Systemic therapies can be used in the treatment of AD as monotherapy or in conjunction with other treatments, for example, in combination with topical corticosteroids. Patient education is essential to create realistic expectations as to the AD prognosis without systemic therapy and with systemic therapy. Systemic therapy is often clinically considered after treatment with topical corticosteroids has failed; therefore, clinicians should revisit the diagnosis to determine if a misdiagnosis caused the topical treatment failure before initiating systemic therapy. The risks and burdens of any course of treatment should be fully explained, along with alternatives, for a shared decision-making approach between clinician and patient.

• Systemic therapy in the treatment of AD is appropriate in select patients in specific clinically scenarios.
• Dupilumab is widely used, and its indications and usages are discussed.
• Current systemic therapy options available in 2019 are safe and effective in treating AD.
• New and emerging systemic therapies are expected with targets for treating atopic dermatitis including barrier defects, keratinocyte cytokines and dysbiosis.

In determining whether to initiate systemic therapy, clinicians should be guided by factors including the clinical response to topical therapy, impact on patient quality of life, and potential efficacy of systemic treatment [1].

• If topical treatment has been aggressive, yet has not yielded adequate control of the disease, and moderate to severe skin lesions persists, systemic therapy should be considered. The threshold of adequate control varies with the patient and depends upon their individual priorities regarding appearance, discomfort, and interference with activities.
• Clinicians should also reconsider the diagnosis (e.g., to rule out infection or allergic contact dermatitis) to ensure that a misdiagnosis does not underlie the topical treatment failure. A biopsy can be considered.
• Systemics may not be warranted in conditions where there is adult onset, sudden worsening, lack of history of atopy in patient or family, atypical morphology, or atypical distribution.
• When recommending systemics, clinicians should offer advice and educate the patient appropriately regarding adherence, as well as potential risks and benefits. Clinicians should also consider phototherapy as a non-toxic option.

• Clinicians should educate patients and caregivers regarding the nature of their AD, long-term expectations, and range of treatment options and results.
• Clinicians should engage patients in shared decision making so that a reasonable expectation of treatment risks and burdens, likely benefits and long-term outcomes, can be assessed in the context of the patients’ comorbidities and quality of life [2].
• Patients should be made aware that the AD is a chronic disease, with no cure, stemming from an over active immune system.
• Patient education should be tailored to a patient’s level of health literacy.
• While many patients have comorbidities such as food allergies that may play a role in other health conditions, clinicians should clearly advise patients when allergic triggers do not underlie the AD.
• The extent to which the AD impacts the patient’1s quality of life is a paramount treatment consideration. Without this information, patients may not be able to weigh risks and benefits of systemics in a full context of alternatives.

Several effective systemic treatment options are currently available, including the following:

• Dupilumab: potential advantages include rapid onset, 80% efficacy, and the potential to be safely used long-term without the need for lab work. Disadvantages include injection administration and potential conjunctivitis in 10-25% of patients.
• Cyclosporine: potential advantages include rapid onset and 80% efficacy. Disadvantages may include hypertension, peripheral neuropathy, drug interactions, renal dysfunction, labs, 1-year limit, drug interactions, and immunosuppressive properties. Cyclosporine is not recommended for patients with uncontrolled hypertension, history of severe malignancy, or systemic infection.
• Methotrexate: potential advantages include the potential for long-term use and 50% efficacy. Achieves Eczema Area and Severity Index (EASI) 50 in 87% of those studied at week 20 and is available for use in children [3]. Disadvantages may include slow onset, liver toxicity, and blood count problems [3].
• Mycophenolate: potential advantages are that there is no renal toxicity or hepatotoxicity and has efficacy comparable to cyclosporine. It is available for use in children and for patient with contraindications to methotrexate [4].
• Azathioprine: potential advantages are lower costs. It is also available for use in children. Potential disadvantages include a lower rate of efficacy than other systemic agents, and adverse effects involving blood count, liver dysfunction and immunosuppression [5].