Antinuclear Cytoplasmic Antibodies Research Articles

Comprehensive Association Analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease

Patients with inflammatory bowel disease (IBD) frequently develop extraintestinal manifestations (EIMs) that contribute substantially to morbidity. We assembled the largest multicohort data set to date to investigate the clinical, serologic, and genetic factors associated with EIM complications in IBD. Data were available in 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs (eg, ankylosing spondylitis [ankylosing spondylitis and sacroiliitis], primary sclerosing cholangitis [PSC], peripheral arthritis, and skin and ocular manifestations) across 4 cohorts (Cedars-Sinai Medical Center, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort). Clinical and serologic parameters were analyzed by means of univariable and multivariable regression analyses using a mixed-effects model. Within-case logistic regression was performed to assess genetic associations. Most EIMs occurred more commonly in female subjects (overall EIM: P= 9.0E-05, odds ratio [OR], 1.2; 95% CI, 1.1-1.4), with CD (especially colonic disease location; P= 9.8E-09, OR, 1.7; 95% CI, 1.4-2.0), and in subjects who required surgery (both CD and UC; P= 3.6E-19, OR, 1.7; 95% CI, 1.5-1.9). Smoking increased risk of EIMs except for PSC, where there was a "protective" effect. Multiple serologic associations were observed, including with PSC (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-flagellin) and any EIM (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-Pseudomonas fluorescens-associated sequence). We identified genome-wide significant associations within major histocompatibility complex (ankylosing spondylitis and sacroiliitis, P= 1.4E-15; OR, 2.5; 95% CI, 2.0-3.1; PSC, P= 2.7E-10; OR, 2.8; 95% CI, 2.0-3.8; ocular, P= 2E-08, OR, 3.6; 95% CI, 2.3-5.6; and overall EIM, P= 8.4E-09; OR, 2.2; 95% CI, 1.7-2.9) and CPEB4 (skin, P= 2.7E-08; OR, 1.5; 95% CI, 1.3-1.8). Genetic associations implicated tumor necrosis factor, JAK-STAT, and IL6 as potential targets for EIMs. Contrary to previous reports, only 2% of our subjects had multiple EIMs and most co-occurrences were negatively correlated. We have identified demographic, clinical, and genetic associations with EIMs that revealed underlying mechanisms and implicated novel and existing drug targets-important steps toward a more personalized approach to IBD management.

CLINICAL PROFILE OF PERIPHERAL NEUROPATHY IN GERIATRIC POPULATION

Objectives: The objective of this study was to describe the clinical profile of peripheral neuropathy (PN) in the geriatric population. Methods: This prospective observational study was done among patients >65 years, found to have PN by Neuropathy Symptom Score, who were undergone history and clinical examination at the Department of Medicine and Gandhi Medical College and associated Hamidia Hospital Bhopal. Nerve conduction study was done in all subjects to observe the pattern and type of various peripheral neuropathies. Special investigations such as Serum Vitamin B-12, toxin screening of lead and arsenic, viral serology using the ELISA method, serum and urine electrophoresis, rheumatoid factor, antinuclear antibodies (ANA), and antinuclear cytoplasmic antibodies (c-ANCA and p-ANCA), and CSF examination were done as and when needed. Results: Most of the patients were in the 60–65 years [93 (46.5%)] of age followed by 66–70 years [54 (27%)]. Most common clinical feature was Tingling [120 (60%)] followed by Tingling and Numbness [36 (18%)]. In most of the subjects, deep tendon reflexes were normal [132 (66%)] whereas in 42 (21%) subjects deep tendon reflexes were impaired and in 26 (13%) subjects deep tendon reflexes were absent. Most of the patients had sensory motor axonal demyelinating neuropathy [8 (4%)]. Conclusion: PN is a heterogeneous disease with diverse pathology. Recognition of the clinical homolog of these pathological processes is the first step in achieving the appropriate form of intervention. Treatment should be individualized such that the particular manifestation and underlying pathogenesis of each patient’s unique clinical presentation are considered.

The impact of coronavirus-19 vaccination on anti-nuclear cytoplasmic antibody vasculitis hospitalisations in a Sydney health network.

