Drug Induced Dermatologic Disorders

irritant

-localized

-allergens

-IV drug extravasation

Allergic

-immune response

-may be systemic

-broad classifications

-first reaction may be dermal but subsequent exposures may become systemic

patient risk factors for developing allergic drug reaction

● prior drug reaction (inducing drug-specific antibodies, etc.)

● multiple drug therapy

● intermittent/repeated use of the same drug vs continuous therapy

● concurrent illnesses (HIV, Epstein-Barr virus, CMV)

● dosage/serum drug level increases (eg, too rapid an IV vancomycin administration rate)

● Topical route of administration (most immunogenic)

○ topical > subcutaneous > intramuscular > oral > IV with respect to immunogenicity

● Genetic factors (certain HLA-B alleles predispose for drug allergies)

● comorbidities (eg, asthma).

fever

What is the main differentiation that can occur with cutaneous drug eruptions that can indicate a more serious problem?

type 1 dermatologic reaction

-IgE-mediated

-activation of mast cells and basophils result in release of chemical mediators (histamine, leukotrines, ect.)

-EX: urticaria, angio-edema, anaphylaxis

Type 2 dermatologic reaction

-cytotoxic reactions

-IgG or IgM mediated

-antibody binding to cells with subsequent binding of complement and cell rupture

-EX: blood cell dyscrasias (eg, hemolytic anemia, autoimmune thrombocytopenia)

Type 3 dermatologic reactions

-immune complex formation

-antigen-antibody immune complexes usually with IgG or IgM

-deposition of immune complexes in skin, kidneys, joints, GI tract, ect.

-EX: serum sickness, vasculitis

Type 4 dermatologic reaction

-delayed cell-mediated hypersensitivity reactions

-T-cell mediated

-can be further divided into subtypes based on T-lymphocyte subset and cytokine expression profiles

-EX: allergic contact dermatitis, SJS/TEN

extravasation

IV drug gets out of the IV space

maculopapular rash

-is the most common allergic skin reaction

-erythematous macules and papules that may be pruritic

-fever, blisters, or pustules are NOT present

macule

flattened red spots

papule

looks like pimples

onset of maculopapular skin reactions

-usually within 7-10 days of starting the offending drug

-takes 7-14 days to resolve after stopping drug

-penicillins

-cephalosporins

-sulfonamides

-some anticonvulsants

What are the common drugs involved with maculopapular skin reactions?

urticaria and angioedema

-is characterized by hives, extremely pruritic red raised wheals, angioedema, and mucous membrane swelling

-caused by drugs in about 5-10% of cases

-Penicillin and related antibiotics

-A.A.

-Sulfonamides

-X-ray contrast media

-Opiates

What are the common drugs that cause urticaria and angioedema?

-foods (likely the most significant offenders)

-physical factors (cold or pressure, infections, and exposure to latex)

-idiopathic

What are the other causes of urticaria and angioedema?

wheals present with urticaria

How does urticaria differ from a maculopapular rash?

fixed drug eruptions

-distinct type of drug eruptions that appear as pruritic, well circumscribed, round or oval-shaped, erythematous macules or edematous plaques

-characteristically recur at the same sites upon re-exposure to the offending drug

-appear within minutes to days and disappear within days, leaving

hyperpigmented skin for months

-tetracyclines

-barbiturates

-sulfonamides

-codeine

-phenolphthalein

-acetaminophen

-NSAIDs

What are the drug culprits for fixed drug eruptions?

Acneiform drug reactions

-pustular eruptions caused by medications that induce acne (whiteheads or blackheads)

-onset is usually between 1 to 3 weeks

-corticosteroids

-androgenic hormones

-some anticonvulsants

-isoniazid

-lithium

What are the drugs that cause acneiform drug reactions?

phototoxic

absorb UVA light, resulting in skin damage

photoallergic

UVA transformation of meds into allergens

-sulfonamides

-sulfonylureas

-thiazides

-NSAIDs

-chloroquine

-Amiodarone

-Tetracycline

-Psoralens

-Coal tar

-Carbamazepine

What are the drug culprits for photosensitivity?

