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Abstract Background The role and importance of skin barrier as an immunologic organ and as a potent way of sensitization is well known. However, antibiotics anaphylaxis following skin sensitization has not been reported. Case presentation We describe the first case of intravenous clindamycin anaphylaxis, with likely sensitization due to previous topical exposure to clindamycin gel for acne in a 14-year-old boy with history of atopy and mild atopic dermatitis. Conclusion This case highlights the potential sensitization to drug allergens, including antibiotics, via the skin.