Organ Involvement In Patients Research Articles

Levels of anti-topoisomerase I antibody correlated with short onset of cardiopulmonary involvement in Thai systemic sclerosis patients

Anti-topoisomerase-I antibody (ATA) is associated with disease severity and internal organ involvement in patients with systemic sclerosis (SSc). The correlation between ATA levels and the clinical course of SSc is unclear. We aimed to determine the correlation between ATA level and survival time and the onset of internal organ fibrosis in SSc patients. This historical cohort study was conducted in adult SSc patients with quantitative tests of ATA between January 2019 and December 2022. Patients with overlap syndrome and no quantitative ATA test were excluded. According to the sample size calculation, and 10% compensated for missing data, a total of 153 patients were needed. The respective mean age on the study date and median ATA level was 59.9 ± 11.3 years and 370 U/mL (range 195–652). Most cases (107 cases; 69.9%) were the diffuse cutaneous SSc subset. According to a multivariable analysis, the ATA titer had a negative correlation with the onset of cardiac involvement (Rho − 0.47, p = 0.01), and had a positive correlation with skin thickness progression (Rho 0.39, p = 0.04). Eleven cases exhibited ATA levels < 7 U/mL and outlier ATA levels were excluded, 142 cases were included in the sensitivity analysis, and multivariable analysis showed the correlation between early onset of ILD and cardiac involvement (Rho − 0.43, p = 0.03 and Rho − 0.51, p = 0.01, respectively). The ATA level was correlated with neither the survival time nor the onset of renal crisis in both analyses. High ATA levels were correlated with a short onset of ILD and cardiac involvement and the presence of extensive skin tightness. Quantitative tests of ATA could serve as an effective tool for identifying patients at risk of an unfavorable prognosis.

Scleroderma-overlap syndromes: capillaroscopy, laboratory, and clinical manifestations and follow-up compared to scleroderma patients.

Overlap syndrome (OS) is a group of systemic connective tissue diseases (CTDs) that meet the criteria of two or more CTDs. In this study, we evaluated clinical, laboratory, and capillaroscopic manifestations of patients with scleroderma OS (SSc-OS) and its subgroups and follow-up progression compared to patients with limited SSc (LcSSc). In a 10-year cross-sectional study, we evaluated 135 adult patients (70 with SSc-OS and 65 with LcSSc) with the same skin score for their baseline and follow-up clinical, laboratory, high-resolution chest tomography (HRCT), echocardiography, and nailfold capillaroscopy data and compared them. Of the 135 patients, 70 had SSc-OS, including 45 (64.3%) cases of SSc-SS (Sjögren's syndrome), 11 (15.7%) of SSc-RA (rheumatoid arthritis), 9 (12.9%) of SSc-myositis and 5 (1.7%) of SSc-SLE (systemic lupus erythematosus), and 65 had LcSSc. Lung and heart involvement and pulmonary arterial hypertension (PAH) did not differ between the two groups (p > 0.05). Musculoskeletal involvement and non-specific pattern of capillaroscopy were higher (p = 0.035 and p = 0.001), and digital ulcer (DU) and scleroderma patterns of capillaroscopy were lower in the SSc-OS group (p = 0.000).No significant relationship was found between capillaroscopic patterns and organ involvement in the two groups (p-value > 0.05). In the follow-up (3.71 ±2.63 years), new DU and progression of lung involvement (p = 0.002) and the progression in capillaroscopic patterns was lower in SSc-OS (p = 0.000). In the follow-up, new DU was not seen in the SSc-OS, with lower progression of lung involvement, skin score, and capillary damage. In SSc-OS patients, the most common subgroup was SSc-SS. Scleroderma OS was associated with lower major organ involvement and capillaroscopy progression than LcSSc. Major organ involvement in patients with SSc-OS was significantly lower than in LcSSc patients. In the follow-up, new DU was not seen in the SSc-OS with lower progression of lung involvement, skin score, and capillary damage.

Syndromic ichthyoses

Abstract Inherited ichthyoses are classified as Mendelian disorders of cornification (MEDOC), which are further defined on the basis of clinical and genetic features and can be divided into non-syndromic and syndromic forms. To date, mutations in more than 30 genes are known to result in various types of syndromic ichthyoses, which, in addition to mostly generalised scaling and hyperkeratosis of the skin, also show additional organ involvement. The syndromic ichthyoses are generally very rare and are classified based on the mode of inheritance, and can be further subdivided according to the predominant symptoms. In our review we provide a concise overview of the most prevalent syndromic forms of ichthyosis within each subgroup. We emphasize the importance of the clinical assessment of complex syndromes even in the era of genetic testing as a first-tier diagnostic and specifically the need to actively assess potential organ involvement in patients with ichthyosis, thereby enabling efficient diagnostic and therapeutic approaches and timely access to specialized centers for rare disorders of cornifications. As part of the Freiburg Center for Rare Diseases a Center for Cornification Disorders was recently established with collaboration of the Institute of Human Genetics and the Department of Dermatology. An early diagnosis of syndromes will be of direct benefit to the patient regarding interventional and therapeutic measures e. g. in syndromes with cardiac or metabolic involvement and allows informed reproductive options and access to prenatal and preimplantation genetic diagnosis in the family.

