Topical therapies help restore skin barrier function, reduce inflammation, and alleviate pruritus. In cAD and hAD, intercellular lipids in the SC, including ceramides, cholesterol, and FAs, are typically diminished, causing increased transepidermal water loss (TEWL) and skin permeability.^2,7

Canine research has demonstrated that topical agents containing ceramides, cholesterol, and FAs can replenish lipids in the skin and improve clinical outcomes. Using a shampoo containing piroctone olamine (an antimicrobial agent), ceramides, cholesterol, and FAs twice per week during a flare, and once weekly thereafter, has been found to significantly alleviate pruritus and improve hydration in cAD.⁴ More recent research suggests that sphingosines (natural derivatives of ceramides) may aid in repairing the skin barrier in cAD.⁴

In children, using soap-free, neutral pH cleansers has been recommended, as soap-based products can strip the skin of natural oils, exacerbating dryness and irritation.¹ Additionally, using a moisturizer twice daily and ideally following a bath has been shown to improve skin hydration, reduce TEWL, and prevent AD flares.^8,9 As with canines, avoiding products with fragrance and known irritants or allergens is important.¹⁰

Topical steroids inhibit pathways that drive pruritus and inflammation, making them a cornerstone in AD management. Various steroid preparations have demonstrated efficacy in improving symptoms of cAD.⁴ However, their use is complicated by challenges such as licking and fur interference.⁴

Topical steroids have long remained the first-line treatment after gentle skin care in hAD.¹¹ For mild cases and those involving the face or skin folds, the literature supports applying a low-potency topical steroid once or twice daily until lesions resolve or for up to two weeks.¹² In moderate to severe cases, more potent topical steroids may be recommended.¹² After a flare has subsided, intermittent use of a low-potency steroid or non-steroidal agent on previously affected areas can help prevent relapse, called proactive or maintenance therapy. A systematic review demonstrated a significant reduction in relapse rates—from 58% to 25%—when proactive treatment was maintained for 16 weeks.¹³

Topical calcineurin inhibitors (TCIs) inhibit T-cell activation and reduce inflammation, making them effective steroid-sparing therapies.^14,15 In cAD, daily tacrolimus use for 4-12 weeks was found to treat localized lesions and reduce clinical signs by 50%. Though more expensive than steroids, it is generally well-tolerated and safe in canines.¹⁴

Tacrolimus and pimecrolimus have been used in hAD. These TCIs are especially useful for more delicate areas and when steroids should be avoided. Tacrolimus 0.03% and pimecrolimus 1% are approved for use in children two years and over.¹⁵ Application to affected areas twice daily during flares and twice weekly for maintenance therapy has been found to be effective.¹⁵ As with cAD, TCIs are well-tolerated and effective in the pediatric population.

Several other topicals have gained attention for their potential to help manage pediatric AD. Tapinarof, an aryl hydrocarbon receptor agonist, has been approved for use in children two years and over. Its mechanism of action improves skin barrier function and reduces inflammation and pruritus.¹⁶ Topical phosphodiesterase 4 (PDE4) inhibitors have also demonstrated promise by reducing production of pro-inflammatory cytokines and interleukins implicated in the pathogenesis of AD.¹⁶ Crisaborole and roflumilast are two PDE4 inhibitors that have been found to be safe and effective for managing mild to moderate AD in children three months and over and six years and over, respectively.¹⁶ Preliminary studies on the use of topical PDE4 inhibitors in cAD are limited and this remains an area of active research.

Topical ruxolitinib, a JAK1/2 inhibitor, is approved for hAD in patients 12 years and over, with trials showing rapid itch relief and minimal systemic absorption.¹⁷ It is not commonly used in veterinary medicine and efficacy data in canines is lacking.

Topical antimicrobials may also aid AD management. Hypochlorous acid-based hydrogels have been used to reduce bacterial colonization and symptom severity.¹⁸ While not a primary treatment for AD, mupirocin can be used for secondary bacterial infections that commonly complicate AD.¹⁸

Despite the growing range of topical therapies available for both cAD and hAD, limitations remain. Tolerability and adherence are key challenges—children may resist preparations that sting, feel greasy, or have an unpleasant odor, while canine treatment may be hindered by licking, fur interference, and caregiver fatigue.^1,4,11,13

Systemic therapies are often necessary for severe, widespread, or refractory AD. They reduce inflammation and provide acute and long-term control. Despite their substantial benefits, they are typically associated with more adverse effects compared to topical therapies.

