anti-Ro Research Articles

Severe Headache in Primary Sjögren's Syndrome Responded to Rituximab.

Primary Sjögren syndrome (pSS) is an immune systemic disease, that may affect the central nervous system. A severe headache unresponsive to treatment is the headache which is persistently nonresponsive to narcotic analgesics. A 48-year-old woman with a 10-year history of pSS was seen in January 2021, complaining of a headache one week previously. The headache was characterised by a dull persistent pressing intensity and was not responding to paracetamol, NSAIDs or codeine. She had no previous history, nor family history. Physical examination revealed bilateral parotid glands enlargement. Laboratory tests showed anaemia, and elevated levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), with positive anti-La and anti-Ro antibodies. She was given topical treatment and different doses of Predlone, in addition to methotrexate10 mg/week. She had received three pulses of methylprednisolone and was started on azathioprine with a mild response to the headaches, so she received two initial IV doses of rituximab 375 mg/m2, then every 2 weeks, with a clinical and laboratory response. Two years later, she had no headache. Headache that may presented in pSS are tension headaches, migraines and cluster headaches. The therapy is disease-modifying antirheumatic drugs, hydroxychloroquine, glucocorticoids and biotherapeutics. Rituximab is used in the treatment of some patients with pSS, especially where it can affect systemic symptoms. Rituximab treatment may be an option for severe headache in patients with pSS. The mechanism is unknown but may be due to depletion of brain auto-reactive B cells. Further research is needed. An unresponsive headache in a patient with primary Sjögren's syndrome treated with tryptophan, opioids and NSAIDs responded successfully to B-cell depletion with rituximab.We hypothesise that brain-autoreactive B cells were involved in the pathogenesis of the headache.

Anti-Ro52 positivity is associated with progressive interstitial lung disease in systemic sclerosis—an exploratory study

BackgroundInterstitial lung disease (ILD) is the most common cause of death in patients with systemic sclerosis (SSc). Prognostic biomarkers are needed to identify SSc-ILD patients at risk for progressive pulmonary fibrosis. This study investigates autoantibodies measured in bronchoalveolar lavage (BAL) fluid and in serum in reference to the clinical disease course of SSc-ILD.MethodsFifteen patients with new onset SSc-ILD underwent bronchoscopy. Autoantibody levels were analyzed using addressable laser bead immunoassay from BAL fluid and the serum. In a separate longitudinal cohort of 43 patients with early SSc-ILD, autoantibodies in serum were measured at baseline and pulmonary function tests were performed at least 2 times over the course of at least 2 or more years. Linear mixed effect models were created to investigate the relationship between specific autoantibodies and progression of SSc-ILD. Finally, lung tissue from healthy controls and from subjects with SSc was analyzed for the presence of the Ro52 antigen using immunohistochemistry.ResultsAmong SSc-ILD patients who were positive for anti-Ro52 (N = 5), 3 (60%) had enrichment of anti-Ro52 in BAL fluid at a ratio exceeding 50x. In the longitudinal cohort, 10/43 patients (23%) were anti-Ro52 positive and 16/43 (37%) were anti-scl-70 positive. Presence of anti-Scl-70 was associated with a lower vital capacity (VC) at baseline (-12.6% predicted VC [%pVC]; 95%CI: -25.0, -0.29; p = 0.045), but was not significantly associated with loss of lung function over time (-1.07%pVC/year; 95%CI: -2.86, 0.71; p = 0.230). The presence of anti-Ro52 was significantly associated with the loss of lung function over time (-2.41%pVC/year; 95% CI: -4.28, -0.54; p = 0.013). Rate of loss of lung function increased linearly with increasing anti-Ro52 antibody levels (-0.03%pVC per arbitrary units/mL and year; 95%CI: -0.05, -0.02; p < 0.001). Immunohistochemical staining localized the Ro52 antigen to alveolar M2 macrophages in peripheral lung tissue both in subjects with and without SSc.ConclusionsThis study suggests that antibodies targeting Ro52 are enriched in the lungs of patients with new-onset SSc-ILD, linking Ro52 autoimmunity to the pulmonary pathology of SSc. Clinical and immunohistochemical data corroborates these findings and suggest that anti-Ro52 may serve as a potential biomarker of progressive SSc-ILD.

Two cases of dermatomyositis associated with neuroendocrine tumors.

Dermatomyositis is an idiopathic inflammatory myopathy with cutaneous manifestations, which is associated with several types of malignancies, yet it has been rarely linked to neuroendocrine tumors (NETs). Here we report two cases of dermatomyositis associated with NETs of differing primary sites. Case 1: A 46-year-old female presented with a facial rash and proximal muscle weakness of both extremities. Investigations revealed elevated creatine kinase (CK) and positive anti-transcriptional intermediary factor 1-γ antibody (TIF1γ). The patient had been diagnosed with dermatomyositis and underwent a total body CT scan, which revealed prominent mediastinal lymphadenopathy, which a subsequent biopsy determined to be neuroendocrine carcinoma of small cell type. Treatment with high-dose corticosteroids was initiated, in addition to chemotherapy-based oncological management. Case 2: A 54-year-old female presented with a facial rash, progressive dyspnea, and general malaise. Laboratory investigations revealed positive anti-melanoma differentiation-associated gene-5(MDA5) and positive anti-Ro antibody, with a normal level of creatine kinase (CK). A chest CT scan revealed multiple ground-glass opacities. Despite treatment with high-dose intravenous methylprednisolone, IVIG and an infusion of the anti-IL-6 sarilumab [Kevzara], the patient rapidly deteriorated and was intubated. Within days, the patient developed bowel ischemia and underwent a laparotomy which was then complicated by an invasive infection. This resulted in patient's death. Pathology results from colonic tissue demonstrated an appendiceal neuroendocrine tumor. These cases demonstrate the heterogeneity and complexity of dermatomyositis in association with neuroendocrine tumors.