There have been reports of COVID-19 vaccination triggering anti-nuclear cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but no robust studies have examined the link. This retrospective cohort study assessed the impact of COVID vaccination on the rate of denovo and relapsed AAV in a Sydney Local Health District from 2018 to 2022. Despite more than 95% of the population receiving vaccination, the case rate of AAV was stable. These findings do not support a relationship between COVID vaccination and AAV.

Small fiber neuropathy associated with ANCA positivity: a case series and brief literature review.

Small fiber neuropathy [SFN] is a common peripheral neurologic disorder with a vast array of implicated etiologies. It has previously been proposed that some forms of immune-mediated small fiber neuropathy are driven by vasculitis, though antinuclear cytoplasmic antibodies [ANCA] antibodies have not commonly been reported in association with SFN, thus far. We present this case series to discuss the observation of a possible novel association between ANCA and SFN. This is a retrospective case series of 6 patients with SFN and ANCA positivity, with and without systemic manifestations. Patients included were diagnosed with SFN by skin biopsy or autonomic function testing and were seropositive for ANCA by ELISA. Six patients are outlined, including 4 females and 2 males. Antigen specific antibodies were MPO alone in 4 cases, PR3 alone in 1 case and both MPO and PR3 in 1 case. Systemic vasculitis was noted in 2 patients. Five patients received immunosuppression. Three patients experienced partial improvement, while symptoms stabilized in 3 patients. This is the first series of patients with suspected immune-mediated SFN and ANCA antibody positivity, raising the possibility of ANCA mediated isolated SFN. This is in contradistinction to the more typical ANCA-mediated peripheral neuropathy manifestations of mononeuropathy multiplex or axonal sensorimotor neuropathy. We cannot unequivocally prove ANCA-associated vasculitis [AAV] causality in these cases; however, the stabilization in SFN symptomatology and associated improvement in ANCA antibody titer, after AAV treatment, may be indicative of an association.

ANSWERS LIE IN THE COMPLETE BLOOD COUNT: A CASE OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS PRESENTING WITH ACUTE ST-WAVE ELEVATION MYOCARDIAL INFARCTION

ANSWERS LIE IN THE COMPLETE BLOOD COUNT: A CASE OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS PRESENTING WITH ACUTE ST-WAVE ELEVATION MYOCARDIAL INFARCTION

Heterozygous E148Q Mutation in an Indian Family with a Milder Form of Familial Mediterranean Fever

Dear Editor, Familial Mediterranean fever (FMF, OMIM no. 249100) is an inherited autoinflammatory disorder resulting from MEFV gene mutations. A 15-year-old girl from Kerala, South India, born of a nonconsanguineous union presented with recurrent fever, diffuse abdominal pain, and left knee joint pain for 1 year. She had fever for 3 days every week associated with left knee arthritis. Some of the episodes were associated with diffuse abdominal pain, oral ulcers, and an erythematous facial rash. She also had right hip and ankle pain with swelling on a few occasions. On examination, she had swollen and warm left knee joint. Her 12-year-old sibling also had similar problems (recurrent fever, diffuse abdominal pain, and joint pain) for 10 months. Both the parents were asymptomatic. Blood tests showed neutrophilic leukocytosis, high erythrocyte sedimentation rate, and C-reactive protein. Ultrasonography of the abdomen showed mild ascites. Immunological testing showed normal C3 complement and the absence of rheumatoid factor, antinuclear, anti-double-stranded DNA, and anti-neutrophilic cytoplasmic antibodies. The periodicity of symptoms and positive family history made us consider inherited autoinflammatory disorder. Targeted mutational analysis showed the MEFV variant E148Q in the heterozygous state in both siblings. No pathogenic variants were identified in the MEFV exon, TNFRSF1A, and MVK genes [Table 1]. The patient and her younger sister were managed with colchicine (1.0 mg daily), and on follow-up up to 1 year, the patients were asymptomatic. Genetic counseling was given to the patient family.Table 1: The results of targeted mutational analysis of the MEFV, TNFRSF1A, and MVK genes in the two siblingsFMF is common among certain ethnic groups of the Eastern Mediterranean region. More than 300 different mutations of the MEFV gene related to FMF have been identified, although only a few are pathogenic.[1] Previous studies testing the pathogenicity of E148Q alteration showed conflicting results. In a study of 646 FMF patients by Tirosh et al., 1% had a heterozygous E148Q variant with a milder clinical phenotype compared with patients having M694V homozygosity.[2] A Turkish FMF cohort of 153 patients had 33 (21.6%) patients with E148Q variant and 34 compound heterozygous patients (with E148Q and exon 10 mutations).[3] E148Q allele frequency among FMF patients was found to be 25% in Jewish, Arab, and Druze patients living in Israel, 20% in Turkish, 34% in Japanese, 17% in Azeri Turk patients living in Iran, and 2% in Armenian patients.[3] Several studies noted that the E148Q mutation was associated with a milder FMF phenotype. However, there was no significant difference in the frequency of clinical findings among the Turkish cohort.[3] Two patients from a South Indian family with recurrent fever, diffuse abdominal pain, and left knee joint pain for 1 year were found to have the MEFV variant E148Q in the heterozygous state. Both of them responded well to colchicine. The diagnosis of a milder phenotype of FMF was thus confirmed. Even though autoinflammatory disorders were reported from the Indian subcontinent,[4,5] we do not have data regarding the E148Q allele frequency and other mutations causing FMF. We report FMF in two members of a family with E148Q mutation which was not previously reported from the Indian subcontinent. This case reminds the readers to consider hereditary periodic fever syndromes when evaluating recurrent fever and the importance of E148Q mutation in the Indian population. Ethics approval All procedures performed in studies involving human participants were by the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Declaration of patient consent The authors certify that informed consent was taken from the father of both patients and assent was obtained from the children for participating in the study. The informed consent from the father and assent from the children were also obtained for using the clinical information to be reported in the journal. The patients and parents understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Физико-химические свойства крови при ревматоидном артрите с офтальмопатиями