Loiasis: An Unusual Cause of Eosinophilia in a Pediatric Patient.

To the Editors: A 9-year-old girl from Equatorial Guinea with spastic tetraparesis and ventriculoperitoneal shunt due to congenital hydrocephalus for which she was periodically checked in Barcelona, Spain, was referred to our department because of eosinophilia. Her family lived in Malabo but had also stayed in the continental part of Equatorial Guinea and had no relevant previous history. The patient was asymptomatic and no new significant findings were found on physical examination. A blood count revealed eosinophilia (eosinophil count, 1600 eo/μL) with mild IgE elevation (IgE, 374 KUI/mL). Biochemistry and iron studies were normal, and allergy screening, Schistosoma/Strongyloides serologies and coproparasitologic studies were negative. Additional serologies including Echinococcus granulosus, Fasciola hepatica, Taenia solium and Toxocara canis were also negative. The microscopic microfilarial study in blood revealed 2 microfilariae/mL (8:30 am), later identified as Loa loa (Fig. 1). The test was repeated at 12 am to accurately quantify microfilaremia, which showed a significant increase in L. loa parasites (132/mL). Provided that coinfection with onchocerciasis could not be excluded and that L. loa parasitemia was low, a single dose of ivermectin 150 μg/kg orally was administered. After this initial management, loiasis was treated with 21 days of diethylcarbamazine (DEC) (progressive ascending dosage up to 9 mg/kg/d). The resolution of eosinophilia and L. loa parasitemia was later confirmed.FIGURE 1.: Microfilaria of Loa loa in a thick blood smear, stained with hematoxylin (100×).L. loa is a nematode responsible for a filariasis transmitted by tabanids of the genus Chrysops endemic in Angola, Chad, Democratic Republic of the Congo, Cameroon, Central African Republic, Equatorial Guinea, Gabon, Nigeria, Republic of Congo and South Sudan.1 The 2 main clinical manifestations are the “Calabar edema” due to a hypersensitivity reaction to the subcutaneous parasite migration, and the “eye worm,” which is the adult form migrating under the bulbar conjunctiva.1,2 Pruritus is also frequent. Nonetheless, a significant number of patients may only present eosinophilia, mild nonspecific symptoms or no symptoms at all.3 Although it has been traditionally considered a “benign” infection, it has recently been associated with an excess mortality rate4,5 and a broad range of vital organ involvement in patients with high microfilaremia.2 The diagnosis is based on the visualization of microfilariae using a blood concentration technique (Ho Thi Sang method with saponin) and subsequent staining of a smear with hematoxylin, extracting blood samples at midday in view of the diurnal periodicity of microfilariae circulation in peripheral blood. First-line medicine is DEC, which acts against both microfilariae and adult worms.3 Before starting the treatment, it is compulsory to exclude onchocerciasis coinfection—in patients coming from areas where both filariasis occur—providing that DEC could cause blindness or disease exacerbation in these cases. Besides, patients with high microfilaremia (>2500/μL) are at risk of encephalopathy after DEC or ivermectin administration. In these cases, a prior course of albendazole should be considered to reduce microfilarial load. This case shows the importance of loiasis screening in patients coming from an endemic country if eosinophilia is present. Universal screening of all pediatric patients coming from endemic areas is still not recommended according to the literature.

A multidisciplinary case report of multiple myeloma with renal and cardiac involvement: a look beyond amyloidosis

BackgroundMultiple myeloma (MM) is a malignant neoplasm associated with kidney involvement in nearly half of the patients. Cast nephropathy, monoclonal immunoglobulin deposition disease (MIDD), and light chain (AL) amyloidosis are the most common monoclonal immunoglobulin-mediated causes of renal injury.Cardiac involvement is also present in MM, characterized by restrictive cardiomyopathy generated by light chain deposit or amyloid. Thromboembolic complications such as deep vein thrombosis or pulmonary embolism are also described.Case presentationWe present an unusual multidisciplinary case of a woman with a newly diagnosed MM associated with severe proteinuria and high natriuretic peptide. A renal and fat pad biopsy with Congo red staining were performed but amyloid deposition was not discovered. While immunofluorescence on fresh frozen unfixed tissue was not contributory, the immunofluorescence on fixed tissue and electron microscopy revealed the correct diagnosis.During subsequent investigations, two intracardiac right-sided masses and massive pulmonary embolism were also detected.ConclusionsThis case highlights that multiple organ involvement in patients with MM may result from a combination of paraprotein-dependent and -independent factors. Moreover, renal diseases induced by monoclonal gammopathies are a group of complex and heterogeneous disorders. Their subtle presentation and their potential multiorgan involvement require the expertise of a multidisciplinary team able to provide the most appropriate diagnostic and therapeutic assessment.

