Search

Background Colchicine is an available, safe, and effective anti-inflammatory drug and has been suggested as a COVID-19 treatment, but its usefulness in hospitalized severe COVID-19 patients has not been thoroughly demonstrated. Objective To address the safety and efficacy of colchicine in hospitalized patients with severe COVID-19. Design We conducted a triple-blind parallel non-stratified placebo-controlled clinical trial. Participants We recruited 116 hospitalized patients with severe COVID-19 in Mexico. Interventions Patients were randomized to receive 1.5 mg of colchicine or placebo at the time of the recruitment in the study (baseline) and 0.5 mg BID PO to complete 10 days of treatment. Main Measures The primary composite outcome was the progression to critical disease or death. Besides, we evaluated immunological features at baseline and after recovery or disease progression in 20 patients. Key Results Fifty-six patients were allocated to colchicine and 60 patients received placebo. The study was suspended after the second interim analysis demonstrated colchicine had no effect on the primary outcome (OR 0.83, 95%CI 0.35–1.93, P = 0.67), nor in the days of ICU and hospital stays. Adverse events were similar between groups (OR 1.63, 95% CI 0.66–3.88, P = 0.37). After colchicine treatment, patients had higher BUN and lower serum levels of IL-8, IL-12p70, and IL-17A. Conclusions Colchicine is safe but not effective in the treatment of severe COVID-19. Trial Registration ClinicalTrials.gov Identifier: NCT04367168.

Introduction Anti-phospatidylserine/prothrombin (aPS/PT) antibodies have been described in cutaneous Polyarteritis Nodosa (PAN) in association with specific manifestations. Objectives To determine aPS/PT antibodies in patients with PAN and its correlation with clinical manifestations. Methods Cross-sectional comparative study including PAN patients and 20 controls (10 Microscopic Polyangiitis [MPA] and 10 Behcet’s disease [BD]). Clinical and demographic variables, treatment, serologic markers, prognosis, activity and damage indexes were evaluated. aPS/PT, anti-cardiolipin (aCL), anti-beta 2 glycoprotein 1 (anti-B2GP1) antibodies, and lupus anticoagulant (LA) were determined. Results Fourteen patients with PAN were included, 11 (79%) women, with disease duration of 207 months, and mostly inactive disease. Only one patient with PAN and one with BD were positive for aPS/PT IgG. LA was the most frequent antibody identified. One patient with MPA and one with BD were positive for aCL IgM; one with MPA for anti-B2GP1 IgG, and one with PAN for anti-B2GP1 IgM. Conclusions aPS/PT antibodies are not frequent in patients with longstanding inactive PAN.

To assess the mean platelet volume (MPV), platelet-to-lymphocyte ratio (PLR), the neutrophil-to-lymphocyte ratio (NLR) and the MPV-to-lymphocyte ratio, and to test them according to the clinical/serological status, shift through time and other comorbidities in APS.We included 96 primary APS patients according to the Sydney classification criteria and/or patients with thrombocytopenia and/or autoimmune hemolytic anemia who also fulfilled the serological criteria. We tested aCL, anti-β2GP-I and aPS/PT antibodies and LA. We first registered the MPV and the aforementioned ratios within at least 6 months after an event of thrombosis or thrombocytopenia/AIHA (baseline determination), and during thrombosis/thrombocytopenia/AIHA onset when available (acute event).A lower baseline MPV and a higher PLR characterized the thrombotic group (n = 74). The AUC for baseline PLR was 0.82 (p 0.001): SE of 69%, SP 91%, PPV 96%, NPV 74%, LR+ 13.67 and LR- 0.19. During the acute event, both variables increased. The thrombocytopenic group (n = 66) had a higher baseline MPV and a lower PLR, and during an acute event the PLR decreased more deeply. The AUC for MPV was 0.64 (p = 0.02): SE 44%, SP 92%, PPV 86%, NPV 40%, LR+ 3.3 and LR- 0.85. These findings were not related with the aPL antibody profile status, titers or comorbidities.Basal MPV and PLR might help to identify APS patients according to their thrombotic or thrombocytopenic phenotype. These variables change during the acute events and might be the reflex of physiopathological or compensatory mechanisms in APS.