Association of anti-Ro52 antibody with depression and anxiety in patients with connective tissue diseases: an observational, single-centre, cross-sectional study.

To explore the risk factors of anxiety and depression, especially their association with serum autoantibodies, in patients with connective tissue diseases (CTDs). Three hundred and fifty-two inpatients with CTDs were recruited and their demographic, serological and imaging data were collected through the medical record system. Depression and anxiety were assessed by the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 Scale (GAD-7) respectively. Analysis of variance (ANOVA), rank sum test, chi-square test and logistic regression were performed to investigate risk factors for depression and anxiety. The prevalence of depression (PHQ-9 ≥ 5) and anxiety (GAD-7 ≥5) in CTD patients was significantly higher than that in the Chinese general population (depression: 44.3% vs. 32.2%, anxiety: 39.5% vs. 22.2%). Sleep time was a protective factor for both depression and anxiety (OR=0.734, 95% CI: 0.616~0.874, p<0.001 and OR=0.684, 95% CI: 0.559~0.835, P<0.001, respectively) while anti-Ro52 antibody was a risk factor for them (OR=5.466, 95% CI: 2.978~10.032, p<0.001 and OR=4.075, 95% CI: 2.073~8.010, p<0.001, respectively). Further analysis showed that anti-Ro52 antibody was a risk factor for depression and anxiety in all four subgroups, namely SLE, SS, RA, and other CTDs. Anti-Ro52 antibody is probably a risk factor for depression and anxiety in patients with connective tissue diseases. CTD patients with the presence of anti-Ro52 antibody are more prone to depression and anxiety than those without it.

Gut microbiota dysbiosis characterized by abnormal elevation of Lactobacillus in patients with immune-mediated necrotizing myopathy.

The gut microbiota plays an important role in human health. In this study, we aimed to investigate whether and how gut microbiota communities are altered in patients with immune-mediated necrotizing myopathy (IMNM) and provide new ideas to further explore the pathogenesis of IMNM or screen for its clinical therapeutic targets in the future. The gut microbiota collected from 19 IMNM patients and 23 healthy controls (HCs) were examined by using 16S rRNA gene sequencing. Alpha and beta-diversity analyses were applied to examine the bacterial diversity and community structure. Welch's t test was performed to identify the significantly abundant taxa of bacteria between the two groups. Spearman correlation analysis was performed to analyze the correlation between gut microbiota and clinical indicators. A receiver operator characteristic (ROC) curve was used to reflect the sensitivity and specificity of microbial biomarker prediction of IMNM disease. P < 0.05 was considered statistically significant. Nineteen IMNM patients and 23 HCs were included in the analysis. Among IMNM patients, 94.74% (18/19) of them used glucocorticoids, while 57.89% (11/19) of them used disease-modifying antirheumatic drugs (DMARDs), and the disease was accessed by MITAX (18.26 ± 8.62) and MYOACT (20.68 ± 8.65) scores. Participants in the groups were matched for gender and age. The diversity of the gut microbiota of IMNM patients differed and decreased compared to that of HCs (Chao1, Shannon, and Simpson indexes: p < 0.05). In IMNM patients, the relative abundances of Bacteroides, Roseburia, and Coprococcus were decreased, while that of Lactobacillus and Streptococcus were relatively increased. Furthermore, in IMNM patients, Lactobacillus was positively correlated with the levels of anti-signal recognition particle (SRP) antibodies, anti-Ro52 antibodies, and erythrocyte sedimentation rate (ESR), while Streptococcus was positively correlated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies and C-reactive protein (CRP). Roseburia was negatively correlated with myoglobin (MYO), cardiac troponin T (cTnT), ESR, CRP, and the occurrence of interstitial lung disease (ILD). Bacteroides was negatively correlated with ESR and CRP, and Coprococcus was negatively correlated with ESR. Finally, the prediction model was built using the top five differential genera, which was verified using a ROC curve (area under the curve (AUC): 87%, 95% confidence interval: 73%-100%). We observed a characteristic compositional change in the gut microbiota with an abnormal elevation of Lactobacillus in IMNM patients, which was accompanied by changes in clinical indicators. This suggests that gut microbiota dysbiosis occurs in IMNM patients and is correlated with systemic autoimmune features.

SARS-CoV-2 infection and increasing autoimmune disorders among ICU-hospitalized COVID-19 patients.