DRESS: drug reaction eosinophilia and systemic symptoms

exanthematous eruption accompanied by fever, hematologic abnormalities(eosinophilia or atypical lymphocytes), lymphadenopathy, and multi-organ involvement (including the kidneys, liver, lung, bone marrow, heart, and brain)

1-4 weeks after starting offending drug

What is the timeline of DRESS?

-Allopurinol

-Sulfonamides

-Some anticonvulsants (barbs, phenytoin, carbamazepine, lamotrigine)

-Dapsone

What are the common drugs involved with DRESS?

Severe Cutaneous Adverse Reactions (SCARs)

-DRESS (drug reaction eosinophilia and systemic symptoms)

-drug hypersensitivity syndrome (DHS) aka DRESS

-Serum sickness like reactions

-SJS/TEN

serum sickness-like reactions s/s

urticarial eruptions presenting with fever, rash (usually urticarial), and arthralgias

1 to 3 weeks after starting offending drug

What is the onset of serum-sickness like reactions?

serum sickness like reactions

most commonly seen in young children (< 6 yo) typically after a second or subsequent course of antibiotics such as cefaclor

-Penicillins

-other antibiotics

-NSAIDs

What are the drug culprits for serum sickness-like reactions?

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

-Acute hypersensitivity cutaneous reactions that present as dermatologic emergencies.

-Considered to be severe forms of erythema multiforme

10%

SJS by definition involves ________ of BSA

30%

TEN involves > ______ BSA

15-30%

SJS/TEN involves ________% BSA.

SJS/TEN s/s

-Erythematous macule with purpuric center (lesions begin on face and trunk then spread rapidly)

-Bullae finally coalesce forming flaccid blisters with full thickness epidermal necrosis and skin sloughing (occular scarring and blindness may occur if mucous membranes of eyes are involved)

Timeline for SJS/TEN

-1 to 3 weeks after exposure to causative agent

-Prodrome- fever, malaise, headache, cough, conjunctivitis

-Skin lesions appear one to three days after the prodrome

-sulfa drugs

-anti-epileptic drugs

-antibiotics

-NSAIDs

What are the common drugs involved in SJS/TEN?

tx of SJS/TEN

-immediate discontinuation of offending drug (most critical intervention)

-hospitalization (ICU/burn unit for extensive disease)

-supportive care

-early speciality involvement

-adjunctive therapies

5-10%

What is the mortality of SJS?

30-40%

What is the mortality of TEN?

exclusion

Typically dermatologic drug reactions are dx of __________

stop offending agent or possible offending agent

What is the first thing you do in dermatologic drug reactions?

tylenol

is the tx of choice for fever bc ASA and NSAIDs can exacerbate skin

IV immunoglobulin (IVIG)

has shown promise in halting disease progression

corticosteroids

use is controversial in dermatologic drug reactions as it may increase risk of infection (if used should use high bolus dose with a fast taper)

antihistamines

Tx for exanthematous drug eruptions:

-antihistamines

-glucocorticoids, systemic: prednisone

-Montelukast (angioedema)

-Epinephrine (severe cases)

What is the tx for urticaria, angioedema, and anaphylaxis?

topical corticosteroids

What is the tx for allergic contact dermatitis?

systemic corticosteroids

What is the tx for drug hypersensitivity syndrome?

-watchful waiting

-topical corticosteroids

-antihistamines

What is the tx for fixed drug eruption?

-antihistamines

-topical corticosteroids

What is the tx for erythema multiforme?

-antihistamines

-NSAIDs (if arthralgia present)

-systemic corticosteroids: Prednisone

What is the tx of serum sickness-like reaction?

-gentle cleansing

-moisturizers

-topical corticosteroids

What is the tx of irritant contact dermatitis?

-sunblock (preventative)

-cool compresses

-NSAIDs

-systemic corticosteroids (severe reactions): Prednisone

-topical corticosteroids

What is the tx of photosensitivity?

topical hydroquinone

What is the tx of hyperpigmentation?

topical tretinoin

What is the tx of melasma?

antihistmaines

What is the tx of pseudoallergy?

Human Leukocyte Antigen B Gene

test for the allele prior to tx with Abacabir in HIV due to reactions