Prognostic implications of clinical phenotype and severity of cardiac involvement in patients presenting with immunoglobulin light chain amyloidosis

Abstract Background Patients with systemic immunoglobulin light chain (AL) amyloidosis may present with a wide array of signs and symptoms due to the multi-systemic organ involved. The presence of cardiac involvement is the key determinant of survival. Cardiac magnetic resonance (CMR) has the unique ability to measure the continuum of cardiac amyloidosis (CA) infiltration providing a deep characterisation from early CA involvement to severe degree of CA burden. Purpose The aim of this study was to characterise the clinical profiles and the severity of organ involvement in patients presenting with AL amyloidosis and to investigate implications for long-term outcome. Methods Patients newly diagnosed with AL amyloidosis at the National Amyloidosis Centre underwent comprehensive clinical, laboratory and instrumental work up, including CMR imaging with left ventricular (LV) mass, late gadolinium enhancement (LGE) and extracellular volume (ECV). The clinical phenotypes were classified in cardiac, renal and other according to the symptoms at presentation. The degree of CA was investigated by CMR: 0= no features of CA (normal LV mass, no LGE and normal ECV); 1=early cardiac amyloid infiltration (normal LV mass, raised ECV no LGE); 2= characteristic of CA with normal mass (diffuse subendocardial or transmural LGE, altered gadolinium kinetics and raised ECV); 3= characteristic of CA with elevated mass (diffuse subendocardial or transmural LGE and raised ECV). The study outcome was all-cause mortality. Results The study population included 241 AL patients presenting with cardiac and renal (22.8%, n=55), cardiac (28.2%, n=68), renal (33.2%, n=80) and other (15.8% n=38) phenotypes. During a median follow up of 33 (IQR 7–52) months, cardiac phenotype either in isolation or in combination with renal phenotype was associated with a higher rate of all-cause mortality compared to the others (p&amp;lt;0.001) (Figure). On CMR imaging, 43.2% of patients without cardiac phenotype (49%, n=118/241) had characteristic scans of CA (CMR grade 2 and 3) whilst 13.8% of patients with cardiac phenotype (51%, n=123/241) had no features of CA on CMR images (CMR grade 0) in (p&amp;lt;0.001). With Kaplan Meier analysis, the risk of all-cause death increased in patients with characteristic features of CA on CMR scan (Figure 1) and in patients with cardiac phenotype and features of CA on CMR scans compared to the others (both p&amp;lt;0.001) (Figure). At multivariable analysis, age at diagnosis (hazard ratio [HR] 1.03, p=0.009), clinical phenotype at presentation (HR 1.35, p=0.014) and ECV measured by CMR (HR 56, p&amp;lt;0.001) emerged as independent prognostic parameters. Conclusions Patients with newly diagnosed AL amyloidosis present most frequently with renal and cardiac phenotypes. CMR detects CA in &amp;gt;40% of patients with non-cardiac phenotype. ECV is an independent predictor of all-cause mortality across the full clinical spectrum of AL amyloidosis. Funding Acknowledgement Type of funding sources: None.

Associations of serum long-chain fatty acids with multiple organ involvement in patients with sarcoidosis

BackgroundFatty acids have diverse immunomodulatory functions and the potential to be associated with inflammatory responses in sarcoidosis.MethodsThe serum levels of multiple long-chain fatty acids (LCFAs) were compared between 63 patients with sarcoidosis and 38 healthy controls. The associations of LCFAs with clinical outcomes of sarcoidosis were also evaluated.ResultsThe patients with sarcoidosis had significantly lower levels of n-3 poly-unsaturated fatty acids (PUFAs) (p < 0.001) and n-6 PUFAs (p < 0.001) than the healthy controls. However, there were no significant differences in the levels of saturated fatty acids (SFAs) and mono-unsaturated fatty acids (MUFAs) between the two groups. On multivariate logistic analysis, lower levels of n-3 PUFAs, n-6 PUFAs, and n-3/n-6 ratio were predictive of sarcoidosis. Among the patients with sarcoidosis, those with multiple organ involvement had significantly lower levels of n-3 PUFAs and n-3/n-6 ratio than those with single organ involvement. There were no significant differences in the levels of n-6 PUFAs, SFAs, and MUFAs between the patients with multiple and single organ involvement. On multivariate logistic analysis, lower levels of SFAs and n-3/n-6 ratio were predictive of multiple organ involvement. The levels of LCFAs had no significant association with radiographic stage or spontaneous remission.ConclusionsAssessment of LCFA profiles may be useful for the diagnosis of sarcoidosis and evaluation of the disease activity.

The relationship between erythema nodosum and prognosis in systemic sarcoidosis: a retrospective cohort study

BackgroundErythema Nodosum (EN) is the most common skin manifestation in sarcoidosis and has often been associated with a good prognosis. ObjectivesTo compare the clinical characteristics and treatment-related features in patients with sarcoidosis according to whether or not EN was seen as a presenting symptom at the time of diagnosis. MethodsA 20-year single-center retrospective study was performed. The following two groups were identified: one group with EN as one of the presenting symptoms at the time of diagnosis of sarcoidosis (EN group) and a second group without EN as a presenting symptom at diagnosis (non-EN group). The clinical characteristics and treatment modalities were collected from the medical records. ResultsA total of 122 patients (31 in the EN group, 91 in the non-EN group) were included. Radiological stages of pulmonary disease were significantly lower in the EN group. Articular involvement was more common in the EN group (p = 0.001), whereas other systemic organ involvements (p = 0.025), especially neurological involvement (p = 0.036), were significantly more common in the non-EN group. In the EN group, a higher percentage of patients were managed without systemic therapy (71.0% vs. 54.9%) and spontaneous remission was more frequent (25.0% vs. 14.1%), however, this wasn’t statistically significant. Study limitationsRetrospective design. ConclusionsThe lower radiological stage of pulmonary sarcoidosis and lower frequency of systemic organ involvement in patients with EN augment the prognostic value of EN highlighted in the literature. However, this study couldn’t confirm that the patients with EN would need less systemic therapy in the course of their disease.

