Johannes Nowatzky

All Publications

• Uveitis as a Correlate of Systemic Manifestations in Patients Diagnosed with Behçet's Disease. Ocular immunology and inflammation Shah, S. V., Wai, K. M., Mruthyunjaya, P., Nowatzky, J., Rahimy, E. 2026: 1-8

  Abstract

  Uveitis is common in Behçet's disease (BD), but risk stratification of potentially severe systemic disease by ocular involvement is still impossible. Here, we aimed to determine whether the risk for systemic manifestations of BD in Patients Diagnosed with Behçet's Disease (PDBD) depended on the presence of intra-ocular inflammation in one of the largest global health research networks.Screening > 150 million Electronic Medical Records (EMR), we compared subjects whose ICD-10 codes selected them as PDBD with or without a BD uveitis-reconcilable coding pattern. Outcomes included relative risk for systemic BD manifestations after diagnosis, likelihood of inpatient consultations, and probability of systemic manifestations over time.3474 subjects met inclusion criteria, with 458 in the ocular cohort. Ocular PDBD had more than a two-fold risk of skin and vascular manifestations than non-ocular PDBD, increased risk for musculoskeletal and central nervous system manifestations, was twice as likely to receive inpatient consultations when hospitalized and showed a much shorter median time to extraocular systemic disease onset (413 days) than non-ocular PDBD (1729 days). The risk for genital lesions and the time to initial diagnosis were similar between the groups.Within the constraints of an EMR-based study, our results indicate a significantly higher risk for extraocular manifestations and an overall more severe disease course for PDBD with uveitis than for those without. Our findings provide rationale for confirmation in cohorts outside of big data and justify an intensified multidisciplinary clinical approach to ocular PDBD to prevent, detect, and treat the associated systemic disease.

  View details for DOI 10.1080/09273948.2026.2735409

  View details for PubMedID 42848921

• Severe Paraneoplastic Anterior and Posterior Scleritis Associated with Myelodysplastic Syndrome. Ocular immunology and inflammation Mehta, P., Apte, A., Sheth, N., Cobbs, L., Mehta, N., Kaden, T., Dedania, V. S., Weseley, P., Wald, K., Nowatzky, J., Francis, J., Modi, Y. 2026: 1-9

  Abstract

  PURPOSE: To describe a rare case of severe anterior and posterior scleritis that led to a diagnosis of high-risk myelodysplastic syndrome.METHODS: We present a case report along with a literature review on cases of paraneoplastic scleritis to highlight commonalities in etiology, presentation, treatment response, and outcomes.RESULTS: A 59-year-old male presented with a severe case of unilateral anterior and posterior scleritis with ciliochoroidal detachment and secondary angle closure. His workup revealed severe macrocytic anemia and thrombocytopenia. A subsequent bone marrow biopsy demonstrated cytogenetic analysis consistent with high-risk myelodysplastic syndrome (MDS). The patient was started on high-dose prednisone but was unable to be tapered below 30 mg without recurrence. Rituximab infusions were initiated followed by resolution of ocular symptoms and a successful taper of prednisone. He initiated chemotherapy and was to receive allogenic bone marrow transplantation. However, while on chemotherapy, he clinically deteriorated and passed away.CONCLUSION: This case of severe scleritis was suspected to be a paraneoplastic syndrome secondary to myelodysplastic syndrome. Paraneoplastic syndromes represent a rare etiology of scleritis. Patients with hematologic abnormalities such as unexplained cytopenias, severe manifestations at presentation, or steroid refractory scleritis may warrant comprehensive evaluation for malignancy, expedited systemic workup with attention to blood counts, and interdisciplinary collaboration between ophthalmology, hematology, and internal medicine. If an underlying malignancy is identified, definitive treatment of the scleritis involves treatment of the cancer.

