What to do if Coamoxiclav (amoxicillin/clavulanic acid) is suspected to cause Stevens-Johnson Syndrome (SJS)?

Management of Co-amoxiclav-Induced Stevens-Johnson Syndrome

If co-amoxiclav is suspected to cause Stevens-Johnson Syndrome, immediately discontinue the drug and transfer the patient to a specialized burn unit or ICU for multidisciplinary supportive care, as this is a life-threatening medical emergency with mortality rates of 1-5% for SJS. 1, 2, 3

Immediate Actions Required

Drug Discontinuation

• Stop co-amoxiclav immediately upon suspicion of SJS/TEN - this is the single most critical intervention that directly impacts survival 1, 4
• Co-amoxiclav is contraindicated in patients with a history of Stevens-Johnson syndrome to amoxicillin or clavulanate 3
• Document all medications taken in the previous 2 months, including over-the-counter products, with exact start dates and any dose changes 1, 4

Severity Assessment and Transfer

• Calculate SCORTEN within the first 24 hours of admission to predict mortality risk (scores range 0-7, with higher scores indicating increased mortality) 1, 2, 4
• Transfer immediately to a specialized burn center or ICU if body surface area (BSA) epidermal detachment exceeds 10% 2, 4
• Even with <10% BSA involvement, transfer to a facility with dermatology expertise and ICU capabilities is strongly recommended 1, 2

Initial Clinical Assessment

• Perform total body skin examination documenting the extent of erythema and epidermal detachment separately using a Lund and Browder chart 1
• Examine all mucous membranes (oral, ocular, genital, perianal) for blistering, erosions, and mucositis 1
• Record vital signs, oxygen saturation, baseline body weight, and assess airway patency 1
• Look specifically for atypical target lesions, purpuric macules, blisters, and positive Nikolsky sign 1, 5

Diagnostic Workup

Laboratory Investigations

• Obtain full blood count with differential, C-reactive protein, urea and electrolytes, liver function tests, coagulation studies, glucose, magnesium, phosphate, bicarbonate, and lactate 1, 4
• Blood cultures if febrile 1
• Urinalysis to assess for associated nephritis 1

Skin Biopsy

• Take a biopsy from lesional skin adjacent to a blister for histopathology showing full-thickness epidermal necrosis and keratinocyte apoptosis 1, 4, 6
• Obtain a second biopsy from periblister lesional skin for direct immunofluorescence to exclude autoimmune blistering disorders 4

Infection Screening

• Bacterial swabs from lesional skin for culture and sensitivity 1
• Consider screening for Mycoplasma pneumoniae and Herpes simplex virus, as these can trigger SJS independent of drugs 1, 6

Ophthalmology Consultation

• Arrange ophthalmology examination within 24 hours of diagnosis by a specialist experienced in ocular surface diseases 1, 2, 4
• Obtain conjunctival swabs for bacteria, chlamydia, HSV, and adenovirus 1

Supportive Care Management

Environmental Control

• Place patient in a temperature-controlled room (25-28°C) with controlled humidity 1, 2, 4
• Use a pressure-relieving mattress 2, 4
• Implement barrier nursing techniques to minimize infection risk 4

Fluid Management

• Establish intravenous access and initiate fluid resuscitation guided by urine output, vital signs, and electrolytes 2, 4
• Avoid overaggressive fluid resuscitation - this causes pulmonary, cutaneous, and intestinal edema 2, 4
• Consider using the formula: body weight/% BSA epidermal detachment to determine replacement volumes 2
• Catheterize if clinically indicated for monitoring urine output 2

Wound Care

• Handle skin with extreme care to minimize shearing forces and prevent further epidermal detachment 1, 2, 4
• Leave detached epidermis in situ to act as a biological dressing 4
• Gently irrigate wounds with warmed sterile water, saline, or chlorhexidine (1:5000) 2, 4
• Apply greasy emollient (50% white soft paraffin with 50% liquid paraffin) over the entire epidermis, including denuded areas 2, 4
• Use nonadherent dressings (Mepitel™ or Telfa™) to denuded dermis with secondary foam or burn dressings to collect exudate 2, 4

Pain Management

• Provide adequate background simple analgesia to ensure comfort at rest 1, 4
• Add intravenous opioid infusions (morphine) for moderate-to-severe pain uncontrolled by simple analgesia 1, 2
• Consider patient-controlled analgesia where appropriate, though hand involvement may limit ability to operate the device 1, 2
• Consider sedation or general anesthesia for dressing changes and patient repositioning 2

Infection Prevention

• Do NOT administer prophylactic systemic antibiotics - this increases skin colonization, particularly with Candida albicans 2, 4
• Take regular bacterial swabs from lesional skin for culture 2, 4
• Institute targeted antimicrobial therapy only when clinical signs of infection are present (confusion, hypotension, reduced urine output, reduced oxygen saturation) 2, 4
• Monitor for monoculture of organisms on swabs from multiple sites, indicating increased likelihood of invasive infection 2