Ревматоидный артрит сопровождается повышением параметров объемной вязкости и времени релаксации сыворотки крови на фоне уменьшения статического (равновесного) поверхностного натяжения и угла тензиограмм, что связано с полом больных, активностью патологического процесса, темпами его прогрессирования, поражением определенных сочленений, характером костно-деструктивных изменений, экстраартикулярными (системными) признаками болезни, степенью иммунных расстройств (в том числе с уровнями антинуклеарных и антинейтрофильных цитоплазматических антител), а в развитии офтальмопатии (увеит, склерит, кератит, конъюнктивит, катаракта, глаукома) участвуют нарушения адсорбционно-реологических свойств крови.

Pulmonary-Renal Syndrome: A Real-World Experience From a Tertiary Care Pulmonary Center in North India.

Background: Pulmonary renal syndrome (PRS) is a simultaneous occurrence of diffuse alveolar hemorrhage (DAH) and glomerulonephritis (GN). The diagnosis of PRS not only requires a high index of clinical suspicion and prompt management, but it is often fatal due to rapidly progressive clinical deterioration despite aggressive treatment. The authors, therefore, share the real-world experience of PRS presenting to tertiary care pulmonary center in north India.Aims: The objectives of the study were to identify etiology, clinical manifestations, treatment modalities and outcomes of patients presenting with PRS.Materials & methods: This was a retrospective observational study undertaken at Metro Centre for Respiratory Diseases of patients diagnosed with PRS during the last two years between 2019 and 2021. The patients diagnosed with PRS based on clinical manifestations, serology and biopsies were included in the study. All cases of non-immunological causes of PRS were excluded from the study. Chi-square and Mann-Whitney U tests were done to look for associations obtained between survivors and non-survivors. Cox regression analysis was done to estimate the hazard ratios of clinical variables on survival in PRS patients.Results: A total of 12 patients of PRS were included in the study and diagnosis was made based on clinical manifestations, serology as well as biopsies. The mean age of presentation was 45.4 (± 17.8) years and 66.7% of the patients were females. The most common etiology was anti-nuclear cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) seen in 83.3% of the cases. The most common symptoms were coughing and fever (80%) followed by dyspnea and hemoptysis (70%) with the mean duration of symptoms being 17.1 (±8.9) days. The mortality of PRS patients in our study was 41.6% and these patients had a higher acute physiology and chronic health evaluation (APACHE) score (median-26) compared to those patients who survived (median - 15.8).Conclusion: The occurrence of PRS, although rare, presents with rapid clinical deterioration leading to a high mortality rate. AAV was the most common cause of PRS as observed in our study. Early recognition and prompt aggressive management strategies with immunosuppressant therapies are essential for better outcomes for the patients.