  View details for DOI 10.1080/09273948.2026.2689365

  View details for PubMedID 42417824

• Omics studies in Behçet's disease. Current opinion in rheumatology Ozguler, Y., Nowatzky, J. 2025; 37 (1): 15-20

  Abstract

  In this review, we aimed to highlight recent findings from "-omics" studies in Behçet's disease.Recent genomic studies in Behçet's disease identified possible risk loci associated with Behçet's disease related uveitis, neurologic involvement and gastrointestinal involvement. Additionally, sex-specific genetic effects were determined in Behçet's disease. Transcriptomic analyses of immune cells in Behçet's disease revealed that key inflammatory pathways such as NF-κB and MAPK have roles in Behçet's disease pathogenesis. Proteomic studies have highlighted the role of immune cell derived extracellular vesicles and identified potential biomarkers for vascular involvement and examined HLA I-bound immunopeptidomes. Metabolomics studies are still limited, but recent research has pointed to alterations in fatty acid metabolism and lipid profiles in Behçet's disease patient.Omics studies have gained importance in the field of Behçet's disease through the generation of large data sets and efforts to extend their application are intensifying. These studies can provide opportunities for understanding Behçet's disease pathogenesis when they lead to testable hypotheses. Current challenges include the choice of appropriately homogeneous patient and control groups, effective data management and sharing, high cost and a rapidly increasing gap between the wealth of observational data generated and the relative paucity of controlled experimental efforts that could lead to mechanistic understanding.

  View details for DOI 10.1097/BOR.0000000000001067

  View details for PubMedID 39513387

• Biology of HLA class I associated inflammatory diseases. Best practice & research. Clinical rheumatology Bordbar, A., Manches, O., Nowatzky, J. 2024; 38 (2): 101977

  Abstract

  Human leukocyte antigen (HLA) class I association is a well-established feature of common and uncommon inflammatory diseases, but it is unknown whether it impacts the pathogenesis of these disorders. The "arthritogenic peptide" hypothesis proposed initially for HLA-B27-associated ankylosing spondylitis (AS) seems the most intuitive to serve as a model for other HLA class I-associated diseases, but evidence supporting it has been scarce. Recent technological advances and the discovery of epistatic relationships between disease-associated HLA class I and endoplasmic reticulum aminopeptidase (ERAP) coding variants have led to the generation of new data and conceptual approaches to the problem requiring its re-examination. Continued success in these endeavors holds promise to resolve a Gordian Knot in human immunobiology. It may ultimately benefit patients by enabling the development of new therapies and precision tools for assessing disease risk and predicting treatment responses.

  View details for DOI 10.1016/j.berh.2024.101977

  View details for PubMedID 39085016

  View details for PubMedCentralID PMC11441793

• How to recognise a Behçet's ulcer from other types of oral ulceration? Defining Behçet's ulceration by an International Delphi Consultation. Clinical and experimental rheumatology Poveda-Gallego, A., Chapple, I., Iacucci, M., Hamburger, J., Murray, P. I., Rauz, S., Wallace, G. R. 2023; 41 (10): 2048-2055

  Abstract

  To define the clinical characteristics of oral ulceration (OU) in Behçet's disease (BD), to allow differentiation from other causes of OU, including aphthous ulcers, by an International Delphi consultation. To develop a clinical guideline on how to recognise BD ulcers.Round 1. 40 clinical images of OU in BD, recurrent aphthous stomatitis (RAS), inflammatory bowel disease (IBD) and mucous membrane pemphigoid (MMP) were shown. Participants answered, independently, which images would be consistent with a BD ulcer. Round 2. The results from marking independently were shown. The panel remarked the questions through iteration process. The images not agreed to be a possible BD ulcer were discarded. Round 3. 10 clinical descriptors that may define BD ulcers were suggested. Participants ranked the level of importance for each descriptor on each image presented. Round 4. Participants re-ranked their level of agreement for each descriptor through iteration process. Whether the clinical pictures would be different from RAS was also explored. A final agreement was reached.This study has shown clear differentiation between BD, IBD and MMP ulcers when defining them by phenotype through clinical images only. On the other hand, no differentiation between RAS and BD ulcers was found. The most important clinical descriptors that define BD ulcers have been agreed.New clinical guidance for Health Care Professionals (HCP) on how to recognise a BD ulcer has been proposed. This should elucidate an earlier diagnosis, quicker access to treatment and control of the disease enhancing patient's quality of life.