Value of (11)C-PiB PET/MRI in the evaluation of organ involvement in primary systemic light chain amyloidosis

目的分析11C标记的匹兹堡化合物B（11C-PiB）PET/MRI在原发性系统性轻链型淀粉样变（pAL）中评估器官受累的价值。方法回顾性分析2019年1月至2021年10月在华中科技大学同济医学院附属协和医院就诊的20例pAL患者及3名健康志愿者的临床资料，比较临床标准评估器官受累和PET/MRI评估的相关性，分析心脏相关生物学指标、疾病分期与心脏最大标准摄取值（SUVmax）之间的关系及24 h尿蛋白定量与肾脏SUVmax之间的关系。结果①纳入20例患者，初诊患者18例，非初诊患者2例。观察到11C-PiB摄取阳性的脏器分别为：心脏15例（75％），肺部8例（40％），骨髓10例（50％），肌肉10例（50％），舌肌7例（35％），甲状腺6例（30％），唾液腺4例（20％），脾脏2例（10％），胃壁1例（5％）。②11C-PiB在心脏及骨髓摄取的阳性率与临床评估标准具有很好的相关性。在肺组织、脾脏、腺体、肌肉和舌肌中，11C-PiB PET/MRI评估的阳性率明显高于临床标准。但对于神经系统受累和脂肪组织的评估11C-PiB PET/MRI具有局限性。③分析18例初诊患者心脏相关生物学指标与心脏SUVmax之间的关系。左心室射血分数（LVEF）<50％且室间隔厚度（ISV）≥1.2 cm的患者相较LVEF≥50％且ISV<1.2 cm的患者其心脏SUVmax更高（P<0.05）。心脏SUVmax值在Mayo2004分期、Mayo2012分期各期之间差异有统计学意义，分期越晚，SUVmax值越高（P<0.05）。心脏SUVmax与心肌肌钙蛋白酶Ⅰ、N 末端前体脑钠肽水平呈明显正相关（P<0.01），肾脏SUVmax与24 h尿蛋白定量无明显相关性（P>0.05）。结论全身11C-PiB PET/MRI作为一种淀粉样蛋白的可视化系统，若用于器官水平的定性评估，具有提高早期无创性诊断pAL水平的潜力；用于器官水平（尤其是心脏）的定量评估，有望更精准评估器官功能和预测疾病预后。

232 A multidisciplinary case of multiple myeloma with cardiac and renal involvement: a look beyond amyloidosis

Abstract Aims Multiple myeloma (MM) is a malignant neoplasm with a frequent cardiac involvement characterized by restrictive cardiomyopathy. Kidney and thromboembolic complications are also described. Methods and results A 52-year-old woman with a history of kidney disease was admitted to nephrology department due to worsening of renal function and refractory hypertension. A bone marrow biopsy revealed the diagnosis of MM. A renal and fat pad biopsy with Congo red staining was performed but amyloid deposition was not observed. Increased cardiac enzymes suggested a cardiac involvement. Indeed, two intracardiac right-sided masses and massive pulmonary embolism were detected. Surgical cardiac intervention was promptly performed and a chemotherapy regimen was started. Meantime, a kidney biopsy revealed a light-chain deposition disease. Conclusions This case highlights that multiple organ involvement in patients with MM may result from a combination of paraprotein-dependent and -independent factors. Moreover, in patients with not acute massive pulmonary embolism and intracardiac right masses, surgical pulmonary embolectomy should be promptly performed to preserve RV function and to avoid prevent pulmonary hypertension development.

How I treat AL amyloidosis

AbstractThe treatment of patients with systemic light chain (AL) amyloidosis is a challenge to hematologists. Despite its generally small size, the underlying clone causes a rapidly progressing, often devastating multiorgan dysfunction through the toxic light chains that form amyloid deposits. Clinical manifestations are deceitful and too often recognized at an irreversible stage. However, hematologists are in the unique position to diagnose AL amyloidosis at a presymptomatic stage, checking biomarkers of amyloid organ involvement in patients with monoclonal gammopathies at higher risk to develop the disease. Adequate technology and expertise are needed for a prompt and correct diagnosis, particularly for ruling out non-AL amyloidoses that are now also treatable. Therapy should be carefully tailored based on severity of organ involvement and clonal characteristics, and early and continual monitoring of response is critical. Three recent randomized clinical trials moved AL amyloidosis to evidence-based era. Above all, the daratumumab-bortezomib combination is a new standard-of-care for newly diagnosed patients, inducing rapid and deep responses that translate into high rates of organ response. The availability of new effective drugs allows to better personalize the therapy, reduce toxicity, and improve outcomes. Patients should be treated within clinical trials whenever possible.

