Erythema multiforme — clinical viva

Q1: Define EM and describe a typical target

Examiner: What is erythema multiforme, and what lesion earns the diagnosis?[1]

Candidate: EM is an acute immune-mediated skin and mucosal eruption recognised by raised target lesions. A typical target is palpable and has three zones: a dusky, purpuric or blistered centre; a paler oedematous ring; and an outer erythematous ring. Lesions are often symmetrical and acral.[1]

Q2: Classify it without creating an overlap

Examiner: Explain EM minor and EM major. What newer approach is clinically useful?[1]

Candidate: Traditionally, EM minor has characteristic skin lesions with no mucosal disease or mild disease limited to one surface. EM major retains the raised-target eruption but has more severe mucosal disease, historically often at two or more surfaces. Because site counting overlaps, current reviewers favour non-severe versus severe EM, based on pain, intake and organ-threatening mucosal disease. A few mild oral erosions should not automatically be labelled EM major.[1]

Q3: Separate EM, SJS/TEN and RIME/MIRM

Examiner: Are these one spectrum?[1][2]

Candidate: EM and SJS/TEN are clinically distinct. Raised acral targets support EM, and a central blister can occur within a raised three-zone target. Painful purpuric macules or flat atypical targets that blister, widespread or confluent blistering, and epidermal detachment support SJS/TEN. Infections and drugs are useful patterns, not absolute rules. RIME is prominent infection-triggered mucositis with variable, often sparse skin disease; MIRM is its Mycoplasma pneumoniae-associated form. MIRM was proposed as distinct from EM and SJS/TEN, while whether RIME overlaps a broad EM spectrum remains debated.[1][2]

Q4: Assess the patient at the bedside

Examiner: What are your immediate examination priorities?[1][3]

Candidate: I document lesion morphology, distribution, pain, blistering and any detachment, then examine oral, ocular, genital and anal mucosae. I assess fluid and food intake, urine symptoms, vital signs and the lungs. Nikolsky sign is typically absent in classic EM; a positive sign or sloughing is a red flag for epidermal necrolysis, but severe or M. pneumoniae-associated EM can show detachment, so the sign is not an absolute standalone test.[1][3]

Q5: Choose investigations selectively

Examiner: Do you order HSV and Mycoplasma serology for everyone?[1]

Candidate: No. Typical mild EM is a clinical diagnosis. I take a complete infection, recurrence, vaccine and medicine timeline. If an active suspicious HSV lesion is present, I sample it for PCR; routine HSV antibody titres do not prove recurrent HSV-associated EM. Severe disease with respiratory features warrants lung examination, chest imaging when indicated, respiratory M. pneumoniae PCR and context-appropriate serology. Other tests are driven by the history and differential, not a shotgun panel.[1]

Q6: Explain what biopsy can and cannot do

Examiner: Is punch biopsy the definitive EM-versus-SJS/TEN discriminator?[1][3]

Candidate: No. Biopsy helps when the morphology is atypical or an immunobullous, connective-tissue or drug reaction is possible. Typical EM shows interface dermatitis, basal vacuolar change, lymphocytes and scattered apoptotic keratinocytes, but confluent necrolysis and detachment can occur. Therefore EM and SJS/TEN may be histologically indistinguishable; the diagnosis remains clinicopathological. Direct immunofluorescence is usually nonspecific and is mainly useful to exclude an autoimmune blistering disorder.[1][3]

Q7: Manage the acute episode

Examiner: Give your stepwise acute plan.[1]

Candidate: First, activate an SJS/TEN pathway if painful flat purpura blisters, blistering is widespread or confluent, epidermal detachment occurs, or a plausible drug makes epidermal necrolysis possible. A central blister within a raised three-zone target remains compatible with EM. Otherwise, assess whether mucosal pain, intake, hydration, eye disease or respiratory compromise requires admission. Support skin with bland emollient and consider topical corticosteroid; provide appropriate analgesia, oral care, hydration and nutrition. Eye disease needs same-day ophthalmology. Treat proven or strongly suspected M. pneumoniae respiratory infection according to local antimicrobial guidance, while explaining that mucocutaneous benefit is uncertain. Starting aciclovir after the EM eruption is established has not been shown to shorten that episode. Systemic corticosteroids remain unproven and are not routine.[1][2][5]

Q8: Prevent recurrence and bound specialist therapy

Examiner: A patient has repeated, burdensome attacks. What is first line, and what if it fails?[4]

Candidate: Recurrent means repeated episodes; it is not defined by an arbitrary six-per-year threshold, and not every case is proven HSV-driven. First line is continuous oral antiviral prophylaxis after diagnostic, renal and medicine review. Aciclovir 400 mg orally twice daily for at least 6 months has placebo-controlled evidence. Review-supported alternatives are valaciclovir 500 mg orally twice daily or famciclovir 250 mg orally twice daily. Responders may continue for 1–2 years before a supervised withdrawal attempt. If attacks continue, I check adherence, dosing and diagnosis before dermatology considers low-certainty options such as dapsone, azathioprine, mycophenolate, thalidomide/lenalidomide or targeted therapy.[4][1][5]

Q9: Give prognosis without false reassurance

Examiner: Is EM always benign and scar-free?[1][2]

Candidate: Many acute episodes resolve over several weeks, but severe mucositis can cause pain, dehydration, weight loss and admission. Ocular or genital disease can scar, and recurrent or persistent EM can be disabling. RIME/MIRM is often survivable but published series report mucosal damage, scarring and recurrence; referral and publication bias limit precise estimates. I safety-net every patient for reduced intake, eye symptoms, respiratory compromise, blistering that becomes widespread/confluent or appears on flat purpuric lesions, or detachment.[1][2]

References

1. [1]Kechichian E, Dupin N, Wetter DA, Ortonne N, Agbo-Godeau S, Chosidow O. Erythema multiforme EClinicalMedicine, 2024.PMID 39583748
2. [2]Canavan TN, Mathes EF, Frieden I, Shinkai K. Mycoplasma pneumoniae-induced rash and mucositis as a syndrome distinct from Stevens-Johnson syndrome and erythema multiforme: a systematic review J Am Acad Dermatol, 2015.PMID 25592340
3. [3]Amode R, Ingen-Housz-Oro S, Ortonne N, Bounfour T, Pereyre S, Schlemmer F, Bequignon E, Royer G, Wolkenstein P, Chosidow O. Clinical and histologic features of Mycoplasma pneumoniae-related erythema multiforme: A single-center series of 33 cases compared with 100 cases induced by other causes J Am Acad Dermatol, 2018.PMID 29559400
4. [4]Tatnall FM, Schofield JK, Leigh IM. A double-blind, placebo-controlled trial of continuous acyclovir therapy in recurrent erythema multiforme Br J Dermatol, 1995.PMID 7888365
5. [5]de Risi-Pugliese T, Sbidian E, Ingen-Housz-Oro S, Le Cleach L. Interventions for erythema multiforme: a systematic review J Eur Acad Dermatol Venereol, 2019.PMID 30680804