Salivary anti-nuclear antibody (ANA) mirrors serum ANA in systemic lupus erythematosus

ObjectivesTo assay salivary anti-nuclear antibody (ANA) and its isotypes in patients with systemic lupus erythematosus (SLE) and to investigate relevant clinical associations.MethodsSaliva samples were collected from SLE patients and assayed for salivary ANA using immunofluorescence (IF). Isotypes of salivary ANA, including IgG-ANA, IgA-ANA, and IgM-ANA, were quantified using enzyme-linked immunosorbent assay. The correlations between clinical parameters and levels of salivary ANA and isotypes were evaluated.ResultsSalivary ANA IF intensities were significantly higher in SLE patients than in healthy controls, irrespective of SLE patient disease activity, and strongly correlated with serum ANA titers. Salivary ANA was detected in 67.14% of SLE patients and 10.00% of healthy controls (p < 0.001). Among ANA-positive samples, 80.85% exhibited a nuclear ANA pattern, and 42.55% exhibited a cytoplasmic ANA pattern. Salivary IgG-ANA, IgA-ANA, and IgM-ANA levels, as assayed by ELISA, were significantly increased in both active and less active SLE patients compared with healthy controls, and levels of each isotype were significantly correlated with serum ANA titer. Salivary IgM-ANA levels correlated with the physician global assessment (PGA), SLE disease activity index (SLEDAI), and negatively with serum C3 and C4. Salivary IgG-ANA also correlated with erythrocyte sedimentation rate (ESR), SLEDAI, and negatively with serum C3.ConclusionSalivary ANA levels correlate with serum ANA titer, and salivary IgM-ANA and IgG-ANA correlate variably with PGA, SLEDAI, ESR and complement levels. These findings underscore the potential of using salivary ANA and ANA isotypes as surrogates for serum ANA, particularly for future point-of-care applications since saliva is easier to obtain than blood.

Native and transplant kidney histopathological manifestations in association with COVID-19 infection: A systematic review.

BACKGROUNDSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in clinically significant multi-system disease including involvement in the kidney. The underlying histopathological processes were unknown at the start of the pandemic. As case reports and series have been published describing the underlying renal histopathology from kidney biopsies, we have started to gain an insight into the renal manifestations of this novel disease.AIMTo provide an overview of the current literature on the renal histopathological features and mechanistic insights described in association with coronavirus disease 2019 (COVID-19) infection. METHODSA systematic review was performed by conducting a literature search in the following websites-‘PubMed’, ‘Web of Science’, ‘Embase’ and ‘Medline-ProQuest’ with the following search terms-“COVID-19 AND kidney biopsy”, “COVID-19 AND renal biopsy”, “SARS-CoV-2 AND kidney biopsy” and “SARS-CoV-2 AND renal biopsy”. We have included published data up until February 15, 2021, which includes kidney biopsies (native, transplant and postmortem) from patients with COVID-19. Data on clinical presentation, histopathological features, management and outcome was extracted from the reported studies.RESULTSThe total number of biopsies reported on here is 288, of which 189 are postmortem, 84 native and 15 transplants. The results are varied and show underlying pathologies ranging from collapsing glomerulopathy and acute tubular injury (ATI) to anti-nuclear cytoplasmic antibody associated vasculitis and pigment nephropathy. There was variation in the specific treatment used for the various renal conditions, which included steroids, hydroxychloroquine, eculizumab, convalescent plasma, rituximab, anakinra, cyclophosphamide and renal replacement therapy, amongst others. The pathological process which occurs in the kidney following COVID-19 infection and leads to the described biopsy findings has been hypothesized in some conditions but not others (for example, sepsis related hypoperfusion for ATI). It is important to note that this represents a very small minority of the total number of cases of COVID-19 related kidney disease, and as such there may be inherent selection bias in the results described. Further work will be required to determine the pathogenetic link, if any, between COVID-19 and the other renal pathologies.CONCLUSIONThis report has clinical relevance as certain renal pathologies have specific management, with the implication that kidney biopsy in the setting of renal disease and COVID-19 should be an early consideration, dependent upon the clinical presentation.

A Case of Clinically Diagnosed ANCA Negative Granulomatosis With Polyangiitis.

