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BackgroundThe recent introduction of biologic agents targeting immunologic checkpoints (immunologic checkpoint inhibitors (ICI)) established immunotherapy as a highly effective cancer therapy. ICI that trigger an anti-tumor response by activation of T cells, may also cause immune-related adverse events (irAEs). Characterization of rheumatic adverse events such as arthritis and data on treatment of irAEs are scarce.ObjectivesTo characterize patients with new-onset arthritis under ICI therapy and to assess the efficacy and safety of treatment that aimed to balance anti-tumor and anti-inflammatory therapy.MethodsIn this prospective observational study, patients with melanoma receiving ICI therapy who experienced arthralgias were evaluated for the presence of musculoskeletal inflammation. Data on demographics, ICI regime, time of onset and response to therapy of musculoskeletal irAEs, imaging, joint count, CRP/ESR, and immune serology were collected. Further, response to anti-inflammatory therapies including NSAR, glucocorticoids (GC) and methotrexate was assessed.ResultsOf 7 patients with arthralgias after initiation of ICI therapy, all had objective signs of musculoskeletal inflammation. Arthritis was demonstrated in 6 patients, 3 oligoarthritis (SpA pattern), 2 polyarthritis (RA pattern), 1 monoarthritis. PMR-like disease with typical ultrasound findings was evident in 1 case. The time from start of ICI therapy to onset of synovitis symptoms varied from 1 to 259 days without a timely association to other irAEs. Upon first visit in our clinic, CRP levels were elevated in 6 of the patients (5.5 to 107 mg/l) while immune serology was positive only in one patient (high titer RF and ACPA). Interestingly, in this patient low RF and ACPA titers had been detected when she presented with arthralgias without synovitis five years prior. This patient developed highly active RA one day after the first infusion of nivolumab. Retrospective analysis of cancer staging imaging studies revealed good sensitivity for PET-CT in the detection of synovitis, as opposed to contrast-enhanced CT. The baseline mean overall disease burden (assessed by VAS for pain, 0–10) was 7.6±0.8 and was significantly reduced after 3 months of anti-inflammatory treatment to 1±1.4. Initially, all patients were treated with systemic and four patients also with intraarticular GC. Four of 7 patients flared on GC treatment upon tapering and were given methotrexate. Remission was achieved in all and prednisolone could be tapered. Patients were followed for a median of 152 days, and no safety signal with regard to tumor reappearance was detected.ConclusionsAll patients with arthralgias upon ICI therapy had arthritis or PMR-like disease suggesting a need for increased awareness for musculoskeletal irAE. Inflammatory manifestations were associated with high disease burden and not self-limiting. While GC therapy is effective, flares were frequent after tapering and, thus, potential side-effects including attenuation of the anti-tumor efficacy of ICI are a concern. Thi...

HAART). In all cases, diagnosis of EV was based on histological examination, and polymerase chain reaction was performed from lesional skin specimens for the identification of HPV.Patient 1 had the EV lesions for 96 months and was treated unsuccessfully with topical application of imiquimod for 2 months and cryosurgery for 6 months. Acitrecin and interferon a-2a were discontinued because of severe dryness and persistent flu-like symptoms, respectively. The administration of isotretinoin at a dose of 0.8 mg/kg proved efficacious for 6 months, leading to significant improvement; however, the lesions relapsed within 3 months after treatment cessation. HAART had no effect on EV lesions.Patient 2 developed EV and TBC and started HAART and a four-drug anti-TBC treatment (isoniazid, rifampicin, pyrazinamide and ethambutol). He did not consent in receiving any therapy for EV; nonetheless, a 50% improvement was noticed after initiation of HAART.Patient 3 under HAART presented widespread wart-like lesions distributed on the trunk, proximal extremities and resembling tinea versicolor. He was treated unsuccessfully with imiquimod and systemic isotretinoin, which was discontinued because of isotretinoin-induced headaches. He is currently under treatment with interferon a-2a with minimal prodromal results.There are either no large series or controlled studies of HIVassociated EV, and none are likely to be done probably because of the sparcity of cases. There is no established treatment for this dermatosis. 2 The role of HAART in EV remains questionable; 3 in our series, only one patient showed a significant improvement attributed to HAART.Acitrecin plus interferon alfa-2a, 2 etretinate 4 and isotretinoin 5 have shown transient effectiveness in the treatment of EV; recurrence has been noticed after the cessation of therapy. The continuous administration of systemic low-dose isotretinoin may achieve prolonged remission status in EV. 5 In our three patients, many different therapeutic regimens were applied; however, no effective modality was achieved. It seems that HIV-associated EV therapy probably has to be individualized, based primarily on the personal experience and preference of the investigators.

