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Infectious disease can activate the immune system favoring a highly inflammatory response. Rheumatoid Arthritis is a long term inflammatory disease characterized by an autoimmune trigger. What happens when SARS COV 2 infection occurs in a patient suffering from early stage of rheumatoid arthritis? In this clinical case we want to highlight that the infection by SARS COV 2 could esacerbate or precipitate a clinical picture of Rheumatoid Arthritis. This condition should make you reflect on the probable therapeutic implications.

BACKGROUND The MARTE study investigated the demographic, clinical, and therapeutic characteristics of rheumatoid arthritis (RA) patients ongoing methotrexate (MTX) treatment for longer than 8 years. METHODS This cross-sectional, observational study considered 587 RA patients from 67 Rheumatology Units across Italy. Data collected included demographic, clinical, and therapeutic characteristics, focusing on MTX prescription patterns (route of administration, dosing regimens, treatment duration, and discontinuation). RESULTS As initial therapy, 90.6% of patients received one conventional synthetic Disease Modifying Anti Rheumatic Drug (csDMARD), with treatment started within the first 3 months from diagnosis in half of the patients. MTX was the first csDMARD in 46.2% of patients. The prevalent route of administration at diagnosis was the intramuscular (60.5%), while at study entry (baseline) 57.6% were receiving subcutaneous MTX. Patients who required a higher MTX dose at study entry were those who received a significantly lower starting MTX dose (P

To conduct a long-term, prospective, randomized controlled trial evaluating rituximab (RTX) therapy for severe mixed cryoglobulinemia or cryoglobulinemic vasculitis (CV). RTX monotherapy represents a very good option for severe CV and can be maintained over the long term in most patients.

L’artrite psoriasica (AP) è una malattia infiammatoria, cronica associata alla psoriasi e che viene classificata nelle Spondiloentesoartriti sieronegative (SpA). Si caratterizza per la eterogeneità della presentazione, delle articolazioni colpite e del decorso clinico. In un elevato numero di pazienti, il coinvolgimento poliarticolare è simile a quello dell’artrite reumatoide e pertanto conduce a disabilità ed è responsabile di un’alterata qualità della vita (1). Diventa necessario là dove il quadro clinico artritico e/o l’evoluzione del danno articolare non siano controllabili, il trattamento con i farmaci biologici anti-TNF-alfa (2). Le “interstiziopatie polmonari diffuse” comprendono un gruppo eterogeneo di malattie caratterizzate da alterazioni infiammatorie su base immunitaria interessanti estensivamente l’interstizio alveolare con possibile coinvolgimento delle strutture bronchiali periferiche. Tali patologie hanno in comune l’alveolite e la fibrosi ma non un’unica eziologia, che nella maggior parte dei casi è sconosciuta (3). Descriviamo il caso clinico di un paziente affetto da AP che, in corso di trattamento con infliximab, ha sviluppato un quadro di ILD. Notevoli problematiche sono state affrontate per il trattamento della patologia articolare che si è dimostrata essere controllata dall’etanercept con contemporaneo controllo della patologia respiratoria.

Background: At present no drug or combination of drugs are clearly effective as disease modifying therapy in systemic sclerosis (SSc). Previous data have pointed out the efficacy of cyclophosphamide (CYC) in the treatment of SSc patients with fibrosing alveolitis, especially in those who had showed altered aspecific inflammation parameters (1). Objectives: To test efficacy, safety, and effects on activation/damage cellular markers of low-dose intravenous CYC in the treatment of "active" SSc. Methods: Eight SSc patients (7 F, 1 M; aging from 17 to 66, median 46 years; 5 with lcSSc and 3 dcSSc; disease duration ranging from 1 to 12, median 7 years) were studied at baseline and after 6-month intravenous CYC treatment (500 mg pulses at week 0, 1, 2, 6, 10, 14, 18, 22) (2). The following circulating activation/damage cellular markers were evaluated: von Willebrand factor (vWF) (ELISA) and intercellular adhesion molecule 1 (ICAM-1) (ELISA) for endothelial cells; soluble interleukin 2 receptor (sIL-2R) (ELISA) for T lymphocytes; procollagen III aminopropeptide (PIIINP) (RIA) for fibroblasts. Besides, for each patient a total skin score was calculated and pulmonary function tests (PFTs) were performed. Results: After the 6-month CYC treatment, a significant reduction of TTS (10.6 ± 9.4 vs. 7.8 ± 8.4, p = 0.02) and a "freezing" of pulmonary function were noted. CYC treatment did not influence circulating levels of the cellular activation markers. Δs (differences between 6-month and baseline values), calculated for each marker, did not correlate with the respective changing of TSS and PFTs. No patient discontinued CYC treatment because of side effects. PIIINP (μg/L) ICAM-1 (ng/mL) vWF (%) sIL-2R (pg/mL) baseline 4.03 ± 0.98 360.2 ± 87.8 130.4 ± 56.3 1025 ± 296 6 month 4.13 ± 1.23 353.9 ± 89.8 123.6 ± 30.3 1005 ± 338 p > 0.05 > 0.05 > 0.05 > 0.05 Conclusion: Our results suggest an efficacy of low-dose intravenous CYC on cutaneous and lung involvement, detached by any influence on circulating markers previously reported as correlated to disease activity. This treatment appears to be a very safe approach. The ascertained validity of TSS as an outcome measure (3) in SSc prompt us to investigate, on a larger series and by a controlled trial, the effect of low-dose intravenous CYC in this condition.1. 1. Akesson A et al. Arthritis Rheum 1994, 37: 729-35;2. 2. Martin-Suarez I et al. Ann Rheum Dis 1997, 56: 481-7;3. 3. Steen VD, Medsger TA. Arthritis Rheum 2001, 44: 2828-35 1. 1. Akesson A et al. Arthritis Rheum 1994, 37: 729-35;2. 2. Martin-Suarez I et al. Ann Rheum Dis 1997, 56: 481-7;3. 3. Steen VD, Medsger TA. Arthritis Rheum 2001, 44: 2828-35