METHODS We conducted a medical records review study (1975-2018) that included patients with childhood- and adult-onset PAN. Demographics, organ involvement, phenotype, treatment, and outcomes were assessed and compared against previously published cohorts. RESULTS Thirty-one patients were included, 20 (64.5%) female, with a median age at diagnosis of 28 years (interquartile range [IQR], 16-42). Seven (23%) were classified as cutaneous; 23 (74%), systemic; and 1 (3%), progressive systemic phenotype. Eleven patients (35%) had childhood-onset PAN. Most common manifestations were musculoskeletal (71%), cutaneous (68%), constitutional (61%), peripheral neuropathy (39%), and gastrointestinal (29%). The median Birmingham Vasculitis Activity Score and Five-Factor Score at diagnosis were 9 (IQR, 4-13) and 1 (IQR, 0-1), respectively. Most patients were treated with glucocorticoids (94%). Twenty-four (80%) achieved complete and 6 (20%) partial remission at a median follow-up time of 30 months (8-192 months). The median Vasculitis Damage Index at last follow-up was 1 (IQR, 0-1). Nineteen (66%) experienced relapses. Patients with childhood-onset PAN more frequently had central nervous system and gastrointestinal involvement (36% vs 5%, p = 0.04 and 64% vs 10%, p = 0.003, respectively), microaneurysms (100% vs 38%, p = 0.02), and lower levels of C-reactive protein (0.3 vs 15.4 mg/dL, p = 0.03), compared with adult-onset PAN patients. CONCLUSIONS Our cohort of PAN patients showed predominantly a systemic phenotype. Outcomes were generally good, with most patients achieving complete remission. Childhood-onset differed from adult-onset PAN in terms of clinical and serological characteristics, whereas clinical manifestations and outcomes may be different than the ones reported in other cohorts.

The clinical utility of serum immunoglobulin free light chains (sFLC) in IgG4-related disease (IgG4-RD) is unknown. Herein we evaluated their association with clinical phenotypes, serology and activity in patients with IgG4-RD. Cross-sectional study that included 45 patients with IgG4-RD, and as controls 25 with Sjögren’s syndrome (SS) and 15 with sarcoidosis. IgG4-RD patients were classified in clinical phenotypes: pancreato-hepato-biliary, retroperitoneum/aorta, head/neck-limited and Mikulicz/systemic; as well as proliferative vs. fibrotic phenotypes. We assessed the IgG4-RD Responder Index (IgG4-RD RI) at recruitment and measured IgG1, IgG4, κ and λ sFLC serum levels by turbidometry. sFLC levels were similar among IgG4-RD, SS and sarcoidosis groups. Regarding the IgG4-RD patients, the mean age was 49 years, 24 (53.3%) were men and 55.5% had activity. Eight (17.7%) belonged to pancreato-hepato-biliary, 6 (13.3%) to retroperitoneum/aorta, 14 (31.1%) to head/neck-limited, 16 (35.5%) to Mikulicz/systemic phenotypes, whereas 36 (80%) to proliferative and 9 (20%) to fibrotic phenotypes. High κ sFLC, λ sFLC and κ/λ ratio were present in 29 (64.4%), 13 (28.9%) and 13 (28.9%) of IgG4-RD patients, respectively. There were no differences in sFLC among IgG4-RD phenotypes. κ sFLC and κ/λ ratio correlated positively with the number of involved organs and IgG4-RD RI. Patients with renal involvement had higher κ sFLC and λ sFLC. The AUC for κ sFLC and λ sFLC, for renal involvement was 0.78 and 0.72, respectively. Active IgG4-RD had higher levels of κ sFLC and more frequently a high κ/λ ratio. The AUC for κ sFLC and κ/λ ratio for predicting active IgG4-RD was 0.67 and 0.70, respectively. sFLC correlated positively with IgG1 and IgG4 levels. sFLC may be useful as a biomarker of disease activity as well as multiorgan and renal involvement. In particular, a high κ/λ ratio may identify patients with active disease.

To evaluate the clinical/serological phenotype and outcomes of IgG4-related kidney disease. Case series of IgG4-related kidney disease from a cohort of 69 patients with IgG4-related disease. We defined kidney involvement as the presence of at least one of the following conditions: (A) laboratory parameters of kidney injury (proteinuria and/or elevated creatinine levels and/or hematuria); and/or (B) contrast-enhanced computed tomography features (multiple low-density lesions and/or nephromegaly and/or hypovascular solitary mass and/or renal pelvic lesion and/or perinephric lesions). We identified 17 patients with kidney involvement (24.6%), with a mean age of 53.6 ± 11.3 years; thirteen (76.5%) were male. Six patients fulfilled the laboratory criteria, six the imaging criteria, and five both. Five patients had a renal biopsy, the main histopathological diagnosis being IgG4 tubulointerstitial nephritis. Sixteen patients received glucocorticoids and 12 also immunosuppressors and/or biologics. Sixteen patients presented either total or partial renal remission at a median follow-up of 26 months, while one patient developed end-stage renal disease. Patients with kidney disease, as opposed to patients without kidney involvement, had a higher number of involved organs, higher IgG4-related disease responder index and IgG4 and IgG1 serum levels, higher prevalence of rheumatoid factor, and lower C3 and C4 levels. Our study emphasizes the systemic nature of IgG4-related disease, highlighting that renal involvement is usually present in a subset of patients with multisystemic disease, high IgG1 and IgG4 levels, and hypocomplementemia. Key Points • IgG4-RKD presents at a younger age in Mexican mestizo patients. • IgG4-RKD presents with proteinuria and kidney injury or as an asymptomatic imaging finding. • IgG4-RKD presents in the context of multisystemic disease, hypocomplementemia, and high IgG1 and IgG4 levels.