In acute conditions, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes multi-organ damage due to the induction of inappropriate immune responses, particularly lung tissue fibrosis. To evaluate the consequence of the deterioration of the immune system, autoimmune markers were assessed. In a case-control study, 108 patients with coronavirus disease 2019 (COVID-19) were admitted to the intensive care unit (ICU), and 158 outpatients with mild clinical symptoms, with SARS-CoV-2 reverse transcription quantitative polymerase chain reaction (RT-qPCR) positive tests, were included for comparison. The demographic and hematologic variables and presence of the main autoantibodies in sera of 40 eligible ICU-hospitalized COVID-19 patients and 40 COVID-19 outpatients were assessed. Out of 108 COVID-19 ICU-hospitalized patients, 40 were selected as the control group (40/158) who had no underlying diseases before hospitalization, according to their self-declaration and clinical records at the time of admission. The results demonstrated that the main complete blood count indices, such as red blood cells and platelets, decreased dramatically in ICU-hospitalized patients. Furthermore, the autoantibody profiles were positive in 45% and 15% of ICU-admitted patients for antinuclear antibodies and antineutrophilic cytoplasmic autoantibodies, respectively. In ICU patients, anti-PM/Scl 100 or AMA-M2 was 33%. Anti SS-A, anti-SS-B, anti-Ro-52, and anti-Jo-1 in 11.5% for each one were reactive. Other autoantibodies of the ICU group were as follows: CENP (5.6%), Rib-protein (5.6%), and nucleosome (5.6%). However, only two individuals in the control group had positive results for SS-A and SS-B (5%). Induction of such particular autoantibodies by the virus can justify the multi-organ involvement and severity of the disease in ICU patients, which may also cause other organ involvement in the long term.

E50 Central Nervous System manifestation of Systemic Lupus Erythematosus: A case presentation

Abstract Background Systemic Lupus Erythematosus (SLE) is a complex, chronic, multisystem autoimmune disease with clinical manifestations in all organ systems. It is characterized by production of autoantibodies to components of the cell nucleus. Pediatric patients tend to have more severe disease and widespread organ involvement. If untreated, the 5-year mortality rate is almost 95%. Literature on SLE, more so pediatric SLE in Sub-Saharan Africa is scarce. Aim To describe the diagnostic journey of a child with CNS lupus in our setting. Method Retrospective chart review of a child with CNS Lupus at a tertiary referral teaching hospital in Nairobi, Kenya. Results We present a case of a 14-year-old boy who was diagnosed with CNS Lupus. He was known to have a convulsive disorder, with a recent history of mutism and was on Lamictal and rivotril for approximately one year. He presented to our facility in status epilepticus, having complained of a sudden onset of headache prior to the onset of the convulsions. He had had an uneventful birth and developmental history with no family history of chronic ailments. On examination, he was found to have bilateral ptosis with no other neurological deficits and otherwise normal systemic examination. Complete blood count initially showed a slight neutrophilia and thrombocytosis. Kidney function was normal and the CSF workup was negative for infection. Chest X ray showed features of aspiration pneumonia for which he received Augmentin, nebulization with hypertonic saline and chest physiotherapy. EEG showed generalized electrical seizures. CT/MRI brain showed acute infarcts in the superior frontal gyrus, post central gyrus and in the right insular cortex. He was managed in the Intensive Care Unit until cessation of the seizures. Post extubation, he was noted to have reduced lower limb power and bulbar dysfunction. A rheumatology consult was requested and revealed speech regression, a prior episode of conjunctivitis, a vasculitic palmar rash, palatial petechiae and suspected right knee arthritis. Urinalysis was suggestive of glomerulonephritis. ANA Antibodies were positive (titers of 1:160), positive anti-Ro antibodies. Anti-Ds DNA, P and C ANCA were negative. Renal histopathology was unremarkable. He was pulsed with IV methylprednisolone for 3 days with improvement and thereafter on follow up as an outpatient in the Pediatric Rheumatology clinic. Conclusion Pediatric SLE has significant morbidity and mortality therefore early intervention is crucial to retard disease progression. Given the vast array of clinical manifestations, it requires a high index of suspicion to enable early, accurate diagnosis and prompt treatment.

Rheumatic manifestations of hepatitis C virus infection are associated with autoantibodies but not viremia.

To investigate the associations between extrahepatic manifestations, autoantibodies, and viremia in patients with hepatitis C virus (HCV) infection. This cross-sectional study recruited patients with HCV infection from the outpatient department of a tertiary medical center in Northern Taiwan between January 2017 and August 2019. Autoantibody profiles and the clinical parameters of HCV infection were evaluated using laboratory tests, and a questionnaire was used to record extrahepatic manifestations. HCV infection status, including inactive HCV infection, active hepatitis, and cirrhosis, was defined according to abdominal ultrasonography findings and alanine transaminase levels. A total of 77 patients with HCV were recruited, with 19.5% and 16.9% of patients, respectively, presenting with arthritis and dry eyes. Autoantibody screening revealed rheumatoid factor (RF), antinuclear antibody (ANA), anti-Ro antibody, and anti-La antibody positivity in 20.8%, 23.4%, 13.0%, and 2.6% of the patients, respectively. The presence of RF was associated with arthritis, whereas the presence of ANA was associated with dry eyes but not dry mouth. Active hepatitis and HCV-related cirrhosis were associated with viremia, but not autoantibody profiles. In this single-center study, the prevalence of extrahepatic manifestations and autoantibodies did not differ in patients stratified by the HCV infection status. Rheumatic manifestations were associated with the presence of autoantibodies but not with viremia.

