Urticaria & Drug Eruptions

• Core 1 (Pre-Clerkship)
  • Integrative Systems
    • Dermatology
      • Intro to Derm
      • Urticaria
      • Pediatric derm
      • Viral exanthems
      • Drug reactions
• Core 2 (Clerkship)
  • Pediatrics 
• Core 3 (Post Clerkship)
  • Electives that may further knowledge: Pediatric dermatology elective, Dermatology elective

 A 7-year-old girl presents with a 24-hour history of a non-painful, mildly itchy rash. 

She was diagnosed with streptococcal pharyngitis two days ago and started amoxicillin yesterday. The rash began on her trunk and has spread to her extremities. She has no fever, respiratory symptoms, or mucosal involvement. On exam, she appears well and has a symmetric, erythematous maculopapular rash on her trunk and limbs without facial swelling, blisters, or target lesions.

Onset, Duration, Location, and Progression:

• When did the rash first appear?
• Is the rash pruritic (itchy)? Raised or flat?
• Where on the body is the rash? Has it spread elsewhere?
• How severe is the rash in terms of extent (localized vs. widespread) and symptoms (mild vs. severe pruritus, pain)?
• Has the rash evolved? (e.g., did it start as macules, papules, or wheals and then progress to blisters or other types of lesions?)
• Does the rash involve mucosal surfaces (e.g., mouth, eyes, genitalia)?
• Did the rash start after any new medication was started?
  • If so, how long after starting the new medication did the rash develop?
  • Has the patient experienced similar rashes in the past with medication?

Associated Symptoms:

• Are there any associated symptoms like fever, joint pain, swelling, or fatigue?
• Any shortness of breath or chest tightness (signs of an allergic reaction or anaphylaxis)?
• Is there any history of angioedema or anaphylaxis following medication use?

Exposure History:

• Has the patient been exposed to any known allergens (e.g., foods, insect stings, or other environmental triggers)?
• Have there been any recent exposures to new environments, vaccinations, or travel?
• Has the patient had any recent viral or bacterial infections, particularly before or around the onset of the rash?
• Did the rash appear after receiving treatment for an infection (e.g., antibiotics)?

Past Medical History:

• Does the patient have a history of allergies, including seasonal or food allergies?
• Any family history of drug allergies, eczema, asthma, or urticaria?
• Does the patient have any underlying chronic conditions (e.g., autoimmune diseases, renal disease, or liver disease) that might alter how medications are metabolized or increase risk for drug reactions?

Medications:

• What medications is the patient currently taking, including over-the-counter drugs, herbal supplements, and recent antibiotics?
• Have any medications been recently added or changed?
• Has the patient ever had a similar reaction to a medication in the past?
• Is the patient on any known high-risk drugs (e.g., penicillins, NSAIDs, antibiotics, anticonvulsants, allopurinol, or ACE inhibitors)?

Allergies:

• Does the patient have a history of allergies to any medications?
  • If so, what was the reaction?

General Assessment:

• Observe first: Before touching the patient, observe their general appearance, activity level, and any visible rashes or lesions.
• Vital signs: Fever, hypotension, tachycardia → suggest systemic involvement or anaphylaxis.
• Sick versus not sick: This is a key initial assessment. Children with life-threatening reactions like anaphylaxis or SJS/TEN need immediate attention!

Dermatologic Assessment:

• Evaluate for specific rash characteristics:
  • Urticaria: Blanchable, raised, erythematous wheals; pruritic; transient (<24h)
  • Maculopapular: Symmetric, widespread erythematous lesions (common drug eruption)
  • Target lesions: Consider erythema multiforme
  • Bullae/Nikolsky sign: Suggests SJS/TEN
  • Fixed drug eruption: Localized, well-demarcated, often recurs in same spot
  • Morbilliform: Measles-like, most common with drug exanthems
  • Distribution: Generalized vs localized (start at trunk vs extremities, mucosal involvement?)
  • Mucosal involvement: Oral, ocular, genital
  • Desquamation: Suggests more severe reactions like SJS/TEN
  • Edema: Angioedema (face, lips, hands, feet)

