International Consensus Diagnostic Criteria Research Articles

Neuromyelitis optica spectrum disorder. Clinical case

Background. Neuromyelitis optica spectrum disorder (NMOSD) has been masked under other diagnoses for many years. Modern diagnostic criteria expand diagnosis possibilities, but they need approbation in real clinical practice. The purpose was through the analysis of a clinical case and literature search to analyze the algorithm for making a diagnosis of neuromyelitis optica based on the new clinical guideline “Diagnosis and treatment of the neuromyelitis optica spectrum disorders” developed in 2023 in Ukraine, to identify marker signs that exclude alternative diagnoses, to analyze the effectiveness of patient treatment in dynamics. Materials and methods. We used the bibliosemantic method, as well as methods of systematic and comparative analysis. We presented the results of our own clinical experience and conducted a dynamic analysis of a clinical case of neuromyelitis optica. Results. Over the past six years, 23 patients diagnosed with neuromyelitis optica were treated at the neurological department of the Lviv Regional Clinical Hospital: 1 patient in 2018, 5 in 2019, 3 in 2020, 6 in 2021, 8 in 2022. We examined the clinical case of a 52-year-old patient who sought medical help at the Department of Neurology of Danylo Halytskyi Lviv National Medical University in 2023. We analyzed the patient’s path to the diagnosis of neuromyelitis optica with the dynamics of changes on magnetic resonance imaging from 2019, considering current diagnostic criteria in which neuromyelitis optica was included in the single term NMOSD. The presence of even one of the six main clinical manifestations, in combination with the presence of AQP4-IgG, gives grounds for making a diagnosis of NMOSD. We carried out a differential diagnosis with other pathologies. Based on this, we identified marker signs to exclude multiple sclerosis, acute disseminated encephalomyelitis, infectious myelitis, and other diseases. Diagnostic aspects of NMOSD and treatment options were considered. An analysis of the effectiveness of the patient’s treatment in dynamics was carried out. Conclusions. The new Ukrainian clinical guideline for neuromyelitis optica spectrum disorder, which is based on international consensus diagnostic criteria, improves the standardization of the approach to patients with NMOSD and can be effectively used in real clinical practice. In our clinical case of a patient with myelitis without optic neuritis, the presence of AQP4-IgG and careful differential diagnosis with other pathologies play a key role in the diagnosing.

Neuromyelitis Optica Spectrum Disorder (NMOSD) or Chronic-Relapsing Inflammatory Optic Neuropathy (CRION)?: A Challenge in Diagnosis and Treatment

Abstract
 Introduction : Neuromyelitis optica spectrum disorder (NMOSD) is a chronic inflammatory, immune-mediated central nervous system disease targeting the AQP4-water channel membrane protein of the optic nerve and the spinal cord. This case report aims to present a case of seroconverting NMOSD which was initially diagnosed as chronic relapsing inflammatory optic neuropathy (CRION).
 Case Illustration : 15-year-old female with recurrent, steroid-dependent optic neuritis of the LE. During the first attack, brain MRI showed optic nerve inflammation with normal brain findings. Initial test for AQP4-IgG, MOG-Ab and ANA profile were negative. The diagnosis of CRION was made. Treatment with corticosteroid and immunosuppressant agent was maintained for one year. After treatment cessation, however, LE optic neuritis recurred with bilateral lower limb weakness. Spinal MRI showed signs of longitudinal extensive transverse myelitis. Re-testing for AQP4-IgG showed positive result. Diagnosis of NMOSD was made, and the patient was treated with high-dose intravenous corticosteroid followed by oral dose, and immunosuppressant. Final visual acuity of the LE was 1.0, with minimal residual visual field defect and good motor function.
 Discussion : During the initial attack, the patient did not meet the 2015 NMOSD international consensus diagnostic criteria. The AQP4-IgG was negative and no other corresponding signs and symptoms. The criteria was met one year after: optic neuritis, LETM and positive seroconversion of AQP4-IgG.
 Conclusion : Diagnosing NMOSD is at times challenging especially during initial attack. Retesting of the AQP4- IgG is at times necessary in seronegative patients, especially in children showing ADEM-like event with optic neuritis and LETM to achieve diagnosis and proper treatment strategy.

Food Protein Induced Enterocolitis Syndrome in an Allergy Department: Adherence to International Consensus Diagnostic Criteria

Food Protein Induced Enterocolitis Syndrome in an Allergy Department: Adherence to International Consensus Diagnostic Criteria

The Clinical Picture of Castleman Disease: A Systemic Review and Meta-Analysis of Almost 2000 Patients