Oral steroids like prednisone and prednisolone have been used for acute flares and chronic management of cAD, providing rapid and significant symptomatic relief.¹⁹ The lowest effective dose should be used for the shortest possible duration due to potential side effects.¹⁹

Currently, the role of systemic steroids in pediatric care is more limited, reserved for short durations in severe, refractory AD or as a bridge to other therapies.²⁰ Guidelines recommend against their use, citing low-certainty evidence for meaningful benefit and growing concerns about significant risks.⁵ While short-term improvement may occur, these effects are often transient and rebound flares can occur following discontinuation.⁵ Adverse effects like growth suppression, adrenal insufficiency, weight gain, increased risk of infection, and topical steroid withdrawal syndrome have been documented, even with short courses.^5,20 Experts also highlight a pattern of repeated steroid bursts in lieu of accessing safer, more effective long-term therapies, reinforcing the recommendation to avoid systemic steroids whenever possible in the pediatric setting.⁵

Despite not being approved for this indication in the United States, systemic cyclosporine has been used in acute flares and maintenance phases of AD.¹ In canine studies, it led to improved clinical signs and prevention of flares.^3,7 However, there was no significant impact on the skin barrier or microbiota.^3,7

In children, cyclosporine is rarely used but may be considered for refractory disease. While it has a rapid onset of action, it has been associated with nephrotoxicity, hypertension, and increased risk of infection and thus warrants close monitoring.^1,5

Methotrexate is a systemic immunosuppressant with a slow onset of action. It also requires baseline and ongoing laboratory monitoring due to potential adverse effects, including bone marrow suppression, hepatotoxicity, and gastrointestinal symptoms.⁵ Although it has been used in select cases of pediatric AD, guidelines advise against its use in AD, citing that the potential harms and treatment burden may outweigh the modest benefits.⁵ Methotrexate is also not commonly used in the treatment of cAD due to limited evidence of efficacy and a higher risk of toxicity, making other agents preferable in veterinary practice.

JAK inhibitors are a newer class of systemic therapies that target enzymes involved in regulating inflammatory and immune responses.²¹ Oclacitinib, a JAK1 inhibitor, has demonstrated efficacy in managing pruritus in cAD.^4,14,22 However, studies have found that prolonged use increases the risk for vomiting, diarrhea, and leukopenia.²³ Additionally, it is contraindicated in canines younger than one year of age or those with serious infections.³

In children over 12 years of age, the oral JAK inhibitors upadacitinib and abrocitinib have been approved for moderate to severe AD in the United States. In clinical trials, upadacitinib (15 mg and 30 mg) has demonstrated significantly higher rates of clear skin at 16 weeks compared to placebo, along with notable improvements in pruritus and Eczema Area and Severity Index (EASI-75) scores.²⁴ Abrocitinib (100 mg and 200 mg), used in combination with topical steroids, has demonstrated clinical improvement observed as early as two days.²⁵ While JAK inhibitors offer rapid symptom relief and are a promising option for patients unresponsive to topicals or biologics, they also carry a boxed warning for serious risks like infections, malignancy, thrombosis, and cardiovascular events.⁵ More common side effects include acne, nausea, and herpes simplex infections.⁵ Given these concerns, their use requires careful patient selection, pre-treatment screening, and ongoing lab monitoring. While effective, especially at higher doses, their long-term safety in pediatric AD remains under investigation.^24,25

MAbs represent a different class of systemic therapy that target specific immune mediators. IL-31, a key itch mediator in cAD, acts on somatosensory neurons and promotes release of proinflammatory mediators.^3,4 Lokivetmab is a MAb against IL-31 that has led to significant improvements in pruritus and other clinical signs of cAD. Initially approved in 2016, it is administered subcutaneously and offers long-lasting relief with minimal side effects.^3,4,14,22

In children, dupilumab is the most widely used MAb, targeting the IL-4 receptor and inhibiting IL-4 and IL-13.¹ It is approved for the use of moderate to severe AD in patients 6 months and over.^1,16 Randomized clinical trials in pediatric populations have demonstrated that dupilumab significantly improves EASI-75 scores compared to placebo.^16,17 The overall prevalence of adverse events has been comparable between dupilumab and placebo, however, a higher incidence of conjunctivitis has been observed in the dupilumab group.¹⁷ Dupilumab is administered subcutaneously every two to four weeks and recent data has shown it offers sustained safety and efficacy over a two-year period. Notably, a 2024 study also found that children aged 6–11 years in the lowest height percentiles experienced greater height percentile gains on dupilumab compared to placebo within 16 weeks—highlighting the importance of early, effective treatment in mitigating potential growth delays associated with severe AD.^16,26 Other MAbs, such as tralokinumab and lebrikizumab, which target IL-13, and nemolizumab, which targets IL-31, have demonstrated positive results in clinical trials and are approved for moderate to severe AD in patients 12 years of age and older.²⁷

Nemolizumab is particularly notable for its mechanism’s dual relevance in both pediatric and canine AD populations, acting on a key itch mediator (IL-31). In phase 2 trials, monthly subcutaneous doses of nemolizumab was well tolerated and associated with significant improvement in pruritus, EASI, SCORAD, and sleep scores.²⁷ While it does not have a boxed warning or require laboratory monitoring, as with all biologics, the need for repeated injections may pose a barrier. Additionally, treatment-related adverse events can occur including exacerbation of AD, respiratory infection, nasopharyngitis, peripheral edema, increased blood creatine phosphokinase level, and injection-site reactions.²⁷

Allergen-specific immunotherapy (AIT) has been well-established in managing allergic rhinitis and asthma, which are atopic diseases often found along with AD. AIT has varying success rates in managing cAD.⁴ Guidelines for hAD recommend adding AIT for appropriate patients with moderate to severe AD given the anti-inflammatory, immunomodulatory, and pro-tolerogenic effects.⁵ However, further research is needed to elucidate how allergens and AIT influence AD and interact with other factors that contribute to disease pathogenesis.

