Management of Adverse Reactions

Introduction to Adverse Reactions

• Adverse reactions can have various causes, including autoimmune, allergic, and infectious etiologies, and require a comprehensive approach to diagnosis and treatment, as recommended by the British Journal of Dermatology 1

Treatment of Grade 3 Reactions

• Systemic corticosteroids, such as prednisone 0.5-1 mg/kg/day for 7 days with tapering over 4-6 weeks, are recommended for Grade 3 reactions, as suggested by the Annals of Oncology 2
• The grading of macules/papules is as follows:

Treatment of Grade 4 Reactions or Anaphylaxis

• IV corticosteroids, such as methylprednisolone 1-2 mg/kg, are recommended for Grade 4 reactions or anaphylaxis, as suggested by the Journal of Clinical Oncology 4
• Epinephrine 0.01mg/kg (1:1000 concentration) IM for anaphylaxis, with a maximum single dose of 0.5mg, is recommended, as advised by 5

Topical and Oral Treatments

• A Class V/VI topical corticosteroid (such as aclometasone, desonide, or hydrocortisone 2.5% cream) is recommended for facial application, applied twice daily for 1-2 weeks, as suggested by 3
• Non-sedating oral antihistamines like cetirizine or loratadine 10 mg daily are recommended, and if sleep disturbance occurs, hydroxyzine 10-25 mg at bedtime may be considered, as suggested by 3
• Emollients with cream or ointment-based, fragrance-free products are recommended for skin care, as suggested by 3
• Combination preparations containing mild corticosteroids with antifungals may be considered to reduce inflammation, as suggested by the Annals of Oncology 2

Treatment of Pruritus

• Non-sedating antihistamines are recommended for generalized pruritus, while sedating antihistamines should be avoided in the elderly except in palliative care, as recommended by the British Journal of Dermatology 1
• Capsaicin cream is effective for uremic pruritus, as suggested by the British Journal of Dermatology 1
• Ciclosporin is effective in about two-thirds of patients with severe autoimmune urticaria, and other immunosuppressants like tacrolimus and mycophenolate mofetil can be considered, as recommended by 6
• Narrow-band UVB phototherapy may be beneficial for pruritus associated with various conditions, and BB-UVB or PUVA can be considered for specific conditions like polycythemia vera, as suggested by the British Journal of Dermatology and [6] [1, 6]
• Gabapentin is useful in elderly patients and uremic pruritus, and nifedipine may reduce pruritus in chronic urticaria, as recommended by the British Journal of Dermatology and [6] [1, 6]

Referral and Follow-up

• Patients should be re-evaluated after 2 weeks of treatment, and if no improvement or worsening is observed, referral to dermatology is recommended, as suggested by the Annals of Oncology 7
• Patients should be referred to a dermatologist or specialist when there is diagnostic doubt, primary care management does not relieve symptoms, the condition is severe or rapidly worsening, or there is suspicion of underlying malignancy or systemic disease, as suggested by the British Journal of Dermatology 1
• Consider dermatology referral, and if pruritus is significant, gabapentin 100-300 mg TID may be considered, as suggested by 3

Special Considerations

• Chronic pruritus can have significant psychological components, and long-term use of sedative antihistamines may predispose to dementia, as recommended by the British Journal of Dermatology 1
• Pruritus alone can rarely be the presenting feature of serious conditions such as bullous pemphigoid, particularly in the elderly, which may require specific investigations like skin biopsy, as recommended by the British Journal of Dermatology 1
• SGLT2 inhibitors, such as Jardiance (empagliflozin), can cause increased urinary glucose excretion, creating an environment conducive to fungal growth, as noted by the American College of Cardiology 8
• Genital mycotic infections are a well-documented side effect of SGLT2 inhibitors, affecting the genital and perianal regions, as reported by the American College of Cardiology 9
• Gentle cleaning of the genital and perianal area with pH-neutral synthetic detergent is recommended, rather than soap, by the Annals of Oncology and the European Society for Medical Oncology 2, 10
• Urgent medical attention is recommended for necrotizing fasciitis of the perineum (Fournier's gangrene), as advised by the American College of Cardiology 9

Treatment Guidelines Based on BSA Affected

Additional Therapies

• IVIG for Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is recommended, as advised by 5
• A slow taper of prednisone combined with steroid-sparing agents like antihistamines and colchicine to prevent rebound inflammation and achieve long-term control in patients experiencing rash flares when stopping prednisone is suggested, as recommended by the European Society of Cardiology 11
• Tranexamic acid can be considered for idiopathic angioedema without weals, as suggested by 6