Acute generalized exanthematous pustulosis

Source: Wikipedia, the free encyclopedia.
Acute generalized exanthematous pustulosis
Other namesToxic pustuloderma, pustular drug eruption
Multiple small subcorneal pustules on erythematous patches
Acute generalized exanthematous pustulosis
SpecialtyDermatology

Acute generalized exanthematous pustulosis (AGEP) (also known as pustular drug eruption and toxic pustuloderma) is a rare skin reaction that in 90% of cases is related to medication.

AGEP is characterized by sudden skin eruptions that appear on average five days after a medication is started. These eruptions are

pustules, i.e. small red white or red elevations of the skin that contain cloudy or purulent material (pus).[1] The skin lesions usually resolve within 1–3 days of stopping the offending medication.[2] However, more severe cases are associated with a more persistent disorder that may be complicated by secondary skin infections and/or involvement of the liver, lung, and/or kidney.[3]

alleles or T-cell receptors and/or their efficiencies in adsorbing, distributing to tissues, metabolizing, and/or eliminating) a particular SCARS-inducing medication. Evidence for these predispositions in AGEP has not been as well-established.[2][4][5]

Signs and symptoms

AGEP is an acute drug eruption characterized by numerous small, primarily non-follicular, sterile skin

pruritic and accompanied by fever, headache, a high number of neutrophils and eosinophils in the blood, and elevated blood levels of markers for inflammation (i.e. erythrocyte sedimentation rate and C-reactive protein). The skin eruptions typically end within a week after causative drug is discontinued.[3]

Rare cases of lung and bone marrow involvement have also been reported to complicate AGEP.[3][7] However, involvement of these organs typically resolve along with the skin eruptions. AGEP typically shows a mild course: usually, it is not associated with life-threatening complicates although superinfections of skin lesions may be serious or even life-threatening. AGEP has a mortality rate of less than 5%.[2][7][8]

Cause

About 90% of AGEP reactions are associated with medications. The remaining cases of AGEP have been associated with infective and other agents.[7]

Medicines

The most frequently reported drugs that have been associated with the development of AGEP include

sulfonamides, hydroxychloroquine, terbinafine, and diltiazem.[7] A more complete list of drugs sorted by their intended actions are:[3][7][9][10][11]

Microbe infections

Infections with

E. coli, and Echinococcus have been reported to be associated with the development of AGEP in the absence of an apparent drug-induced cause. The pathophysiology for the development of these drug-independent cases of AGEP is unclear.[7] Viral infections have also been observed to be associated with the development of SJS, SJS/TEN, and TEN in the absence of a causative drug.[7][10][15]

Other agents

Herbal medications, spider bites,

radiocontrast), lacquers, mercury, psoralen (combined with ultraviolet A to treat psoriasis), and xenobiotics have been associated with the development of AGEP in case reports.[11]

Pathophysiology

Main article: Severe cutaneous adverse reactions § Pathophysiology

Like other drug-induced SCARs disorders, AGEP is a

innate immune and autoimmune responses (Interleukin 22).[2][7][8]

AGEP also differs from the other SCARs disorders in respect to the level of evidence supporting the underlying mechanism by which a drug or its metabolite stimulates CD8+ T or CD4+ T cells. Studies indicate that the mechanism by which a drug or its metabolites accomplishes this stimulation involves subverting the

serotypes to stimulate T cells and the human population expresses some 13,000 different HLA serotypes while an individual expresses only a fraction of them. Since a SCARs-inducing drug or metabolite interacts with only one or a few HLA serotypes, their ability to induce SCARs is limited to those individuals who express HLA serotypes targeted by the drug or metabolite.[5][8] Thus, only rare individuals are predisposed to develop SCARs in response to a particular drug on the basis of their expression of HLA serotypes.[16] Studies have identified several HLA serotypes associated with development of DRESS syndrome, SJS, SJS/TEN, and TEN in response to various drugs which elici these disorders, developed tests to identify individuals who express these serotypes, and thereby determined that these individuals should avoid the offending drug. HLA serotypes associated with AGEP and specific drugs have not been identified.[5] A study conducted in 1995 identified of HLA-B51, HLA-DR11, and HLA-DQ3 of unknown serotypes to be associated with development of AGEP but the results have not been confirmed, expanded to identify the serotypes involved, nor therefore useful in identifying individuals predisposed to develop AGEP in response to any drug.[2] Similarly, a specific T cell receptor variant has been associated with the development of DRESS syndrome, SJS, SJS/TEN, and TEN but not AGEP.[2][17]

