Introduction Discussion Objectives Conclusions 1. Barbosa NS, Wetter DA, Wieland CN, Shenoy NK, Markovic SN, Thanarajasingam U. Scleroderma Induced by Pembrolizumab: A Case Series. Mayo Clin Proc. 2017;92(7):1158-1163.10. 2. Tjarks BJ, Kerkvliet AM, Jassim AD, Bleeker JS. Scleroderma-like skin changes induced by checkpoint inhibitor therapy. J Cutan Pathol. 2018;45(8):615-618. 3. Sheik Ali S, Goddard AL, Luke JJ, et al. Drug-associated dermatomyositis following ipilimumab therapy: a novel immune-mediated adverse event associated with cytotoxic T-lymphocyte antigen 4 blockade. JAMA Dermatol. 2015;151(2):195-199. 4. Blakeway EA, Elshimy N, Muinonen-Martin A, Marples M, Mathew B, Mitra A. Cutaneous lupus associated with pembrolizumab therapy for advanced melanoma: a report of three cases. Melanoma Res. 2019;29(3):338-341. 5. Liu RC, Sebaratnam DF, Jackett L, Kao S, Lowe PM. Subacute cutaneous lupus erythematosus induced by nivolumab. Australas J Dermatol. 2018;59(2):e152- e154. 6. Zitouni NB, Arnault JP, Dadban A, Attencourt C, Lok CC, Chaby G. Subacute cutaneous lupus erythematosus induced by nivolumab: two case reports and a literature review. Melanoma Res. 2019;29(2):212-215. Disclosures: None declared. References Results Cutaneous Connective Tissue Disease Associated with Immune Checkpoint Inhibitor Therapy: A Retrospective Analysis Ai-Tram N. Bui, B.A. 1 , Jesse Hirner, M.D. 2 , Sean Singer, B.S. 1 , Kiki Cunningham-Bussel M.D., P.h.D. 3 , Cecilia LaRocca, M.D. 2,4 , Christine G. Lian, M.D. 5 , Joseph F. Merola, M.D. 2 , Nicole R. LeBoeuf, M.D., M.P.H. 2,4 1 Harvard Medical School, Boston, MA, 2 Department of Dermatology, Brigham and Women’s Hospital, Boston, MA, 3 Department of Rheumatology, Brigham and Women’s Hospital, Boston, MA, 4 Center for Cutaneous Oncology, Department of Dermatology, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA, 5 Department of Pathology, Brigham and Women’s Hospital, Boston, MA • Immune checkpoint inhibitors (ICIs) are associated with distinct inflammatory eruptions such as bullous pemphigoid or lichenoid eruptions 1 . • Less is known about the development of autoimmune/autoinflammatory disorders including cutaneous connective tissue diseases (CTD) from immunotherapy; frequency of these eruptions remain to be studied 1. • There are reports of de novo cutaneous connective tissue diseases (CTD) associated with ICI therapy including scleroderma, dermatomyositis, cutaneous lupus, eosinophilic fasciitis, and lupus nephritis 1-6 . To evaluate the frequency, demographics, presentation, diagnostics, treatment, and impact on immunotherapy of de novo cutaneous CTD among patients on ICIs. Methodology • After institutional review board approval, we queried electronic medical records and found 4,487 patients on ICI therapy. • We retrospectively reviewed and identified patients among this cohort who had possible de novo cutaneous CTD after ICI therapy. • We searched for patients with de novo scleroderma, systemic sclerosis, dermatomyositis, cutaneous lupus, subacute cutaneous lupus, systemic lupus erythematosus, eosinophilic fasciitis, and discoid lupus. • We identified 11 patients of 4,487 patients (5 females, 6 males) treated with ICIs and developed a cutaneous CTD for frequency of 0.025%.There were 8 cases of subacute cutaneous lupus erythematosus (SCLE), 1 case meeting the new ACR/EULAR criteria for systemic lupus erythematosus (SLE), 1 case of eosinophilic fasciitis, and 1 case of dermatomyositis (Table 1). Pt Age, Sex Cancer & Stage ICI & onset Autoantibody & pertinent laboratory markers Histopathology & Direct Immunofluorescence ICI Interruption Subacute cutaneous lupus erythematosus cases 1 54, F Lung, small cell, IV Nivolumab ANA: 1:5120, speckled Anti-Ro(SSA): >8.0 