  View details for DOI 10.55563/clinexprheumatol/joeacu

  View details for PubMedID 37902271

• Immunopathogenesis of Behçet's disease. Clinical immunology (Orlando, Fla.) Al-Obeidi, A. F., Nowatzky, J. 2023; 253: 109661

  Abstract

  Behçet's disease (BD) is a multi-system inflammatory disorder with vasculitic features. It does not suit any of the current pathogenesis-driven disease classifications well, a unifying concept of its pathogenesis is not unanimously conceivable at present, and its etiology is obscure. Still, evidence from immunogenetic and other studies supports the notion of a complex-polygenic disease with robust innate effector responses, reconstitution of regulatory T cells upon successful treatment, and first clues to the role of an, as of yet, underexplored adaptive immune system and its antigen recognition receptors. Without an attempt to be comprehensive, this review aims to collect and organize impactful parts of this evidence in a way that allows the reader to appreciate the work done and define the efforts needed now. The focus is on literature and notions that drove the field into new directions, whether recent or more remote.

  View details for DOI 10.1016/j.clim.2023.109661

  View details for PubMedID 37295542

  View details for PubMedCentralID PMC10484394

• EULAR study group on 'MHC-I-opathy': identifying disease-overarching mechanisms across disciplines and borders. Annals of the rheumatic diseases Kuiper, J. J., Prinz, J. C., Stratikos, E., Kuśnierczyk, P., Arakawa, A., Springer, S., Mintoff, D., Padjen, I., Shumnalieva, R., Vural, S., Kötter, I., van de Sande, M. G., Boyvat, A., de Boer, J. H., Bertsias, G., de Vries, N., Krieckaert, C. L., Leal, I., Vidovič Valentinčič, N., Tugal-Tutkun, I., El Khaldi Ahanach, H., Costantino, F., Glatigny, S., Mrazovac Zimak, D., Lötscher, F., Kerstens, F. G., Bakula, M., Viera Sousa, E., Böhm, P., Bosman, K., Kenna, T. J., Powis, S. J., Breban, M., Gul, A., Bowes, J., Lories, R. J., Nowatzky, J., Wolbink, G. J., McGonagle, D. G., Turkstra, F. 2023; 82 (7): 887-896

  Abstract

  The 'MHC-I (major histocompatibility complex class I)-opathy' concept describes a family of inflammatory conditions with overlapping clinical manifestations and a strong genetic link to the MHC-I antigen presentation pathway. Classical MHC-I-opathies such as spondyloarthritis, Behçet's disease, psoriasis and birdshot uveitis are widely recognised for their strong association with certain MHC-I alleles and gene variants of the antigen processing aminopeptidases ERAP1 and ERAP2 that implicates altered MHC-I peptide presentation to CD8+T cells in the pathogenesis. Progress in understanding the cause and treatment of these disorders is hampered by patient phenotypic heterogeneity and lack of systematic investigation of the MHC-I pathway.Here, we discuss new insights into the biology of MHC-I-opathies that strongly advocate for disease-overarching and integrated molecular and clinical investigation to decipher underlying disease mechanisms. Because this requires transformative multidisciplinary collaboration, we introduce the EULAR study group on MHC-I-opathies to unite clinical expertise in rheumatology, dermatology and ophthalmology, with fundamental and translational researchers from multiple disciplines such as immunology, genomics and proteomics, alongside patient partners. We prioritise standardisation of disease phenotypes and scientific nomenclature and propose interdisciplinary genetic and translational studies to exploit emerging therapeutic strategies to understand MHC-I-mediated disease mechanisms. These collaborative efforts are required to address outstanding questions in the etiopathogenesis of MHC-I-opathies towards improving patient treatment and prognostication.