Nutritional Support

• Provide continuous enteral nutrition throughout the acute phase, either orally or via nasogastric feeding if oral intake is precluded by buccal mucositis 1, 4
• Deliver 20-25 kcal/kg daily during the early catabolic phase 1, 4
• Increase to 25-30 kcal/kg daily during the anabolic recovery phase 1, 4

Mucosal Management

Ocular Care

• Apply preservative-free lubricant eye drops every 2 hours throughout the acute illness 4
• Perform daily ocular hygiene by an ophthalmologist or ophthalmically trained nurse to remove inflammatory debris and break down conjunctival adhesions 4
• Use topical antibiotics when corneal fluorescein staining or ulceration is present 2, 4
• Consider topical corticosteroid drops under ophthalmologist supervision to reduce ocular surface damage 2, 4

Oral Care

• Apply anti-inflammatory oral rinse containing benzydamine hydrochloride every 3 hours, particularly before eating 4
• Use antiseptic oral rinse twice daily 4
• Provide topical anesthetics such as viscous lidocaine 2% or cocaine mouthwashes 2-5% for severe oral discomfort 4
• Monitor for and treat secondary infections with appropriate antifungals or antivirals 4

Urogenital Care

• Urinary catheterization when urogenital involvement causes dysuria or retention, or to monitor output 4
• Regular examination of urogenital tract during acute illness 4
• Apply white soft paraffin ointment to urogenital skin and mucosae every 4 hours 4
• Consider vaginal dilators or tampons wrapped in Mepitel to prevent vaginal synechiae formation 4

Systemic Immunomodulatory Therapy

Corticosteroids

• Administer IV methylprednisolone (or equivalent) 0.5-1 mg/kg if started within 72 hours of onset 1, 2, 4
• Convert to oral corticosteroids on response, with tapering over at least 4 weeks 1, 2
• The usual prohibition of corticosteroids for SJS does not apply when the mechanism is drug-induced T-cell immune-directed toxicity - adequate immune suppression is necessary 1

Cyclosporine

• Consider cyclosporine 3 mg/kg daily for 10 days, tapered over 1 month, as it has shown benefit with reduced mortality compared to predicted rates 4

Other Immunomodulatory Options

• High-dose intravenous immunoglobulin (IVIG) may be considered under specialist supervision 6, 7, 8

Additional Supportive Measures

• Administer low molecular weight heparin as prophylactic anticoagulation against venous thromboembolism in immobile patients 1
• Provide proton pump inhibitor to protect against upper gastrointestinal stress ulceration if enteral nutrition cannot be established 1
• Consider recombinant human G-CSF if neutropenia develops to reduce risk of life-threatening sepsis 1

Multidisciplinary Team Coordination

• Coordinate care through a team led by a dermatologist or plastic surgeon with expertise in skin failure 2, 4
• Include intensive care physicians, ophthalmologists, and specialist skincare nurses 2, 4
• Involve additional specialists as needed: respiratory medicine, gastroenterology, gynecology, urology, oral medicine, microbiology, pain team, dietetics, physiotherapy, and pharmacy 2

Discharge Planning and Long-Term Management

Patient Education

• Provide written information about co-amoxiclav and all beta-lactam antibiotics to avoid permanently 1, 4, 3
• Inform about potentially cross-reactive medications (other penicillins and cephalosporins) 3
• Encourage wearing a MedicAlert bracelet bearing the name of the culprit drug 4

Documentation and Reporting

• Document the drug allergy prominently in the patient's medical records 4
• Inform all healthcare providers involved in the patient's care 4
• Report the adverse drug reaction to pharmacovigilance authorities 4

Follow-up Arrangements

• Arrange dermatology follow-up within weeks of discharge 2
• Schedule ophthalmology follow-up to monitor for chronic ocular complications 4
• Inform patients about potential fatigue and lethargy for several weeks following discharge 4
• Consider referral to support groups 4

Common Pitfalls to Avoid

• Delayed transfer to a specialized unit significantly increases mortality risk 2, 4
• Continuing the culprit medication even briefly will worsen the condition and increase mortality 4
• Indiscriminate use of prophylactic antibiotics increases skin colonization with resistant organisms, particularly Candida 2, 4
• Overaggressive fluid resuscitation causes complications rather than preventing them 2, 4
• Failure to involve ophthalmology within 24 hours leads to permanent visual impairment 1, 2, 4
• Neglecting daily examination of all mucosal sites results in preventable long-term sequelae 2
• Inadequate pain control compromises patient cooperation with essential care 1, 2