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DR12.1-5 | Eczemas Erythroderma Drug Reactions — PBL Case

CLINICAL SETTING

You are the intern on night duty in a general medicine ward at a district hospital. It is 11 PM. You are called urgently to see Mrs Sunita Rao, a 28-year-old primary school teacher, who was admitted 18 hours ago with a presumed urinary tract infection and started on co-trimoxazole DS (160/800 mg) twice daily. The nursing staff report that she has developed widespread skin blistering over the past 6 hours and is now in pain and distress. The ward has no dermatologist on call tonight. You are the first doctor to see her. Your initial assessment: She is conscious but anxious, heart rate 104 bpm, blood pressure 98/62 mmHg (baseline was 118/76 at admission), temperature 37.8°C, RR 20/min. Her oral mucosa has two shallow erosions on the inner cheeks. Her lips are cracked and crusted. Her conjunctivae appear red bilaterally. On skin examination, there is a positive Nikolsky sign over the trunk. You estimate approximately 8% of her BSA has epidermis that can be sheared off with lateral pressure (detachment), and another 10% has a dusky purple discolouration with intact but tense bullae. She is extremely tender when you touch the affected areas. Her blood reports from earlier today (before co-trimoxazole): FBC normal, renal function normal, LFTs normal, CRP 14 mg/L.

Trigger 1: Trigger 1 — Initial Assessment and Immediate Classification

Mrs Rao is clearly unwell. The nursing staff are asking you what has happened. Co-trimoxazole was her only new medication. She is HIV-negative (tested at admission). She has no prior history of skin disease. She reports she has taken co-trimoxazole once before 3 years ago without any problems. The admitting doctor's note says she was well 24 hours ago. You recall the classification of Stevens-Johnson syndrome and toxic epidermal necrolysis: - SJS: epidermal detachment < 10% BSA - SJS/TEN overlap: detachment 10–30% BSA - TEN: detachment > 30% BSA Current detachment: 8% BSA. Another 10% has tense bullae that have not yet detached.

DISCUSSION POINTS

  • Apply the BSA classification: what does 8% detachment classify this as right now? How would the clinical picture change your classification if the bullae (10%) also detach overnight?
  • What does a positive Nikolsky sign tell you about the mechanism of this reaction? How does this differ from the Nikolsky sign seen in pemphigus vulgaris (where the mechanism of epidermal separation is different)?
  • Co-trimoxazole was started only 18 hours ago, but the student recalls that SJS/TEN typically has a latency of 1-3 weeks. How do you reconcile this? (Hint: is this her first exposure to co-trimoxazole?)
  • What is your most pressing concern for the next 2 hours of this patient's care, based on her vital signs alone?
Click to reveal Trigger 2: Trigger 2 — Mucosal Involvement and Systemic Assessment (discuss previous trigger first!)

Trigger 2: Trigger 2 — Mucosal Involvement and Systemic Assessment

You examine the patient more carefully. The mucosal findings are: two erosions on the buccal mucosa, crusted lips, bilateral conjunctival injection with early mucopurulent discharge from the left eye. You are concerned about urogenital involvement and carefully examine externally — there is erythema around the urethral meatus but no erosions yet. A urine dipstick (just done) shows nitrites positive, consistent with the original UTI. A medical student on the call asks: 'Can this be staphylococcal scalded skin syndrome? The Nikolsky sign is positive too.' You pause and think through the differential. The patient's blood pressure has dropped to 94/60 mmHg. She has received 500 mL of IV normal saline since admission (for the UTI).

DISCUSSION POINTS

  • Compare SJS/TEN with staphylococcal scalded skin syndrome (SSSS): age group, mucosal involvement, level of epidermal cleavage (histology), and causative mechanism. Which diagnosis fits this patient and why does SSSS not fit?
  • Mucosal involvement in SJS/TEN affects at least two mucosal surfaces. Name four mucosal surfaces that can be affected and explain why ophthalmological involvement requires urgent specialist assessment.
  • The patient is hypotensive (94/60 mmHg) after only 18 hours. Explain the pathophysiology of haemodynamic instability in SJS/TEN — what has happened to the skin's barrier function and how does this cause fluid loss?
  • You are in a district hospital with no dermatologist. List five immediate stabilisation actions you can take right now, before transferring this patient. Order them by priority.
Click to reveal Trigger 3: Trigger 3 — Drug Cessation, Mimics, and the Burning Question (discuss previous trigger first!)