Background: Castleman disease (CD) encompasses a spectrum of rare disorders with characteristic histopathological features, including unicentric (UCD), idiopathic multicentric (iMCD) and cases that are associated with the human herpesvirus 8 (HHV8+ MCD). As treatment options for each type of CD vary, it is important to be able to distinguish their clinical presentation from their subtypes and determine the correct diagnosis. To our knowledge, there are no major review articles summarising the clinical features of different CD subtypes. The aim of this study was to describe and compare the clinical presentation of different CD subtypes reported in the literature. Methods: We performed a systematic review of publications reporting ≥5 cases of CD between 1995 and 2021, following the PRISMA guidelines. Publications were cross-checked by study location, data collection period and investigators to identify duplicated patients. Where a patient may have been included in >1 study, the publication with the fewest patients or least symptom data was excluded. For each subtype of CD within each study, we extracted data on demographics, clinical symptoms and laboratory parameters as stated in the international consensus diagnostic criteria for iMCD. We estimated the mean percentage of patients meeting each diagnostic criterion for each CD subtype using meta-analyses conducted with random-effects logistic regression models. Results: We analysed 32 studies with 1998 patients from 16 countries, including 559 UCD, 1023 iMCD and 416 HHV8+ MCD cases. There was a predominance of males not only in HHV8+ MCD (88.5% males) but also in iMCD (59.1% males). Patients with UCD tended to be younger than patients with iMCD and HHV8+ MCD. Most patients with iMCD (91.8%) and UCD (84.7%) were of Asian ethnicity. Only 58 patients (6.4%) with iMCD were White. In contrast, almost all patients with HHV8+ MCD (93.7%) were White or Black/African American. Many symptoms and laboratory abnormalities occurred at similar rates in patients with iMCD and HHV8+ MCD (Table 1). There were no significant differences in laboratory findings between patients with iMCD and HHV8+ MCD. However, compared with patients with HHV8+ MCD, patients with iMCD had significantly lower rates of constitutional symptoms (46.6% vs 98.6%, p=0.038) and splenomegaly (48.2% vs 89.2%, p=0.031). In contrast, renal dysfunction seemed to appear more commonly in iMCD (36.9% vs 17.4%, not statistically significant). Patients with UCD had significantly lower rates of laboratory abnormalities vs those with iMCD and HHV8+ MCD (p<0.05 for all parameters listed in Table 1). Except for cutaneous findings, patients with UCD had significantly lower rates of symptoms than patients with either iMCD or HHV8+ MCD (p<0.05 for all non-cutaneous parameters in Table 1). However, elevated C-reactive protein (CRP), anaemia and hypergammaglobulinaemia occurred in almost 20% of patients with UCD and pulmonary findings were observed in 15.3% of cases. We identified five additional publications including 88 paediatric patients with UCD. Paediatric patients with UCD had more signs of systemic inflammation than adult UCD patients. Elevated CRP was reported in 45.1% (95% CI 20.9-71.8, n=50) of paediatric UCD patients (vs 19.7% of adults [95% CI 11.2-30.9]). Constitutional symptoms were reported in 44.4% (95% CI 21.5-69.2, n=18) of patients - significantly higher than the rate reported in adult patients with UCD (4.5%, 95% CI 1.6-12.3; p=0.0005). Conclusions: This systematic review complements the diagnosis and management guidelines for iMCD and UCD and provides a detailed description of the clinical presentation of HHV8+ MCD. We found several distinct differences between iMCD and HHV8+ MCD, probably reflecting the heterogeneity of the underlying pathomechanisms and/or different comorbidity burdens of these CD subtypes. We confirmed that systemic symptoms may be present in up to 20% of patients with UCD. Whether these cases represent a distinct entity and whether intermediate CD cases require systemic therapy beyond surgery remains to be elucidated.

IgG4-related uveitis. A French cohort and literature review

IntroductionIgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder that can affect almost any organ. IgG4-related ophthalmic disease is a protean condition involving the orbit and ocular adnexa. Although a few cases of uveitis have been reported, the exact pattern of IgG4-related intraocular manifestations remains unclear. Here, we report on a nationwide French multicenter cohort of patients with IgG4-RD and uveitis and conducted a literature review. MethodsPatients with uveitis and a concomitant definite diagnosis of IgG4-RD (Revised Comprehensive Diagnostic criteria, American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-RD, International Consensus Diagnostic Criteria for auto-immune pancreatitis, or diagnostic criteria for IgG4-related hypophysitis), were screened from our national IgG4-RD and systemic fibrosis database. Concomitantly, we conducted a PubMed literature review and selected cases of definite IgG4-RD with uveitis. ResultsWe reported on 16 patients (8 from our database and 8 from the literature) and a total of 30 episodes of uveitis. Uveitis cases represented 3 % of total IgG4-RD patients in the national database on IgG4-RD and systemic fibrosis. Uveitis was inaugural in IgG4-RD in 4/16 cases (25 %) (appearing before any other IgG4-related symptom, at a median of 9 months), occurred concurrently to other IgG4-related symptoms in 9/16 cases (56 %) (at a median of 15 months before IgG4-RD diagnosis), and appeared during follow up in 3/16 patients (19 %) (at a median of 57 months after first IgG4-related symptoms). When uveitis occurred during follow up, it was associated with IgG4-RD manifestations in other organs in 6/9 patients (67 %). Uveitis was bilateral in 8/16 cases (50 %) and granulomatous in 5/10 cases (50 %). It was anterior in 8/13 (62 %), intermediate in 3/13 (23 %), and global (panuveitis) in 4/13 patients (31 %). Median serum IgG4 at diagnosis was 3.2 g/L. Median follow up time was of 6 years, during which 8/16 patients (50 %) experienced at least one relapse of uveitis. Treatment data was available for 29/30 uveitis flares. Steroids were used in 28/29 episodes of uveitis (97 %), leading to remission of uveitis in 16/28 cases (57 %). Methotrexate and rituximab (in combination with systemic steroids) were administered as second- or third-line therapy in 6/29 (21 %) and 5/29 (17 %) episodes of uveitis, respectively, and led to remission of uveitis in 4/6 cases (67 %) and 4/5 cases (80 %), respectively. One third of uveitides required at least two different lines of treatment for remission induction (mainly a combination of both systemic steroids and methotrexate or rituximab). Discussion and conclusionsUveitis may be one of the initial symptoms of IgG4-RD, and IgG4-RD should be considered in the diagnostic workup of uveitis. Its early onset in IgG4-RD may help with early diagnosis and treatment of the disease. Steroid monotherapy may be sufficient to treat IgG4-related uveitis, yet relapses were frequent (50 %) and ultimately a third of patients required at least two lines of treatment. Hence, steroid-sparing agents can be considered at early stages of the disease, particularly for patients with a high risk of relapse or steroid-related complications.