To validate the renal risk score in a cohort of patients with advanced kidney damage. A total of 72 patients with biopsy-proven ANCA glomerulonephritis with >12 months of follow-up were studied. The renal risk score was calculated and evaluated by survival analysis for time of renal survival. Cohort-specific clinical, histopathologic, and post-treatment factors associated with renal survival were determined by Cox regression analysis. Kidney biopsies were classified as focal, crescentic, mixed, and sclerotic classes in 6 (8%), 4 (6%), 25 (35%), and 37 (51%) patients, respectively. The 1-, 3-, and 5-year renal survival rates were 79%, 73%, and 68%, respectively. Patients were segregated by the risk score in low- (18%), medium- (47%), and high-risk (35%) groups. Patients in the low-risk group had 36-, 60-, and 84-month renal survival of 100%; those in the medium risk 85% (95% CI 72–92), 81% (95% CI 66–95), and 76% (95% CI 60–92), respectively; and those in the high risk 37% (95% CI 17–57), 26% (95% CI 7–45), and 18% (95% CI 1–36), respectively. Six (43%) of the 14 patients in the high-risk group recovered renal function after the initial episode, and 2 (14%) remained dialysis-free. Other parameters associated with renal survival included age, proteinuria, general symptoms, cellular crescents, glomerulosclerosis, tubulointerstitial lesions, best post-treatment eGFR, and renal relapses. We validated the renal risk score as a prognostic tool in a cohort with predominantly mixed and sclerotic histologic categories. Since patients in the high-risk group still benefited from immunosuppressive therapy, this score should be used in conjunction with other predictive parameters to aid therapeutic decisions.

Summary Background Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. Methods In this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behcet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. Findings Of 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behcet's syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31–1·57]), were male compared with female (1·38 [1·05–1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23–1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50–3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49–3·02]). Risk factors varied among different disease subtypes. Interpretation Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases. Funding American College of Rheumatology and the European Alliance of Associations for Rheumatology.

Background The tendency of IgG4-related disease (IgG4-RD) to form pseudotumors, as well as its multisystemic nature, makes it the perfect mimicker of many conditions. Moreover, some clinical, serological, radiological, or histological features of the disease might be shared with some mimickers.Recently, 4 clinical phenotypes have been identified, and patients grouped in each phenotype have distinctive demographic, clinical, and serological features and outcomes, and, as expected, for each phenotype, a set of differential diagnoses should be considered. Summary of the literature The main differential diagnoses for the pancreato-hepato-biliary phenotype are pancreatic adenocarcinoma and cholangiocarcinoma. Other differential diagnoses include type 2 autoimmune pancreatitis and primary sclerosing cholangitis. In patients with retroperitoneal/aortic phenotype, inflammatory conditions such as idiopathic retroperitoneal fibrosis and large vessel vasculitides should be ruled out, and most of the time, a biopsy will be needed to exclude malignancies. In head and neck limited phenotype, autoimmune conditions (eg, granulomatosis with polyangiitis, Graves orbitopathy, sarcoidosis), malignancies, and histiocytosis should be ruled out, whereas the main differential diagnoses of the Mikulicz/systemic phenotype are Sjogren syndrome, granulomatosis with polyangiitis, and multicentric Castleman disease. Conclusions Approaching a patient with probable IgG4-RD through a clinical phenotype framework will ease the diagnostic algorithm and facilitate the prompt recognition of the disease. There are certain clinical, serological, radiological, and histological features in each clinical phenotype that, if present, increase the likelihood that a patient may have IgG4-RD instead of the mimicker condition. Those clues that point toward IgG4-RD diagnosis should be actively sought in the workup of patients.

The clinical utility of serum immunoglobulin free light chains (sFLC) in IgG4-related disease (IgG4-RD) is unknown. Herein we evaluated their association with clinical phenotypes, serology and activity in patients with IgG4-RD. Cross-sectional study that included 45 patients with IgG4-RD, and as controls 25 with Sjögren's syndrome (SS) and 15 with sarcoidosis. IgG4-RD patients were classified in clinical phenotypes: pancreato-hepato-biliary, retroperitoneum/aorta, head/neck-limited and Mikulicz/systemic; as well as proliferative vs. fibrotic phenotypes. We assessed the IgG4-RD Responder Index (IgG4-RD RI) at recruitment and measured IgG1, IgG4, κ and λ sFLC serum levels by turbidometry. sFLC levels were similar among IgG4-RD, SS and sarcoidosis groups. Regarding the IgG4-RD patients, the mean age was 49 years, 24 (53.3%) were men and 55.5% had activity. Eight (17.7%) belonged to pancreato-hepato-biliary, 6 (13.3%) to retroperitoneum/aorta, 14 (31.1%) to head/neck-limited, 16 (35.5%) to Mikulicz/systemic phenotypes, whereas 36 (80%) to proliferative and 9 (20%) to fibrotic phenotypes. High κ sFLC, λ sFLC and κ/λ ratio were present in 29 (64.4%), 13 (28.9%) and 13 (28.9%) of IgG4-RD patients, respectively. There were no differences in sFLC among IgG4-RD phenotypes. κ sFLC and κ/λ ratio correlated positively with the number of involved organs and IgG4-RD RI. Patients with renal involvement had higher κ sFLC and λ sFLC. The AUC for κ sFLC and λ sFLC, for renal involvement was 0.78 and 0.72, respectively. Active IgG4-RD had higher levels of κ sFLC and more frequently a high κ/λ ratio. The AUC for κ sFLC and κ/λ ratio for predicting active IgG4-RD was 0.67 and 0.70, respectively. sFLC correlated positively with IgG1 and IgG4 levels. sFLC may be useful as a biomarker of disease activity as well as multiorgan and renal involvement. In particular, a high κ/λ ratio may identify patients with active disease.