Associations between occupational and environmental exposures and organ involvement in sarcoidosis: a retrospective case-case analysis

BackgroundSarcoidosis most commonly affects lungs and intrathoracic lymph nodes, but any other organ can be involved. In epidemiological studies, many occupational and environmental exposures have been linked to sarcoidosis but their relationship with the disease phenotype has barely been studied.ObjectiveTo investigate how occupational and environmental exposures prior to diagnosis relate to organ involvement in patients with sarcoidosisMethodsWe retrospectively studied patients seen at a sarcoidosis clinic between 2017 and 2020. Patients were included if they had a clinical presentation consistent with sarcoidosis and histologically confirmed epithelioid granulomas or had Löfgren syndrome. In a case–case analysis using multivariable logistic regression we calculated odds ratios (OR) of prespecified exposure categories (based on expert ascertainment) for cases with a given organ involvement versus cases without this organ involvement.ResultsWe included 238 sarcoidosis patients. Sarcoidosis limited to pulmonary involvement was associated with exposure to inorganic dust prior to diagnosis (OR 2.11; 95% confidence interval [CI] 1.11–4.17). Patients with liver involvement had higher odds of contact with livestock (OR 3.68; 95% CI 0.91–12.7) or having jobs with close human contact (OR 4.33; 95% CI 1.57–11.3) than patients without liver involvement. Similar associations were found for splenic involvement (livestock: OR 4.94, 95% CI 1.46–16.1; close human contact: OR 3.78; 95% CI 1.47–9.46). Cardiac sarcoidosis was associated with exposure to reactive chemicals (OR 5.08; 95% CI 1.28–19.2) or livestock (OR 9.86; 95% CI 1.95–49.0). Active smokers had more ocular sarcoidosis (OR 3.26; 95% CI 1.33–7.79).ConclusionsOur study indicates that, in sarcoidosis patients, different exposures might be related to different organ involvements—hereby providing support for the hypothesis that sarcoidosis has more than one cause, each of which may promote a different disease phenotype.

Biomarker-Based Screening of Organ Dysfunction in Patients with MGUS Allows Early Diagnosis of AL Amyloidosis

Introduction. Despite availability of newer effective therapies, approximately 30% of patients with AL amyloidosis still die within 1 year from diagnosis due to advanced, irreversible cardiac involvement at presentation. In 40% of patients the diagnosis is made more than 1 year after the onset of symptoms, and, once amyloid organ involvement becomes symptomatic, organ dysfunction is often already advanced (Kourelis et al. AJH 2014, Lousada et al. Adv Ther 2015). Biomarkers [(N terminal pro natriuretic peptide (NT-proBNP) for the heart, albuminuria for the kidney, and alkaline phosphatase (ALP) for the liver] can detect organ involvement before symptoms appear and can facilitate early diagnosis. Moreover, increased circulating free light chains (FLC) precede the presentation of AL amyloidosis by 4 years or more (Weiss et al. JCO 2014). Thus, we advocated the screening with biomarkers of amyloid organ involvement of all patients with monoclonal gammopathy of undetermined significance (MGUS) and abnormal FLC ratio (Merlini et al. Hematology Am Soc Hematol Educ Program 2012, Merlini et al. Blood 2013). Here we present the clinical features and outcome of patients with MGUS diagnosed with AL amyloidosis while asymptomatic during biomarker-based screening.Methods. The prospectively-maintained database of the Pavia Amyloidosis Research and Treatment Center was systematically searched for patients diagnosed with AL amyloidosis during biomarker-based screening of MGUS. Patients who had amyloid-related symptoms at the time of diagnosis were excluded. The diagnosis of AL amyloidosis was established on abdominal fat or organ biopsy in all cases, and typing by immuno-electron microscopy confirmed that the amyloid fibrils were formed by a light chain of the same isotype as the monoclonal protein.Results. Thirteen patients were identified between January 2012 and December 2016. Six were males and their median age was 67 years (range 38-79 years). The median time from the identification of MGUS to diagnosis of AL amyloidosis was 4.2 years (range 0.7-19.8 years). The monoclonal components were IgAl in 1 patient, IgDl in 1, IgGk in 1, IgGl in 7, and IgMl in 3. The median dFLC value was 67 mg/L (range 21-283 mg/L). The biomarker found abnormal during follow-up was proteinuria (median 1.01 g/24h, range 0.7-1.32 g/24h, predominantly albumin) in 8 patients, elevated NT-proBNP in 8 (median 789 ng/L, range 441-2935 ng/L), and ALP in 1 (509 U/L, upper reference limit 279 U/L). In 4 patients more than 1 biomarker was elevated. Cardiac troponin I was <0.1 ng/mL in all but 1 of the 7 patients with heart involvement, resulting in cardiac stage II in 7 subjects and IIIa in 1. Median left ventricular wall thickness at echocardiography was 13.2 mm (range 10.0-14.4 mm) and median ejection fraction was 62% (range 50-70%) in patients with elevated NT-proBNP. Estimated glomerular filtration rate was >50 mL/min in all patients with proteinuria, resulting in renal stage I in all cases. All the patients are alive and none required dialysis after a median follow-up of 30 months. Eight patients received cyclophosphamide / bortezomib / dexamethasone (CyBorD), 2 (diagnosed in 2009) melphalan / dexamethasone (MDex), and 3 bortezomib / rituximab / dexamethasone. Ten patients obtained complete or very good partial (CR/VGPR) response plus organ response (OR) after upfront treatment. The remaining 3 subjects received second-line therapy, bortezomib /dexamethasone, lenalidomide / dexamethasone, and autologous stem cell transplant and reached CR/VGPR plus OR after rescue treatment.Discussion. Biomarker-based screening for amyloid organ involvement in patients with MGUS allowed pre-symptomatic diagnosis of systemic AL amyloidosis at early stages, resulting in excellent outcomes in all cases, including those who fail to respond to upfront therapy. Larger, prospective studies are warranted to assess the impact of this approach. DisclosuresPalladini:Prothena: Honoraria, Other: Travel grant; Celgene: Other: Travel grants; Jannsen-Cilag: Membership on an entity's Board of Directors or advisory committees. Varettoni:Jannsen: Consultancy, Other: travel expenses.