Autoimmune pancreatitis associated with inflammatory bowel diseases: A retrospectively bidirectional case-control study in China.

Autoimmune pancreatitis (AIP) is a rare and enigmatic immune-mediated inflammatory disease. We aimed to investigate the prevalence, characteristics, and associated factors of AIP-inflammatory bowel disease (IBD) in China. A retrospective bidirectional case-control study was performed. The diagnoses of IBD and AIP were made based on the European Crohn's and Colitis Organization guidelines and the International Consensus Diagnostic Criteria. IBD controls were matched by age, sex, and IBD type at a ratio of 1:4, while AIP controls were matched by AIP types. The age-standardized prevalence of AIP-IBD patients in the IBD and AIP population were 292.0 and 8151.93 per 100 000 population, respectively. IBD patients had a higher risk of AIP compared to non-IBD patients (odds ratio 8.4, 95% confidence interval 4.7-14.9, P < 0.0001), and AIP patients had a higher risk of developing IBD compared to the general population in China. The mean age at diagnosis of IBD and AIP was 34.83 years and 40.42 years. IBD was diagnosed before AIP in seven cases. The median total IBD and AIP duration was 43.5 months and 13.5 months. Use of mesalamine and tuberculosis were associated with AIP in IBD patients (P = 0.031). And fecal occult blood test was associated with IBD in AIP patients (P = 0.008). Most AIP-IBD patients had ulcerative colitis and type 2 AIP. IBD patients are more likely to develop AIP compared to the general population, and vice versa. Use of mesalamine and tuberculosis infection were associated with AIP, and fecal occult blood test was associated with IBD.

Etiology of Pancreatitis in Patients at a Tertiary Care Center

Objective: To compare etiological frequencies in patients of acute pancreatitis presenting to our setup with international data.&#x0D; Study Design: Cross-sectional study&#x0D; Place and Duration of Study: Department of Gastroenterology, Pakistan Emirates Military Hospital &amp; Combined Military Hospital, Rawalpindi Pakistan, from Aug 2020 to Jan 2022.&#x0D; Methodology: Patients over 12 years suffering from pancreatitis were recruited using a convenience sampling technique based upon predefined criteria for diagnosis of pancreatitis on a questionnaire. Relevant basic lab tests, including chemistries and imaging, including Ultrasound abdomen and CECT abdomen, were analyzed to establish aetiology. Data were continuously uploaded into an electronic data sheet. International Consensus Diagnostic Criteria (ICDC) algorithms were applied to diagnose autoimmune pancreatitis.&#x0D; Results: Out of 120 patients, 74(61.7%) were males, and 46(38.3%) were females. Biliary pancreatitis was the most common aetiology 50(41.7%), followed in descending order by idiopathic 36(30%), drug-induced pancreatitis (DIP) 9(7.5%), Post ERCP Pancreatitis (PEP) 8(6.7%), tumours 5(4%), Autoimmune pancreatitis (AIP), Hypertriglyceridemia and alcohol-induced pancreatitis each 2(1.7%).&#x0D; Conclusion: Biliary pancreatitis has the highest frequency, followed by idiopathic and drug-induced pancreatitis.

A Better Understanding of Pediatric Autoimmune Pancreatitis: Over 13 Years of Experience.

Pediatric autoimmune pancreatitis (P-AIP) is an uncommon disease whose diagnosis requires strong clinical suspicion. Late diagnosis increases morbidity. We aimed to compare the usefulness of the 2011 International Consensus Diagnostic Criteria (ICDC) for Autoimmune Pancreatitis with the 2018 INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE) criteria. We retrospectively analyzed demographics and clinical, laboratory, radiological, and histological findings at diagnosis and during long-term follow-up in children diagnosed with AIP in 2 tertiary hospitals between 2008 and 2021. We included 11 patients [6 girls; median age at diagnosis, 12.5 (range 2.8-15.7) years]. The most common symptom was abdominal pain. Pancreatic enzymes were elevated in 10 patients, and serum immunoglobulin G4 was elevated in 1. Magnetic resonance imaging showed enlargement of the pancreatic head in 10 patients and general pancreatic enlargement in 1. Pancreatic and papilla tissue were obtained from 9 patients. All patients received corticosteroids (prednisolone), and 4 also received azathioprine. According to the ICDC, all patients were classified as probable or non-otherwise specified AIP. According to INSPPIRE criteria, all patients were classified as AIP. Using the INSPPIRE criteria would have avoided biopsies in 6 patients who responded well to corticosteroids. The INSPPIRE criteria are useful. Using the ICDC in pediatric patients can delay diagnosis and result in unnecessary invasive tests.