Objectives To evaluate the prevalence and meaning of antineutrophil cytoplasmic antibodies (ANCA) positivity in a cohort of IgG4-related disease (IgG4-RD). Methods We identified patients with ANCA determination from a retrospective cohort of 69 patients with IgG4-RD. ANCA were measured by indirect immunofluorescence microscopy (IIF) and/or proteinase 3 (PR3)-ANCA and MPO-ANCA by ELISA. IIF patterns were classified as perinuclear (P-ANCA), cytoplasmic (C-ANCA) and atypical (X-ANCA). We compared the ANCA-positive vs the ANCA-negative IgG4-RD group. Results Out of 69 patients, 31 IgG4-RD patients had an ANCA determination. Four patients with concomitant systemic autoimmune diseases were excluded. We found positive ANCA by IIF in 14 (56%) of 25 patients tested. The most common IIF pattern was C-ANCA in eight (57.1%), followed by dual C-ANCA/X-ANCA in four (28.6%) and P-ANCA and dual C-ANCA/P-ANCA in one each (7.1%). Of the 20 patients with ANCA determination by both IIF and ELISA, four have positive ANCA by ELISA (three for MPO-ANCA and one for PR3-ANCA). Of the two patients with only ELISA determination, one was positive for MPO-ANCA. The prevalence of ANCA positivity by ELISA was 22.7% (5 out of 22 patients). ANCA was more frequent in the Mikulizc/systemic phenotype (42.9%) compared with other phenotypes (P = 0.04). ANCA-positive IgG4-RD patients had more frequently lymph node and kidney involvement, high IgG1 levels and erythrocyte sedimentation rate, and positive antinuclear antibodies. Conclusion ANCA are found in a significant number of patients with IgG4-RD and differed from the ANCA-negative group in terms of clinical and serological features.

BACKGROUND In patients with rheumatoid arthritis (RA) exercise improves muscle strength and decreases fat mass, whereas the consumption of a Mediterranean diet (MD) also has been associated with higher grip strength. Therefore, it is important to explore the combined effects of these interventions on hand grip strength and weight in RA. OBJECTIVE To determine the combined effect of an MD and a dynamic exercise program (DEP) on hand grip strength in women with RA. METHOD In a randomized clinical trial, 106 women with RA were included and assigned to the DEP-MD, DEP and MD groups. Weight, body circumferences, Disease Activity Score-28, Health Assessment Questionnaire Disability Index [HAQ-DI], and hand grip strength were measured at baseline and 24 weeks after the interventions. RESULTS After 24 weeks, hand grip strength showed a significant increase in the DEP group (median 2 kg) compared with DEP-MD (median 0.5 kg) and MD (median -0.5 kg) groups (p = 0.03). In the MD group weight and waist circumference showed a significant decrease (-2.2 kg and -4.3 cm) compared with DEP-MD (0.85 kg and 1.9 cm) and DEP (0.35 kg and 0.5 cm) groups (p