Background: Cognitive dysfunction has been recently found in patients with systemic sclerosis (SSc) (1). Objectives: To evaluate the occurrence of cognitive dysfunction in patients with SSc admitted to a tertiary centre of Rheumatology. Methods: Twenty-six SSc consecutive patients (22 F, 4 M; age ranging from 17 to 69 years, median 53) admitted to the Rheumatology Unit of the Second University of Naples were studied to analyse the relationship between the cognitive impairment and the demographic (age and school attendance) and clinical (disease duration, activity, disability, and coexistence of mental illnesses) variables. In all patients were performed, at Neurological Unit of the Second University of Naples, neuropsychological and neuropsychiatric tests for the evaluation of the Mini-Mental State Examination (MMSE), the Mental Deterioration Battery (MDB), the Montgomery and Asberg's Depression Rating Scale. Results: According to the criteria of MDB, 14 patients showed a decreased cognitive performance and, in detail, an early stage of cognitive dysfunction was noted. The neuropsychological state did not differ among patients divided according to the demographic variables (age, and school attendance) and the presence or not of neuropsychiatric alterations. Patients with the diffuse form of the disease showed a greater incidence of cognitive dysfunction. Conclusion: Our results suggest that an early cognitive dysfunction in SSc seems to be related to disease severity as defined by clinical subset.1. Nobili F.,Cutolo M., Castaldi A., et al. Impaired quantitative cerebral blood flow in scleroderma patient. J Neurol Sci 1997, 152, 63 1. Nobili F.,Cutolo M., Castaldi A., et al. Impaired quantitative cerebral blood flow in scleroderma patient. J Neurol Sci 1997, 152, 63

Our objective was to investigate the phenotype of helper T cells in the peripheral blood of patients with systemic sclerosis (SSc). PBMC from 15 patients with SSc and 15 sex- and age-matched controls were investigated for lymphocyte subpopulations (CD3, CD4, CD8, CD19, CD16/CD56, CD3-DR); IL-2, IL-4, and IFN-gamma mRNAs; and the relative cytokines in their cytoplasm. The last assay was carried out both in unstimulated and in PMA-activated PBMC. SSc patients presented a higher percentage of activated T cells, CD3+ DR+ (19.7 +/- 9.9 vs 5.1 +/- 2.5%; P < 0.0001); 12 of them presented IFN-gamma mRNA-positive cells; and none IL-2 or IL-4 mRNAs. Under basal conditions, PBMC from six SSc patients contained IL-2, IL-4, and IFN-gamma (i.e., they showed both Th1 and Th2 activation), and 1 IFN-gamma only. PMA-stimulated PBMC of patients differed from those of controls only in the increased percentage of IFN-gamma positive cells (52 +/- 12 vs 37 +/- 11%; P < 0.01). Our study demonstrates that Thl activation occurs in the peripheral blood of SSc patients. This evidence must be faced with from both a pathogenetic and a therapeutical point of view.