  View details for DOI 10.1136/ard-2022-222852

  View details for PubMedID 36987655

  View details for PubMedCentralID PMC10313995

• Inflammatory eye disease for rheumatologists. Current opinion in rheumatology Corbitt, K., Nowatzky, J. 2023; 35 (3): 201-212

  Abstract

  This review provides a framework for understanding inflammatory eye disease diagnosis, differential diagnosis, and management for rheumatologists. Uveitis, scleritis, episcleritis, peripheral ulcerative keratitis, and orbital inflammation are all discussed. The goal is to facilitate the development of approaches to inflammatory eye diseases that will help rheumatologists co-manage these patients with eye care providers specializing in ocular inflammation.In recent years, studies have aimed to advance biologic treatments and define standard-of-care therapy. Inflammatory eye diseases are highly heterogeneous and often rare, which poses significant challenges to their research and the interpretation of existing data. To date, glucocorticoids, mycophenolate, methotrexate, and TNF inhibitors remain the mainstay of treatment options for many of these diseases.Patients with inflammatory eye diseases require multidisciplinary care for best outcomes, frequently including rheumatologists. Understanding the differentials, diagnostics, and treatment are essential to preserving vision in these patients. The diverse nature of the disease processes within this field requires focusing on specific disease phenotypes and endotypes in research and clinical practice.

  View details for DOI 10.1097/BOR.0000000000000933

  View details for PubMedID 36943695

  View details for PubMedCentralID PMC10461883

• Hedgehog and Platelet-derived Growth Factor Signaling Intersect during Postnatal Lung Development. American journal of respiratory cell and molecular biology Yie, T. A., Loomis, C. A., Nowatzky, J., Khodadadi-Jamayran, A., Lin, Z., Cammer, M., Barnett, C., Mezzano, V., Alu, M., Novick, J. A., Munger, J. S., Kugler, M. C. 2023; 68 (5): 523-536

  Abstract

  Normal lung development critically depends on HH (Hedgehog) and PDGF (platelet-derived growth factor) signaling, which coordinate mesenchymal differentiation and proliferation. PDGF signaling is required for postnatal alveolar septum formation by myofibroblasts. Recently, we demonstrated a requirement for HH in postnatal lung development involving alveolar myofibroblast differentiation. Given shared features of HH signaling and PDGF signaling and their impact on this key cell type, we sought to clarify their relationship during murine postnatal lung development. Timed experiments revealed that HH inhibition phenocopies the key lung myofibroblast phenotypes of Pdgfa (platelet-derived growth factor subunit A) and Pdgfra (platelet-derived growth factor receptor alpha) knockouts during secondary alveolar septation. Using a dual signaling reporter, Gli1lZ;PdgfraEGFP, we show that HH and PDGF pathway intermediates are concurrently expressed during alveolar septal myofibroblast accumulation, suggesting pathway convergence in the generation of lung myofibroblasts. Consistent with this hypothesis, HH inhibition reduces Pdgfra expression and diminishes the number of Pdgfra-positive and Pdgfra-lineage cells in postnatal lungs. Bulk RNA sequencing data of Pdgfra-expressing cells from Postnatal Day 8 (P8) lungs show that HH inhibition alters the expression not only of well-established HH targets but also of several putative PDGF target genes. This, together with the presence of Gli-binding sites in PDGF target genes, suggests HH input into PDGF signaling. We identified these HH/PDGF targets in several postnatal lung mesenchymal cell populations, including myofibroblasts, using single-cell transcriptomic analysis. Collectively, our data indicate that HH signaling and PDGF signaling intersect to support myofibroblast/fibroblast function during secondary alveolar septum formation. Moreover, they provide a molecular foundation relevant to perinatal lung diseases associated with impaired alveolarization.

  View details for DOI 10.1165/rcmb.2022-0269OC

  View details for PubMedID 36693140

  View details for PubMedCentralID PMC10174164

• Behçet's disease risk-variant HLA-B51/ERAP1-Hap10 alters human CD8 T cell immunity. Annals of the rheumatic diseases Cavers, A., Kugler, M. C., Ozguler, Y., Al-Obeidi, A. F., Hatemi, G., Ueberheide, B. M., Ucar, D., Manches, O., Nowatzky, J. 2022; 81 (11): 1603-1611

