Erythema multiforme and drug eruption Notes

NOTES NOTES ERYTHEMA MULTIFORME & DRUG ERUPTION GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES DIAGNOSIS ▪ Skin, mucous membrane conditions ▪ Associated with medication use/infection LAB RESULTS CAUSES OTHER DIAGNOSTICS ▪ Exact mechanism unclear, severe immune reaction against foreign antigen ▪ Skin biopsy ▪ Clinical history TREATMENT COMPLICATIONS ▪ Initial rash may → epidermal layer loss ▪ Identify/remove/treat offending agent/ infection SIGNS & SYMPTOMS ▪ Desquamating skin, mucous membrane rash ERYTHEMA MULTIFORME osms.it/erythema-multiforme PATHOLOGY & CAUSES ▪ Immune-mediated, acute, self-limiting skin condition ▪ Type IV hypersensitivity CAUSES ▪ Suspected deposition of primarily IgMbound immune complexes in superficial skin, oral mucous membranes Infection (most) ▪ Viral ▫ Herpes simplex primary cause 16 OSMOSIS.ORG ▪ Bacterial ▫ Hemolytic Streptococci, Legionella, Mycobacterium, Mycoplasma pneumoniae, Neisseria meningitidis, Pneumococcus, Salmonella, Staphylococcus ▪ Parasitic ▫ Trichomonas, Toxoplasma gondii Drugs (rarely) ▪ Non-steroidal anti-inflammatories (NSAIDs), sulfonamides, phenytoin, barbiturates, phenylbutazone, penicillin, allopurinol

Chapter 3 Erythema Multiforme & Drug Eruption Physical factors ▪ Sunlight, radiotherapy, cold Autoimmune disease ▪ Vasculitides Hematological malignancy ▪ Non-Hodgkin lymphoma, leukemia, myeloid metaplasia RISK FACTORS ▪ < 20 years old ▪ ↑ frequency in biological males SIGNS & SYMPTOMS ▪ “Multiforme” denotes wide associated lesion variety ▪ Target lesions ▫ Initially round erythematous papules → dusky central area/blister, surrounded by dark red inflammation, surrounded by pale edematous ring, erythematous region on periphery ▪ Pruritus in affected area ▪ Painful lesions ▪ If severe ▫ Fever, weakness, malaise Erythema multiforme minor ▪ Often herpes simplex ▪ Involves skin (little/no mucous membrane involvement) ▪ Favors skin of extremities, face ▪ Symmetrical circular lesions ▪ Lesions become classic “target” lesions (red border, small white center) ▪ Rash spreads towards body center Erythema multiforme major ▪ Often drug-related ▪ Epidermal detachment/skin loss progression ▪ Erythematous, confluent, bullous lesions ▪ Involves mucous membranes ▪ Nikolsky’s sign (lightly rub skin with firm object for few seconds → blister forms) DIAGNOSIS LAB RESULTS ▪ Biopsy to exclude other skin disorders OTHER DIAGNOSTICS ▪ Identify offending agent/infection ▫ Identification: target lesions, symmetrical distribution TREATMENT ▪ Often self-resolving in 1–2 weeks MEDICATIONS ▪ Control primary cause ▫ Treat/remove identifiable causes ▫ Herpes simplex suspected: oral acyclovir/valaciclovir/famciclovir ▫ Eliminate possible offending drugs Figure 3.1 The abdomen of a child displaying numerous target lesions in a case of erythema multiforme. Mild disease ▪ Topical corticosteroids ▪ Antihistamines Severe Disease ▪ Glucocorticoids ▪ In severe cases, prednisone considered OSMOSIS.ORG 17

Recurrent disease ▪ Systemic antivirals (up to 6 months) ▪ Immunosuppression if antivirals fail STEVENS–JOHNSON SYNDROME & TOXIC EPIDERMAL NECROLYSIS osms.it/stevens-johnson_syndrome osms.it/toxic-epidermal-necrolysis PATHOLOGY & CAUSES ▪ Same underlying pathology (severity spectrum) ▫ Stevens–Johnson syndrome (lower end), toxic epidermal necrolysis (upper end) ▪ Severity, classification ▫ Body surface involvement % ▪ Severe mucocutaneous reaction → epidermal detachment COMPLICATIONS ▪ Dehydration, sepsis, pneumonia, multiple organ failure, renal tubular necrosis, acute renal failure, phimosis, vaginal synechiae (adhesions), inside eyelid-tissue scarring → corneal vascularisation → vision loss CAUSES ▪ Cytotoxic T cell mediated destruction of keratinocytes expressing foreign antigen Medications ▪ Most common ▪ Allopurinol, sulfa drugs (e.g. sulfonamide antibiotics), lamotrigine, carbamazepine, nevirapine, phenylbutazone, thiacetazone, oxicam NSAIDS Infections ▪ Mycoplasma pneumoniae most common infective agent RISK FACTORS HIV/AIDS Systemic lupus erythematosus > 40 years old Genetic carbamazepine interaction predisposition (HLA-B*15:02, HLAA*31:01 alleles) ▪ ↑ frequency in biological females ▪ ▪ ▪ ▪ 18 OSMOSIS.ORG Figure 3.2 An individual with Stevens– Johnson syndrome.

Chapter 3 Erythema Multiforme & Drug Eruption DIAGNOSIS SIGNS & SYMPTOMS Systemic ▪ Before skin eruptions occur ▪ Fever, sore throat, fatigue, cough Mucocutaneous ▪ Burning eyes, skin ▪ Red-purple macules → skin blisters → peels, forms painful raw areas ▪ Mucous membranes (often) → painful crusts, erosions ▪ Starts on trunk → rest of body ▪ Spontaneous ulceration of skin, mucous membranes (often eyes/lips) ▪ Conjunctivitis (often accompanied by purulent discharge) ▪ Round ulcerating lesions (approx. 2.5cm/1in diameter) ▫ Arise on face, trunk, arms, legs, soles of feet (scalp spared) ▪ Nikolsky’s sign ▪ Stevens–Johnson syndrome: < 10% skin involvement ▪ SJS/TEN overlap: 10–30% ▪ Toxic epidermal necrolysis: > 30% LAB RESULTS ▪ Skin biopsy OTHER DIAGNOSTICS ▪ Clinical history, suspected agents TREATMENT MEDICATIONS ▪ Analgesics (non-opioid for non-severe, opioids for severe pain) ▪ Antihistamines ▪ Intravenous immunoglobulin Infection control ▪ Culture-specific antibiotic initiation OTHER INTERVENTIONS ▪ ▪ ▪ ▪ Transfer to burn/intensive care unit Fluid support Oral feeding, nasogastric tube Room temperature 30–32°C/86–90°F (minimize heat loss) Infection control ▪ Sterile handling ▪ Skin disinfection ▫ Antiseptic solution ▪ 48 hourly skin, blood, indwelling line culture Figure 3.3 An individual with toxic epidermal necrolysis ten days after the onset of symptoms. OSMOSIS.ORG 19

Figure 3.4 A histological section of skin demonstrating epidermal necrolysis. The epidermis is detached from the dermis and the keratinocytes have undergone necrosis. This can be seen in erythema multiforma, Stevens-Johnson syndrom and toxic epidermal necrolysis. 20 OSMOSIS.ORG