Antihistamines have long been used to manage pruritus in AD. In cAD, first- and second-generation antihistamines like hydroxyzine and cetirizine have been prescribed, though their effectiveness is limited due to the multifactorial nature of pruritus.^3,14,19 Antihistamines have also been used in hAD, though again evidence for their efficacy is weak. However, first-generation antihistamines like diphenhydramine may be beneficial when children experience sleep disturbances secondary to pruritus.¹ Otherwise, second-generation antihistamines are usually preferred in children because they have fewer sedative effects and are more suitable for long-term use.¹

Various therapies have gained attention as adjuncts to conventional AD management, especially when disease is persistent, refractory, or negatively impacts quality of life. Evidence is less robust and sometimes anecdotal, but supportive approaches may augment symptom management and improve quality of life. In canines and children, options like probiotics, vitamin D, vitamin E, zinc, essential FAs, and coconut oil may enhance skin structure and reduce inflammation.^1,3 Canines may also benefit from behavioral treatments such as anxiolytics when stress is thought to be a major contributor.¹⁹ In children, AD management often incorporates wet wrapping and bath-based therapies, as well as narrowband UVB phototherapy, whereas these are not routinely used in veterinary practice.^1,16 Nonetheless, adjuncts reflect a growing interest in integrative strategies that complement conventional treatment and augment long-term disease management across species.

Given the potential role of dietary factors in AD, research has explored whether diet may contribute to disease management. In veterinary medicine, food-induced cAD is a recognized diagnosis and elimination diet trials have been recommended for dogs with year-round symptoms to identify food allergens that may exacerbate the condition.¹⁹ While children with AD have a higher risk for food allergies than those without, current guidelines suggest against the use of elimination diets compared with an unrestricted diet, as avoidance of food allergens has been associated with promoting the development of IgE-mediated food allergy.⁵ However, this is a conditional recommendation with low-certainty evidence and additional research is needed to clarify the connection of food-specific innate and adaptive immunities to hAD.⁵

Last but not least, both canines and children with AD face increased risk for cutaneous infections. Staphylococcus pseudintermedius is a commonly reported bacterium that causes cutaneous infections in canines with cAD.⁴ Systemic antibiotics along with chlorhexidine-based shampoos have been effective in treating Staphylococcus pseudintermedius infections and reducing bacterial load.⁴ In hAD, Staphylococcus aureus is associated with cutaneous colonization and infection.²⁸ Extensive Staphylococcus aureus infections usually require oral antibiotics (eg, cephalosporins or penicillinase-resistant penicillins).²⁸ Although dilute bleach baths were once thought to possess antibacterial properties, multiple studies have shown that their concentration is not sufficient to exert antimicrobial effects on human skin.²⁹ Instead, their therapeutic benefits are more likely attributed to anti-pruritic, anti-inflammatory, and skin barrier-repairing properties in hAD.²⁹ Both canines and children may experience fungal infections, with the Malassezia species being the most common and requiring treatment with appropriate antifungal regimens.^4,12 Addressing secondary infections remains a cornerstone of comprehensive AD management across species.

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We confirm that this manuscript is original, has not been published previously or under consideration by another journal, does not infringe upon any copyright of a third party, and will not be published elsewhere whether online or in print once accepted.

Peter Lio reports research grants/funding from AbbVie, AOBiome; is on the speaker’s bureau for AbbVie, Arcutis, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche-Posay/L’Oréal, MyOR Diagnostics, ParentMD, Pfizer, Pierre-Fabre Dermatologie, Regeneron/Sanofi Genzyme, Verrica; reports consulting/advisory boards for Alphyn, AbbVie, Almirall, Amyris, Arcutis, ASLAN, Boston Skin Science, Bristol-Myers Squibb, Burt’s Bees, Castle Biosciences, Codex Labs, Concerto Biosci, Dermavant, Eli Lilly, Galderma, Janssen, Johnson & Johnson, Kimberly-Clark, LEO Pharma, Lipidor, L’Oréal, Merck, Micreos, MyOR Diagnostics, Regeneron/Sanofi Genzyme, Skinfix, Theraplex, UCB, Unilever, Verrica Yobee Care; stock options with Codex, Concerto Biosciences and Yobee Care. In addition, Dr. Lio has a patent pending for a Theraplex product with royalties paid and is a Board Member and Scientific Advisory Committee Member of the National Eczema Association.

Jennifer Roux and Miranda An have no conflicts of interest or relationships to disclose.