Background: Hypophysitis is an inflammatory process of the pituitary gland with different origins. Infundibulum may be also involved, called infundibulum-hypophysitis. Sometimes, enlargement of pituitary gland causes mass effect and anterior or posterior hormonal dysfunction, including hypopituitarism, and diabetes insipidus (DI), respectively. Hypophysitis is a rare autoimmune disease, however, the number of cases have been recently increasing due to higher detection related with more magnetic resonance imaging (MRI) studies. In addition, hypophysitis may be related with autoimmune rheumatologic disease (ARD) such as generalized lupus erythematosus (GLE), granulomatosis with polyangeitis (GPA), IgG4-related disease, and rheumatoid arthritis (RA). Aim: to compare the clinical and biochemical findings among patients with hypophysitis grouped depending on the presence of coexistent ARD activity. Methodology: it is a comparative and cross-sectional study. We registered all data from cases followed-up in Neuroendocrinology and Rheumatology units, from January 1987 to July 2019. Results: 24 patients showed confirmed diagnosis of hypophysitis. Majority of them (n=17, 71%) do not have coexistent diagnosis of ARD. However, 7 cases (29%) presented pituitary involvement with coexistent activity of GPA (n=4, 17%), GLE (n=1, 4%), RA (n=1, 4%) and IgG4-related disease (n=1, 4%). Female gender predominate in hypophysitis cases with and without ARD (p=0.9). Interestingly, age of hypophysitis diagnosis was significantly younger in cases without (38±14) vs. with (49±5) ARD (p=0.01). MRI results showed similar and typical findings related with hypophysitis independently of the presence of ARD. Hypopituitarism was present in the majority of cases, however, none of cases with hypophysitis and ARD showed hypogonadism (p=0.02). DI was present in 15 patients (63%), three of them with ARD (all with GPA). All cases received only medical therapy (i.e., glucocorticoids, rituximab, or azathioprine). Surgery or radiotherapy was not necessary in any case. Conclusions: Almost a 30% of cases with hypophysitis may have coexistent ARD. Pituitary function should be evaluated in cases with previous ARD diagnosis. However, hypogonadism was not present in cases with ARD and hypophysitis. Patients with ARD presented hypophysitis at older age. The remaining clinical and radiological data were similar between groups. References: 1) Clinical Diabetes and Endocrinology. December 2016;2(1). 2) Clin Rheumatol. 2019 Aug 24. doi: 10.1007/s10067-019-04735-7

We aimed to estimate the frequency of overlap of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with systemic autoimmune diseases. Retrospective single-center study to identify patients with AAV diagnosis and concomitant autoimmune systemic diseases, simultaneously, before or after the diagnosis of AAV. Sociodemographic characteristics, such as comorbidities; follow-up time; type of AAV; disease duration; relapses; treatment and response; clinical, serological, and histological characteristics; disease activity and damage; prognosis; dialysis requirements, and death were assessed. Twenty-eight of two hundred and forty-seven patients (11.3%) with AAV had a concomitant diagnosis of autoimmune disease. The predominant AAV type was renal-limited vasculitis (39%), followed by granulomatosis with polyangiitis (29%), mycroscopic polyangiitis (25%), and eosinophilic granulomatosis with polyangiitis (7%). Mean age at AAV diagnosis was 50 ± 17 years and 24/28 were ANCA positive. The main clinical manifestations were renal (79%), otorhinolaryngologic (43%), and pulmonary and peripheral neuropathy (32%). Sixteen patients (57%) experienced partial or total remission at a median follow-up of 34 months, and four patients (14%) died. The most frequent autoimmune disease overlapped was rheumatoid arthritis (39%), followed by Sjögren's syndrome and systemic sclerosis (14%), mixed connective tissue disease (11%), systemic lupus erythematosus and juvenile idiopathic arthritis (7%), and ankylosing spondylitis and IgG4-related disease (4%). In nine patients (32%), both diagnoses were simultaneous; in the rest, median time elapsed between the autoimmune disease and AAV diagnosis was 173 months. The prevalence of overlap AAV with other autoimmune diseases was low. The most common AAV phenotype was renal-limited vasculitis, and the most frequent overlap disease was rheumatoid arthritis.

