Cutaneous Drug Eruptions Flashcards

1
Q

Skin eruption is one of the most common adverse drug reactions - T/F?

A

True - About 30% of adverse drug reactions are cutaneous

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2
Q

What is the range of severity of cutaneous drug reactions?

A

Wide range which mimic a wide variety of skni conditions from a mild rash to life threatening toxic epidermal necrolysis

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3
Q

What are the two main types of adverse cutaneous drug reactions ?

A
  • Immunologically-mediated reactions (“allergic”)
  • Non immunologically mediated reactions (“non-allergic”)
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4
Q

Give some examples of Immunologically-mediated reactions (“allergic”)

A
  • Type I. Anaphylactic reactions - Urticaria
  • Type II. Cytotoxic reactions - Pemphigus & pemphigoid
  • Type III. Immune complex-mediated reactions - Purpura/rash
  • Type IV. Cell-mediated delayed hypersensitivity reactions - T-cell mediated. Erythema/rash
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5
Q

Give some examples of Non immunologically mediated reactions (“non-allergic”)

A
  • Eczema
  • Drug-induced alopecia
  • Phototoxicity
  • Skin erosion or atrophy from topically applied 5-fluorouracil or steroids
  • Psoriasis
  • Pigmentation
  • Cheilitis, xerosis
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6
Q

Which of the two main types of adverse drug reactions are affected by the dose of drug given ?

A

Immunologically mediated - is not affected by dosage

Non-immunologically mediated - can be affected by the dosage

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7
Q

In what patients should you consider an cutaneous drug reaction ?

A

Any patient who is taking medication and develops a symmetric skin eruption of sudden appearance.

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8
Q

What are some of the risk factors for the development of drug eruptions ?

A

•Age

Young adults>infants/elderly

•Gender

–Females>males

  • Genetics
  • Concomitant disease

–Viral infections (HIV/EBV/CMV); cystic fibrosis

Previous drug reaction or positive skin test

•Chemistry

–Β-lactam compounds, NSAIDs

–High molecular weight/hapten-forming drugs

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9
Q

What is the most common drug eruption?

A

Exanthematous Drug Eruptions (90%)

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10
Q

What specific type of drug eruption is an exanthematous drug eruption?

A

T-cell mediated delayed type hypersensitivity (Type IV) reaction.

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11
Q

What are the signs and symptoms of Exanthematous Drug Eruptions?

A
  • Usually mild & self limiting but can priogress to life-threatening reaction
  • Widespread symmetrically distributed rash which usually appears on the trunk & the spreads to the limbs & neck
  • Rash consists of pink-red flat macules or papules
  • Lesions mostly blanch with pressure
  • Mucous membranes, hair & nails are not affected
  • Pruritus (itch) is common.
  • Mild fever is common.
  • Onset is 4-21 days after first taking drug.
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12
Q

What is shown in the pic ?

A

Exanthematous drug reaction

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13
Q

What are the clinical indicators for a severe exanthematous drug reaction?

A
  • Involvement of mucous membrane and face.
  • Facial oedema & erythema.
  • Widespread confluent erythema.
  • Fever (>38.5⁰C).
  • Blisters, purpura, necrosis.
  • Lymphadenopathy, arthalgia.
  • Shortness of breath, wheezing.
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14
Q

Give some examples of the drugs associated with exanthematous drug eruptions

A

Most common drugs:

  • Beta-lactam antibiotics (penicillins, cephalosporins)
  • Sulfonamides
  • Allopurinol
  • Anti-epileptic drugs
  • NSAID’s

Note many others can cause it

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15
Q

What is the 2nd most common adverse drug reaction ?

A

Drug-induced acute urticaria

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16
Q

What is drug-induced acute urticaria ?

A

Drug-induced urticaria is the term used when urticaria is caused by a drug, most often penicillin, a non-steroidal anti-inflammatory agent (NSAID), or sulfamethoxasole in combination with trimethoprim

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17
Q

What are the clinical features of drug-induced acute urticaria ?

A

The clinical features and treatment for drug-induced urticaria are identical to those for urticaria not related to drugs:

  • Red patches & weals on the surface of the skin
  • Usually very itchy & may have a burning sensation
  • Pain & tenderness uncommon
  • Can affect any skin site & tends to be distributed widely, weals shape is variable - may be round, form rings, map-like, target like lesion or form giant patches
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18
Q

How quickly does drug-induced urticaria usually come on ?

