Drug eruption

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Drug eruption
photosensitivity reaction.
SpecialtyDermatology Edit this on Wikidata

In

itching without outward skin changes.[3]

The use of synthetic pharmaceuticals and biopharmaceuticals in medicine has revolutionized human health, allowing us to live longer lives. Consequently, the average human adult is exposed to many drugs over longer treatment periods throughout a lifetime.[4] This unprecedented rise in pharmaceutical use has led to an increasing number of observed adverse drug reactions.[4]

There are two broad categories of adverse drug reactions. Type A reactions are known side effects of a drug that are largely predictable and are called, pharmatoxicologic.[5] Whereas Type B or hypersensitivity reactions, are often immune-mediated and reproducible with repeated exposure to normal dosages of a given drug.[5] Unlike type A reactions, the mechanism of type B or hypersensitivity drug reactions is not fully elucidated. However, there is a complex interplay between a patient's inherited genetics, the pharmacotoxicology of the drug and the immune response that ultimately give rise to the manifestation of a drug eruption.[5]

Because the manifestation of a drug eruption is complex and highly individual, there are many subfields in medicine that are studying this phenomenon. For example, the field of pharmacogenomics aims to prevent the occurrence of severe adverse drug reactions by analyzing a person's inherited genetic risk.[6] As such, there are clinical examples of inherited genetic alleles that are known to predict drug hypersensitivities and for which diagnostic testing is available.[6]

Classification

Some of the most severe and life-threatening examples of drug eruptions are

drug induced hypersensitivity syndrome (DIHS), erythroderma and acute generalized exanthematous pustulosis (AGEP).[4] These severe cutaneous drug eruptions are categorized as hypersensitivity reactions and are immune-mediated. There are four types of hypersensitivity reactions and many drugs can induce one or more hypersensitivity reactions.[4]

Hypersensitivity Reactions[4]
Reaction Description Mediator Mechanism Clinical phenotype
Type I Immediate IgE antigen binds to mast cell/

basophil surface receptors

Urticarial (hives), anaphylaxis,

angioedema

TypeII Antibody-mediated IgM, IgG antibody binds antigen leading to

complement-driven cell lysis

drug-induced thrombocytopenia,

hemolytic anemia, Goodpasture's, ANCA vasculitis

Type III Immune complex IgM, IgG, IgA antigen-antibody complex deposits

in tissues-triggers recruitment of

leukocytes

 Serum sickness, Henoch-Schonlein Purpura
Type IV Delayed-type T-lymphocytes Activated T-cells produce cytokines causing

inflammation leading to tissue destruction

Drug reaction with eosinophilia and systemic symptoms (i.e. DRESS syndrome or DIHS), Stevens–Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis

By appearance

The most common type of eruption is a

angiotensin converting enzyme inhibitors
).

By mechanism

The underlying mechanism can be immunological (such as in

Sweet's syndrome following the administration of colony-stimulating factors[9]
).

By drug

The culprit can be both a

over-the-counter medication
.

Examples of common drugs causing drug eruptions are

psychotropic drugs. Common examples include photodermatitis due to local NSAIDs (such as piroxicam) or due to antibiotics (such as minocycline), fixed drug eruption due to acetaminophen or NSAIDs (Ibuprofen), and the rash following ampicillin in cases of mononucleosis.[2]

Certain drugs are less likely to cause drug eruptions (rates estimated to be ≤3 per 1000 patients exposed). These include: digoxin, aluminum hydroxide, multivitamins, acetaminophen, bisacodyl, aspirin, thiamine, prednisone, atropine, codeine, hydrochlorothiazide, morphine, insulin, warfarin and spironolactone.[2]

Diagnosis and screening tests

Drug eruptions are diagnosed mainly from the

clinical examination. However, they can mimic various other conditions, thus delaying diagnosis (for example, in drug-induced lupus erythematosus, or the acne-like rash caused by erlotinib). A skin biopsy, blood tests or immunological
tests can also be useful.

Drug reactions have characteristic timing. The typical amount of time it takes for a rash to appear after exposure to a drug can help categorize the type of reaction. For example,

Drug Reaction with Eosinophilia and Systemic Symptoms usually occurs between 15 and 40 days after exposure. Toxic epidermal necrolysis and Stevens–Johnson syndrome typically occur 7–21 days after exposure. Anaphylaxis occurs within minutes. Simple exanthematous eruptions occur between 4 and 14 days after exposure.[2]

TEN and SJS are severe cutaneous drug reactions that involve the skin and mucous membranes. To accurately diagnose this condition, a detailed drug history is crucial.[4] Often, several drugs may be causative and allergy testing may be helpful.[4] Sulfa drugs are well known to induce TEN or SJS in certain people. For example, HIV patients have an increased incidence of SJS or TEN compared to the general population and have been found to express low levels of the drug metabolizing enzyme responsible for detoxifying sulfa drugs.[5] Genetics plays an important role in predisposing certain populations to TEN and SJS. As such, there are some FDA recommended genetic screening tests available for certain drugs and ethnic populations to prevent the occurrence of a drug eruption.[5] The most well known example is carbamezepine (an anti-convulsant used to treat seizures) hypersensitivity associated with the presence of HLA-B*5801 genetic allele in Asian populations.[6]

Pharmacogenetic alleles associated with cutaneous drug reactions[5]
Drug Allele Population Clinical syndrome FDA recommended Pharmacogenetic testing
Abacavir HLA-B*5701 US European

US African

Australian

DIHS Yes
Allopurinol HLA-B*5801 Han, Korean,

Thai, European

SJS, TEN, DIHS No
Carbamezepine HLA-B*1502 Han, Thai,

Malaysian, Korean

SJS, TEN Yes
Dapsone HLA-B*1301 Chinese DIHS No
Lamotrigine HLA-B*38

HLA-B*1502

European,

Han

SJS, TEN no recommendation available
Methazolamide HLA-B*5901 Korean SJS, TEN No
Phenytoin HLA-B*1502 Thai, Han SJS, TEN Warning

DIHS is a delayed onset drug eruption, often occurring a few weeks to 3 months after initiation of a drug.[2] Worsening of systemic symptoms occurs 3–4 days after cessation of the offending drug.[5] There are genetic risk alleles that are predictive of the development of DIHS for particular drugs and ethnic populations.[5] The most important of which is abacavir (an anti-viral used in the treatment of HIV) hypersensitivity associated with the presence of the HLA-B*5701 allele in European and African population in the United States and Australians.[5]

AGEP is often caused by antimicrobial, anti-fungal or antimalarial drugs.[4] Diagnosis is often carried out by patch testing. This testing should be performed within one month after resolution of the rash and patch test results are interpreted at different time points: 48 hours, 72hours and even later at 96 hours and 120 hours in order to improve the sensitivity.[4]

[10]

See also

References

  1. PMID 7762478
    .
  2. ^
    ISBN 978-0723435716
    .
  3. ^
    S2CID 25391301
    .
  4. ^
    OCLC 798579099.{{cite book}}: CS1 maint: others (link
    )
  5. ^
    ISBN 9781447167280
    .
  6. ^
    OCLC 793223356.{{cite book}}: CS1 maint: others (link
    )
  7. PMID 11405768
    .
  8. PMID 12952753
    .
  9. PMID 17655751
    .
  10. PMID 7794310
    .

External links

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