Table 2.
Description of rheumatic and musculoskeletal IRAE from included case reports and series
| Author, Year | Drug | Indication | Clinical Presentation/s | Labs, imaging, and other testing |
Treatment |
|---|---|---|---|---|---|
| Anti-CTLA-4 | |||||
| Bostwick 2015 | Ipilimumab | Metastatic melanoma |
Pre-existing ulcerative colitis. Disease flared while
on ipilimumab initially responding to immunosuppression but ultimately requiring urgent colectomy. |
Colonoscopy after ipilimumab: erosions, ulcerations and pseudo polyps |
Infliximab, Azathioprine, corticosteroids. |
| Conry 2015 | Ipilimumab | Metastatic melanoma |
Arthralgias, myalgias, fevers, progressive
neurologic symptoms (ataxia, aphasia, confusion). |
ANA, anti-dsDNA, RF negative |
Encephalopathy responded to high dose IV corticosteroids |
| Fadel 2009 | Ipilimumab | Metastatic melanoma |
Drug induced lupus nephritis: Nephrotic
range proteinuria after two injections of ipilimumab, also microscopic hematuria. Subsequent venous thrombosis of left kidney. |
Positive ANA (1:100), anti- dsDNA. Biopsy with extramembranous and mesangial deposits of IgG, IgM, C3, C1q. |
Prednisone 1 mg/kg and anticoagulation. |
| Gieliesse 2014 | Ipilimumab | Metastatic melanoma |
Pre-existing Crohn’s disease, monitored with
serial endoscopies before and during treatment. |
Endoscopy before treatment showed no active inflammation; after treatment erosions and small ulcerations. |
None reported. |
| Golstein 2014 | Ipilimumab | Metastatic melanoma |
Two cases of polymyalgia rheumatica/giant cell
arteritis. One with scalp tenderness, headache, jaw claudication. Second patient with arthralgias, morning stiffness in shoulders, left sided facial swelling. |
Both elevated CRP, one with elevated ESR Temporal artery biopsies: one with active arteritis both with intimal proliferation and disruption of elastic lamina. |
Prednisone 50 mg daily and 60 mg daily. |
| Henderson 2015 |
Ipilimumab | Metastatic melanoma |
Presented with conjunctival injection, foreign
body sensation, limited ocular range of motion. Found to have orbital myositis. |
MRI showed inflammation of extraocular muscles. |
Prednisone, dose not stated. |
| Hunter 2009 | Ipilimumab | Metastatic melanoma |
Dysphagia and weakness in facial muscles, neck
flexion, proximal and distal extremities. |
CK > 5000 U/L. EMG showed irritable myopathy. Biopsy showed endomysial inflammatory infiltrate. |
Treated with IVIG and IV methylprednisolone 1 g/day followed by prednisone 1 mg/kg and taper. Improvement of all symptoms to near baseline. |
| Izzedine 2014 | Ipilimumab | Metastatic melanoma |
2 cases of Acute Interstitial
Nephritis. Pre-existing Sjogren’s syndrome in one patient. |
Negative ANA Renal biopsies: interstitial inflammation, tubular injury in one |
Prednisone 1 mg/kg for 4 weeks followed by taper. |
| Minor 2013 | Ipilimumab | Metastatic melanoma |
Uterine lymphocytic vasculitis. Presented with mass
in uterus and pelvic lymphadenopathy. |
Lymphocytic vasculitis involving uterine and ovarian vessels. ANA negative. |
Hysterectomy due to concern for malignancy. No further treatment. |
| Pedersen 2014 |
Ipilimumab | Metastatic melanoma |
Pre-existing ulcerative colitis treated with Ipilimumab.
No flares while treated. |
No evaluation of ulcerative colitis described. |
None. |
| Sheikh 2015 | Ipilimumab | Metastatic melanoma |
Dermatomyositis. Erythematous photodistributed
rash with Gottron’s papules and proximal muscle weakness. |
CK 1854 U/L. Aldolase 23 U/L. ANA 1: 640 speckled, anti-Jo1 negative. |
Prednisone 80 mg daily tapered over 8 weeks + discontinuation of ipilimumab. |
| Anti-PD-1 | |||||
| De Valasco 2015 |
Nivolumab | Metastatic renal cell carcinoma |
Joint pain and stiffness in fingers, uveitis, and
ultimately developed partially reducible swan neck deformities in hands. |
Hand radiographs- no erosions, thought to be consistent with Jaccoud arthropathy. |
None for arthropathy. Intraocular steroids for uveitis. |
| Yoshioka 2015 | Nivolumab | Metastatic melanoma |
Polymyositis with proximal muscle weakness
and respiratory involvement. |
CK 2812 U/L | Prednisone 30 mg daily + discontinuation of Nivolumab. |
| Chan 2015 | Pembrolizumab | Metastatic melanoma |
2 cases of polyarticular inflammatory arthritis.
One involving wrist, knee, ankles. Other involving PIPs, wrist, elbow, knees. |
ANA, RF, anti-CCP negative. Synovitis and tenosynovitis on MRI in both |
NSAIDs in both. Pamidronate in one, hydroxychloroquine in other. |
| Khoja 2016 | Pembrolizumab | Metastatic melanoma |
Patient presented with myalgias and feeling of
heaviness in muscles. Found to have eosinophilic fasciitis and encephalopathy |
Elevated eosinophil count, MRI of arm with fascial edema. |
Corticosteroids 1 gram daily, then taper |
| Manusow 2014 |
Pembrolizumab | Metastatic melanoma |
Retinal vasculitis in the setting of ocular metastasis
after pembrolizumab treatment. Not certain if was due to pembrolizumab or paraneoplastic |
Fluoroscein angiography showed retinal vasculitis with leaking from vessels. |
Improvement with vitrectomy |
CK: creatinine kinase. ANA: antinuclear antibodies. RF: rheumatoid factor. dsDNA: double stranded DNA antibodies. CCP: cyclic citrullinated peptide antibodies. EMG: electromyography. CRP: C reactive protein. ESR: erythrocyte sedimentation rate.