1 / 27

Drug Eruptions

Drug Eruptions. David McSwain, M.D. Drug Eruptions. DRESS Sydrome Urticaria Angioedema/anaphylaxis Drug-induced exanthems Hypersensitivity vasculitis Exfoliative dermatitis/Erythroderma SJS/TEN Fixed drug eruption Photosensitivity. DRESS Syndrome.

gillian-livingston
Download Presentation

Drug Eruptions

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Drug Eruptions David McSwain, M.D.

  2. Drug Eruptions • DRESS Sydrome • Urticaria • Angioedema/anaphylaxis • Drug-induced exanthems • Hypersensitivity vasculitis • Exfoliative dermatitis/Erythroderma • SJS/TEN • Fixed drug eruption • Photosensitivity

  3. DRESS Syndrome • Drug Rash with Eosinophilia and Systemic Symptoms • Formerly called Hypersensitivity Syndrome (HSS) • Typically presents with rash and fever (87%), classically erythematous follicular papules and pustules, but may also include bullae or purpura. • Other severe systemic manifestations such as hepatitis (51%), arthralgias, lymphadenopathy (75%), interstitial nephritis (11%), or hematologic abnormalities (30%). • Hematologic abnormalities include eosinophilia, thrombocytopenia, neutropenia, and atypical lymphocytosis. • Other symptoms: pruritis, nephritis, oliguria, hepato-renal syndrome, athralgia, and asthenia. • Can affect any organ system (lungs, CNS, GI, etc.) • DDx includes SJS/TEN, hypereosinophilic syndrome, and Still’s disease. • Skin biopsy is non-specific.

  4. DRESS Syndrome • Common causes: aromatic anticonvulsants (oxcarbazepine, carbamazepine, phenytoin, phenobarbital, etc.) and sulfonamides. • Other drugs implicated: • lamotrigine • allopurinol • NSAIDs • captopril • CCBs • mexiletine • fluoxetine • dapsone • metronidazole • minocycline • antiretrovirals.

  5. DRESS Syndrome • Overall risk for phenytoin is between 0.1-0.01%. • Usually occurs 2-6 weeks after initiation of the medication, which is later than most drug eruptions. May be difficult to distinguish from serum sickness and vasculitis. • Median onset of DRESS syndrome after initiation of therapy with Trileptal is 13 days (range 4-60). • No definite evidence of cross-reactivity with other agents, but it is a possibility. • Treatment is supportive. • Medication should be stopped as soon as the diagnosis is suspected. • Severity is dependent upon the amount of time the drug is continued after hypersensitivity occurs. • Corticosteroids have been required in some cases, but their use is controversial.

  6. Urticaria • Time to onset: immediate, accelerated (hours), or delayed (days). • Type I hypersensitivity reactions: antibiotics (especially PCN, cephalosporins, and sulfonamides), local anesthetics, radiocontrast media, blood products, and gamma globulin. • Non-immune urticaria: radiocontrast media and long-acting ACE-inhibitors (due to changes in vascular response to bradykinin). • Mast cell degranulation by non-IgE mechanisms: opiate analgesics, anesthetic muscle relaxants, and Vancomycin (Red Man Syndrome, which can be worsened by concommitant opiate use).

  7. Angioedema/Anaphylaxis • Caused by degranulation of mast cells in the deeper dermis and subcutaneous tissues. • May occur along with urticaria (50% of cases) • Can be life-threatening if it causes laryngeal edema or tongue swelling. • Can be non-mast cell mediated, as in the case of ACE-inhibitors.

  8. Drug-induced Exanthems • Account for close to 75% of all drug eruptions. • Morbilliform, maculopapular eruptions. • Most commonly implicated medications are the most commonly prescribed medications (antibiotics, sulfa). • Usually begin in dependent areas and generalize. • Often associated with pruritis, low-grade fever, eosinophilia. • May be the early stage of more severe reactions such as toxic epidermal necrolysis, DRESS, or serum sickness • Onset within 2 weeks of starting a new drug, or within days of re-exposure. • Delayed (type IV) hypersensitivity is most likely etiology. • More common in patients with altered immunity, such as those with HIV or mononucleosis (“ampicillin rash”). • Treatment is dicontinuation of the drug. Antihistamines, topical steroids, and topical antipruritics may also help.