Other Exam Findings:

• HEENT:
  • Eyes: Conjunctival injection (→ serum sickness, DRESS, SJS/TEN), periorbital edema, discharge (watery, mucopurulent)
  • Mouth: Oral mucosal involvement (erosions, ulcerations, crusting), lip swelling (angioedema), tongue swelling or discoloration
  • Ears/Nose: Swelling, erythema, or signs of angioedema, nasal congestion or discharge (in allergic reactions)
• Respiratory:
  • Airway patency: Stridor or hoarseness → airway angioedema or anaphylaxis
  • Wheezing or rales: Possible sign of systemic allergic response
  • Respiratory rate and effort: Increased work of breathing may indicate systemic reaction
• Cardiovascular:
  • Heart rate: Tachycardia can indicate fever, dehydration, or anaphylaxis
  • Perfusion: Delayed cap refill or cool extremities may suggest shock
  • Blood pressure: Hypotension → worrisome for anaphylaxis or severe drug reaction
• Gastrointestinal:
  • Abdominal tenderness: can be seen in DRESS, serum sickness
  • Hepatomegaly: can be seen in DRESS
  • Nausea, vomiting, diarrhea → systemic drug reaction or part of anaphylaxis
• Genitourinary:
  • Perineal rash or ulcers: consider SJS/TEN, fixed drug eruption
  • Dysuria or hematuria: Possible systemic involvement or adverse drug effect
• Musculoskeletal:
  • Arthralgia/arthritis: Common in serum sickness–like reactions
  • Swelling or tenderness in joints: particularly knees, ankles
• Neurologic:
  • Mental status: Assess alertness and orientation. Altered mental status could suggest a serious systemic drug reaction (e.g., DRESS).
  • Irritability or lethargy in infants may be subtle signs of systemic illness

Mild to Moderate Reactions:

Severe or Systemic Reactions:

• General Measures
  • Discontinue the suspected drug immediately
  • Supportive care
    • Antihistamines (e.g., diphenhydramine, cetirizine)
    • Skin care: emollients, gentle cleansing)
    • Cool compresses, calamine for itching
  • Labs to consider: CBC with differential, peripheral blood smear, kidney function tests, liver function tests, cardiac enzymes, amylase/lipase, molecular or serologic testing for infections (e.g., HHV-6, EBV, CMV, viral hepatitis, HSV, mycoplasma pneumoniae)
  • Imaging: Ultrasound, CT scan to assess for internal organ involvement. Echo or cardiac MRI if concern for cardiac involvement.
  • Skin biopsy: Histopathologic examination if diagnosis unclear based on history/physical and/or to rule-out other conditions
• Mild to Moderate Reactions
  • Urticaria, exanthematous rash, photosensitivity
    • Non-systemic: outpatient management
    • Oral antihistamines, consider topical corticosteroids
    • Consider short course of oral steroids (e.g., prednisone) if widespread or symptomatic
  • Severe or Systemic Reactions
    • Anaphylaxis (IMMEDIATE MANAGEMENT):
      • Assess airway, breathing, circulation (ABCs)
      • Administer Epinephrine IM immediately
        • Repeat as clinically indicated every 5-15 minutes
      • Respiratory medications
        • Inhaled albuterol
        • Racemic epinephrine
      • Vasopressor medications
        • Epinephrine
        • Dopamine
      • Adjunctive medications
        • H1 + H2 blockers (e.g., diphenhydramine, cetirizine, famotidine)
        • Corticosteroids (e.g., methylprednisolone, prednisone/prednisolone, dexamethasone)
      • Admit to ICU if airway/respiratory compromise
    • DRESS Syndrome:
      • Discontinue offending drug
      • Treat based on symptom severity:
        • Topical corticosteroids +/- systemic corticosteroids
        • Oral cyclosporine for corticosteroid-refractory DRESS
      • Monitor for organ involvement (CBC, BMP, LFTs)
      • Admit inpatient versus ICU if moderate/severe
    • SJS/TEN:
      • Discontinue offending drug
      • Supportive care: fluid management, pain control, wound care, nutrition optimization, infection prevention
      • Ophthalmology, derm, ID consults
      • Immunomodulatory therapy (e.g.,IVIG, cyclosporine) in select cases
      • Admit to burn unit/ICU for close monitoring
    • Erythema multiforme major:
      • Discontinue offending drug +/- treat underlying infection
      • Treatment of specific site involvement with supportive care ± corticosteroids
      • Ophthalmology, derm, ID consults
      • Admit inpatient if mucosal involvement or systemic illness
    • Patient & Family Education
      • Explain the drug reaction and the importance of avoiding the trigger
      • Provide written documentation of the allergy
      • Discharge with epi pen if concern for anaphlaxis
      • Consider referral to allergy/immunology for further evaluation or drug desensitization if needed
      • Document clearly in EMR and communicate with primary care

