Introduction Managing atopic diseases, such as severe or refractory eczema, can be challenging in otherwise uncomplicated patients. Treating patients, especially young children, with additional chronic skin conditions presents unique challenges. Case Description A 20-month old male presents for evaluation of eczema and environmental allergies with underlying diagnosis of autosomal recessive dystrophic epidermolysis bullosa (DEB), pathogenic variants in COL7A1 gene. After diagnosis of DEB, eczematous lesions (confirmed by dermatologist as eczema) were noted around age 3 months. Initially a food trigger was suspected, but elimination diet did not resolve flares. Worsening eczema was noticed with environmental triggers at times of rhinitis and conjunctivitis symptoms and with weather changes. His skin care regimen is extensive and includes dressings on exposed skin below the neck for his DEB, with addition of topical tacrolimus, topical corticosteroids, oral antihistamines, and emollient use for his eczema, though he still flares. Discussion DEB is a skin and mucous membrane disorder leading to fragility, blistering, and scarring. Children with DEB are not at increased risk of atopic diseases, but they can coexist, which presents unique diagnostic and treatment challenges. With this patient, his atopy leads to significant discomfort and pruritus, with itching leading to blister formation and scarring. Patient had symptom improvement with addition of fexofenadine and montelukast, but topical regimens remain challenging due to his skin fragility. If feasible, future directions may include compassionate use of a biologic like dupilumab.