  9. Hypersensitivity vasculitis • American College of Rheumatology proposed the following five criteria. The presence of three or more had a sensitivity of 71% and a specificity of 84% for the diagnosis • Age > 16 • Use of possible offending drug in temporal relation to symptoms • Palpable purpura • Maculopapular rash • Biopsy of a skin lesion showing neutrophils around an arteriole or venule. • Most likely due to drugs that can act as haptens to stimulate the immune response: PCN, cephalosporins, sulfonamides, phenytoin, and allopurinol. • Additional findings: fever, urticaria, arthralgias, LAD, low complement levels, and elevated ESR.

  10. Exfoliative dermatitis/ Erythroderma • Erythroderma is defined as a cutaneous reactional state with chronic erythema and scale involving greater than 50% of the body surface area. It can result from drugs, atopic dermatitis, psoriasis, and malignancies such as cutaneous T-cell lymphoma. • Drugs, including gold, arsenic, mercury, PCN, and barbituates, are implicated in about 10% of cases. • Usually begins as an eczematous or morbilliform eruption and progresses.

  11. SJS/TEN • Stevens-Johnson Syndrome and toxic epidermal necrolysis are likely two manifestations on the same spectrum. The disease is best termed SJS when epidermal detachment involves less than 10% of the body surface area, whereas TEN involves greater than 30%. • SJS is distinct from erythema multiforme major, which is usually caused by infections and runs a benign course. SJS is usually drug induced and can be fatal. • SJS and TEN usually occur 1-3 weeks after exposure, but can occur more rapidly with re-exposure, which suggests an immunologic mechanism. • Mucosal involvement is seen in 90% of cases, including painful crusts and erosions on the oral mucosa, conjuntivae, and genital mucosa.

  12. SJS/TEN • Frozen section of the denuded epidermis will reveal full-thickness epidermal necrosis. • Differential includes exfoliative erythroderma, paraneoplastic pemphigus, acute exanthematous pustulosis, and staph scalded skin syndrome, but none of these disorders displays full-thickness epidermal necrosis. • Patients are best managed as burn victims. • Corticosteroids are not recommended.

  13. Fixed Drug Eruptions • Drug eruption that occurs at the same location every time a particular medication is used. • Begins as an erythematous, edematous plaque with a grayish center or frank bullae, then progresses to dark, post-inflammatory pigmentation. • Sites include the mouth, genetalia, face, and acral areas. • Causes include phenolphthalein, tetracyclines, barbituates, sulfonamides, NSAIDs, and salicylates.

  14. Photosensitivity • Two types include phototoxic eruptions and photoallergic eruptions. • Phototoxic eruptions are due to absorption of UV light (usually UVA) by the drug, which causes a release of energy and damage to cells. Looks like a bad sunburn, which may blister. • Photoallergic eruptions are a lymphocyte-mediated reaction caused by exposure to UVA, which converts the drug to an immunologically active compound that activates lymphocytes, causing an eczematous reaction in a photodistribution. • Usually due to topical agents including fragrances and biocides in soaps. • Both types can be caused by phenothiazines, chlorpromazine, sulfa, and NSAIDS, although phototoxic reactions are more common with these agents.

  15. Reference • Volcheck, GW. “Clinical evaluation and management of drug hypersensitivity.” Immunol Allergy Clin N Am. 24(2004): 357-371. • UpToDate. “Drug Eruptions.” Andrew D. Samuel, MD. Topic last revised 12/11/2002. Http://www.uptodate.com • Images provided by the Dermatology Image Atlas - Johns Hopkins University. http://dermatlas.med.jhmi.edu/derm/ • Novartis. “Important Drug Warning.” 4/18/2005

More Related