• The most common drug eruption in children (and generally) are exanthematous drug eruptions, which present as a maculopapular rash and subsides after the offending agent is stopped.
• Always have high suspicion for anaphylaxis whenever a patient describes an acute onset of urticaria, and check for other signs of anaphylaxis (wheezing, hypotension, vomiting/diarrhea) to see if they meet criteria for true anaphylaxis.
• It is worthwhile to have patients follow-up with allergy if there is suspicion of a drug allergy – marking a patient with an allergy they do not have can subject them to much more intense treatment alternatives when the first-line treatment may be perfectly safe.

• Article
  • AAP Textbook of Pediatric Care: Drug Eruptions, Erythema Multiforme, Stevens-Johnson Syndrome
• Podcast
  • Curbsiders: #161 A Rash Approach to Rashes
• Pathways
  • Anaphylaxis Emergent Care (CHOP)
  • Penicillin Drug Allergy (CHOP)
  • Urticaria or Angioedema (CHOP)

Answers: 

Q1: c. Exanthematous drug eruption

 This is a classic presentation of an exanthematous (morbilliform) drug eruption, the most common type of drug-related skin reaction, especially to beta-lactam antibiotics like amoxicillin. It typically begins several days after starting the medication and presents as a symmetric, non-tender, pruritic maculopapular rash beginning on the trunk and spreading outward.

Incorrect Answers:

a. Urticaria

Urticaria presents as raised, transient, blanching wheals with significant pruritus, not a fixed maculopapular rash.

b. Stevens-Johnson Syndrome

SJS would involve mucosal lesions, systemic symptoms, and potentially skin sloughing—none of which are present here.

 d. Erythema multiforme

EM typically presents with target lesions and may involve mucous membranes; it is usually associated with infections like HSV rather than recent medication use alone.

Q2: c. Complete blood count with differential and liver function tests

 This child has classic features of DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), a serious drug-induced hypersensitivity reaction. Evaluation should focus on identifying eosinophilia, atypical lymphocytosis, and organ involvement—most commonly the liver, but also kidneys and lungs. These labs are essential for both diagnosis and monitoring severity.

 Incorrect Answers:

 a. Abdominal ultrasound

 While this may detect hepatomegaly, it does not assess liver function or help diagnose the systemic features of DRESS.

b. Epstein-Barr virus serology

 EBV can cause a rash, fever, and hepatomegaly, but the timing (3 weeks post-medication) and drug exposure point strongly to DRESS.

 d. Skin biopsy

May be supportive but is not necessary to confirm diagnosis and does not evaluate internal organ involvement, which is critical here.

• Basic Dermatology: Drug Reactions (Cases and Questions) (American Academy of Dermatology)
• Basic Dermatology: Urticaria (Cases and Questions) (American Academy of Dermatology)