eye drops which cause eyelash growth
trichomegaly of eyelashes also caused by EGFR inhibitors
(long, thick, rigid hairs)
what effect does chloroquine have on hair?
Reversible greying in red/blonde haired people
what effect does etretinate have on hair?
darkening, lightening, curling, kinking
What are effects of retinoids on nails?
thinning, fragility, onycholysis, onychoschizia, nail shedding, onychomadesis, ingrowing nails, periungual granulation tissue, paronychia
What are effects of tetracyclines on nails?
yellow discolouration + onycholysis + photo-onycholysis
Psoralens cause same things
what drugs cause gingival hyperplasia?
CsA, nifedipine, phenytoin, felodepine, verapamil, diltiazem
what are ‘Ara-C ears’?
bilateral red swollen ears due to Cytarabine
which chemo drugs cause inflammation of ‘keratoses’?
AKs – 5-FU, capecitabine, pentostatin
Seb Ks – Cytarabine, Taxanes
DSAP – 5-Fu + prodrugs, Taxanes
T/F
Doxorubicin (with ketoconazole) can cause sticky skin
T
Acquired cutaneous adherence
can also be caused by retinoids
what is serpentine supravenous hyperpigmentation ? what drugs are responsible?
sclerosis and hyperpigmentation along the vein following IV infusion
- 5-FU, Doxorubicin, Docetaxel, Vinorelbine, alkylating agents
What is Taxane-induced HFS?
distinct subtype of acral ertyhema (HFS)
5-10% ot pfts on taxanes e.g. Docetaxel, Paclitaxel
Erythematous plaques on dorsal hands, achilles tendons and malleoli (not palms and soles like in other drugs so nota cause of PPK)
+ often have associated nail toxicity
– onycholysis, Beau lines, nail melanosis, subungual haemorrhage, paronychia.
What are AEs of EGFR inhibitors?
Eg. Cetux, pmab, erlotinib, gefitinib
‘EGFR makes(MEK) a fast car’ (rhymes) - if you have a fast car you get ‘MPH PRIDE’
Mucositis
Photosensitivity
Hair changes eg hypertrichosis, hirsuitism, trichomegally of eyelashes + Alopecia (androgenetic or rarely scarring)
Papulopustular eruption
Regulatory changes in hair
Itching
Dryness
Easy breaking nails (brittle) + paronychia + onycholysis + pyogenic granulomas
NB; MEK inhibitors have same side effects eg. Seletanib, trametinib
What are AEs of BRAF inhibitors?
Eruptions (75%)
squamoproliferative lesions - kAs, SCCs, verrucal keratoses
photosensitivity
KP-like reaction, seb derm-like eruption,
Grover’s
hyperkeratotic hand-foot reaction, panniculitis, melanocytic lesions, vitiligo
Cymotrichous (wavy hair)
what are the grades of hyperkeratotic hand foot sundrome due to multikinase inhibitors?
what is the mangement of each grade?
E.g. Sorafenib, sunitinib, pazopanib, vandetanib
Grade 1 – painless mild changes. Rx: emollients, keratolytics, gel/foam shoe inserts
Grade 2 – painful changes limiting instrumental ADLs. Rx: as for grade 1 + potent TCS for 7-10 days and consider 50% dose reduction
Grade 3 – severe pain and limits self-care ADLs. Rx: as per grade 2 + local antiseptic baths + stop drug for at least 1 week and restart when HFSR toxicity grade 0/1
T/F
combined use of BRAF and MEK inhibitor has worse side effect profile than either alone?
F AE profile than single agent therapy but regular derm check ups still recommended Much lower SCC risk Much lower verrucal keratosis risk Much lower Grover’s disease risk Increased folliculitis Other AEs at similar rates
T/F
side effect profile of MEK inhibitors same as BRAF inhibitors
F
same as EGFR inhibitors
what are cutaneous AEs of mTOR inhibitors such as rapamycin?
Mouth ulcers
Inflammatory eruptions – common. Can be morbilliform, eczematoid or acneiform. Erythematous follicular pustules and papules most common. Onset first 2 wks. Trunk>limbs>face. Variable histo. Onset, course + Rx similar to EGFR inhibitor rash.