An uncommon cause of pancreatitis with obstructive jaundice

A 56-year-old man with a history of diabetes mellitus poorly controlled recently (HbA1c: 7.5%, <6%) presented with a 3-month history of postprandial epigastric pain, 10-kg weight loss, steatorrhea, tea-colored urine, and clay-colored stool. Physical examination revealed yellowish skin and icteric sclera but no peripheral stigmata of cirrhosis. Laboratory investigation was significant for elevated aspartate aminotransferase (289 IU/L, 8-31 IU/L), alanine aminotransferase (613 IU/L, 0-41 IU/L), alkaline phosphatase (595 U/L, 34-104 U/L), γ-glutamyl transferase (758 U/L, 0-26 U/L), total and direct bilirubin (8.0/6.1 mg/dL, 0.3-1/0.03-0.18 mg/dL), and carbohydrate antigen 19-9 (289 U/mL, <37 U/mL). Contrast-enhanced computed tomography revealed diffuse enlargement of the pancreas (arrow) and dilatation of the common bile duct (CBD) without identifiable stone or a mass lesion (arrowhead; Figure 1A). Endoscopic ultrasound (EUS) demonstrated hyperechoic foci and strands in the enlarged pancreas (arrow) and layer-by-layer whole wall thickening with a hyper-hypo-hyperechoic series (sandwich pattern) of CBD (arrowhead) as well as gallbladder (star; Figure 1B). Magnetic resonance cholangiopancreatography (MRCP) showed dilated CBD with distal tapering near the pancreatic head (arrow; Figure 1C). The diagnosis of autoimmune pancreatitis was confirmed by serologic immunoglobulin G4 (IgG 4) elevation (IgG 4: 2880 mg/dL, 3-201 mg/dL) and favored type I according to nonductal Level 1/Level 2 criteria of international consensus diagnostic criteria.1 The patient recovered from jaundice and gained weight after treatment of prednisone 40 mg/d for 4 weeks, then taper by 5 mg/wk. The 8-week follow-up EUS demonstrated normalization of pancreatic size (arrow) and CBD morphology (arrowhead; Figure 2).2 Autoimmune pancreatitis mimicking pancreatic cancer is a rare cause of obstructive jaundice with an estimated incidence of 1 per 100 000.3 In summary, we demonstrated a case of autoimmune pancreatitis diagnosed by complement image study and elevating serum IgG 4, which achieved successful medical treatment of obstructive jaundice without further invasive procedures.1 The authors declare no conflict of interest. This report was approved by the Research Ethical Committee of Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (No. CR111-08).

The mortality burden of cachexia in patients with colorectal or pancreatic cancer: A systematic literature review.

87 Background: Cancer-associated cachexia is a multifactorial wasting disorder characterized by anorexia, unintentional weight loss (WL, skeletal muscle mass with or without loss of fat mass), progressive functional impairment, and poor prognosis. This systematic literature review (SLR) examined the relationship between cachexia and survival in patients with colorectal or pancreatic cancer. Methods: The SLR was conducted following PRISMA guidelines. Embase and PubMed were searched to identify articles published in English between 1 Jan 2016 and 10 Oct 2021 reporting survival in adults with cancer and cachexia or at risk of cachexia, defined by International Consensus (IC) diagnostic criteria (Fearon et al., Lancet Oncol 2011;12:489–95) or a broader definition of any WL. Included publications were of studies in ≥100 patients with colorectal or pancreatic cancer. Results: Twenty-six publications in patients with colorectal (n=13) or pancreatic cancer (n=13) met eligibility criteria. Included studies were observational and primarily from Europe and the United States. Eleven studies (42%) reported cachexia using IC criteria and 15 studies (58%) reported any WL. An association between survival and cachexia/WL was assessed across studies using multivariate (n=23) or univariate (n=3) analyses and within each study across multiple WL categories. Cachexia/WL was associated with a statistically significantly poorer survival in at least one WL category in 16 of 23 studies that used multivariate analyses and in 1 of 3 studies (33%) that used univariate analyses. Of the 17 studies demonstrating a significant association, 9 were in patients with colorectal cancer and 8 were in patients with pancreatic cancer. Conclusions: Cachexia/WL was associated with significantly poorer survival in patients with colorectal or pancreatic cancer in nearly two-thirds of the studies. The classification of WL varied across and within studies (multiple categories were evaluated) and may have contributed to variability. Nonetheless, awareness of cachexia and routine assessment of weight change in clinical practice in patients with colorectal or pancreatic cancer could inform early disease management strategies that may improve prognosis.