  Abstract

  The endoplasmic reticulum aminopeptidase (ERAP1) haplotype Hap10 encodes for a variant allotype of the endoplasmic reticulum (ER)-resident peptide-trimming aminopeptidase ERAP1 with low enzymatic activity. This haplotype recessively confers the highest risk for Behçet's diseases (BD) currently known, but only in carriers of HLA-B*51, the classical risk factor for the disease. The mechanistic implications and biological consequences of this epistatic relationship are unknown. Here, we aimed to determine its biological relevance and functional impact.We genotyped and immune phenotyped a cohort of 26 untreated Turkish BD subjects and 22 healthy donors, generated CRISPR-Cas9 ERAP1 KOs from HLA-B*51 + LCL, analysed the HLA class I-bound peptidome for peptide length differences and assessed immunogenicity of genome-edited cells in CD8 T cell co-culture systems.Allele frequencies of ERAP1-Hap10 were similar to previous studies. There were frequency shifts between antigen-experienced and naïve CD8 T cell populations of carriers and non-carriers of ERAP1-Hap10 in an HLA-B*51 background. ERAP1 KO cells showed peptidomes with longer peptides above 9mer and significant differences in their ability to stimulate alloreactive CD8 T cells compared with wild-type control cells.We demonstrate that hypoactive ERAP1 changes immunogenicity to CD8 T cells, mediated by an HLA class I peptidome with undertrimmed peptides. Naïve/effector CD8 T cell shifts in affected carriers provide evidence of the biological relevance of ERAP1-Hap10/HLA-B*51 at the cellular level and point to an HLA-B51-restricted process. Our findings suggest that variant ERAP1-Hap10 partakes in BD pathogenesis by generating HLA-B51-restricted peptides, causing a change in immunodominance of the ensuing CD8 T cell response.

  View details for DOI 10.1136/ard-2022-222277

  View details for PubMedID 35922122

  View details for PubMedCentralID PMC9585993

• Generation of Human Regulatory T Cell Clones. Journal of visualized experiments : JoVE Nowatzky, J., Manches, O. 2020

  Abstract

  Human regulatory T cells (Treg) are notoriously difficult to isolate in high purity given the current methods of Treg enrichment. These methods are based on the identification of Treg through several activation-dependent cellular surface markers with varying expression levels in different physiologic and pathologic conditions. Populations isolated as "Treg" therefore often contain considerable numbers of non-Treg effector cells (i.e., Teff) which hamper the precise phenotypic and functional characterization of these cells, their genomic and proteomic characterization, their reliable enumeration in different states of health and disease, as well as their isolation and expansion for therapeutic purposes. The latter, in particular, remains a major hurdle, as the inadvertent expansion of effector cells homing in Treg-relevant cellular compartments (e.g., CD4+CD25+ T cells) may render Treg-based immunotherapy ineffective, or even harmful. This work presents a method that circumvents the problems associated with population-based isolation and expansion of Treg and shows that the generation of Treg candidate clones with the subsequent selection, culture, and expansion of only carefully vetted, monoclonal cells, enables the generation of an ultrapure Treg cell product that can be kept in culture for many months, enabling downstream investigation of these cells, including for possible therapeutic applications.

  View details for DOI 10.3791/61075

  View details for PubMedID 32478733

  View details for PubMedCentralID PMC7424846

• Flow Plex-A tool for unbiased comprehensive flow cytometry data analysis. Immunity, inflammation and disease Nowatzky, J., Resnick, E., Manasson, J., Stagnar, C., Al-Obeidi, A. F., Manches, O. 2019; 7 (3): 105-111

  Abstract

  The information content of multiparametric flow cytometry experiments is routinely underexploited given the paucity of adequate tools for unbiased comprehensive data analysis that can be applied successfully and independently by immunologists without computational training.We aimed to develop a tool that allows straightforward access to the entire information content of any given flow cytometry panel for immunologists without special computational expertise. We used a data analysis approach which accounts for all mathematically possible combinations of markers in a given panel, coded the algorithm and applied the method to mined and self-generated data sets.We developed Flow Plex, a straightforward computational tool that allows unrestricted access to the information content of a given flow cytometry panel, enables classification of human samples according to distinct immune phenotypes, such as different forms of autoimmune uveitis, acute myeloid leukemia vs "healthy", "old" vs "young", and facilitates the identification of cell populations with potential biologic relevance to states of disease and health.We provide a tool that allows immunologists and other flow cytometry users with limited bioinformatics skills to extract comprehensive, unbiased information from flow cytometry data sets.