Nailfold capillaroscopy changes associated with anti-RNP antibodies in systemic lupus erythematosus.

Anti-U1RNP antibody is associated with distinct organ involvement in patients with systemic lupus erythematosus (SLE). Nailfold capillaroscopy (NFC) allows non-invasive assessment of microvascular abnormalities in several connective tissue diseases. The objective of this study is to determine the association of anti-U1RNP antibody with microvascular changes by NFC in RNP-positive SLE patients in comparison with RNP-negative SLE patients (negative disease controls) and mixed connective tissue disease (MCTD) cases (positive disease controls). NFC examination was performed in consecutive patients with SLE with or without anti-U1RNP positivity. MCTD patients were recruited as disease controls. Abnormalities noted in the three groups were compared using non-parametric tests. Ordinal logistic or linear regression was used wherever applicable. 81 patients were studied, of whom 28 were diagnosed as RNP-positive SLE (age 30.0 ± 10.37; 26 females), 26 were RNP-negative SLE (age 29.42 ± 9.20; 25 females) and 27 had MCTD (age36.5 ± 9.70; 25 females). RNP-positive SLE patients had more frequent giant capillaries, enlarged capillaries and ramified capillaries as compared to RNP-negative SLE (p = 0.05, < 0.01 and 0.03, respectively). The capillary density was lower in patients with MCTD as compared with patients withRNP-positive SLE (5.11 ± 1.69/mm vs 7.25 ± 1.38/ mm, p < 0.01) and RNP-negative SLE (8.92 ± 1.13/mm, p < 0.01). The reduction in capillary density was less severe in patients withRNP-negative SLE as compared with RNP-positive SLE (OR = 0.1058 [95% CI = 0.02-0.546], p < 0.01) which wasindependent of the presence of Raynaud'sphenomenon, interstitial lung disease and disease duration. Presence of anti-U1RNP antibody is associated with notable patterns of microvascular abnormalities in SLE. These NFC abnormalities are noted more profoundly in patients with MCTD and are less marked in RNP-negative SLE patients.

Specific Tests and Inflammatory Biomarkers in the Evaluation of Brucellosis Disease

Brusellosis is the world's most common bacterial zoonotic infection and is still endemic in many developing countries. The clinical appearance of brucellosis is not specific, but the course and severity of the infection varies. In this study, it was aimed to determine the relationship between laboratory parameters and clinical response and organ involvement in patients with Brucellosis diagnosed with specific diagnostic tests. In the study, 100 patients without previous diagnosis of Brucellosis who have admitted to the Department of Infectious Diseases and Clinical Microbiology and had positive Brucella tube agglutination tests and whose clinic was compatible with Brucellosis were evaluated prospectively. Patients were invited to be checked in the 1st, 2nd and 6th weeks . Patients with hip pain and low back pain were evaluated with sacroiliac magnetic resonance imaging (MRI) and lumbar MRI for sacroiliitis and spondylodiscitis. Patients with liver and bone marrow involvements, sacroiliitis, spondylodiscitis and orchitis were recorded as the patients with organ involvement. After six weeks, the decline of the complaints was considered as a clinical response. In the 6th week of the treatment, it was observed that platelet distribution width (PDW) and mean platelet volume (MPV) levels were lower in patients with a clinical response compared to the patients with no clinical response which was statistically significant (p= 0.01, p= 0.02). Platelet and platelet lymphocyte ratio (PLR) level in patients with organ involvement in the 1st and 6th weeks of the treatment, were observed to be lower than the patients without organ involvement which was statistically significant (week 1: p= 0.001, p= 0.01; week 6: p= 0.03, p= 0.01). Among patients with organ involvement and non-organ involvement, the area under the curve was 66% in the ROC curve analysis for PLR at the onset of the treatment. When the cut-off value was taken as 128.8%, the sensitivity was 55%, and the specificity was 78%. Depending on the level of platelet at the beginning of the treatment, in the ROC curve analysis carried out among patients with organ involvement and non-organ involvement, the area under the curve was 73% and when the cut off value was taken as 256000, the sensitivity was 71%, and the specificity was 68%. In the 6th week of the treatment, the area under the curve was observed as 67% in the ROC curve analysis of the PDW level among patients from whom clinical responses were received and not received. When the cut-off value was taken as 10.75%, the sensitivity was 65%, and the specificity was 70%. In the ROC curve analysis of the MPV value for clinical response, the area under the curve was 66%, and when the cut-off value was taken as 9.95, the sensitivity was observed as 52%, and the specificity was 74%. As a result, in the evaluation of the clinical response, which is important in the termination of the treatment in patients with Brucellosis, the use of MPV and PDW values in the evaluation of organ involvement and platelet level and PLO in the follow up, are cheap, easily accessible biomarkers that can be used clinically.