A Case of NMO Presenting with Hyperthyroidism

Neuromyelitis optica (NMO) is an autoimmune disease of central nervous system with extensive clinical presentations but based on the international consensus diagnostic criteria 2015. The horizon has broadened to a larger entity called NMOSD or NMO spectrum disorders. Nonneurological systemic autoimmune diseases especially thyroid disorders are commonly associated with NMOSD, among which Hashimoto’s thyroiditis is common, whereas not much literature is available regarding the association of Graves’ disease with NMOSD. A 38-year-old male presented with acute onset upper motor neuron quadriparesis along with features of hyperthyroidism with a prior history of sudden onset bilateral decreased vision of both eyes 3 years back. Magnetic resonance imaging (MRI) showed T2 hyperintensity involving cervicodorsal cord from C4 to D6 indicating a longitudinally extensive transverse myelitis (LETM) but brain MRI was normal. Serum antiaquaporin 4 antibody in the cell-based assay was positive. Serum thyroid stimulating hormone was very low with high free T4 and positive thyroid stimulating hormone receptor antibody and anti-thyroid peroxidase Ab. With optic neuritis, transverse myelitis (LETM), and positive antiaquaporin 4 antibody, he was diagnosed with NMO with Graves’ disease. Autoimmune thyroid diseases are associated with NMO in many studies but precise clinical and serological quantification of thyroid disorders especially Graves’ disease is still lacking. We are presenting a case of NMO with Graves’ disease who presented with symptoms of hyperthyroidism before myelitis. Our patient developed myelitis almost 3 years after having optic neuritis, but before myelitis, he was having symptoms of hyperthyroidism. Hence, patients of suspected NMO must be monitored for other nonneurological autoimmune diseases both clinically and serologically even in early stage when they are not fulfilling the diagnostic criteria.

Castleman's Disease:Clinicopathological Characteristics of a Cohort of Hispanic Patients

Introduction Castleman Disease (CD) depicts a group of heterogeneous hematologic disorders with characteristic histopathological features. Two forms of CD are recognized,unicentric (UCD) or multicentric (MCD). This classification relies on the number of regions of lymph node involvement. Objetives To describe the clinicopathological characteristics of a cohort of Hispanic patients with Castleman's Disease. Material Patients with CD diagnosis that were followed at the Monoclonal Gammopathies Clinic in INCMNSZ, from January 2006 to July 2022 were included.A team of pathologists that included a trained hematopathologist reviewed the biopsies, extended the immunohistochemical panel and classified the cases according to the International, evidence-based consensus diagnostic criteria for HHV8 negative/idiopathic MCD. Results Twenty-seven patients were included. The cases corresponded as follows:16 hyaline vascular/hypervascular variety (HV), 10 mixed variant (MV) and 1 plasma cell variant (PC). Cases were more frequently reclassified in MCD, particularly those with characteristic features of both HV and PC (Fig.1). Thirty-seven percent (10) were UCD and 63% (17) were MCD; median age at diagnosis was 37 years and 41 years, respectively; a difference in sex predominance was found, with 80 % of women in UCD and 76 % of men in MCD (p=0.018). In UCD the most frequent nodal areas affected were cervical in 40% (4) and mesenteric in 40% (4). Media nodal size was 7.1 cm (SD 3.5). Eighty percent (8) was HV variety and 20% VM. Successful surgical removal was performed in all cases, therefore none required chemo or radiotherapy. The group of MCD was distributed as follows: 59% (10) were idiopathic MCD (iMCD), 35% (6) were associated to POEMS syndrome and 6% (1) to HHV8. The 64% had involvement of 3-5 nodal regions. Fifty-nine percent (10) experienced B symptoms, fever was the most frequent; 70% presented fluid retention (5 edema, 3 pleural effusion and 4 ascites); 35% (6) experienced skin involvement. Hepatomegaly was present in 88% (15) and splenomegaly in 53% (9), mean 18.3 cm (SD 19.9% and 14.6 cm (SD 2), respectively. The treatment received by sixteen patients with MCD was: 63% (10) received rituximab, 19% as monotherapy (3), 19% with corticosteroids (3) and 25% (4) with CHOP-like chemotherapy. Thirty-seven percent (6) received only chemotherapy. Response to treatment was evaluable in 13 patients, 38% (5) achieved a complete response, 38% (5) a partial response, 15% (2) stable disease and one patient progressive disease. At 66 months follow-up, median overall survival and progression free survival (PFS) have not been reached. Estimated medians are 153.7 months and 107.7 months, respectively. Patients with MCD associated to POEMS Syndrome relapsed more frequently 83% (5) vs 17% (1) (p=0.005) (Fig. 2), therefore they received more cycles of treatment 7.5 vs 4.4 (p=0.016). None of the patients with UCM have relapsed. A univariate analysis showed a tendency towards rituximab to reduce relapse risk OR 0.125 (CI 95% 0.013 - 1.245), p=0.076. Uni and multivariate analysis revealed that the association to POEMS Syndrome increased relapse risk OR 50 (IC 95% 2.559 - 976), p=0.010 and OR 31.64 (IC 95% 1.48-676), p=0.027, respectively. Median PFS in this group was 53 months vs non reached in patients with iMCD or associated to HHV8 (p=0.031). Conclusions To our knowledge, this is the first series of CD cases in the Latin American population that includes a complete description of the clinical and histopathological characteristics with a reclassification of the same according to current diagnostic criteria. The revision of the cases, along with the extension of the immunohistochemical panel, and the application of the international evidence-based consensus diagnostic criteria for HHV8 negative/idiopathic multicentric Castleman disease derived in the reclassification of 11% of the cases and opposed to data reported in the literature, the MV corresponded to 20% of UCD and a predominance of cervical nodal involvement. This study has a longer median follow-up time, 66 months vs 59 months (UC) and 39 months (MCD) in one a series of cases in our country, which allows a better description of the outcomes. Progression-free survival was inferior in patients with MCD associated to POEMS Syndrome, median 53 months vs non reached (p = 0.031). The poor outcome of this association had not been previously described. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Clinical Pictures of Castleman Disease Subtypes - Do They Differ?