A

Usually occurs within 36hr but may develop within minutes on re-challenge

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19
Q

What are Pustular/Bullous drug eruptions?

A

Adverse drug reactions that result in fluid-filled blisters or bullae

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20
Q

What are the different Pustular/Bullous drug eruptions? and give examples of drugs which cause them

A

Acne - Glucocorticoids, Androgens (therapeutic), lithium, isoniazid, phenytoin

Acute generalised exanthematous pustulosis (AGEP) - Antibiotics, calcium channel blockers, antimalarials

Drug-induced bullous pemphigoid - ACE inhibitors, penicillin, furosemide

Linear IgA disease - Vancomycin

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21
Q

What is meant by fixed drug eruptions ?

A

Fixed drug eruptions (FDEs) characteristically recur in the same site or sites each time a particular drug is taken; with each exposure however, the number of involved sites may increase. Fixed drug eruption is a type of allergic reaction

22
Q

Describe the presentation of fixed drug eruptions

A
  • Well demarcated round/ovoid plaques of redness & swelling which are painful.
  • Sometimes plaques are surmounted by a blister
  • Hands, genitalia, lips common sites. Occasionally oral mucosa.
  • Resolves with persistent pigmentation when the drug is stopped.
  • Can re-occur on the same site on re-exposure to the drug.
  • Usually mild when restricted to a single lesion.
  • Can present as eczematous lesions, papules, vesicles or urticaria.
23
Q

What are some of the drug associated with fixed drug eruptions ?

A
  • NSAIDS
  • Paracetamol
  • Carbamazepine
  • Tetracycline, doxycycline
24
Q

How quickly do fixed drug eruptions occur ?

A
  • lesions develop 1 to 2 weeks after a first exposure.
  • May persist for years and only re-appear after drug exposure at exact same area within 24 hours
25
Q

What is shown in this pic ?

A

A fixed drug eruption

26
Q

What is Stevens-Johnson syndrome and what is it caused by?

A

A form of toxic epidermal necrolysis, is a life-threatening skin condition, in which cell death causes the epidermis to separate from the dermis.

Usually caused by an unpredictable adverse reaction to certain medications e.g:

  • allopurinol
  • carbamazepine
  • NSAIDS
27
Q

What is Drug reaction with eosinophilia and systemic symptoms (DRESS)?

A

Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) is caused by exposure to certain medications that may result in a rash, fever, inflammation of internal organs, lymphadenopathy, and characteristic hematologic abnormalities such as eosinophilia, thrombocytopenia, and atypical lymphocytosis

28
Q

What is acute generalized exanthematous pustulosis AGEP?

A

Acute generalized exanthematous pustulosis (AGEP) (also known as “Pustulardrug eruption,” and “Toxic pustuloderma”) is a rare cutaneous reaction pattern that in 90% of cases is related to medication administration, characterized by a sudden eruption that appears on average five days after the medication is started

29
Q

What is drug-induced photosensitivity ?

A

Drug-induced photosensitivity occurs when certain photosensitising medications cause unexpected sunburn or dermatitis (a dry, bumpy or blistering rash) on sun-exposed skin (face, neck, arms, backs of hands and often lower legs and feet). The rash may or may not be itchy

30
Q

What are the common causes of drug-induced photosensitivity?

A
  • quinine, thiazide
  • Abx’s
  • Retinoids
  • Diuretics
  • NSAID’s
  • Hypogylcaemics
  • Anti-psychotics
31
Q

What is erythema nodosum ?

A

An inflammatory disorder affecting subcutaneous fat. It presents as tender red nodules on the anterior shins.

32
Q

Who is erythema nodosum most common in ?

A

Can affect anyone but most common in women aged 25-40

33
Q

What are the causes of erythema nodosum ?

A
  • Infection - throat (streptococcal or viral), TB, leprosy etc
  • Systemic disease - sarcoidosis, IBD, Behcet’s
  • Malignancy/lymphoma
  • Drugs - penicillins, sulphonamides, COCP
  • Pregnancy
  • Idiopathic
34
Q

What are the clinical features of erythema nodosum ?

