Introduction: T cell checkpoint inhibitors targeting Programmed cell Death protein-1 (PD-1) have emerged as novel immunotherapy agents showing remarkable efficacy in head and neck squamous cell carcinoma (HNSCC). Despite important clinical benefits, they are associated with side effects that occur as a consequence of general immunological stimulation due to loss of T cell inhibition. Herein, we report the unusual case of inflammatory arthritis induced by anti-PD-1 agent pembrolizumab.Case report: A 55-years old male was treated with pembrolizumab at a dose of 200 mg every 3 weeks for a metastatic hypopharyngeal carcinoma. Following two cycles of immunotherapy, and while complete response of lung metastases was achieved, the patient presented with stiffness, swelling and pain of the right knee. Clinical examination and synovial fluid analysis revealed a seronegative inflammatory arthritis. Pembrolizumab therapy was interrupted and low-dose prednisone was administered with remarkable clinical improvement. Pembrolizumab was reintroduced, but after the fifth cycle, the patient developed inflammatory polyarthritis involving both knees and interphalangeal joints of both hands resulting in severe clinical deterioration. At that time, treatment with pembrolizumab was permanently discontinued. High-dose prednisone and methotrexate treatment led to remission of clinical symptoms.Conclusion: Pembrolizumab-induced inflammatory arthritis is an unusual rheumatic immune-related adverse event that physicians are likely to encounter as ICI use expands. Multidisciplinary management and rheumatology consultation are necessary to provide immediate treatment and avoid permanent joint damage.
Background:Psoriatic arthritis (PsA) affects both sexes equally, however there seem to be significant differences in disease expression between the genders.Objectives:To investigate gender differences in disease manifestations, patient-reported outcomes and comorbidities among patients with PsA.Methods:This cross-sectional study of patients with PsA followed at an academic rheumatology outpatient clinic between 1/6/2017 and 1/12/2019. We compared clinical characteristics, patient-reported outcomes, disease activity and comorbidities in male and female patients with PsA. All patients were over 18 years of age and fulfilled the CASPAR criteria for PsA. Differences between gender in values of continuous variables were assessed by T-tests or Mann-Whitney tests. The association between categorical variables and gender was assessed by Pearson chi-square test or Fisher’s exact test.Results:135 patients, 83 (62%) women and 52 (38%) men were included. Factors studied for gender differences are shown in Table 1. Women had significantly more tender (11 vs 3 p 0.001) and swollen (10 vs 3, p 0.013) joints, worse VAS (Visual Analogue Scale 0-10) pain (6 vs 5, p <0.001), higher ESR (20 vs 11, p 0.001) and worse DAPSA(Disease Activity in Psoriatic Arthritis) (33 vs 18 p 0.006) and presented with more enthesitis (32.5% vs 13.5%, p 0.013). In contrast, men achieved Minimal Disease Activity (MDA) more frequently (26.9% vs 3.6% p<0.001)and had significantly more comorbidities than women. Polyarthritic disease was more frequent in women (62% vs 31%), although at non-significant levels.Conclusion:Male patients with PsA have more comorbidities, while female patients have greater disease activity, worse patient reported outcomes and achieve MDA less frequently.References:[1]Determinants of Patient-Reported Psoriatic Arthritis Impact of Disease: An Analysis of the Association with Gender in 458 Patients from 14 Countries.[2]Orbai AM, Perin J, et al Arthritis Care Res (Hoboken). 