Variations in

excreting a drug) has been found to occur in cases of the DRESS syndrome, SJS, SJS/TEN, and TEN. These variations influence the levels and duration of a drug or drug metabolite in tissues and thereby impact the drug's or drug metabolite's ability to evoke SCARs.[18]

In rare cases, the development of AGEP has been reported to occur in individuals with

T cells. It does so by binding to, but not stimulating, these cytokines' receptors, IL1RL2 and IL1RAP, thereby interfering with the interleukin-36 cytokines' binding to and stimulating IL1RL2 and IL1RAP. However, the IL36RN loss of function mutation has been reported in cases of generalized pustular psoriasis.[3][19] The presence of this mutation in two seemingly unrelated disorders has led to suggestions that the classification of AGEP as a SCARs or a form of psoriasis requires study.[19]

Diagnosis

The diagnosis of AGEP may be forthright in typical cases in which an individual: has taken a drug known to cause the disorder; develops multiple sterile

chicken pox
).

Several tests have been proposed to be useful for supporting the diagnosis of and/or implicating a particular drug as the cause of AGEP particularly in individuals who develop skin lesions while taking multiple drugs. These include

granulysin) are measured have likewise not been broadly adopted because of their lack of specificity.[8]

Classification

The disorder is classified in the group of

drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and Stevens–Johnson/toxic epidermal necrolysis overlap syndrome (SJS/TEN). SJS, SJS/TEN, and TEN, while initially described as distinct adverse drug-induced cutaneous reactions are now regarded as manifestations of epidermal necrolysis differing only in extent of skin involvement. While all of five SCARs disorders are potentially lethal, AGEP has the lowest mortality of the group.[2][7]

Treatment

The treatment of AGEP begins with the immediate cessation of the offending drug. For individuals developing AGEP while taking multiple drugs, non-essential drugs should be discontinued and essential drugs should be replaced by chemically unrelated drugs that are used as alternatives to the discontinued drug(s). In cases of multiple drug intake, skin and/or in vitro testing may be of some use in identifying the offending drug. Beyond identifying and discontinuing the offending drug, individuals with mild symptoms may require no further treatment. Those troubled by more significant symptoms such as itching or fever may require

antihistamines, topical corticosteroids, systemic corticosteroids, and/or antipyretics. Individuals with liver, lung, kidney, and/or severe skin complications may require high dosage systemic corticosteroids and organ-specific interventions. Skin infections, which may lead to sepsis, are potentially lethal complications of AGEP; preventative methods and rapid treatment of such infections with appropriate antibiotics and, where needed, further supportive measures are critical in the treatment of this complication. Overall, however, AGEP has a lethality of less than 5% with recent reports showing no fatalities. Typically, individuals with AGEP have rapid rates of recovery even in when experiencing the cited complications.[3][8][9][21]

See also

References

  1. ISBN 0-7216-2921-0
    .: 124 
  2. ^
    S2CID 333724
    .
  3. ^
    S2CID 21325754
    .
  4. S2CID 205434868
    .
  5. ^
    PMID 28345177
    .
  6. ISBN 978-1-4160-2999-1
    .
  7. ^
    PMID 27472323
    .
  8. ^
    S2CID 9506967
    .
  9. ^
    PMID 26783390
    .
  10. ^
    PMID 26354880
    .
  11. ^
    PMID 20548906
    .
  12. ^ "HYDROXYZINE HYDROCHLORIDE tablet". Daily Med. U.S. National Library of Medicine. Retrieved 25 October 2020.
  13. PMID 27075126
    .
  14. ^ "Acute generalised exanthematous pustulosis | DermNet NZ". dermnetnz.org. Retrieved 2021-01-14.
  15. S2CID 46796285
    .
  16. PMID 27960170
    .
  17. S2CID 9183824
    .
  18. PMID 28256714
    .
  19. ^
    S2CID 4436573
    .
  20. PMID 29226159
    .
  21. ^ Canadian Medical Association Journal, September 15, 2009, pp 393-396

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=Acute_generalized_exanthematous_pustulosis&oldid=1161990142"