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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.

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Drug Eruptions

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  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

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