Granulomatosis with polyangitis (GPA) is a systemic necrotizing vasculitis comprising of inflammation of small and medium-sized vessels.1 It typically presents with involvement of the upper and lower airways as well as the kidneys. If left untreated, end-organ damage may occur. Hematological investigations typically demonstrate the presence of antinuclear cytoplasmic antibodies (ANCA).2 Here, we discuss an unusual presentation of ANCA negative GPA, presenting initially with nasal symptoms.

Prevalence and clinical correlation of cytoplasmic anti-nuclear antibody patterns in a tertiary care hospital

Prevalence and clinical correlation of cytoplasmic anti-nuclear antibody patterns in a tertiary care hospital

Myositis specific antibodies are associated with isolated anti-Ro-52 associated interstitial lung disease.

Anti-Ro-52 antibody positivity might be associated with the presence of interstitial lung disease (ILD) among patients with autoimmune features. However, the clinical significance of isolated anti-Ro-52 positivity (i.e. the presence of anti-Ro-52 antibodies but the absence of anti-Ro-60 antibodies; anti-Ro-52+Ro-60-) in patients with ILD is not clear. This is a prospective and observational study of Chinese ILD patients with isolated anti-Ro-52 positivity. According to their myositis specific antibody (MSA) status, patients were split into groups, and their clinical and radiological features were compared. Of the 158 enrolled patients with ILD and isolated anti-Ro-52 positivity (isolated anti-Ro-52-ILD), there were 130 patients with a positive MSA status and 28 patients with a negative MSA status. Anti-synthetase antibodies (ASAs) were found in 61.5% of patients with MSA+-ILD, and anti-melanoma differentiation associated protein 5 (anti-MDA-5) antibodies were found in the remaining 38.5% of patients. The anti-nuclear antibody (ANA) pattern was associated with ASA and anti-MDA-5 positivity (x2 = 70.7, P < 0.001; Cramer's value 0.47, P < 0.001): ANA negativity was associated with anti-MDA-5 positivity, and cytoplasmic ANA positivity was associated with ASA positivity. There were statistically significant differences in the high-resolution CT patterns between patients with isolated anti-Ro-52 positivity with different MSA statuses (x2 = 29.8, P < 0.001; Cramer's value 0.31, P < 0.001): OP pattern was more common in patients with anti-MDA-5 antibodies than in those without anti-MDA-5 antibodies. Patients with isolated anti-Ro-52-ILD showed high positivity of MSA. Isolated anti-Ro-52 positivity with cytoplasmic ANA positivity was strongly associated with ASA+-ILD, while ANA negativity was associated with anti-MDA-5+-ILD.

The significance of cytoplasmic antinuclear antibody patterns in autoimmune liver disease.

We aimed to determine the significance of cytoplasmic antinuclear antibody (ANA) patterns using computer-aided immunofluorescence microscopy in patients with autoimmune liver diseases (AILD). ANA staining pattern was identified by treating cultured human epithelial type 2 (HEp-2) cells with the sera of the patients. Medical records of patients with suspected AILD who had positive cytoplasmic ANA patterns between February 2017 and November 2019 were retrospectively reviewed for clinical, laboratory, and immunological data. Cytoplasmic ANA patterns of AILD and non-AILD groups were compared. Further subgroup analysis of patients with AILD who had reticular or speckled cytoplasmic ANA patterns was conducted. We found that among the 196 patients with positive cytoplasmic ANA patterns, 113 (57.6%) were diagnosed with AILD. The percentage of reticular cytoplasmic pattern was higher in the AILD group than that in the non-AILD group (64.0% vs. 21.9%, p < 0.001). Furthermore, patients with AILD who exhibited a reticular ANA pattern demonstrated a higher positive rate for anti-mitochondrial antibodies (66.7% vs. 2.6%, p < 0.001) than those who exhibited the speckled ANA pattern. Moreover, AILD patients with the reticular ANA pattern displayed a lower positive rate for anti-smooth muscle antibodies (0% vs. 45%, p < 0.001) and nuclear ANA pattern (73.2% vs. 97.5%, p = 0.003) than those with the speckled ANA pattern. Therefore, cytoplasmic ANA patterns could be used to guide AILD characterization in suspected AILD cases, especially as the reticular ANA pattern is strongly associated with AILD. Thus, it is important to check cytoplasmic ANA patterns for AILD evaluation, even when nuclear ANA patterns are negative.