Background: Castleman disease (CD) encompasses a spectrum of rare disorders with characteristic histopathologic features. It is important to distinguish unicentric CD (UCD) from idiopathic multicentric CD (iMCD), and to identify MCD associated with human herpes virus 8 (HHV8-positive MCD). Diagnostic guidelines are available for both UCD and iMCD, but not for HHV8+MCD. The aim of this study was to compare the clinical presentations of these different CD subtypes. Methods: A systematic review was performed of all publications following the PRISMA guidelines to identify publications reporting on ≥5 patients with CD between 1995 and 2021. For each type of CD within each study, we extracted data on patients' demographics, clinical symptoms, and laboratory parameters, as stated in the 2017 international consensus diagnostic criteria for iMCD. As many of the included studies were published prior to these criteria and precise clinical and laboratory data were not reported, we extended the criteria to capture symptoms and laboratory parameters beyond the ranges defined in the consensus diagnostic criteria. We then estimated the mean percentage of patients meeting each diagnostic criterion for each CD subtype using meta-analyses conducted with random-effects logistic regression models to account for between-study heterogeneity. Results: A total of 47 studies were included in the analysis, including 32 studies (n=2055 patients) with aggregated cohort-level data and 15 studies (n=335 patients) with patient-level data. Not surprisingly, the aggregated cohort-level data showed that patients with UCD had lower rates of symptoms and laboratory abnormalities than those with iMCD and HHV8+MCD. Many symptoms and laboratory abnormalities occurred at similar rates in patients with iMCD and HHV8+MCD. However, renal dysfunction and potentially hypoalbuminemia were more common among patients with iMCD versus HHV8+MCD, while constitutional symptoms and hepatosplenomegaly were less frequent (Table 1). Analysis of patient-level data largely confirmed these findings. Conclusions: This systematic review revealed that some systemic symptoms may be present in patients with UCD. We found many similarities among the clinical presentations and laboratory findings in patients with iMCD and HHV8+MCD, but also some important differences. These differences probably reflect the heterogeneity of the underlying pathophysiology and/or the different comorbidity burdens of these MCD subtypes. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Analysis of Neuromyelitis Optica Spectrum Disorder in an Indian Cohort using International Consensus Diagnostic Criteria.

Updates on clinical, investigatory, and therapeutic aspects of neuromyelitis optica (NMO) spectrum disorders are rapidly evolving. Recently published international consensus diagnostic criteria (ICDC) allowed clinicians to rapidly diagnose the expanding spectrum of NMO spectrum disorders more accurately. The aim of the study was to retrospectively analyze 36 consecutive cases of comprehensively evaluated NMO spectrum disorders using the ICDC. We retrospectively collected 36 cases of NMO spectrum disorders who attended our unit between August 2012 andOctober 2016 and fulfilled the ICDC. All patients underwent magnetic resonance imaging (MRI) of the brain and whole spine with contrast, anti-aquaporin 4 antibody, and detailed blood investigations to rule out systemic vasculitis and other alternate diagnoses. Female-to-male ratio was 6.2:1; 50% of the cases were in the 20-40-year age group. Six patients (16.67%) had combined optic neuritis and myelitis.Nine patients (25%) had pure longitudinally extending transverse myelitis LETM with positive anti aquaporin 4 antibody AQ4Ab. Fourteen patients (38.9%) had myelitis and optic neuritis separately. Nine patients (25%) had area postrema syndrome. Two patients (5.6%) had acute brainstem syndrome and one (2.8%) had hypothalamic syndrome. LETM was commonly found in the cervical level (69.4%).Four patients (11.1%) had no spinal cord involvement. Anti-aquaporin 4 antibody was positive only in 23 cases (63.9%). Initial presentation of NMO spectrum disorder is often due to brain lesions. The ICDC criteria have enhanced clinician's ability to diagnose NMO spectrum disorder in the early stages. In our study, ICDC criteria helped us to diagnose 33% additional cases that would have been missed if the old 2006 revised criteria was applied.

Utility of Endoscopic Ultrasound-Guided Fine-Needle Aspiration and Biopsy for Histological Diagnosis of Type 2 Autoimmune Pancreatitis.