Background:There is a paucity of information on the current phenotypes, ethnic and geographic differences of PAN. A global PAN study group has been working for clinical subphenotype and GWAS studies.Objectives:This study is aimed to look for target organ associations in PAN.Methods:PAN patients fulfilling the EMA vasculitis classification algorithm were recruited. In addition to baseline characteristics, treatment and outcome data, occurrence of any of the clinical manifestations related to PAN during disease course was recorded.Factor analysis was used to analyse target organ associations of 306 patients. Five factors were identified by factor analysis of variables sex, paediatric-onset, HBV, monogenic disease relationship, cutaneous features, musculoskeletal symptoms, constitutional symptoms and involved areas (abdominal, renal, neurologic, ENT, cardiac, pulmonary).Results:PAN cohort from 7 countries were used (Italy: n=59, Japan: n=39, Mexico: n=29, Slovenia: n=14, Sweden:11, TUR: n=106, UK: n=48). 306 (M/F: 171/135 and Caucasian 77.1%, Asian 13.4%, and Hispanic 9.5%) patients were included. 8 were HBV-related, and 22 of TUR patients had a monogenic form of disease (FMF n=15, DADA2 n=7). 21.8% of patients were cutaneous-only PAN patients. 48.4% of patients had radiologic, 64% had biopsy-proven PAN. Median age at disease onset was 40 (IQR 27.0-57.5) years. During a median 57 (16-120) months follow-up, 39 (13%) patients died.Factor analysis revealed 5 factors that explained 54.1% of the original information on the matrix as follows:Factor 1,represented the association between gastrointestinal and renal involvement, male gender and negatively associated with cutaneous features;Factor 2,the association between monogenic relationship with paediatric onset disease;Factor 3,any of musculoskeletal findings with positive constitutional symptoms;Factor 4any neurologic involvement was associated with ENT and pulmonary findings;Factor 5cardiac involvement in non-HBV patients (Table).The eigenvalues of the 5 factors were 2.034, 1.470, 1.427, 1.079 and 1.030, in decreasing order, i.e., the highest contribution to the overall variance in the matrix came from the togetherness of the 4 clinical and demographic characteristics that made up Factor 1.Conclusion:Target organ associations could support distinctive subphenotypes in PAN. Factor 1 seems the most severe form. Patients with FMF or DADA2 have distinct target organ associations. The jury is out to decide whether these patients should be classified as ‘vasculitis associated with probable etiology’ just as HBV-related-PAN. Factor 4 might define a different subphenotype (ANCA- medium vessel vasculitis?).Disclosure of Interests:Omer Karadag: None declared, Ertugrul Cagri Bolek: None declared, Shunsuke Furuta: None declared, Giacomo Emmi: None declared, ALOJZIJA HOCEVAR: None declared, Andrea Hinojosa-Azaola: None declared, Aladdin J Mohammad Speakers bureau: lecture fees from Roche and Elli Lilly Sweden, PI (GiACTA study), Serdal Ugurlu: None declared, Fatma Alibaz-Oner: None declared, Ayten Yazici: None declared, Luca Quartuccio: None declared, Enrica Bozzolo: None declared, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI, Giuseppe Alvise Ramirez: None declared, Luca Cantarini: None declared, Gina Gregorini: None declared, Jeannin Guido: None declared, Sara Monti: None declared, Eduardo Martin-Nares: None declared, Franco Schiavon: None declared, Roberto Padoan: None declared, Hajime Kono: None declared, Augusto Vaglio: None declared, Saadettin Kiliçkap: None declared, Ali İhsan Ertenli: None declared, Haner Direskeneli: None declared, Seza Özen Consultant of: Novartis, Pfizer, Speakers bureau: SOBI, Novartis, David Jayne Grant/research support from: ChemoCentryx, GSK, Roche/Genentech, Sanofi-Genzyme, Consultant of: Astra-Zeneca, ChemoCentryx, GSK, InflaRx, Takeda, Insmed, Chugai, Boehringer-Ingelheim

Background: The lacrimal gland is frequently involved in both IgG4-related disease (IgG4-RD) and Sjogren’s syndrome (SS) and presents with swelling and/or dry eye symptoms. Although a distinct chemokine and cytokine tear profile might distinguish SS from idiopathic dry eye, as of today no study has assessed this issue in IgG4-RD. Objectives: To evaluate and compare a set of chemokine/cytokine in the tears of patients with IgG4-RD and primary SS. Methods: We included 11 patients with IgG4-RD according to the Comprehensive Diagnostic Criteria for IgG4-RD and 17 with primary SS according the AECG criteria, who attended a tertiary referral center in Mexico City. Schirmer-I test were performed using two standardized sterile tear strips, and then immediately frozen at -86°C until assayed. Once defrosted, the tears were extracted from the strips using a buffer containing 0.5 M NaCl and 0.5% Tween-20. Then, the amount (pg/mL) of the following selected chemokines and cytokines were measured by Luminometry: CCL11, G-CSF, IFN-γ, IL-12p40, IL-12p70, IL-13, IL-17A, IL-1α, IL-1β, IL-4, IL-7, CXCL10, CCL2, CCL3, CCL4 and TNF-α. Results: Patients with IgG4-RD were younger (51.3±14.7 vs. 55.7±10.6) and more frequently men (45.5% vs. 5.9%) than SS patients. Regarding the IgG4-RD group, 7 (63.6%) had lacrimal gland involvement, 5 (45.5%) dry eye symptoms and 6 (54.5%) positive Schirmer-I test. We observed multi-organic involvement in 9 patients (81.8%), median number of involved organs of 5, 9 (81.8%) patients had active disease, median IgG4-RD responder index of 6 points, 8 (72.7%) patients had high IgG4 serum levels, and 9 (81.8%) biopsy proven diagnosis. We found higher levels of IL-7 and CCL2, and a trend for G-CSF in the IgG4-RD group. Conversely, primary SS patients had higher levels of IL-12p40, IL-1α, IL-1β, CCL3 and CCL4. At the logistic regression analysis, the variables that remained associated with IgG4-RD were IL-7 (OR 1.43 95% CI 1.06-1.93, p=0.01) and IL12p40 (OR 0.92, 95% CI 0.84-0.99, p=0.01). In a sensitivity analysis, including only 7 IgG4-RD patients with dacryoadenitis, we also observed higher levels of IL-7 and G-CSF in the IgG4-RD group vs primary SS. Conclusion: The chemokine and cytokine profile of tears of patients with IgG4-RD is characterized by a mixed immune response (Th1/Th2/Th17) compare with a predominantly Th1 response in primary SS. Our results also suggest a possible role of IL-7 in the pathogenesis of IgG4-RD. References: [1] Hernandez-Ruiz M, Zlotnik A, Llorente L, Hernandez-Molina G. Markedly high salivary and lacrimal CXCL17 levels in primary Sjogren’s syndrome. Joint Bone Spine. 2018May;85(3):379-380. Disclosure of Interests: None declared