Current laboratory and clinical practices in reporting and interpreting anti-nuclear antibody indirect immunofluorescence (ANA IIF) patterns: results of an international survey

BackgroundThe International Consensus on Antinuclear Antibody (ANA) Patterns (ICAP) has recently proposed nomenclature in order to harmonize ANA indirect immunofluorescence (IIF) pattern reporting. ICAP distinguishes competent-level from expert-level patterns. A survey was organized to evaluate reporting, familiarity, and considered clinical value of ANA IIF patterns.MethodsTwo surveys were distributed by European Autoimmunity Standardization Initiative (EASI) working groups, the International Consensus on ANA Patterns (ICAP) and UK NEQAS to laboratory professionals and clinicians.Results438 laboratory professionals and 248 clinicians from 67 countries responded. Except for dense fine speckled (DFS), the nuclear competent patterns were reported by > 85% of the laboratories. Except for rods and rings, the cytoplasmic competent patterns were reported by > 72% of laboratories.Cytoplasmic IIF staining was considered ANA positive by 55% of clinicians and 62% of laboratory professionals, with geographical and expertise-related differences.Quantification of fluorescence intensity was considered clinically relevant for nuclear patterns, but less so for cytoplasmic and mitotic patterns. Combining IIF with specific extractable nuclear antigens (ENA)/dsDNA antibody testing was considered most informative.Of the nuclear competent patterns, the centromere and homogeneous pattern obtained the highest scores for clinical relevance and the DFS pattern the lowest. Of the cytoplasmic patterns, the reticular/mitochondria-like pattern obtained the highest scores for clinical relevance and the polar/Golgi-like and rods and rings patterns the lowest.ConclusionThis survey confirms that the major nuclear and cytoplasmic ANA IIF patterns are considered clinically important. There is no unanimity on classifying DFS, rods and rings and polar/Golgi-like as a competent pattern and on reporting cytoplasmic patterns as ANA IIF positive.

MANAGEMENT DILEMMA: A RARE CASE OF PULMONARY HISTOPLASMOSIS WITH SARCOID LIKE REACTION

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Co-existence of histoplasmosis with sarcoidosis is an increasingly recognized disease.1 Here we present a 59 years old gentleman who was diagnosed with histoplasmosis on lymph node biopsy. He had an incomplete response to Itraconazole with persistent symptoms and was subsequently required systemic steroids for what looked like a severe sarcoid like reaction. CASE PRESENTATION: 59 years old never smoker Caucasian male with allergic rhinitis and obstructive sleep apnea was evaluated for worsening fatigue, exertional dyspnea, subjective fevers, polyarthralgia, and resolving lower extremity rash of four week duration. He had two dogs at home, with no bird exposure. On admission, his complete blood workup including ESR and CRP were completely unremarkable. Extensive hilar and mediastinal lymphadenopathy on CT scan of his chest led to bronchoscopy and trans-bronchial tissue biopsies. Lung biopsies were negative for any pathology, but lymph node aspiration showed necrotic lymph nodes with necrotizing granulomas. Within granulomas were small fungal elements consistent with histoplasmosis. HIV and syphilis screen were negative, as were anti-nuclear antibodies (ANA) and anti-nuclear cytoplasmic antibodies (ANCA). He was started on itraconazole for histoplasmosis. Cardiac MRI was completely unremarkable. Due to his incomplete recovery on itraconazole and persistent symptoms, alternative diagnosis was sought after and histoplasmosis with sarcoid like reaction/ sarcoidosis was thought of as one of the likely possibilities. After a long discussion involving a multidisciplinary team, the patient was started on steroids and continued itraconazole. He had remarkable subjective improvement with steroids and was able to resume his daily routines. He was continued on itraconazole and steroids and for about one month and plan to continue itraconazole and taper the steroids thereafter. DISCUSSION: Sarcoidosis and histoplasmosis have a striking resemblance in terms of clinical presentation, lab abnormalities, and radiographic findings.2 What made the case more unique and challenging to manage was an inadequate response to standard treatment and the patient’s persistent symptoms. His persistent and eventually worsening symptoms led to additional investigations to rule out disease complications and alternative diagnoses. There have been case reports where the transformation of histoplasmosis to sarcoidosis has been described.3 It was particularly challenging to whether to attribute non-caseating granulomas to natural history of Histoplasma infection or a co-existing separate process like sarcoidosis. CONCLUSIONS: Co-existence of sarcoidosis with Histoplasma infection is now being increasingly recognized. Patients with pulmonary histoplasmosis and incomplete response to standard treatment, coexisting alternative diagnosis and possible coexistence of sarcoidosis should be sought after. Reference #1: 1.Wheat LJ, French ML, Wass JL. Sarcoidlike manifestations of histoplasmosis. Arch Intern Med. 1989;149(11):2421-2426. Reference #2: 2.Mathur P, Zurlo JJ, Crook TJ. The intricate relationship of histoplasmosis and sarcoidosis: a case report. J Med Case Rep. 2014;8:235. Published 2014 Jun 27. doi:10.1186/1752-1947-8-235 Reference #3: 3.Wynbrandt JH, Crouser ED. Transformation of pulmonary histoplasmosis to sarcoidosis: a case report. Respir Med. 2007;101(4):863-864. doi:10.1016/j.rmed.2006.08.01 DISCLOSURES: No relevant relationships by Vincent Chan, source=Web Response No relevant relationships by Adrian Estepa, source=Web Response No relevant relationships by Ahmad Raza, source=Web Response