Mortality risk in patients with anti-MDA5 dermatomyositis is related to rapidly progressive interstitial lung disease and anti-Ro52 antibody.

This study aimed to describe the clinical characteristics and analyze the poor prognostic factors in patients with anti-MDA5 dermatomyositis. A total of 126 adults with anti-MDA5 dermatomyositis were enrolled in this retrospective study. Information on survival time, cause of death, and baseline characteristics was collected. Patients were divided into two groups: a survival group and a non-survival group. Items with clinical significance that showed significant differences between the two groups were screened by Kaplan-Meier and Cox regression analyses to identify the predictors of poor survival. Thirty-two patients were included in the non-survival group, most of whom died from respiratory failure, with pulmonary infection accounting for half. Epstein-Barr virus infection was relatively common in both groups. Aspartate transaminase, lactate dehydrogenase, and ferritin levels; erythrocyte sedimentation rate; and anti-Ro52 antibody levels were significantly higher, while the lymphocyte count was lower in the non-survival group compared with the survival group. Notably, patients in the non-survival group were more likely to present with rapidly progressive interstitial lung disease than those in the survival group. Kaplan-Meier and Cox multivariate regression analyses revealed that the prevalence of rapidly progressive interstitial lung disease, levels of anti-Ro52 antibody, and age > 57 years were important prognostic factors independent of multiple clinical parameters. Rapidly progressive interstitial lung disease, anti-Ro52 antibody levels, and age > 57 years are possible predictors of mortality risk in patients with anti-MDA5 dermatomyositis.

Ground-glass opacity score predicts the prognosis of anti-MDA5 positive dermatomyositis: a single-centre cohort study

ObjectiveDermatomyositis (DM) positive with anti-melanoma differentiation-associated gene 5 (anti-MDA5-DM) is a systemic autoimmune disease with high mortality. This study aimed to explore the risk factors of death in anti-MDA5-DM and validate a prediction model for all-cause mortality in anti-MDA5-DM.MethodWe conducted a retrospective study using a single-centre cohort of patients with newly onset anti-MDA5-DM from June 1, 2018 to August 31, 2021. Patients were divided into four groups according to baseline ground-glass opacity (GGO) score: Group A, GGO ≤ 1; Group B, 1 < GGO ≤ 2; Group C, 2 < GGO ≤ 3; Group D, GGO > 3. The primary outcome was death during the follow-up. Secondary outcomes included death within 3, 6, 12 months, severe infection, and remission during the first 12 months.ResultsA total of 200 patients were included in the study. Based on multivariable Cox regression, the prognostic factors at baseline were identified as CRP > 5 mg/L, serum ferritin (SF) > 600ng/ml, positive anti-Ro52 antibody, prophylactic use of compound sulfamethoxazole (SMZ Co), four-category GGO score: GGO ≤ 1, 1 < GGO ≤ 2, 2 < GGO ≤ 3, GGO > 3. The final mortality of four groups was 16.4, 22.2, 48.5, 92.0%, respectively. Compared with Group A, the Hazards Ratio (HR) of Group B was 1.408, (p = 0.408), HR of Group C was 3.433 (p = 0.005), HR of Group D was 4.376 (p = 0.001).ConclusionsGGO score is a reliable predictor for risk stratification in anti-MDA5-DM and may provide guidance for individualized managements of patients.

Prevalence of anti-synthetase antibodies among systemic sclerosis patients

Backgroundwe aimed to estimate the prevalence of Amino acyl-transfer ribonucleic acid synthetase antibodies (Anti-ARS); myositis specific antibodies, among patients with systemic sclerosis (SSc), to evaluate the clinical associations of anti-ARS antibodies in SSc patients and to identify risk factors for development of interstitial lung disease (ILD) in SSc. MethodsA prospective study of 71 systemic sclerosis patients in our rheumatology clinic in Israel. Sera were tested for myositis antibodies. Data on patients clinical and serological manifestations and treatment were collected and compared according to anti-ARS antibodies and ILD. ResultsPrevalence of anti-ARS antibodies was 6% (4/71) with anti PL-7, anti- OJ and Jo-1 positivity. Anti Ro-52 was found in 27%, anti-PM/Scl 75, anti-PM/Scl 100 and anti-SRP in 6%, anti-Ku in 3%, anti-Mi-2 beta and anti-Mi-2 alfa in 4%, anti- NXP2 and anti-TIF1gamma in 1%. ILD complication was observed in 42% of patients and was associated with anti RNAP-III, anti Scl-70 and Anti-ARS antibodies. In multiple logistic regression, anti Scl-70 was associated with 6-fold higher risk for ILD. ConclusionAnti-ARS antibodies were observed in 6% of SSc patients. All of them had ILD. Due to the low prevalence of anti-ARS, this study could not describe clinical associations of anti-ARS antibodies in SSc patients.