In Japan, type 1 autoimmune pancreatitis (AIP) is the most common type of AIP; type 2 AIP is rare. The aim of this study was to clarify the usefulness of endoscopic ultrasound-guided fine-needle aspiration and biopsy (EUS-FNAB) for the diagnosis of type 2 AIP. We analyzed the tissue specimens of 10 patients with suspected type 2 AIP who underwent EUS-FNAB at our hospital between April 2009 and March 2021 for tissue volume and histopathological diagnostic performance. The male-to-female ratio of the patients was 8:2, and the patient age (mean ± standard deviation) was 35.6 ± 15.5 years. EUS-FNAB provided sufficient tissue volume, with high-power field >10 in eight patients (80.0%). Based on the International Consensus Diagnostic Criteria (ICDC), four patients (40.0%) had histological findings corresponding to ICDC level 1, and five patients (50.0%) had histological findings corresponding to ICDC level 2. The results of this study show that EUS-FNB can be considered an alternative method to resection and core-needle biopsy for the collection of tissue samples of type 2 AIP.

1616P The mortality burden of cachexia in patients with non-small cell lung cancer: A systematic literature review

Cancer-associated cachexia is a multifactorial wasting disorder that includes anorexia, involuntary weight loss (WL) and decreased skeletal muscle mass, and is an indicator of poor prognosis. As such, international consensus (IC) diagnostic criteria for cancer cachexia have been proposed (Fearon et al., Lancet Oncol 2011;12:489–95). This systematic literature review (SLR) examined the relationship between cachexia and survival in patients with non-small-cell lung cancer (NSCLC). The SLR was conducted following PRISMA guidelines. Embase® and PubMed were searched to identify articles published in English between 1 Jan 2016 and 10 Oct 2021 reporting survival in adults with cancer and cachexia or at risk of cachexia, as defined by IC criteria or a broader definition of any WL. Included publications were of randomized/non-randomized clinical trials and retrospective/prospective observational studies in ≥100 patients with NSCLC. Forty-two publications in patients with NSCLC met eligibility criteria (41 observational studies; 1 pooled analysis of clinical trials). Included studies were primarily from Europe (40%), Asia (21%) or the United States (19%). Twelve studies (29%) reported cachexia using IC criteria and 30 studies reported either any WL or WL >5%. Four studies reported prevalence of cachexia, which ranged from 5.3% to 48.1%. Thirty-one studies reported prevalence of any WL; of these, 16 studies reported prevalence of WL ≥5% (prevalence range: 7.4%–58.9%). An association between survival and cachexia/WL was assessed across 41 studies that used multivariate (n=34) or univariate (n=7) analyses. Cachexia/WL was associated with a statistically significantly poorer survival in 30 of 34 studies (88.2%) that used multivariate analyses. This SLR found that less than a third of studies used the IC criteria to identify cachexia in the context of NSCLC. Nonetheless, cachexia/WL was associated with significantly poorer survival in these patients. An awareness of cachexia in NSCLC would allow early implementation of disease management strategies that may improve prognosis in these patients.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is the most recently defined inflammatory demyelinating disease of the central nervous system (CNS). Over the last decade, several studies have helped delineate the characteristic clinical-MRI phenotypes of the disease, allowing distinction from aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) and multiple sclerosis (MS). The clinical manifestations of MOGAD are heterogeneous, ranging from isolated optic neuritis or myelitis to multifocal CNS demyelination often in the form of acute disseminated encephalomyelitis (ADEM), or cortical encephalitis. A relapsing course is observed in approximately 50% of patients. Characteristic MRI features have been described that increase the diagnostic suspicion (e.g., perineural optic nerve enhancement, spinal cord H-sign, T2-lesion resolution over time) and help discriminate from MS and AQP4+NMOSD, despite some overlap. The detection of MOG-IgG in the serum (and sometimes CSF) confirms the diagnosis in patients with compatible clinical-MRI phenotypes, but false positive results are occasionally encountered, especially with indiscriminate testing of large unselected populations. The type of cell-based assay used to evaluate for MOG-IgG (fixed vs. live) and antibody end-titer (low vs. high) can influence the likelihood of MOGAD diagnosis. International consensus diagnostic criteria for MOGAD are currently being compiled and will assist in clinical diagnosis and be useful for enrolment in clinical trials. Although randomized controlled trials are lacking, MOGAD acute attacks appear to be very responsive to high dose steroids and plasma exchange may be considered in refractory cases. Attack-prevention treatments also lack class-I data and empiric maintenance treatment is generally reserved for relapsing cases or patients with severe residual disability after the presenting attack. A variety of empiric steroid-sparing immunosuppressants can be considered and may be efficacious based on retrospective or prospective observational studies but prospective randomized placebo-controlled trials are needed to better guide treatment. In summary, this article will review our rapidly evolving understanding of MOGAD diagnosis and management.

Unraveling the relationship between autoimmune pancreatitis type 2 and inflammatory bowel disease: Results from two centers and systematic review of the literature.