2019 Oct 14. doi: 10.1002/acr.24090.FactorWomen (n=83)Men (n=52)P valueMedian (25th-75thpercentile)Age55.1 (46.8-63)56.6 (50-65.7)0.419*BMI27.9 (24.9-35)30.1 (26.8-33.3)0.181#Pso duration/ PsA duration (years)8.3 (3.9-24.5)/ 2.4 (0-5.7)14.3 (4.7-22.7)/ 2.8 (0-6.4)0.451#/0.605#Smoking (Packyears)15 (5-30)27.5 (0-46)0.002#TJC/SJC11 (4-16)/ 10 (5-17)3 (0-13)/ 3 (0-14)0.001#/0.013#VASPain/ VASGA6 (5-8)/ 5 (3-6)5 (1-6)/ 4 (2-5)<0.001*/0.121*CRP/ ESR1.4 (0.4-3.2)/20(11-33)1.1 (0.2-2.7)/ 11 (7-18)0.398#/0.001#BSA/PASI0 (0-2)/0(0-2)2 (0-6)/1(0-4.8)0.139#/0.258#DAPSA33 (24.1-45)18 (9.3-45)0.006#n (%)Enthesitis/ Dactylitis27 (32.5)/ 20 (24.1)7 (13.5)/ 10 (19.2)0.013***/ 0.508***Dyslipidemia33 (40.2)31 (59.6)0.029***Liver3 (3.6)7 (13.5)0.046**Eyes0 (0)3 (5.8)0.055**Uricemia3 (3.6)8 (15.4)0.023**Depression or anxiety16 (19.3)11 (21.1)0.817***CAD2 (2.4)12 (23.1)<0.001**DM14 (16.9)12 (23.1)0.392MDA3 (3.6)14 (26.9)<0.001*: T-test with unequal variances;#: Mann-Whitney test; **: Fisher’s exact test; ***: Pearson chi2 test;Pso: Psoriasis; PsA: Psoriatic arthritis; BMI: Body mass index; TJC: Tender joint count; SJC: Swollen joint count; VASPain: Visual analogue scale 0-10 for pain; VASGA: Visual analogue scale 0-10 for general assessement; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; BSA: Body surface area; PASI: Psoriasis area severity index; DAPSA: Disease activity in psoriatic arthritis; CAD: Coronary artery disease; DM: Diabetes mellitus; MDA: Minimal disease activity;Disclosure of Interests:ALEXANDROS GRIVAS: None declared, IRENE KAPNIARI: None declared, KIMON TZANNIS: None declared, Dimitrios Tseronis: None declared, Michail Aggelakos: None declared, Dimitra Kassara: None declared, KATERINA HAVATZA: None declared, Sofia Flouda: None declared, Dionysis Nikolopoulos: None declared, Theofanis Karageorgas: None declared, EVAGELIA PAPADAVID: None declared, DIMITRIOS BOUMPAS Grant/research support from: Unrestricted grant support from various pharmaceutical companies, PELAGIA KATSIMPRI: None declared
3600 mg/dl; IgM 126 mg/dl), elevated serum amyloid A levels (160 mg/ml) and decreased CD4/CD8 T cell ratio. Autoantibody (ANA, ENA, anti-DNA) and HLA B 27 were negative. WES analysis showed the de novo heterozygous missense variation c.C1132A (p.H378N) in PIM-1 gene (NM_001243186). This variation was never described in on-line database (HGMD, Exac, 1000 g, ESP6500). The second patient was an adult female with a clinical history of persistent microcytic anemia, splenomegaly, striking hypergammaglobulinemia (IgG > 3000 mg/dL) and recurrent protracted fever episodes during childhood. At 13 years, she underwent splenectomy because of hypersplenism. At 28 years she presented a cerebral oligoastrocytoma that was removed by surgery. No mutations were found in genes associated with autoimmune lymphoproliferative syndromes and histiocytosis (FAS, FASLG, XIAP, TNFRSF13B, UNC13D, CASP9, CASP10). The direct sequencing of PIM-1 revealed again the above described de novo mutation in PIM-1. Conclusion:We propose that these patients represent two cases of a novel syndrome associated with a specific mutation in PIM-1 gene (PLAS). First, the two cases share significant overlap of autoinflammatory and proliferative features involving the endothelial and the immune systems. Second, the gene mutation identified was never described in healthy people or in patients with other disorders and is predicted to be pathogenic based on all the bionformatic tools. Finally, previous functional studies showed that PIM-1 pathway is relevant to immune activation and indeed somatic mutations in this gene have been reported in association with lymphomas, and it is thought to contribute to survival of cancerous cells. Disclosure of Interest None Declared O6Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset systemic autoinflammatory disease