Serum antinuclear antibodies associate with severe disease activity in neuromyelitis optica spectrum disorder

BackgroundStudies suggest that antinuclear antibodies (ANAs) may correlate with the long-term prognosis of Neuromyelitis optica spectrum disorder (NMOSD). In this study, we investigated ANAs in Chinese patients with NMOSD and their relationship with disease outcomes. MethodsWe retrospectively collected data from 525 patients diagnosed with NMOSD at West China Hospital between September 1, 2009, and October 1, 2021. Patients were classified into two groups: NMOSD with ANA (+) or without ANA (−). We compared the clinical characteristics, relapse rate, severe attacks, laboratory tests, Expanded Disability Status Scale (EDSS), and prognosis between the two groups. ResultsAmong the 525 NMOSD patients, those with ANA showed a higher frequency of AQP4-IgG (94.1% vs 79.3%, p < 0.001, false discovery rate (FDR) corrected p < 0.001), and anti-SSA (p < 0.001, FDR corrected p < 0.001), anti-SSB (p < 0.001, FDR corrected p < 0.001), anti-Ro52 antibodies (p < 0.001, FDR corrected p < 0.001), than those without ANA. ANA was detected in 403 patients during the acute phase. Patients with ANA (+) had higher EDSS scores in the acute stage (4.0 vs. 3.75, p = 0.013, FDR corrected p = 0.029) and at final follow-up (p = 0.032, FDR corrected p = 0.064). NMOSD patients with ANA (+) had a higher frequency of severe acute myelitis attack, severe acute myelitis and optic neuritis attack, motor and visual disability, compared to those with ANA (−) (42.1% vs. 27.8%, p = 0.001, FDR corrected p = 0.004, 19.3% vs. 10.3%, p = 0.004, FDR corrected p = 0.018, and 11.1% vs. 4.8%, p = 0.008, FDR corrected p = 0.022 respectively). The two groups had no significant difference in the annual recurrence rate (ARR). ConclusionANA may be associated with more severe disease activity and disability in NMOSD.

Diagnostic dilemma: Multiple Autoimmune Syndrome versus incomplete Graham-Little-Piccardi-Lassueur Syndrome overlap mixed connective tissue disease

Objectives. We present a very rare case of incomplete Graham-Little-Piccardi-Lassueur syndrome (GLPLS) overlap with Mixed Connective Tissue Disease (MCTD) versus Multiple Autoimmune Syndrome (MAS). Case Presentation. A 53- year-old female with a long history of more than two years of patchy hair loss on scalp like “footprints in the snow”, partial loss of eyebrows' hair, face erythema, scaly atrophied red/brown patches on face, grouped follicular papules 2-3 mm in diameter with a pointed or hair-like horny spine extending approximately 1-2 mm around the tip of the follicle on lumbar area. The histopathological results from biopsies of scalp and lumbar areas confirmed the clinical diagnosis of cicatricial alopecia induced by lichen plan pilaris (LPP) and also presence of lichen spinulosus (LS) on lumbar area. The description provided by pathologist is however borderline regarding so called interface dermatosis like chronic cutaneous lupus erythematous (CCLE) or Pseudopelade of Brocq (PPB) as the end stage of CCLE or LPP. Blood tests showed both Antinuclear antibodies and U1-nRNP in high titers and the absence of anti-Sm, anti SS-A, anti SS-B and anti-dsDNA antibodies, and also peculiar antibody patterns of MCTD. Outcome. After thorough investigation, MCTD was proven by antibodies results. After one year of treatment a lot of clinical features dramatically responded under therapy. Conclusions. Clinical manifestations in the pathology with strictly cutaneous or systemic localization in conjunction or overlap with other autoimmune diseases (grouped in the MAS) represent a rare diagnostic in daily practice.

P07 Not just simple hand eczema: a case of Jo-1-positive antisynthetase syndrome (‘mechanic’s hands’)

Abstract Antisynthetase syndrome is a rare inflammatory muscle disease related to dermatomyositis and polymyositis. Anti-Jo-1 antibodies are the most detected antibodies in antisynthetase syndrome. The main clinical features of antisynthetase syndrome are myositis, polyarthritis, interstitial lung disease, mechanic’s hands and Raynaud phenomenon. A 50-year-old man with a background of inflammatory muscle disease and interstitial lung disease, for which he is under the care of respiratory and rheumatology teams, was referred to the dermatology department by his general practitioner with refractory xerotic dry fissured skin on his fingers and feet. He reported itchy, sore and painful dry, cracked skin on both his hands, mainly on the fingertips. It did not affect the rest of his body. He trialled potent topical steroids and emollients, but his condition did not improve. He was on a reducing course of prednisolone 15 mg daily and on long-term oxygen therapy at home for interstitial lung disease. On clinical examination, he had an eczematous-looking eruption. The appearance of his hands was in keeping with ‘mechanic’s hands’. Together with the underlying diagnosis of interstitial lung disease, a diagnosis of antisynthetase syndrome was suspected. Blood tests revealed a fibrinogen of 5.39 g L−1 [reference interval (RI) 1.50–4.50], lupus creatine kinase of 1591 IU L−1 (RI 40–320), positive antibodies to Ro (SS-A) and positive antibodies to Jo-1. Jo-1 antibodies are found in dermatomyositis or polymyositis. Ro antibodies are associated with Sjogren syndrome (primary or secondary) or systemic lupus erythematosus, and serum may be antinuclear antibody negative. Therefore, we suspected a diagnosis of antisynthetase syndrome. A patch test showed a positive reaction to nickel, which was deemed to be in keeping with antisynthetase syndrome hand eruption, or ‘mechanic’s hands’. The patient was commenced on mycophenolate, a low dose of acitretin 10 mg and emollients and reported a significant improvement in symptoms. Repeat blood tests were scheduled for 3 months, including lipid profile and liver function test, for monitoring purposes. A follow-up was arranged for 12 weeks. He had a background of recurrent hospital attendance with pericardial effusions and chest symptoms and was tested for COVID-19 multiple times. This case demonstrates the importance of multidisciplinary coordination with rheumatology and respiratory colleagues in antisynthetase syndrome.

