Rheumatic manifestations among cancer patients treated with immune checkpoint inhibitors

Generalized morphea in the setting of pembrolizumab

“…Of patients treated with pembrolizumab, 30‐40% experience dermatologic irAEs . Six cases of sclerodermoid changes in the setting of anti‐PD‐1 therapy have been reported, including morphea, systemic sclerosis, and eosinophilic fasciitis . The timing for these skin changes varies, with onset from after 5 to 36 cycles of therapy.…”

Immune checkpoint inhibitor–induced inflammatory arthritis as a model of autoimmune arthritis

“…There is a paucity of epidemiologic data for ICI‐IA. The prevalence of IA may range from 3% to 7.5% in those treated with ICIs, but there is a lack of prospective data, and clinical trial data are limited. Unlike RA or some forms of SpA, which are more prevalent in women or men, respectively, there does not seem to be a relationship between sex and developing ICI‐IA, as most cohorts are 50%‐65% male .…”

“…Thus far, most reports are from small case series or single‐center cohort studies and the assays used to detect seropositivity are not uniform between studies. Despite these limitations, aggregation of the data from multiple studies reveals a low rate of seropositivity among patients developing IA following treatment with ICI therapy with 5.5% (12/217; range 0%‐36%) positive for RF and 5% (11/217; range 0%‐11%) positive for ACPAs . In a study comparing ICI‐IA patients to ethnically matched counterparts with RA, 7.7% of ICI‐IA patients were positive for RF or ACPAs, whereas 64.6% of RA patients were positive for ACPAs and 56.7% positive for RF, with 49.3% being positive for both .…”

“…Since autoantibodies can develop years or decades prior to the onset of RA, analysis of pretreatment serum is critical for addressing this question. While not uniformly tested, some studies have analyzed banked serum from patients prior to ICI exposure . For example, in the previously mentioned study by Belkhir et al, out of three patients who were ACPA‐positive post–ICI treatment and had pretreatment serum available, two patients were already positive for ACPAs pretreatment .…”

“…While ANA is not specific for a particular subgroup, it does correlate with an increased incidence of JIA‐associated uveitis, particularly iridocyclitis . Aggregate analysis of ANA positivity in patients with ICI‐IA, as defined by a titer greater than 1:40, from several published studies revealed that 15.3% (32/209; range 0%‐89%) of patients were positive for ANA . In addition, antibodies against specific nuclear antigens, dsDNA, Ro, and La (usually seen in patients with systemic lupus erythematosus or Sjögren's syndrome), have been detected in ICI‐IA patients .…”