Efficacy and safety of rituximab biosimilar in refractory lupus

AimsTo characterise patients with refractory SLE receiving rituximab biosimilar (CT-P10) and to explore short-term efficacy and safety associated with rituximab biosimilar use.MethodsWe retrospectively analysed data from the medical records of...

PREVALENCE AND CHARACTERISTICS OF HYPOTHYROIDISM AND ITS ASSOCIATION WITH NON-ORGAN RELATED MANIFESTATIONS IN US PATIENTS WITH SARCOIDOSIS

SESSION TITLE: Diffuse Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Little is known about the prevalence, clinical characteristics and impact of hypothyroidism in patients with sarcoidosis. We aimed to determine the prevalence rate and clinical features of hypothyroidism and its relation to organ involvement in patients with sarcoidosis. We also studied its association with non-organ manifestations in sarcoidosis patients. METHODS: We conducted a national registry-based study investigating 3,836 respondents to the Sarcoidosis Advanced Registry for Cures Questionnaire in the period between June 2014 and August 2019. This registry is based on a self-reported, web-based questionnaire that provides data related to demographics, diagnostics, sarcoidosis manifestations and treatment. We compared sarcoidosis patients with and without hypothyroidism. We used multivariable logistic regression and adjusted for gender, race, age at time of sarcoidosis diagnosis, use of steroids, multi-organ involvement and other sarcoidosis related comorbidities to determine the association of hypothyroidism with non-organ sarcoidosis manifestations. RESULTS: Fourteen-percent of the sarcoidosis patients had hypothyroidism and were generally middle-aged white women. Hypothyroidism presented with a cluster of other endocrine diseases and was more likely to be noted in sarcoidosis with multiorgan involvement, especially with cutaneous, ocular and musculoskeletal involvement. Sarcoidosis patients with hypothyroidism more frequently reported depression (29% vs 23%, p=0.003), obesity (26% vs 17%, p<0.001), sleep apnea (27% vs 18%, p<0.001), chronic fatigue (28% vs 18%, p<0.001) and fibromyalgia (18% vs 10%, p=0.049). On multivariable logistic regression analysis adjusting for potential confounders, hypothyroidism was associated with depression (adjusted odd ratio (aOR)= 1.3; 95% confidence interval (CI): 1.01-1.6), use of anti-depressants (aOR=1.3; CI: 1.1-1.7), obesity (aOR=1.5; CI:1.2-1.9), sleep apnea (aOR=1.8; CI:1.4-2.3), chronic fatigue syndrome (aOR=1.5; CI:1.1-1.9) and fibromyalgia (aOR=1.4; CI:1.01-1.8). Physical impairment was more common in patients with hypothyroidism. CONCLUSIONS: Hypothyroidism is a frequent comorbidity in sarcoidosis patients that might be a potentially reversible contributor to fatigue, depression and physical impairment in sarcoidosis. CLINICAL IMPLICATIONS: We recommend considering routine screening for hypothyroidism in sarcoidosis patients especially with multi-organ sarcoidosis, fatigue and depression. Future studies should assess the impact of treatment of hypothyroidism has on the non-organ related symptoms in patients with sarcoidosis DISCLOSURES: No relevant relationships by Tamara Al-Hakim, source=Web Response No relevant relationships by Bashar Alzghoul, source=Web Response Own stock relationship with American airline, United Airlines and Delta Airlines Please note: $1001 - $5000 Added 06/01/2020 by Bara Alzghoul, source=Web Response, value=Own stock No relevant relationships by Farah Amer, source=Web Response No relevant relationships by Chen Bai, source=Web Response No relevant relationships by Diana Gomez Manjarres, source=Web Response No relevant relationships by Ayoub Innabi, source=Web Response No relevant relationships by Mamoun Mardini, source=Web Response No relevant relationships by Divya Patel, source=Web Response No relevant relationships by Noopur Singh, source=Web Response

P169 Analysis of left ventricle dysfunction, pulmonary disease and nailfold videocapillaroscopy patterns in asymptomatic patients with early systemic sclerosis