Background: IgG4-related ophthalmic disease (IgG4-ROD) may present as a cause of orbital myositis leading to proptosis and diplopia. This clinical scenario can be mistakenly diagnosed as Graves’ orbitopathy (GO), preventing a timely and adequately treatment. Objectives: To elucidate if there are specific radiological features that might differentiate between IgG4-ROD and GO by imaging. Methods: We included 19 patients with diagnosis of IgG4-related disease (IgG4-RD) according to the Comprehensive Diagnostic Criteria for IgG4-RD, who regularly attended a tertiary referral center in Mexico City. All the patients had ophthalmic involvement and available computed tomography (CT) and/or magnetic resonance imaging (MRI) of the orbits. We also included 32 patients with GO with available CT and/or MRI of the orbits. Imaging studies were evaluated by a blinded head and neck radiologist for the following features: exophthalmos, extraocular muscles (EOM) size and morphology, lacrimal gland enlargement, orbital fat involvement, stretching of the optic nerve (ON), ON sheath thickening and orbital bone changes. Results: Both groups were similar in age (49.1±15.8 vs. 51.6±14.7, p=0.58) and gender (men 58.9% vs. 40.6%, p=0.23). In addition to ophthalmic involvement, 18 (94.7%) IgG4-RD patients had extra-ophthalmic involvement with a median number of organs involved of 7 (1-12), mainly submandibular glands (73.7%), lymph nodes (68.4%), parotid glands (63.2%) and pancreas (47.4%). Three patients were misdiagnosed as GO before IgG4-RD diagnosis. Graves’ disease was the underlying thyroid disorder in 28 (87.5%) GO patients, Hashimoto’s thyroiditis in 2 (6.3%), papillary thyroid carcinoma in one (3.1%) and one patient was euthyroid with positive thyroid stimulating immunoglobulin. The prevalence of exophaltmos (78.9% vs. 93.8%), bilateral involvement (78.9% vs. 87.8%) and overall EOM involvement (47.4% vs. 68.8%) was similar between IgG4-ROD and GO groups. However, IgG4-ROD patients had a higher frequency of lacrimal gland involvement (73.7% vs. 10.7%, p=0.001) and a tendency for the lateral rectus to be the most frequently involved EOM (22.2% vs. 0%, p=0.07); conversely they had a lower prevalence for the inferior rectus to be the most frequently involved EOM, (33.3% vs. 72.7%, p=0.04), orbital fat involvement (47.4% vs. 81.3%, p=0.01), ON stretching (57.9% vs. 87.5%, p=0.02) and orbital bone changes (0% vs. 25%, p=0.02). EOM bellies were involved in all the IgG4-ROD and GO cases, whereas EOM tendon involvement was present in 9% of GO and in none of the IgG4-ROD group. Patients with IgG4-ROD had more frequently the combination of lacrimal gland and lateral rectus (31.6% vs. 3.1%, p=0.008) and less frequently the combination EOM and orbital fat involvement (21.2% vs. 59.4%, p=0.008). At the logistic regression analysis we found an association of lacrimal gland involvement (OR 64.4.0, 95% CI 6.8-609.5, p=0.001) with IgG4-ROD. In a second model including combined variables, the combination of lacrimal gland and lateral rectus involvement was associated with IgG4-ROD (OR 62.5, 95% CI 3.31-1000), P=0.006), whereas the presence of EOM and orbital fat involvement was protective (OR 0.05, 95% CI 0.006-0.48, p=0.009). Conclusion: Imaging features may reliably differentiate between IgG4-ROD and GO. The presence of both lacrimal gland and lateral rectus enlargement must alert clinicians to consider IgG4-ROD diagnosis. References: [1] Tiegs-Heiden CA, Eckel LJ, Hunt CH, et al. Immunoglobulin G4-related disease of the orbit: imaging features in 27 patients. AJNR Am J Neuroradiol. 2014Jul;35(7):1393-7. Disclosure of Interests: None declared

Objective: To evaluate if major salivary gland enlargement in patients with IgG4-related disease (IgG4-RD) is associated with systemic involvement.Methods: We included 47 patients with diagnosis of...

The footnote of Figure 2 in the published original version of the above article went missing and the correct figure is presented in this article.

Sjogren's syndrome is a systemic autoimmune disease characterized by immune- mediated injury of exocrine glands, as well as a diverse array of extraglandular manifestations. B cell over-activation is a key feature of the disease, attested by the wide spectrum of autoantibodies detected in these patients. Up to date, anti- Ro/SSA and anti-La/SSB antibodies are traditional biomarkers for disease classification and diagnosis. On the other hand, the detection of novel autoantibodies in SS has increased in the last years, opening a window of opportunity to denote particular stages of the disease, to establish clinical phenotypes, and to predict long-term complications such as lymphoma. For instance, anti-SP-1, anti-CA6 and anti-PSP antibodies occur in an earlier stage than anti-Ro/La antibodies, and may identify a subset of primary Sjogren's syndrome patients with mild or incomplete disease, whereas anti-cofilin-1, anti- alpha-enolase and anti-RGI2 antibodies are potential biomarkers of MALT lymphoma. Antibody detection is also important to elucidate new aspects of SS pathophysiology, and in the future to permit a phenotype-specific patient approach. Herein we review the literature regarding new autoantibodies in SS and attempt to dissect their usefulness as diagnostic tools, pathogenic role, identification of clinical phenotypes and as predictors of an overlap syndrome.