Background:Interstitial pneumonia with autoimmune features (IPAF)1describes a group of patients with interstitial lung disease and autoimmune features who do not meet the classification criteria for a specific connective tissue disease. Limited data regarding IPAF are available so far.Objectives:To identify the epidemiological and clinical characteristics of patients with IPAF and to observe disease progression, response to treatment and frequency of infections in 1-year follow-up period.Methods:Thirty-nine patients from ‘Attikon’ University Hospital of Athens fulfilling the IPAF criteria were enrolled. Clinical and laboratory findings, comorbidities, medications, pulmonary outcomes assessed with repeated pulmonary function tests (PFTs) and chest HRCT and complications in a 1-year follow-up period were documented for each patient. Univariate models were performed in order to identify determinants of infection and clinically significant difference in PFTs (defined as change of ≥ 10% in FVC and/or ≥ 15% in DLCO).Results:The mean age at the time of IPAF diagnosis was 63.2 (±11) years and 62% of the patients were female. The most common clinical features included in the IPAF criteria were arthritis (82%) and Raynaud’s phenomenon (26%). A morbilliform and/or polymorphic rash of the face, neck and extremities (not included in the IPAF criteria) was noted in 54% of patients. ANA (59%) and anti–Ro (21%) were the most common auto-antibodies. Non-specific Interstitial Pneumonia (NSIP) was the most prevalent radiological pattern (61.5%) as shown in table 1. Treatment comprised corticosteroids and immunosuppressants including hydroxychloroquine, methotrexate, azathioprine, mycophenolate and cyclophosphamide. PFTs following treatment at 6 and 12 months from baseline showed a trend of improvement (Table 2, p> 0.05). At 1 year from baseline, 20.5% of patients showed a clinically significant deterioration while 25% had a clinically significant improvement. Infections were observed in 23.1% of patients during the first semester and in 12.8% during the second semester of the follow-up period. All were respiratory tract infections and two patients (5.1%) required hospitalization. All infections occurred in patients with non-UIP pattern (p=0.02) which might be attributed to higher doses of corticosteroids used in these patients (mean initial prednisolone dose = 27 (±18) mg/d in patients with non-UIP pattern versus 17 (±16) mg/d in patients with UIP pattern, p=0.4).Table 1.Prevalence of HRCT patterns in 39 patients.Radiological patternNo (%)NSIP24 (61,5%)OP2 (5,1%)NSIP with OP overlap2 (5,1%)LIP1 (2,6%)UIP7 (18%)NSIP and UIP3 (7,7%)NSIP: Non-specific Interstitial Pneumonia, OP: Organizing Pneumonia, LIP: Lymphocytic Interstitial Pneumonia, UIP: Usual Interstitial Pneumonia.Table 2.PFTs at baseline, 6 and 12 months.PFTs (% of predicted value ± SD)Baseline6 months12 monthsP valueFVC79% (±19%)82% (±18%)84% (±17%)nsDLCO49% (±16%)52% (±17%)53% (±17%)nsConclusion:Rash is a common feature in IPAF and may be considered for inclusion into IPAF criteria. A trend of improvement in PFTs and a significant risk of respiratory tract infections mainly in the first semester of treatment and in patients with non-UIP radiological pattern were observed. Larger prospective studies are warranted in order to elucidate IPAF’s prognosis and to identify effective management approaches.References:[1]Fischer A, et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J 2015; 46: 976-987.Disclosure of Interests:Maria Karampeli: None declared, Konstantinos Thomas: None declared, Dimitrios Tseronis: None declared, Michail Aggelakos: None declared, Dimitra Kassara: None declared, Katerina Havatza: None declared, Sofia Flouda: None declared, Dionysis Nikolopoulos: None declared, Antigoni Pieta: None declared, Vasiliki Tzavara: None declared, Pelagia Katsimbri: None declared, Dimitrios Boumpas Grant/research support from: Unrestricted grant support from various pharmaceutical companies, Theofanis Karageorgas: None declared
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