Table 2

Autoimmune disease phenotype, antibodies and treatment for included patients

Date of first ICI exposureAutoimmune disease phenotypeDate of IRAETreatment of IRAEIRAE response to treatmentImaging, synovial fluid and other findingsAutoantibody results

Inflammatory arthritis

2/2015: reported
16/6/2015: seen
Prednisone 120 mg daily, tapered off over 3 months. ICI held for 3 months

Prednisone 10 mg daily with suboptimal response. ICI stopped and prednisone increased to 40 mg daily. Continued disease activity, so MTX 15 mg weekly and adalimumab weekly added to regimen with improvement
Resolution of colitis. Able to go back on ICI

Improvement with adalimumab and MTX. Able to come off prednisone

MRI: tibiotalar and subtalar joint effusions with marked synovitis

ANA, RF, CCP, Ro, La, dsDNA, RNP, Sm, myositis panel*, Scl70, HLA-B27 negative
27/2013Colitis (on anti-CTLA-4)


Inflammatory arthritis (on anti-PD-1)


Prednisone 1 mg/kg/day

Prednisone 40 mg, tapered to 7 mg/day

Resolution of colitis

Poor response to steroids (4 months)
Poor response to MTX (5 months)
Initial response to infliximab, d/c due to AE (nausea, chills)
Marked response to etanercept

Synovial fluid: WBC 12 700 (75% PMN)

Ultrasound: Doppler-positive synovitis in the right ankle

RF, CCP negative
314/11/2014Inflammatory arthritis3/8/2015—reported
Intra-articular triamcinolone
Prednisone 40 mg daily, tapered off over 1 month. ICI stopped, resumed 40 mg prednisone
Temporary relief from intra-articular triamcinolone, partial relief from 40 mg prednisone but not smaller dosesUltrasound: Doppler-positive synovitis and erosions at elbow

Subsequently developed metastatic lesion at distal humerus
ANA, RF, CCP, Ro, La, RNP, Sm, dsDNA, P-ANCA, C-ANCA, HLA-B27, Scl70, RNA pol III, cardiolipin, β-2-glycoprotein antibodies negative

Inflammatory arthritis

Prednisone starting at 160 mg daily tapered off over 1 month

Prednisone 120 mg daily tapered down to 40 mg daily
Intra-articular triamcinolone
Adalimumab initiated

Initial steroid treatment with no improvement, after 2 weeks high-dose steroids some improvement in pain and swelling. Marked improvement with adalimumab allowing steroid taper

Synovial fluid: 11 950 WBCs (92% PMN)

ANA, RF, CCP, Ro, La, RNP, Sm, dsDNA, P-ANCA, C-ANCA, HLA-B27, Scl70, cardiolipin antibodies, β-2-glycoprotein antibodies negative
526/3/2015Inflammatory arthritis21/5/2015—reported
Prednisone 10 mg daily, tapered to 7.5 mg daily after 3 monthsGood response with improvement of symptomsNone availableANA 1:80 (speckled)
Anti-Ro positive

RF, CCP, RNP, Sm, Scl70, myositis panel negative

Reactive arthritis (inflammatory arthritis, conjunctivitis)

5/2/2014 (recurrence after re-dosing with ICI 1 month prior)


7/3/2014 (flare after infliximab)
Prednisone 80 mg/day tapered to 20 mg/day

Infliximab (one dose)
Prednisone 80 mg/day tapered to 20 mg/day
Infliximab (two doses)
Hormone replacement
Prednisone 40 mg/day tapered over 1 months to 10 mg/day
Intra-articular triamcinolone
Prednisone 1 mg/kg/day
Intra-articular triamcinolone
Initial response high dose steroids, recurrence with steroid taper
Resolved with infliximab

Poor response to high dose steroids
Adverse event (pneumonia)
Initial response to prednisone 40 mg, with recurrence of joint pain and stiffness at 10 mg/day
Improved with steroid injection
Improved with steroids
Improved with adalimumab
Colonoscopy: mild, left-sided colitis (descending colon, sigmoid colon and rectum notable for mild erythema
without ulceration)