EP25 Blau syndrome: a lifetime of sarcoid

Case report - IntroductionHere we explore a case of a 31-year-old female treated with juvenile arthritis rebranded as Blau syndrome. This is characterised by sarcoid involvement principally of her eyes as well as skin, kidneys, and joints. We aim to explore her management challenges and complications.Case report - Case description31 MS of Afro-Caribbean descent was diagnosed with early onset sarcoidosis at the age of 18 months. She was later found to be NOD2 gene positive but has no significant family history. Her health has been further complicated by her diagnoses of growth hormone deficiency and hyperthyroidism secondary to multinodular goitre.Clinically MS has a short stature and profound deafness. A legacy of the ophthalmic morbidity, panuveitis, has led to a visual acuity is 6/15 in her left eye and her right reduced to counting fingers due to developing endophthalmitis in 2019. Her arthritis is stable, but there are flexion deformities primarily involving her proximal interphalangeal joints reducing her grip function. In adulthood she does not have significant cutaneous changes.Investigations have revealed her to be anti-nuclear and anti-neutrophil cytoplasmic antibody negative. Radiologically, hand films show sparing of erosive changes, radiocarpal subluxation, and deformity of carpi in keeping with bilateral Madelung deformity. MRI has never suggested synovial enhancement of sacroiliac joints.Therapeutically she has trialled conventional disease modifying therapy including azathioprine, mycophenolate, and methotrexate. Disease activity continues to be high despite anti-TNF biologic DMARDs (adalimumab, infliximab and golimumab). Use of anti-TNF therapy has been complicated by development of CMV disease and identification of anti-infliximab antibodies following interruption.Ongoing steroid use from 18 months, hyperthyroidism and a chronic inflammatory state has led to osteoporosis. DEXA Z-scores reveal lumbar -2.7, right femoral neck -3.2 and left femoral neck -4.7. Systemic corticosteroid has tried to be offset through dexamethasone intravitreal implants.Consequentially, uncontrolled disease burden has also led to significant input from orthopaedics, including bilateral total knee replacements by age 28.However, with MS, we are hopeful with the commencement of anti-IL6 receptor therapy (Tocilizumab) that this may represent a new line of effective treatment.Case report - DiscussionBlau syndrome is a juvenile sarcoidosis characterised by the triad of granulomatous arthritis, recurrent uveitis, and dermatitis. It is inherited in an autosomal dominant pattern due to a missense mutation in the gene encoding for nucleotide-binding oligomerisation domain containing protein 2 (NOD2/CARD15). It is proposed that NOD2 as intracellular receptors, for antigen such as lipopolysaccharide, may subsequently act like toll-like receptors to cascade NF-kappa B and downstream inflammatory pathways. Its role is also implicated in other inflammatory conditions such as Crohn’s disease.As represented in our case, uveitis presents the highest morbidity, with median age of eye disease presenting at 60 months and remains persistent despite topical or systemic therapy in more than 50% of patients. In comparison to Juvenile idiopathic arthritis, Blau often leads to a pan rather than anterior segment only uveitis and in a greater proportion of cases.In addition to biological factors, much of MS’s treatment decisions have been guided by her and her psychology. In attempting to address the difficulties of her condition, including coordinating several specialities clinics whilst developing as a young woman, she has frequently discontinued therapy which may represent an area that she can exact control given little perceived benefit.TNF-alpha inhibitors have been validated through randomised controlled trials for the use of refractory sarcoidosis. However recent literature has highlighted the use of targeting the IL-6 pathway in multisystem chronic sarcoidosis. It is believed this may represent a key cytokine in promoting Th17 effector cells that have been implicated in sarcoidosis bio-pathology. However ongoing case reports and ideally large-scale studies are needed.Case report - Key learning pointsBlau syndrome as a rare lifelong form of early onset sarcoidosis offers insight into challenging therapeutic decision making where limited clinical trial data is available.