CPC05 A case of extensive hypertrophic lupus erythematosus responsive to topical steroids

Abstract Hypertrophic lupus erythematosus (HLE) is a rare variant of lupus erythematosus, occurring in 2% of cases of chronic cutaneous lupus erythematosus (CCLE). It is an exaggerated proliferative epithelial response manifesting as verrucous-appearing hypertrophic indurated lesions occurring on sun-exposed sites. We present a case of the development of extensive HLE in a patient with subacute cutaneous lupus erythematosus (SCLE) with underlying pulmonary malignancy. A 74-year-old woman with Sjögren syndrome presented to dermatology with a 2-month history of a rash affecting her face and décolletage. Laboratory studies illustrated elevated antinuclear and anti-Ro antibodies. Biopsy from her chest confirmed SCLE. Malignancy screening revealed T1aN0 pulmonary lepidic adenocarcinoma, which was successfully managed with a lower lobectomy. Hydroxychloroquine was initially trialled but required discontinuation following intolerable side-effects. Mepacrine was then initiated, which allowed clearance of the rash, alongside yellow discoloration of the skin. Six months later, she developed a raised pruritic rash on her arms, legs and buttocks, resistant to current management alongside a trial of mycophenolate mofetil. Examination revealed violaceous hypertrophic plaques affecting 40% of her body-­surface area. The differential included hypertrophic lichen planus, nodular prurigo and HLE. Repeat lesional biopsies highlighted a lichenoid inflammatory infiltrate with overlying scale, favouring HLE. Owing to patient choice, topical mometasone furoate 0.1% was used to manage cutaneous disease, with a reduction in lesion size. HLE is a distinct subset of CCLE, regarded as a separate entity to SCLE. Twenty per cent of patients with SCLE also exhibit other types of cutaneous lupus erythematosus (CLE) lesions. No cases in the literature describe progression from SCLE to CCLE, or HLE, in particular. Hallmarks of HLE include verrucous lesions, chronicity and treatment resistance. Early recognition and follow-up are essential as malignancy may arise in long-standing lesions. Lung adenocarcinomas and hypertrophic lupus are both associated with p53 mutations and decreased granzyme B expression. Mutated p53 results in constitutive cell proliferation and DNA damage can accumulate in cells. Granzyme B is a protease in cytotoxic T cells involved in immune-mediated cell lysis. Both processes result in the potential to produce exaggerated hyperproliferative lesions, such as those observed in HLE and the lepidic adenocarcinomas. HLE is a rare clinical entity that can be easily misdiagnosed clinically and histopathologically. Increased awareness of this condition is essential to highlight the variety of clinical presentations of uncommon variants of CLE, to ensure they are considered while approaching clinical diagnosis.

P13 A rare case of Sjögren syndrome in a White woman with Kikuchi–Fujimoto disease

Abstract A 36-year-old White woman was seen in May 2022 for a rash on her upper back, shoulders, cheeks, forehead and extensor surfaces of the upper limbs. It had developed following sun exposure on the beach despite regularly applying SPF50. Over time, the rash became sore but exhibited no signs of vesicles or oozing. Of note, the patient had been recently diagnosed with Kikuchi–Fujimoto disease (KFD) following a lymph node biopsy. She gave history of Raynaud phenomenon since childhood, and arthralgia primarily affecting the small joints of hands. She also experienced episodic dry eyes, dry mouth, peripheral oedema, dyspnoea, abdominal pain and constipation. For the previous month, she had felt fatigued with some undocumented weight loss. Clinical examination revealed an erythematous rash with discrete nonblanching macules and plaques of varying sizes, oval-to-circular in shape, on the involved areas. Lymph nodes were not palpable. Differential diagnosis included cutaneous lupus, other connective tissue disorders, and—less likely—polymorphic light eruption. Skin biopsy showed focal compact hyperkeratosis and parakeratosis with focal subtle spongiosis, intraepidermal neutrophils and lymphocyte exocytosis, with the presence of perivascular and periappendageal chronic inflammation. There was mild basement membrane thickening with focal deposition of fibrinogen at the basement membrane zone on direct immunofluorescence. She was positive for anti-Ro antibodies, with a titre of 84 kU L−1 (normal &amp;lt; 11 kU L−1). A diagnosis of Sjögren syndrome with KFD was made. The patient was advised on photoprotection with a high-potency topical steroid, and referred to rheumatology for review of her joint problems. After 4 weeks, the patient had only some improvement with topical therapy and was started on oral hydroxychloroquine. At the 12-week follow-up, there was significant improvement. Her skin was clear, with improvement in joint pain and fatigue. KFD, also known as necrotizing lymphadenitis, is a benign and self-limited disorder, characterized by regional cervical lymphadenopathy with tenderness, usually accompanied with mild fever and night sweats. Rarely, the skin and joints are involved. There is an established association between KFD and connective tissue disorders, especially Sjögren syndrome (Gates GA, Li Y, Magyar C, Sarantopoulos GP. Kikuchi–Fujimoto disease with unusual cutaneous findings. Am J Dermatopathol 2021; 43:e213–17). This is more prevalent among Asians and rarely reported in White people (Perry AM, Choi SM. Kikuchi-Fujimoto disease: a review. Arch Pathol Lab Med 2018; 142:1341–6), where it may cause diagnostic difficulties. This case highlights the importance of lateral thinking while formulating a differential diagnosis, despite the time pressures of a busy clinic. Although the reported prevalence of KFD among White people has been negligible (Perry et al.), it should not be dismissed solely based on a patient’s ethnicity. Timely and adequate management of rare conditions can reduce patient morbidity and improve their quality of life.