Knee radiographs: large suprapatellar effusion, no erosions

Synovial fluid analysis: WBC 28455 (70% PMNs)

ANA, RF, CCP, antihistone negative
73/3/2015Inflammatory arthritis


Prednisone 10 mg daily
Intra-articular triamcinolone
Colchicine 0.6 mg daily

Propranolol initially, Levothyroxine for subsequent hypothyroidism
Improvement of symptoms on 10 mg prednisone, but progressive symptoms involving the shoulder, knee, wrist and elbow requiring 40 mg prednisone for reliefUltrasound: Synovitis with positive Doppler signal in knee, elbow

Synovial fluid: 9854 WBC (86% PMN, 14% mononuclear, monosodium urate crystals present)
ANA, RF, CCP, Ro, La, RNP, Sm, dsDNA, P-ANCA, C-ANCA, HLA-B27, Scl70, RNA pol III, cardiolipin antibodies, β-2-glycoprotein antibodies negative
826/2/2015Inflammatory arthritis5/2015—reported
Dexamethasone 8 mg daily for brain metastasis, no additional corticosteroids addedImprovement of joint symptoms on dexamethasoneNoneANA, RF, CCP, Ro, La, RNP, Sm, dsDNA, P-ANCA, C-ANCA, HLA-B27, Scl70, RNA pol III, cardiolipin antibodies, β-2-glycoprotein antibodies negative
916/7/2015Inflammatory arthritis12/2015—reported
Celecoxib twice daily, intra-articular triamcinoloneNone availableANA, RF, CCP, Ro, La, RNP, Sm, dsDNA, P-ANCA, C-ANCA, Scl70, cardiolipin antibodies, β-2-glycoprotein antibodies negative

Acute sicca

Prednisone 80 mg daily, tapered over 2 months

Pilocarpine for symptoms
Improvement of imaging and symptoms

Improvement of xerostomia
None available
ANA 1:320 (nucleolar)
RF 38 (ULN 35)
Anti-EJ antibodies positive, rest of myositis panel negative.
Ro, La, RNP, Sm, Scl70 negative
1124/4/2015Acute sicca6/2015Prednisone 0.5 mg/kg/day, increased to 1 mg/kg/day, tapered to until discontinued
Cevimeline for symptoms
No improvement

No benefit
ANA 1:320 homogenous
Ro, La, RF negative

Acute sicca

Interstitial nephritis

Insulin-dependent diabetes




Prednisone 1 mg/kg/day

Prednisone 1 mg/kg/day

Dexamethasone 8 mg twice a day tapered then discontinued
Improvement in xerostomia

Improvement in creatinine

Maintained on insulin
Resolved with steroids

Creatinine 3.1
BUN 36
Renal biopsy: acute and evolving chronic interstitial inflammation with some T cells and focally numerous eosinophils suggesting a hypersensitivity reaction. The T-cell-rich lymphocytic infiltrate in the interstitial kidneys suggested an autoimmune interstitial nephritis
ANA 1:80 speckled
Ro, La, RF, P-ANCA, C-ANCA negative
131/4/2015Acute sicca with parotid swelling12/2015Prednisone 40 mg daily

Cevilemine for symptomatic relief of xerostomia
Improved parotid swelling, prednisone tapered off over 6 weeksUltrasound bilateral parotid glands: hypoechoic foci consistent with lymphocytic aggregates, >50% of gland involvedLa/SSB antibodies positive. ANA, Ro, RNP, Sm, RF, CCP, myositis panel, anti-dsDNA, P-ANCA, C-ANCA negative
  • *Myositis panel tests for antibodies to Jo-1, SRP, EJ, OJ, PL-7, PL-12, Mi-2, Ku.

  • AE, adverse events; ANA, antinuclear antibody; ANCA, antineutrophil cytoplasmic autoantibody; BUN, blood urea nitrogen; CCP, cyclic citrullinated peptide; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; HLA, human leucocyte antigen; ICI, immune checkpoint inhibitor; MTX, methotrexate; PMN, polymorphonuclear leucocytes; RF, rheumatoid factor; RNP, ribonuclear protein antibody; ULN, upper limit of normal; WBC, white blood cells.