Chronic spontaneous urticaria and angioedema in a patient with autoimmune thyroid disease resolved after thyroidectomy

The link between chronic urticaria and accompanying thyroid disease is still not understood, with current treatment focusing on antihistamines and levothyroxine. A 35-year-old female patient presented with chronic idiopathic urticaria and facial angioedema for 9 months prior to evaluation. Oral corticosteroid therapy, antihistamines, leukotriene-antagonists, selenium, and omalizumab were all administered, with the disease relapsing within several days, accompanied with facial angioedema of varying severity. Laboratory results were negative for antinuclear antibodies (ANA) and cytoplasmic antineutrophil antibodies (ANCA). Immunoglobulins and complement levels were normal. Autologous serum testing, and skin-prick test for common inhalatory allergens were all normal. Levothyroxine was then administered with no effect on the symptoms. After considering all of the available treatment options, the patient decided to undergo total thyroidectomy. Urticaria and angioedema subsided on the third postoperative day, and she remains free of symptom recurrence during 10 months of postoperative follow-up. Her antiTPO titer decreased from > 1300 to 31.1 kIU/L and antiTG decreased from 272 to 4.9 kIU/L three months after the surgery. The most important element in this case report is an unexpected extra-thyroid presentation of an autoimmune thyroid disease, with a newly described association with facial angioedema. Additional important evidence may confirm the hypothesis that both conditions are indeed caused by a common immunological patohogenetic pathway that should be routinely evaluated in patients presenting with chronic idiopathic urticaria.

Thrombosis and necrosis of the feet in the course of vasculitis associated with perinuclear anti-neutrophil cytoplasmic antibodies.

Thrombosis and necrosis of the feet in the course of vasculitis associated with perinuclear anti-neutrophil cytoplasmic antibodies.

Clinical significance of thyroid hormone and antibodies in patients with idiopathic interstitial pneumonia.

BackgroundHypothyroidism was recently reported to be common and to predict mortality in patients with idiopathic pulmonary fibrosis (IPF). In addition, a high prevalence of hypothyroidism was shown in patients with idiopathic pleuroparenchymal fibroelastosis. However, in idiopathic interstitial pneumonia (IIP), a clinical significance of thyroid function has not been clarified in detail. The goal of this study was to investigate the clinical significance of thyroid function and the presence of thyroid antibodies in IIP.MethodsWe have reviewed IIP patients, and analyzed the positivity of thyroid antibodies at first. Next, the relationship of clinical characteristics with thyroid function and the positivity of thyroid antibodies was analyzed. Lastly, the positivity of thyroid antibodies and other autoantibodies was evaluated.ResultsIn IIP patients, thyroglobulin and thyroid peroxidase antibodies were positive in 17 and 16%, respectively, and 22% of patients had either or both antibodies. Subclinical and/or overt hypothyroidism was confirmed in 7% of IIP patients. The free thyrotropin level had a significant positive correlation with vital capacity and a significant negative correlation with the C-reactive protein and surfactant protein-A levels, and erythrocyte sedimentation ratio (ESR). In addition, autoantibodies suggestive of connective tissue diseases (CTDs) were positive in more than two thirds of IIP patients with the thyroid antibody, and the positive rate of antinuclear and proteinase-3 anti-neutrophil cytoplasmic antibodies was significantly higher in IIP patients with thyroid antibodies than those without the antibodies.ConclusionsAlthough thyroid dysfunction is not frequent, thyroid hormones and thyroid antibodies are possibly involved in the pathogenesis of IIP and their evaluation may be clinically useful to identify the clinical phenotype of IIP with autoimmune features.