Cutaneous Connective Tissue Disease Associated with ......erythematosus, eosinophilic fasciitis, and...

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.

Cutaneous Connective Tissue Disease Associated with ......erythematosus, eosinophilic fasciitis, and...

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