Serological and clinical associations of autoantibodies in Chinese patients with new-onset systemic lupus erythematosus

To study the clinical significance of autoantibodies in Chinese patients with new-onset systemic lupus erythematosus (SLE), we enrolled 526 new-onset patients who met the 1997 Updated American College of Rheumatology SLE Classification Criteria for a retrospective cohort study. Chi-square test and Wilcoxon rank-sum test were used to detect the relationship of autoantibodies with clinical manifestations and serological results respectively. Our results demonstrated that the positive rate of anti-ribosomal P protein (anti-P) antibody in female patients was higher than that in male patients (41.2% vs. 22%, P = 0.008). Patients with anti-SSB (43.95 ± 73.12 vs. 40.92 ± 75.75, P = 0.004; 63.93 ± 103.56 vs. 55.06 ± 120.84, P = 0.008 respectively) antibodies had higher levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), whereas those with anti-P antibody (28.90 ± 25.70 vs. 50.08 ± 93.00, P = 0.014; 38.51 ± 48.19 vs. 69.95 ± 142.67, P = 0.047, respectively) had lower levels of them. Anti-dsDNA antibody (P = 0.021) was associated with pulmonary arterial hypertension (PAH). The patients with anti-Ro60 (P = 0.044), anti-P (P = 0.012) and anti-dsDNA (P = 0.013) antibodies were less likely to develop Interstitial lung disease. Anti-SmRNP antibody was correlated to lower prevalence of neuropsychiatric symptoms (P = 0.037), and patients with anti-centromere antibody (ACA) were more likely to develop serositis (P = 0.016).We identified five clusters of SLE-related autoantibodies, confirmed previously reported associations of autoantibodies, and discovered new associations.

#6663 PRIMARY SJöGREN SYNDROME WITH BIOPSY PROVEN RENAL INVOLVEMENT: A SINGLE CENTER EXPERIENCE

Abstract Background and Aims Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease, characterized by inflammation and destruction of the exocrine glands and the involvement of multiple organs. A wide variety of kidney manifestations associated with pSS have been described. The prevalence of kidney involvement is not clear. Our aim was to describe the renal involvement of patients with pSS diagnosed by kidney biopsy (KB). We also analyzed the clinical manifestations, laboratory and immunological characteristics, clinical outcomes and treatments received in patients with pSS referred to a specialized kidney centre. Method Observational, retrospective study of adult patients (age &amp;gt; 18 years) diagnosed with pSS (EULAR criteria) referred and treated at a kidney referral centre (Fundació Puigvert) in Barcelona, Spain. We collected data from the clinical records registry including demographic variables, laboratory parameters, biopsy results and adverse outcomes, defined by the need of renal replacement therapy (RTT) and/or death. Absolute frequencies, percentages, means and standard deviations were used for statistical analysis. Multivariate analysis was performed as appropriate in SPSS V28.0 Results A total of 27 patients with pSS underwent KB from January 1994 to July 2022; all patients were female, with a median age of 58.4 years (SD ±12.4); 85% were Caucasian. The mean baseline glomerular filtration rate (eGFR) was 65.9 mL/min (SD ±16) (before nephrologist referral), with 8 of 27 patients (29.6%) having eGFR less than 60 mL/min at baseline. The main indication for nephrological evaluation was acute kidney injury (AKI) (63%), followed by the presence of non-nephrotic proteinuria with dysmorphic haematuria (29.6%). The most common finding in KB was acute interstitial nephritis (AIN) (55.6%), as an isolated AIN kidney lesion in twelve patients (44.4%). Mild interstitial nephritis was noted in the context of a predominant glomerular lesion in three other patients (one membranoproliferative glomerulonephritis, one IgA nephropathy and one AA amyloidosis). Nine patients (33.3%) had glomerular lesion (see Table 1). In 18.5% of patients, the diagnosis of pSS was made after the renal biopsy. The percentage of patients receiving ACEI/ARB was 77.8%. A total of 25 patients received some type of immunosuppression (IS). Corticosteroids being the most frequently used (77.8%), followed by the combination IS treatment (44%) and rituximab (33.3%). At the time of the KB, the mean eGFR was 46.3 mL/min (SD ±24), compared to eFGR of 45.2 mL/min (SD ±22) one-year after KB. During follow-up, seven patients (25.9%) required RRT and three (11.1%) died from non-renal causes, mainly by infections associated with immunosuppression. Factors associated with adverse renal outcomes were AKI (p = 0.01), baseline eGFR CKD-EPI less than 60 mL/min (p = 0.005), presence of anti-Ro60 antibodies (p = 0.046), use of plasmapheresis (p = 0.013), use of cyclophosphamide (p = 0.013) and the presence of tubulointerstitial atrophy with glomerular sclerosis on kidney biopsy (p = 0.010). Conclusion Our study included a larger cohort than previously reported before in a single centre. In our cohort of patients with pSS who were evaluated by KB, AIN was the leading cause of renal involvement, as has been seen in other studies. The presence of eGFR below 60 mil/min at baseline and the finding of chronicity in the KB are associated with an adverse outcome, as well as is the presence of AKI. Early referral to nephrologist may be important for prognosis, and KB is necessary for accurate diagnosis of kidney involvement to allow targeted treatment.