A
  • Discrete tender nodules which may become confluent
  • Lesions continue to appear for 1-2 weeks and leave bruise like discolouration as they resolve
  • Lesions are warm, oval, round or bow shaped
  • Lesions do not ulcerate & resolve without atrophy or scarring
  • The shins are the most common site
35
Q

What is shown in this pic ?

A

Erythema nodosum

36
Q

What is the clinical course of erythema nodosum?

A

Usually resolves spontaneously

37
Q

What is shown in this pic ?

A

Drug-induced erythema multiforme - pic shows characteristic target lesions

38
Q

Define what vasculitis is & specifically what small vessel vasculitis is

A
  • Vasculitis is a disorder in which there are inflamed blood vessels. These may include capillaries, arterioles, venules and lymphatics.
  • Small vessel vasculitis is the most common form of vasculitis affecting arterioles and venules.
39
Q

Define what cutaneous vasculitis is

A
  • Cutaneous vasculitis is a group of disorders in which there are inflamed blood vessels in the skin. Presenting as purpura.
  • It may be due to - idiopathic/primary, or secondary to infection, drug or disease
  • In a minority of patients cutaneous vasculitis is associated with systemic (small, medium & large vessel vasculitis) However, n most cases, an underlying cause is not found and the disease is self-limiting.
40
Q

What is cutaneous vasculitis due to a known drug or infection called?

A

Hypersensitivity vasculitis

41
Q

What are the clinical features of cutaneous vasculitis ?

A
  • Prominent involvement of lower legs with fewer lesions on proximal sites
  • Palpable purpura (purple, non-blanching papules and plaques)
  • Sometimes, petechiae and ecchymoses
  • Haemorrhagic bullae, necrosis and superficial ulceration
  • Local pruritus, burning pain and swelling
42
Q

List some of the common drug causes of hypersensitivity vasculitis

A

Allopurinol, amiodarone, NSAIDs, thiazide, penicillins, sulphonamides, hydralazine

43
Q

What is key to exclude when someone presents with cutaneous vasculitis ?

A

Systemic vasculitis

44
Q

What is shown in this pic?

A

Drug induced erythroderma - widespread erythema (>90%) associated with exfoliation (skin peeling off in scales or layers) seen

45
Q

What is shown in this pic?

A

Lichenoid drug eruption

46
Q

What is the main different between typical bullous phemphigoid and drug-induced bullous phemphigoid ?

A

Patients tend to be younger than in typical bullous pemphigoid.

47
Q

List some of the common causes of drug-induced bullous phemphigoid

A
  • Furosemide, penicillamine, penicillin, sulphasalzine
  • Captopril, gold

Note - clinical features are the same as typical bullous phemphigoid

48
Q

What is shown in this pic and list the common causes

A

Drug-induced hyperpigmentation = blue-grey or dark brown pigmentation affecting the skin

common causes include:

  • Minocycline
  • Chlorpromazine
  • NSAID’s
  • Heavy metals
  • Anti-psychotics
  • Tetracyclines
  • Amidoarone
49
Q

What are the investigations carried out when suspecting a drug eruption?

A

Usualy physcial examination and history is enough but in less clear situations:

Phototesting done for suspected phototoxic drug reactions

Biopsies may be useful for identifying the type of drug reaction and exclusion of other diseases.

Patch and photopatch tests - Eg. for suspected allergic contact dermatitis (Type IV)

Skin prick/intradermal tests for specific drugs - Eg. for suspected allergic reactions (Type I)

50
Q

Why is skin testing not indicated for serum sickness reactions (Type III) or for T-cell mediated reactions (Type IV)?

A

As they can cause SJS, TEN & DRESS, also not indicated for those with severe cutaneous adverse drug reactions

51
Q

What is the management for drup eruptions?

A
  • Discontinue the drug (if possible). Use an alternative.
  • Topical steroids may be useful.
  • Antihistamines may be useful.
  • Allergy bracelets are useful for some drugs.
  • Drug eruptions should be reported via the Yellow Card scheme (Medicines and Healthcare products Regulatory Agency).
52
Q

Appreciate the summary of this lecture

A
  • Cutaneous drug eruptions are common.
  • Presentation can mimic other diseases.
  • They affect quality of life, can trigger unnecessary investigations and can be life-threatening (SJS/TEN).
  • Some infections/diseases increase the risk of drug eruptions.
  • A detailed history is critical, especially if investigations are to be performed