Autoimmune systemic diseases (ASD) may show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed to evaluate the seroconversion after the vaccination cycle and at 6-12-month follow-up, as well the safety and efficacy of vaccines in preventing COVID-19. The study included 478 unselected ASD patients (mean age 59 ± 15 years), namely 101 rheumatoid arthritis (RA), 38 systemic lupus erythematosus (SLE), 265 systemic sclerosis (SSc), 61 cryoglobulinemic vasculitis (CV), and a miscellanea of 13 systemic vasculitis. The control group included 502 individuals from the general population (mean age 59 ± 14SD years). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was evaluated by measuring serum IgG-neutralizing antibody (NAb) (SARS-CoV-2 IgG II Quant antibody test kit; Abbott Laboratories, Chicago, IL) on samples obtained within 3 weeks after vaccination cycle. The short-term results of our prospective study revealed significantly lower NAb levels in ASD series compared to controls [286 (53–1203) vs 825 (451–1542) BAU/mL, p < 0.0001], as well as between single ASD subgroups and controls. More interestingly, higher percentage of non-responders to vaccine was recorded in ASD patients compared to controls [13.2% (63/478), vs 2.8% (14/502); p < 0.0001]. Increased prevalence of non-response to vaccine was also observed in different ASD subgroups, in patients with ASD-related interstitial lung disease (p = 0.009), and in those treated with glucocorticoids (p = 0.002), mycophenolate-mofetil (p < 0.0001), or rituximab (p < 0.0001). Comparable percentages of vaccine-related adverse effects were recorded among responder and non-responder ASD patients. Patients with weak/absent seroconversion, believed to be immune to SARS-CoV-2 infection, are at high risk to develop COVID-19. Early determination of serum NAb after vaccination cycle may allow to identify three main groups of ASD patients: responders, subjects with suboptimal response, non-responders. Patients with suboptimal response should be prioritized for a booster-dose of vaccine, while a different type of vaccine could be administered to non-responder individuals.

Autoimmune systemic diseases (ASD) show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed at evaluating the seroconversion elicited by COVID-19 vaccine over the entire vaccination cycle including the booster dose. Among 478 unselected ASD patients originally evaluated at the end of the first vaccination cycle (time 1), 344 individuals were re-evaluated after a 6-month period (time 2), and 244 after the booster vaccine dose (time 3). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was assessed by measuring serum IgG-neutralizing antibody (NAb) on samples obtained at the three time points in both patients and 502 age-matched controls. In the 244 ASD group that received booster vaccine and monitored over the entire follow-up, the mean serum NAb levels (time 1, 2, and 3: 696.8±52.68, 370.8±41.92, and 1527±74.16SD BAU/mL, respectively; p&nbsp

OBJECTIVE: In this study we performed single-cell analysis of the intracellular cytokine expression in peripheral CD4+ and CD8+ lymphocytes from patients with Hashimoto's thyroiditis (HT) to investigate the type-1 response separately for the two lymphocyte sub-populations. DESIGN AND METHODS: Twenty-nine patients affected by HT and 20 healthy subjects, matched for sex and age, were enrolled. After the analysis of the lymphocyte sub-populations, the intracellular content of interferon-gamma (IFN-gamma) in phorbolmyristate acetate (PMA)-stimulated CD4+ and CD8+ lymphocytes was assayed. Moreover, the CD4+ lymphocytes were also evaluated for the intracellular expression of IL-4. RESULTS: No significant differences in CD3+, CD4+ and CD8+ lymphocytes were found between HT patients and control subjects. However, the HT patients showed higher numbers of CD4+ IFN-gamma+, CD4+ IL-4+ and CD8+ IFN-gamma+ (t-test, P< or =0.001) cells than the control subjects. Analysing the intracellular expression of IFN-gamma and IL-4 in relation to thyroid function, we found that the euthyroid patients (18 cases) showed more expression of IL-4 in CD4+ lymphocytes than the control subjects, without any significant modification of IFN-gamma expression in CD4+ and CD8+ lymphocytes. However, the hypothyroid patients (11 cases) showed an increase of IFN-gamma expression in both CD4+ and CD8+ lymphocytes with respect to the control subjects and the euthyroid patients. Moreover, the expression of IL-4 in CD4+ cells from hypothyroid patients was significantly lower than that seen in the euthyroid cases and comparable to that found in the control subjects. CONCLUSIONS: Our study has demonstrated that the peripheral CD4+ and CD8+ T lymphocytes from the HT patients show a type-1 activation strictly correlated to the occurrence of hypothyroidism. Further studies will be needed to clarify the exact role of peripheral lymphocytes in HT and whether they could provide a reliable marker of thyroid immune involvement.

CD40-CD154 interactions play a key role in regulating immune response and are involved in the development of some autoimmune diseases. We analysed the expression of CD154 antigen in CD3-activated PBMC from 10 systemic sclerosis (SSc) patients and 10 control subjects by immunofluorescence. PBMC from SSc patients showed an increased expression of this molecule, since, 6 h following CD3 stimulation, the percentage of CD154(+)cells was of 17. 53+/-2.0 (mean+/-SE) in control and 25.33+/-2.93 in patient cells (P0.03). The higher expression of CD154 antigen was ascribible to CD4(+)cells. The enhanced induction of CD154 following CD3 stimulation depended on protein synthesis, since was abolished when the cells were stimulated via CD3 in the presence of cycloheximide. By analysing the expression of the CD40-induced antigen CD80, we verified that a blocking anti-CD40 antibody inhibited CD80 appearance in SSc activated monocytes, indicating that CD154 molecule was functional. These results show an enhanced expression of a functional CD154 molecule in SSc CD4(+)activated T lymphocytes.