Abstract Background Systemic sclerosis (SSc) is a multi-system connective tissue disease characterized by microvascular damage, inflammation and fibrosis. The aim of our study is to investigate a possible correlation between nailfold videocapillaroscopy patterns and internal organ involvement in patients with early SSc. Methods We enrolled 40 patients with early SSc according to LeRoy criteria and performed echocardiogram, pulmonary function tests (PFTs) and nailfold videocapillaroscopy. Results 20 patients had early pattern and 20 active pattern. A comparative analysis between SSc patients and healthy controls showed an alteration of mitral annular plane systolic excursion (MAPSE) (1.5±0.1 vs 1.7±0.1; p &amp;lt; 0.001), respectively; an increased occurrence of diastolic dysfunction (11/40 vs 0/21; p = 0.01) respectively; a higher values of systolic pulmonary arterial pression (PAPs) (32±6 vs 22±6; p &amp;lt; 0.001) and a higher frequency of patients with pulmonary hypertension (12/40 vs 0/21; p = 0.005) in SSc group. The patients with an active capillaroscopic pattern showed a trend of reduction in MAPSE, diastolic dysfunction, contractility of the right ventricle and pulmonary function tests parameters. We observed a correlation between myocardial and pulmonary vascular damage and between myocardial and pulmonary fibrosis, with lower DLCO value in patients with diastolic dysfunction (64±17 vs 85±9; p &amp;lt; 0.0001). Conclusion A subclinical myocardial damage in these patients may be observed also in the absence of symptoms. In fact, in our study it can be noted that asymptomatic patients present a reduction in the linear myocardial contractility. Furthermore, we observed the presence of grade I diastolic dysfunction in 27.5% of cases, a sign of an initial stiffening of the wall, likely due to a fibrotic damage. In our study linear contractility emerges to be not correlated with the presence of diastolic dysfunction. Such data is very intriguing if we consider that in many studies the resolution of linear contractility with conserved ejection fraction correlated with subendocardial damage induced by microcirculation alterations. The hypothesis is the presence of a double framework at the myocardial level: a vascular damage and the presence of increased inflammation and fibrosis. The presence fibrosis is correlated between the various organs, with the values of DLCO strongly correlating with the presence of diastolic dysfunction; instead DLCO values do not correlate with pulmonary pressure values. The analysis of the capillaroscopic parameters we observed how in the early pattern the presence of vascular damage with MAPSE and PAPs alterations and presence of pulmonary hypertension emerge, while passing from early to active the presence of fibrotic damage becomes evident, the diastolic dysfunction passing from 15% to 40% and DLCO passing from 83% to 75%. The presence of subclinical cardiac and pulmonary damage in patients with systemic sclerosis and that this damage is closely related to the capillaroscopic pattern. Disclosures F. Masini: None. L. Monaco: None. K. Gjeloshi: None. E. Pinotti: None. R. Ferrara: None. T. Salvatore: None. G. Cuomo: None.

Correlation between serological biomarkers of extracellular matrix turnover and lung fibrosis and pulmonary artery hypertension in patients with systemic sclerosis

To determine the value of serological biomarkers of collagen degradation/turnover as serum markers of organ involvement in patients with systemic sclerosis (SSc). Serum samples were obtained from 79 SSc patients and 19 healthy control subjects. Types I to VI collagen turnover, excluding type II collagen, were evaluated using nine serological biomarkers. Organ involvement, such as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), esophageal motility disorder, lower gastrointestinal lesions, joint contractures and digital ulceration, were evaluated and correlated with serum biomarkers. Among multiple serological biomarkers of collagen turnover, the mean level of C5M was higher in SSc (3.9ng/mL) than healthy subjects (2.6ng/mL). In addition, PRO-C6 (12.6ng/mL vs 5.4ng/mL) and C6M (26.0ng/mL vs 16.7ng/mL) were higher in SSc than the controls. The modified Rodnan skin score correlated with PRO-C3 and PRO-C6. Serum level of C6M was higher in patients with ILD. Furthermore, serum levels of PRO-C3, PRO-C6, and C6M were higher in patients with PAH. The use of high levels of these biomarkers as risk factors of PAH showed that all patients with PAH had high levels of risk factors. Of note, two-third of patients with serum PRO-C3, PRO-C6 and C6M values above the respective cut-off values had PAH. Our study indicated that collagen turnover abnormality, especially type VI collagen, is not only important pathologically in skin sclerosis but also in organ involvement. These biomarkers of collagen turnover are potentially clinically useful as biomarkers of organ involvement in SSc.

Frequency of systemic involvement in patients with acute dengue fever - the expanded dengue syndrome: A retrospective review from a tertiary care hospital in Karachi

Background: Dengue is globally the most common arboviral disease. As the primary immunopathological target in dengue is the endothelium, presentations beyond the typical triad of fever, myalgias, and thrombocytopenia are increasingly encountered. Severe systemic organ involvement can occur even without evidence of dengue hemorrhagic fever (DHF). These manifestations of dengue have been termed the “expanded dengue syndrome” by WHO. Aim: To observe the types and frequency of organ involvement in patients admitted with acute dengue fever. Methods: This is a retrospective cross-sectional study. Records of patients above 18 years admitted with acute dengue fever from December 2016 to December 2017 were reviewed. Patients fulfilling WHO criteria for probable or confirmed acute dengue fever were included. Patients with definite laboratory evidence of other systemic infections and patients with autoimmune or hematological disease were excluded. Data were obtained for 129 patients and analyzed using IBM-SPSS-21. Frequencies of clinical manifestations and organ involvement were noted. Results: Gastrointestinal manifestations occurred in 89% of patients. Transaminitis, organomegaly, and serositis were common. About 19% had pulmonary involvement, and 9% of patients had neurological features. Renal dysfunction, dyselectrolytemia, ophthalmic, muscular, and lymphoreticular abnormalities were also seen. Conclusion: Systemic involvement in dengue is not uncommon, and organ dysfunction can occur in the absence of severe DHF. Recognition of myriad range of organ involvement is crucial for optimal management.