After 1 year of dual biologic therapy, the patient experienced near-complete resolution of symptoms. The psoriasis completely resolved from an initial body surface area of 5%, and the AD body surface area decreased from 30% to 2% (Figure 3). The patient reported no adverse effects from treatment.
FIGURE 3. A and B, Nearcomplete resolution of symptoms approximately 1 year after dual biologic treatment with guselkumab and dupilumab was initiated.
Comment
Atopic dermatitis and psoriasis involve complex immunopathology and a spectrum of cytokines that might explain the overlap in their clinical and histopathologic presentations.
Atopic dermatitis—Atopic dermatitis involves TH1, TH2, TH9, TH17, and TH22 cells; TH2 cells release IL-4, IL-5, and IL-13, all of which are key cytokines in the inflammatory pathway of AD.9,10 Activation of the helper T-cell subset and the release of cytokines differ slightly based on the subcategory of AD and the stage of exacerbation. In addition to TH2-cell activation, TH1 cells and TH22 cells—which release IL-12 and IL-22, respectively—are active in both intrinsic and extrinsic AD. TH17 cells and TH9 cells—which release IL-17 and IL-9, respectively—are more prominent in the intrinsic pathway than in the extrinsic pathway.9 Intrinsic AD is recognized by a lack of eosinophilia, female predominance, and delayed onset compared to extrinsic AD; there also is a lack of history of atopy.1 Extrinsic AD is characterized by eosinophilia as well as a personal and family history of atopy.11 Our patient—a female with onset in older adulthood, lack of eosinophilia, and a family history of atopy—displayed features of both intrinsic and extrinsic AD.
Psoriasis—The immunopathology of psoriasis involves stimulation of dendritic cells, which activate TH17 cells through IL-23. TH17 cells then release IL-17 and IL-22. Therefore, both AD and psoriasis involve activation of TH22 and TH1 cells, with increased IL-17 and IL-22 production.3,10,12 IL-17 and IL-22 induce epidermal hyperplasia; IL-22 also contributes to skin barrier dysfunction.12 Therefore, it might be reasonable to consider psoriasis and AD as diseases that exist across a T-cell axis spectrum, thereby accounting for some overlap in disease characteristics.3
Dual Biologic Therapy—Dupilumab blocks the IL-4 receptor α subunit, a receptor for IL-4 and IL-13, which are key cytokines in the pathogenesis of AD.10 Guselkumab inhibits IL-23, thus blocking the inflammatory cascade of TH17 cell activation and release of IL-17 and IL-22 in the psoriasis pathway.13 Although an immunopathological spectrum exists between the 2 diseases, the continued presence of AD symptoms after blocking the IL-23 cascade suggests that additional blockade of TH2 cells is required to control AD in patients with true concurrent disease.
Accurate diagnosis of AD and/or psoriasis is important when considering targeted treatment of these conditions with biologics. The use of dual biologics is limited by a paucity of data regarding the safety of these agents when given in combination. A recent meta-analysis of dual biologic therapy in patients with inflammatory bowel disease demonstrated acceptable safety results with a pooled adverse reaction rate of 31%.14
Anchoring Bias—Anchoring bias can occur when a clinician’s decisions are influenced by a particular event or reference point, which might cause them to disregard subsequent evidence. Our case illustrates the importance of critically assessing the response to treatment and being mindful of the potential influence of anchoring bias on the differential diagnosis. Although overcoming biases in conditions with clinical overlap can be challenging, it is important to consider coexisting AD and psoriasis in patients with extensive hand involvement when multiple treatments have failed and only a partial response to targeted pathways has been achieved. In our case, the patient also had contact hypersensitivity to tixocortol-21-pivalate, which indicates hypersensitivity to many prescription topical corticosteroids, oral prednisone, and over-the-counter hydrocortisone; however, topical corticosteroids continued to be prescribed for her, which might have contributed to the lack of improvement and even exacerbated the rash.
Future Considerations—A consideration for the future in this case is discontinuing guselkumab to observe whether symptoms recur. We discussed this option with the patient, but she opted to continue treatment with dupilumab and guselkumab because of the symptom resolution.
Conclusion
Concomitant disease can present as an overlapping pattern in the same area, whereas other regions might have geographically isolated disease. Our patient’s overlap of symptoms, the failure of multiple treatments, and the partial improvement she experienced on guselkumab made diagnosis and management challenging; however, dual biologic therapy was successful.