Others – nail toxicity esp paronychia, pyogenic granuloma-like lesions, alopecia, facial hypertrichosis, poor wound healing, pruritus, xerosis, oedema, vasculitis.
what are main mucocutaneous AEs of vismodegib?
alopecia (60%) - usually mild
dysguesia (up to 75%) - treat w/ zinc
What are the major AEs of imunomodulatory agents; Ipalimumab (CTLA-4 inhibitor used for melanoma) and programmed death 1 inhibitors (Nivolumab, Pembrolizumab)
Autoimmune dermopathy (40%) is most common immune side effect, followed by colitis.
Pruritis in 30% or fewer, morbilliform eruption in 10-50%
Vitiligo-like melanoma-associated hypopigmentation – portends good prognosis
Rarely – prurigo nodularis, lichenoid exanthems, papulopustular eruptions, pyoderma-gangrenosum-like ulcerations, photosensitivity, XRT recall, DRESS, TEN
Also; diarrhoea/colitis, pruritus/dermatitis, endocrine problems/hypophysitis, hepatitis, neuritis, death (esp from severe colitis)
Symptoms mainly dose-dependent and resolve after Rx
Drug reactions are common in HIV and independent of CD4 count
F
common but more so if CD4 count between 100-400
what are AEs of multikinase inhibitors eg sorafenib?
Inflammatory eruptions
Hyperkeratotic hand-foot skin reaction (HFSR)
stomatitis
hair changes
genital eruptions eg psoriasifrom rash
Uncommon;
seb-derm like facial rash, yellowing of skin, facial oedema, pyoderma gangrenosum-like lesions, eruptive naevi, hyperkeratotic squamoproliferative lesions like in BRAF inhibitors, asymptomatic nail splinter haemorrhages, acute folliculitis, dryness, photosensitivity
whta drugs cause SJS/TEN or DRESS?
Sulphur drugs – co-trimoxazole, sulphonamides
Allopurinol
Tetracyclines
Anticonvulsants - barbiturates, phenytoin, lamotrigine, carbamazepine
NSAIDs - esp COX2 + oxicams
In what conditons can you see a Jarisch-Herxheimer reaction?
Classically associated with penicillin treatment of early syphilis Also seen in; Borreliosis/erythema chronicum migrans (penicillin or minocycline) Leptospirosis Onchocerciasis (diethylcarbamazine) Strongyloides (thiabendazole) Q fever Bartonellosis & cat scratch disease Brucellosis Tularaemia Typhoid fever Trypansomiasis
What is the Wolff-Chaikoff effect?
Ingesting large amounts of iodine inhibits iodination of thyroglobulin in the thyroid and thyroid hormone levels are reduced.
Can occur when using potassium iodide
Patients on KI may also get an iodide goitre
which drug can cause Dupuytrens contracture?
Phenytoin
the ‘pyt’ in both words is very similar
T/F
starting TNFα blockers can trigger frontal fibrosing alopecia
T
which drugs can cause hypertrichosis?
Phenytoin, cyclosporine, EGFR inhibitors
oral or topical minoxidil
systemic or topical corticosteroids
topical latanoprost
what are skin side effects of BRAF inhibitors?
GP VACKS Grovers of folliculitis PPK, Panniculitis, Photosensitivity Vitiligo, Verrucal keratoses, Verruca vulgaris AK, Acneiform rash, Alopecia Cysts, Cymotrichous (wavy hair) Keratosis Pilaris SCC
Lithium can trigger or flare which skin conditions?
Psoriasis
Dariers
HS
What loop diuretic can be recommended for pts who develop allergy to frusemide?
Ethacrynic acid
Unlike the other loop diuretics, ethacrynic acid is not a sulfonamide and thus, its use is not contraindicated in those with sulfa allergies
Which drugs cause a scarletiniform drug eruption?
penicillin, beta lactams, allopurinol, barbiturates, codeine, quinidine, mercury, indandiones