Trigger 3: Trigger 3 — Drug Cessation, Mimics, and the Burning Question

At 1 AM, after your initial stabilisation measures, you review the case with the senior resident by phone. She asks you to recheck two things: (1) Was the co-trimoxazole given again at 10 PM (the nurse confirms it was — the second dose was given 1 hour before the skin reaction was noticed), and (2) Are there any other new drugs in the chart? You check — no other new drugs. As you write the stop order for co-trimoxazole, the nurse asks: 'The UTI is still not treated — can we switch her to nitrofurantoin?' You also notice the wound dressing kit in the ward contains silver sulfadiazine cream. The patient's repeat vitals after 1 L IV fluid: BP 104/68 mmHg, HR 96 bpm. Urine output in the last 2 hours: 40 mL.

DISCUSSION POINTS

  • Why is stopping co-trimoxazole the single most important therapeutic action in this case? Explain why continuing the second dose worsened the reaction — reference the T-cell-mediated pathogenesis of SJS/TEN.
  • The nurse proposes silver sulfadiazine cream for wound care. Evaluate this suggestion critically. What is silver sulfadiazine's chemical class, and why would it be contraindicated here? Name an acceptable non-sulfonamide wound dressing alternative.
  • Can nitrofurantoin be safely used to complete the UTI treatment? Identify the key principle when choosing an alternative antibiotic in a patient who has had SJS/TEN from a specific drug.
  • The urine output is 40 mL over 2 hours (borderline oliguria at this weight — assume 60 kg). Using the burns-model analogy, what does this urine output tell you about the adequacy of fluid resuscitation, and what should your target urine output be?
Click to reveal Trigger 4: Trigger 4 — Long-term Implications and Learning Issues (discuss previous trigger first!)

Trigger 4: Trigger 4 — Long-term Implications and Learning Issues

Mrs Rao is transferred to a tertiary burns unit the next morning. She recovers over 3 weeks. On discharge, the dermatologist gives her a drug allergy card listing co-trimoxazole as a lifelong contraindication. Three months later, she comes to your primary care clinic for a routine check-up. She has healed well, but she has developed dry eye syndrome and requires artificial tears. She asks: - 'My sister also takes co-trimoxazole sometimes — should she be tested for this reaction risk?' - 'I still have some patches of darker skin where the blisters were — is this normal?' - 'If I ever get another skin infection, which antibiotics are safe for me?' - 'Could this reaction have been predicted or prevented?'

DISCUSSION POINTS

  • Explain the post-SJS/TEN sequelae this patient has developed (dry eye from conjunctival scarring). What other long-term complications of SJS/TEN should you screen for at this follow-up visit?
  • The patient asks about genetic risk to her sister. Discuss the pharmacogenomic basis of SJS/TEN risk (HLA associations — specifically HLA-B*1502 and its association with aromatic anticonvulsants in South/East Asian populations, and HLA-B*5801 and allopurinol). Does co-trimoxazole have a known HLA association? What is the practical advice for the sister?
  • Address the post-inflammatory hyperpigmentation at healed sites. Explain its mechanism and expected natural history.
  • Synthesise the preventability question: what pre-prescription steps (drug history, allergy documentation, HLA screening where applicable) could have reduced the risk in this patient?

Learning Issues

Research these questions and bring your findings to the discussion.

  1. [DR12.3] What is the definition of erythroderma and how does it differ from the mechanism of skin failure in SJS/TEN?
  2. [DR12.4] How do you classify SJS vs SJS/TEN overlap vs TEN by BSA detachment, and what are the distinguishing features from SSSS?
  3. [DR12.4] What is the mechanism of DRESS vs SJS/TEN — why do they produce different clinical phenotypes despite both being T-cell-mediated?
  4. [DR12.5] What is the primary care burns-model protocol for SJS/TEN before specialist transfer?
  5. [DR12.5] What are the long-term sequelae of SJS/TEN and how are they monitored at primary care level?