Maternal Anti-Ro Antibody Titers Obtained With Commercially Available Immunoassays Are Strongly Associated With Immune-Mediated Fetal Heart Disease.

Anti-Ro antibody-positive mothers are frequently referred for serial echocardiography due to the fetal risk of developing heart block and endocardial fibroelastosis. Little is known why only some and not all offspring develop these cardiac manifestations of neonatal lupus (CNL). This prospective study examined associations between anti-Ro antibody titers and fetal CNL. Antibody-positive mothers referred since 2018 for fetal echocardiography at risk of CNL (group 1; n=240) or with CNL (group 2; n=18) were included. Maternal antibody titers were measured with a chemiluminescent immunoassay (CIA). Additional testing on diluted serum samples was used to quantify anti-Ro 60 antibody titers above the analytical measuring range (AMR) of the standard CIA (≥1,375 chemiluminescent units [CU]). Among 27 total mothers with a fetal diagnosis of CNL, all displayed anti-Ro 60 antibody titers that exceeded the AMR of the CIA at least 10-fold. Of 122 mothers in group 1 who underwent additional anti-Ro 60 antibody testing, event rates of CNL (n=9) were 0% (0 of 45) among mothers with anti-Ro 60 antibody titers from 1,375-10,000 CU, 5% (3 of 56) among mothers with titers from 10,000-50,000 CU, but 29% (6 of 21) among mothers with titers >50,000 CU (odds ratio 13.1, P = 0.0008). Of mothers in group 2 with a primary diagnosis of CNL, 0% (0 of 18 mothers) had anti-Ro 60 antibody titers <10,000 CU, 44% (8 of 18 mothers) had titers from 10,000-50,000 CU, and 56% (10 of 18 mothers) had titers >50,000 CU. CNL is associated with substantially higher anti-Ro antibody titers than are obtained using a standard CIA. Enhancing the assay measuring range allows an improved specificity of identifying pregnancies at risk of CNL.

Deep Morphea in an Immunosuppressed Patient With Anti-U1RNP Myositis: A Case Report

Introduction: Morphea is an inflammatory skin disease characterized by skin thickening due to increased collagen deposition in the dermis or subcutaneous tissues. Anti-U1RNP myositis is a newly described entity characterized by myositis, arthritis, interstitial lung disease, and Raynaud phenomenon. We present a case of a unique combination of deep morphea in a patient with anti-U1RNP myositis. Case presentation: A 64-year-old male with 5-year history of proximal muscle weakness, polyarthritis, Raynaud phenomenon, and dyspnea on multiple immunosuppressives presented with localized infiltrated, tight, and hyperpigmented plaques over the posterior thighs and mid-to-lower back developing over the last 2 years and limiting his movement. Autoimmune workup revealed a positive ANA, anti-U1RNP antibody, anti-Jo1 antibody, and anti-Ro52 antibody. Further workup showed restrictive lung disease, kidney disease, and arthritis. Patient was diagnosed with anti-U1RNP myositis. Skin biopsy of the back lesion showed deep morphea. Discussion: Association of deep morphea with anti-U1RNP myositis is not described prior in the literature. Treatment of morphea is challenging since the patient is already on immunosuppressive medications. The patient failed methotrexate prior and is currently on Mycophenolate mofetil and Deflazacort which are reported as potential treatment for morphea. Therefore, physical therapy plus topical Tacrolimus were suggested as an initial measure to preserve the range of motion of his posterior thighs and back. This is a case of progressive deep morphea developing in a patient with a unique autoimmune profile on immunosuppressive drugs. Conclusion: Anti-U1RNP myositis is a challenging diagnosis and should be always thought of in patients with positive anti-U1RNP, myositis, interstitial lung disease, arthritis, kidney disease, and Raynaud phenomenon. Moreover, deep morphea treatment in immunosuppressed patients is challenging and different measures should be considered.