Background:Viral respiratory infections are common in the general population and result in a spectrum of outcomes ranging from effective viral clearance with no symptoms, to a maladaptive immune response that can result in severe symptomatic disease and death. Although patients with immune-mediated inflammatory diseases (IMID) are considered susceptible to poor outcomes from infectious syndromes, it is not known whether IMID patients are overall more prone to manifest common viral infection symptoms.Objectives:To explore frequency patterns of common viral infection symptoms in IMID patients.Methods:We previously recruited patients with IMIDs and individuals with no IMIDs for a seroprevalence study between February 1st and April 30th 2020 (1). Participants were questioned for the presence of eleven common viral disease symptoms. We clustered these data using an unsupervised binary data clustering algorithm (2) into 6 symptom clusters based on symptom frequency. Three major clusters (broadly symptomatic, intermediately symptomatic and oligo-/asymptomatic) and 2 sub-clusters (higher and lower frequency) for each major cluster. In addition, qualitative symptom clustering was done. We estimated standardized residuals to quantify the over/underrepresentation of IMID diagnosis frequencies in each subject cluster. We used Poisson regression to compare symptom counts by diagnosis.Results:We analyzed 1909 participants (757 with IMIDs; 1152 non-IMID controls; Table 1). Within each major subject cluster (Figure 1A), IMID patients showed the highest positive deviation from the expected frequencies in lower frequency sub-clusters while non IMID controls showed the highest positive deviations in the higher frequency sub-clusters (Figure 1B). Inflammatory bowel disease and psoriasis were remarkably overrepresented in the lower frequency sub-cluster of the broadly-symptomatic cluster while RA was overrepresented in the lower frequency sub-clusters of intermediate and oligo-/asymptomatic clusters. X axis of Figure 1A presents qualitative symptom clusters. Regression analysis shows that RA patients among other IMIDs reported overall less symptoms (RR= 0.69, 95%CI, 0.58 - 0.80) compared to non-IMID controls.Figure 1.A) distribution of common viral respiratory disease symptoms across patient and symptom clusters. B) Standardized residuals indicating deviation from expected frequencies of IMID diagnoses across patient clusters. sob: shortness of breath, mskpain: musculoskeletal painConclusion:This analysis shows that symptoms of common respiratory viral infections are less frequent in RA patients and to a lesser extent in other IMID patient. As major clusters in this analysis can also be considered to represent exposure categories, these data suggest that IMIDs or their treatments may mitigate common respiratory viral infection symptoms.References:[1]Simon D. et al. Nat Commun (2020) 11, 3774[2]Bhatia P. et al. J. Stat. Softw (2017) 76(9)Table 1.Participant characteristics and distribution of IMID diagnoses across subject clusters.ClustersBroad SymptomaticIntermediate SymptomaticOligo-AsymptomaticOverallHigherLowerHigherLowerHigherLowerN190910185412259283769Age, years, mean (SD)45.4(15.2)42.4(13.3)47.3 (15.2)42.4(12.9)50.4(15.5)41.8(14.9)46.8(15.9)Male1080 (56.6)42 (41.6)38 (44.7)196 (47.6)137 (52.9)178 (62.9)489 (63.6)Diagnosis, n(%)No-IMID1152 (60.3)72 (71.3)44 (51.8)280 (68.0)112 (43.2)207 (73.1)437 (56.8)RA226 (11.8)7 (6.9)5 (5.9)29 (7.0)56 (21.6)17 (6.0)112 (14.6)IBD178 (9.3)5 (5.0)15 (17.6)46 (11.2)29 (11.2)19 (6.7)64 (8.3)SpA142 (7.4)7 (6.9)5 (5.9)23 (5.6)25 (9.7)14 (4.9)68 (8.8)Psoriasis89 (4.7)4 (4.0)9 (10.6)14 (3.4)8 (3.1)13 (4.6)41 (5.3)Other122 (6.4)6 (5.9)7 (8.2)20 (4.9)29 (11.2)13 (4.6)47 (6.1)Symptom count/patient, mean (SD)1.2 (1.7)6.0 (1.3)3.9 (1.1)2.2 (1.0)1.5 (0.6)0.5 (0.5)0.0 (0.0)IBD, inflammatory bowel disease.Acknowledgements:This study was supported by the Deutsche Forschungsgemeinschaft (DFG- FOR2886 PANDORA and the CRC1181), the Bundesministerium für Bildung und Forschung (BMBF; project MASCARA), the H2020 GA 810316 - 4D-Nanoscope ERC Synergy Project, the IMI funded project RTCure, the Emerging Fields Initiative MIRACLE of the Friedrich-Alexander-Universität Erlangen-Nürnberg as well as the Schreiber Stiftung gemeinnützige Gesellschaft mbH.Disclosure of Interests:None declared