IntroductionThe relationship between autoimmune pancreatitis (AIP) type 2 and inflammatory bowel disease (IBD) has been established and previously described within International Consensus Diagnostic Criteria. However, it is unknown if the presence of IBD changes the natural disease course of AIP type 2. Our aim was to investigate the association between AIP type 2 and IBD as well as to systematically summarize all the existing evidence in the literature.MethodsElectronic medical record analysis was conducted in two centers (in Stockholm, Sweden, and Milan, Italy; records dated between January 2001 and June 2021). Additionally, we conducted a systematic review of the literature.ResultsA total of 35 patients (18 females, 51.4%) fulfilled the diagnostic criteria of AIP type 2 and were included in the study. A diagnosis of IBD was established in 29 patients (82.8%), ulcerative colitis in 17 (58.6%) and Crohn's disease in 11 (37.9%). Median follow‐up was 54 months. AIP patients with IBD commonly presented with abdominal pain and/or acute pancreatitis at diagnosis, the latter was prevailing in concomitant and later IBD onset. These patients more frequently used steroids, but there were no differences in relapse rates. Concomitant onset of IBD was associated with the development of diabetes mellitus. There were no cases of colon or pancreatic malignancy during follow‐up. In our systematic analysis, a total of 693 AIP type 2 patients were included from 24 single‐center retrospective studies and 8 multicenter retrospective studies. A diagnosis of IBD was reported in 330 (47.8%) patients. Relapse rate was 20.0%.ConclusionsClinical and radiological remission of AIP type 2 was high, while the cumulative incidence of relapse is around 20%. Our results show that concomitance of IBD imposes no obvious risk of a different disease course for AIP type 2.

HLA-DRB1∗16 and -DQB1∗05 alleles are strongly associated with autoimmune pancreatitis in a cohort of hundred patients

Background/objectivesAutoimmune diseases are often associated with human leukocyte antigen (HLA) haplotypes, indicating that changes in major histocompatibility complex (MHC)-dependent self-peptide or antigen presentation contribute to autoimmunity. In our study, we aimed to investigate HLA alleles in a large European cohort of autoimmune pancreatitis (AIP) patients. MethodsHundred patients with AIP, diagnosed and classified according to the International Consensus Diagnostic Criteria (ICDC), were prospectively enrolled in the study. Forty-four patients with chronic pancreatitis (CP) and 254 healthy subjects served as control groups. DNA was isolated from blood samples and two-digit HLA typing was performed with sequence-specific primer (SSP-) PCR. HLA allele association strength to AIP was calculated as odds ratio. ResultsWe uncovered a strong enrichment of HLA-DQB1 homozygosity in type 1 and type 2 AIP patients. Moreover, a significantly increased incidence of the HLA-DRB1∗16 and HLA-DQB1∗05 alleles and a concomitant lack of the HLA-DRB1∗13 allele was detected in AIP type 1 and type 2 patients. In contrast, the HLA-DQB1∗02 allele was underrepresented in the ‘not otherwise specified’ (NOS) AIP subtype. We detected no significant difference in the HLA-DRB3, HLA-DRB4 and HLA-DRB5 allele frequency in our cohort. ConclusionsAlthough AIP type 1 and type 2 are characterized by distinct histopathological characteristics, both subtypes are associated with the same HLA alleles, indicating that the disease might rely on similar immunogenic mechanisms. However, AIP NOS represented another subclass of AIP.

The Clinical Phenotype of Chinese Patients With Autoimmune Pancreatitis Differs Significantly From Western Patients

AimTo characterize the clinical features of autoimmune pancreatitis (AIP) in China and compare differences between our Chinese cohort and Western cohorts.MethodsThis was a retrospective study of patients with AIP that was carried out in the China-Japan Friendship Hospital between January 2010 and April 2021. We included a total of 50 patients (46 males and 4 females) aged between 27 and 86 years who fulfilled the international Consensus Diagnostic (ICD) Criteria. For comparative purposes, we included data from seven representative Western cohorts.ResultWhen comparing Chinese and Western patients, we found that obstructive jaundice was the most frequent initial symptom (68 vs. 43%, P < 0.001). Extra-pancreatic organ involvement was more common in Chinese patients (68 vs. 30%, P < 0.001). Sclerosing cholangitis was the most frequent extrapancreatic lesion (48 vs. 24%, P = 0.001). The elevation of serum IgG4 was more obvious in our cohort (86 vs. 49%, P < 0.001). Conversely, the rates of ANA-positivity were significantly higher in Western populations (17 vs. 50%, P = 0.006). With regards to imaging, diffuse swelling was significantly more common in China (44 vs. 27%, P = 0.021). Steroid therapy was used more frequently in our Chinese patients (84 vs. 59%, P = 0.001). The steroid-response rate was also significantly higher in our Chinese patients (85 vs. 54%, P = 0.001); However, the rate of resection was higher in Western cohorts (2 vs. 31%, P < 0.001). There was no significant difference between the two populations with regards to recurrence rate (33 vs. 33%, P = 1.000).ConclusionThis study identified significant differences between Chinese and Western populations of patients with AIP. Within the Chinese population, AIP was more likely to have jaundice and extra-pancreatic organ involvement, and elevated serum IgG4 levels. Chinese patients were also showed favorable responses to treatment with glucocorticoids.