Table 1.

Summary of median voting scores and percent agreement for general statements and items for the identification and management of D-irAEs

General statements Round 1	Score	Measure
Please rate how accurately the lists of specific and non-specific morphologies capture the range of possible D-irAE presentations.	7.7 (62%)	Accuracy
This list of core diagnoses was created from epidemiologic and insurance claims data. Please rate your agreement with the list of included D-irAE core diagnoses.	7.7 (96%)	Agreement
Please rate the usability of this framework of increasing diagnostic specificity in your primary work setting. Consider whether you could practically apply this classification to your patients.	7 (62%)	Usability
Please rate the overall appropriateness of the diagnostic workup. For the proposed tests, consider the value of the diagnostic information and whether the benefits outweigh any risks.	8 (88%)	Appropriate
Timing and tempo: To be considered a D-irAE, symptoms must begin within 12 months of last infusion of the ICI therapy. Most D-irAEs, however, occur within 12 weeks of starting a new ICI. New onset D-irAEs beyond 6 months of starting a therapy are less common. Later onset D-irAEs generally develop insidiously whereas early onset D-irAEs are more likely to present acutely or subacutely.	7.7 (65%)	Agreement
Exclusion of other etiologies: The diagnosis of all D-irAEs requires that other potential etiologies have been excluded by a work-up tailored to each patient. A careful history, baseline dermatologic exam, and ancillary data can help exclude or confirm pre-ICI dermatologic disease. Patients with known dermatologic disorders, particularly immune-mediated dermatologic conditions, are recommended to have a dermatologic examination prior to starting ICI therapy and be under a dermatologist’s or dermatology subspecialist’s care during ICI therapy, depending on the complexity of the patient’s dermatologic illness.	9 (85%)	Agreement
Consideration of concurrent irAEs: Patients frequently have irAEs affecting multiple organ systems. The presence of a concurrent non-dermatologic irAE can be a clue that dermatologic symptoms represent an irAE. A dermatologic irAE can also prompt evaluation of other organ systems when known patterns of overlapping disease exist (ie, dermatomyositis).	8.3 (85%)	Agreement
Improvement on holding drug and/or initiating corticosteroids: While improvement on holding ICI therapy or initiating corticosteroids is non-specific, this is expected in most patients with D-irAEs. Lack of improvement, particularly after several weeks of treatment with corticosteroids or another irAE therapy, should prompt re-consideration of diagnosis.	7.7 (69%)	Agreement
For table 2, please rate how accurately the examples illustrate differing levels of severity for each dermatologic syndrome.	8 (73%)	Accuracy
Autoantibodies: Some irAEs are associated with pathophysiologic antibodies. These antibodies may be known prior to ICI administration or be detected during evaluation of a D-irAE. These definitions do not distinguish whether there is an antibody present or not; they have instead been constructed to include criteria that ensure a relationship with immunotherapy such as onset after ICI and improvement with ICI cessation. Even if a patient has a known antibody prior to immunotherapy administration, the temporal association of irAE with an ICI suggests that the immunotherapy has contributed in some part to these symptoms. When naming a D-irAE in a patient with a known antibody, we recommend including the antibody as part of the diagnosis (for example, ‘Definite immune related bullous pemphigoid with BPAG 180 antibody’ or ‘probable immune-related bullous pemphigoid with positive 230 antibody’). Patients may additionally have abnormal antibodies after ICI therapy that are typically low titer. As many of these antibodies are non-specific and may be unrelated, a patient’s syndrome should be referenced back to known antibody syndromes before establishing a diagnosis with a given antibody.	8 (81%)	Agreement
Paraneoplastic syndromes: Patients may have paraneoplastic syndromes exacerbated or triggered by ICI therapy. The distinction between a process that is driven by an underlying cancer and a process that is an irAE can have significant, often opposing, treatment implications. Similar to the approach to autoantibodies, these definitions have been constructed to include criteria that ensure a relationship with ICIs such as improvement after stopping the ICI. A patient may therefore initially have a ‘Possible’ or ‘Probable’ diagnosis before it becomes ‘Definite’ or an alternate diagnosis. The clinical decision for how to treat a patient is beyond the scope of these guidelines but will typically benefit from multidisciplinary collaboration.	9 (96%)	Agreement
Please rate your agreement with the written statement on clinical trial adjudication.	8 (96%)	Agreement

Round 2
Please rate how accurately the lists of specific and non-specific morphologies capture the range of possible D-irAE presentations.	8 (86%)	Accuracy
Please rate the usability of this framework of increasing diagnostic specificity in your primary work setting. Consider whether you could practically apply this classification to your patients.	8 (81%)	Usability
(Revised statement) Timing and tempo: To be considered a D-irAE, symptoms must begin within 12 months of last infusion of the ICI therapy. Most D-irAEs, however, occur within 12 weeks of starting a new ICI. New onset D-irAEs beyond 6 months of starting a therapy are less common.	8 (86%)	Agreement
(Revised statement) Improvement on holding drug and/or initiating corticosteroids: While not necessarily first line treatment, holding ICI therapy or initiating topical or systemic corticosteroids usually leads to improvement of D-irAEs. Lack of improvement, particularly after several weeks of treatment with topical or systemic corticosteroids or another irAE therapy, should prompt re-consideration of the D-irAE classification and diagnosis.	7 (81%)	Agreement

Each component could be scored on a scale of 1 to 9 (1–3, not usable; 4–6, uncertain; 7–9, usable). Agreement was defined as <1/3 of ratings outside the 3-point range containing the median. Green indicates consensus was reached, defined by when the median rating fell in the 7–9 range with agreement. Pink indicates consensus was not reached.

D-irAEs, dermatologic immune-related adverse events; ICIs, immune checkpoint inhibitors.