Systemic lupus erythematosus is a chronic autoimmune disease with a relapsing and remitting course characterized by disease flares. Flares are a major cause of hospitalization, morbidity and mortality in patients with systemic lupus erythematosus. Some triggers for these exacerbations have been identified, including infections, vaccines, pregnancy, environmental factors such as weather, stress and drugs. We report a patient who presented with a lupus flare with predominantly mucocutaneous, serosal and cardiac involvement after being bitten by a spider and we present the possible mechanisms by which the venom elicited such a reaction. To the best of our knowledge, this is the first such case reported in the literature.

Background IgG4-related disease (IgG4-RD) is an immune-mediated condition which clinical spectrum encompasses single or multiple organ involvement. Enlargement of major and minor salivary glands is one of the main disease features. Whether salivary gland enlargement is associated with systemic involvement has not been previously evaluated. Objectives To elucidate if salivary gland enlargement is associated with systemic disease. Methods We included patients with an established diagnosis (definitive: organ involvement, biopsy proven and high IgG4 levels, probable: organ involvement, biopsy proven without high IgG4 levels, possible: organ involvement, high IgG4 levels without histology) of IgG4-RD according to the Comprehensive Diagnostic Criteria, who regularly attend a tertiary referral center in Mexico City (2000–2017). We retrospectively collected demographics, clinical (organ involvement, disease activity and damage assessed by the IgG4-RD Responder Index [IgG4-RD RI] at basal and at 6 months of follow-up, number of relapses, remission and treatment), basal laboratory (C3, C4, ESR, PCR, total eosinophil count, IgG4 levels) as well as imaging and histologic data. Results We included 32 patients, 17 (53.1%) men, mean age 50.2±14.1 years and median disease duration 20.5 months. Seven (21.9%) have a definitive diagnosis, 12 (37.5%) probable and 13 (40.6%) possible. Overall we identified 21 anatomic sites affected, mainly pancreas 56.2%, lymph nodes 56.2%, lacrimal glands 37.5% and bile duct 34.3%. Salivary gland involvement was present in 12 (37.5%) patients (2 parotid, 3 minor salivary gland and 7 both). Among these patients, only 5 (41.6%) referred dry mouth and in 7 patients (58.3%) glandular enlargement was the onset disease feature. Salivary glandular enlargement was identified only radiologically in 5 patients (41.6%) and both clinical and radiologically in 7 (58.3%) patients. When we compared patients with (n=12) vs. without (n=20) salivary gland enlargement, the first group had a higher number of affected organs (6.5 vs. 2, p=0.0001) and absolut eosinophil9s count (348 vs. 137.5/mm3, p=0.05), a higher prevalence of lacrimal glands (75% vs. 15%, p=0.002), lymph nodes (91.7% vs. 35%, p=0.002) and lung involvement (33.3% vs. 0%, p=0.01), azathioprine use (83.3% vs. 30%, p=0.003), as well as a higher basal IgG4-RD RI (12 vs. 6, p=0.001) and a longer delay in diagnosis (64 month vs. 6.5 months, p=0.001). We did not find differences regarding gender, age, IgG4 serum levels, C3, C4, ESR, PCR, antinuclear antibodies, rheumatoid factor, anti-Ro/SSA and anti-La/SSB antibodies (negative in all patients), number of relapses, remission at 6 months and damage. We performed a logistic regression analysis (only including the number of organs, the basal IgG4-RD RI and time of follow-up) and found an association of salivary glandular enlargement with the basal IgG4-RD RI (OR 1.63, 95% CI 1.12–2.35, p=0.009). Conclusions Our study highlights the systemic nature of IgG4-RD. Patients with salivary gland enlargement should be routinely screened for systemic involvement. References Carruthers M, Stone J, Deshpande V, et al. Development of an IgG4-RD Responder Index. Int J Rheumatol. 2012;2012:259408. Acknowledgements No acknowledgements to report. Disclosure of Interest None declared

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a hypersensitivity reaction with rash, fever and multiorgan dysfunction potentially lethal in up to 10% of cases. It often affects liver function, but it can also affect kidney, lungs, and heart. Severe gastrointestinal involvement is rare. We present a case of a 31-year-old hispanic woman with pseudomembranous colitis associated with lamotrigine-induced DRESS syndrome. To the best of our knowledge, this is the fourth reported case of severe involvement of the gastrointestinal tract and the first to report pseudomembranous colitis in the setting of DRESS syndrome.