Anti-La(SSB): >8.0 HE: mild focal interface dermatitis changes DIF: N/P Not interrupted 2 54, F Ovarian, IV PD-1 inhibitor ANA: 1:80 Anti-Ro(SSA): <0.2 Anti-La(SSB): <0.2 HE: minimal focal interface dermatitis changes DIF: 1+ granular C3, IgM, and IgG along the DEJ DIF: N/P Held & re-started at full dose 1 mo later 3 57, F Breast, IV Atezolizumab ANA: 1:320, speckled Anti-Ro(SSA): >8.0 Anti-La(SSB): 0.4 HE: interface dermatitis changes with eosinophils DIF: wnl Discontinued 2 mo prior to initial presentation 4 60, M Melanoma, IV Nivolumab ANA: 1:320, speckled Anti-Ro(SSA): >8.0 Anti-La(SSB): 0.4 HE: lichenoid dermatitis with prominent interface changes and bullous formation, with damaged keratinocytes and colloid bodies DIF: wnl Not interrupted by SLE, held for ICI- associated acute kidney injury and restarted at full dose 1 mo later 5 65, M Lung, small cell Pembrolizumab ANA: 1:320, speckled Anti-Ro(SSA): >8.0 Anti-La(SSB): <0.2 HE: Lichenoid dermatitis with prominent interface changes DIF: negative Not interrupted, d/c for disease progression 6 55, M Esophageal, IV Pembrolizumab Not performed HE: Lichenoid interface dermatitis with eosinophils DIF: N/P Not interrupted 7 69, M Lung, squamous cell, IV Atezolizumab ANA: 1:40, speckled SS-A(Ro): 91.91 SS-B(La): 1.11 Cytoplasmic Ab: 1:160 HE: Subacute spongiotic and focal interface dermatitis DIF: N/P D/c 3 mo prior to initial presentation 8 61, F Non-small cell lung cancer, IV Pembrolizumab ANA: 1:1280, speckled Anti-Ro(SSA): 143.9 Anti-La(SSB): 26.1 Smith antibodies: 4.12 Anti-dsDNA: 1:10 HE: Interface dermatitis with follicular involvement, thickening of the epidermal basement membrane, dermal mucin deposition and superficial perivascular lymphocytic infiltrate. DIF: N/P D/c 5 mo prior to initial presentation Systemic lupus erythematosus case 9 69, M Melanoma, IV Ipilimumab, nivolumab ANA: 1:160, diffuse pattern dsDNA: 2 SS-A(Ro): 1 SS-B(La): 0 Sm Ab: 2 RNP Ab: 0 Platelets: 91 HE: Interface dermatitis and interface folliculitis, vacuolar type with perivascular chronic inflammation. DIF: N/P Not interrupted by SLE, but for ICI- induced colitis Eosinophilic fasciitis case 10 59, M Neuroendocrine carcinoma, IV Nivolumab Eosinophils: 2.9 SPEP: negative PFTs: wnl HE: Skin: Diffuse dermal and subcutaneous sclerosis Fascia: Prominent fascial sclerosis DIF: not performed MRI (forearm): mild intrafascial and intrafasicular enhancement Not interrupted Dermatomyositis case 11 53, F Melanoma, IV Ipilimumab Muscle biopsy: Skeletal muscle with type II fiber atrophy MRI: Mild short TI inversion recovery hyperintensity of the bilateral vastus lateralis and rectus femoris muscles N/P Permanently d/c • Approximately 0.025% of patients treated with immune checkpoint inhibitor therapy at our institutions developed de novo CTD including subacute cutaneous lupus erythematosus (SCLE), systemic lupus erythematosus (SLE) meeting ACR/EULAR criteria, eosinophilic fasciitis, and dermatomyositis. • Among our cohort, there was a disproportionate finding of immunotherapy-associated SCLE. • A major finding of this study was the disproportionate finding of 8 SCLE cases (72.7%). There was 1 case of de novo SLE based on the new ACR/EULAR criteria for SLE and no other cases of cutaneous lupus erythematosus in our cohort. • SLE may be more challenging to diagnose as it presents with a broad spectrum of clinical and laboratory findings in comparison to SCLE, which typically has characteristic and pronounced presenting features. • It is unclear if immunotherapy-associated SLE has discerning features from idiopathic SLE. • Early diagnosis and appropriate management can prevent interruption of life-prolonging immunotherapy and minimize use of globally immunosuppressive treatment.