  View details for DOI 10.1002/iid3.246

  View details for PubMedID 31016894

  View details for PubMedCentralID PMC6688088

• OMIP-053: Identification, Classification, and Isolation of Major FoxP3 Expressing Human CD4+ Treg Subsets. Cytometry. Part A : the journal of the International Society for Analytical Cytology Nowatzky, J., Stagnar, C., Manches, O. 2019; 95 (3): 264-267

  Abstract

  WE designed and optimized an inter-convertible flow cytometry panel for the analysis and sorting of human CD4+ regulatory T cells (Treg) utilizing all of the major, currently accepted marker combinations for Treg identification. The panel is optimized for use with peripheral blood mononuclear cells (PBMC). In addition, the panel allows for the identification, classification, and isolation of activated, antigen-experienced Treg, and provides estimates of proliferation and suppressive capacity. To this end we created two, easily inter-convertible sub-panels: ATREG—which includes intra-nuclear markers, and BTREG—using surface markers only. Both sub-panels have been tested on cryopreserved PBMC from healthy donors and those with human autoimmune diseases, as well as on long-term cultured human Treg and non-Treg cell lines and clones.

  View details for DOI 10.1002/cyto.a.23704

  View details for PubMedID 30584695

  View details for PubMedCentralID PMC6497402

• Brainstem astrocytoma as a neuro-Behçet's disease mimic. BMJ case reports Manasson, J., Howard, J., Nowatzky, J. 2018; 11 (1)

  Abstract

  A 58-year-old man with a history of recurrent aphthous ulcers since childhood was admitted to the hospital with acute neurological decline characterised by loss of motor dexterity, dysarthria, dysphagia and unsteady gait. MRI brain was significant for symmetrical hyperintense T2 fluid attenuated inversion recovery (FLAIR) in the corticospinal tracts, including parts of the pons and the mesodiencephalic junction. Though initial concern was for neuro-Behçet's disease, brain biopsy ultimately revealed a diagnosis of astrocytoma. This report demonstrates a mimic of neuro-Behçet's disease and the importance of confirming the correct diagnosis prior to initiating therapy.

  View details for DOI 10.1136/bcr-2018-226945

  View details for PubMedID 30567204

  View details for PubMedCentralID PMC6301524

• Modulation of human Th17 cell responses through complement receptor 3 (CD11 b/CD18) ligation on monocyte-derived dendritic cells. Journal of autoimmunity Nowatzky, J., Manches, O., Khan, S. A., Godefroy, E., Bhardwaj, N. 2018; 92: 57-66

  Abstract

  Apoptotic cell receptors contribute to the induction of tolerance by modulating dendritic cell function following the uptake of apoptotic cells or microparticles. Dendritic cells that have bound or ingested apoptotic cells produce only low amounts of pro-inflammatory cytokines and fail to prime effector T cell responses. Specifically, ligation of the apoptotic cell receptor CR3 (CD11 b/CD18) on human monocyte-derived dendritic cells (moDC) down-modates proinflammatory cytokine secretion, but the consequences for human Th17 cell homeostasis and effector responses remain unknown. Here, we aimed to establish whether CD11b-ligated moDC modulate Th17 cell effector reponses to assess their potential for future use in moDC-based suppressive immunotherapy.We generated a bead-based surrogate system to target CD11b on monocyte-derived human dendritic cells and examined the effects of CD11b ligation on Th17-skewing cytokine secretion, priming, expansion and functional plasticity in DC/T cell co-culture systems at the poly- and monoclonal level.We show that Th17 cell expansion within the human memory CD4+ T cell compartment was efficiently constricted by targeting the CD11b receptor on moDC. This tolerogenic capacity was primarily dependent on cytokine skewing. Furthermore, ligation of CD11b on healthy homozygous carriers of the rs11143679 (ITGAM) variant - a strong genetic susceptibility marker for human systemic lupus erythematosus - also down-modulated the secretion of Th17-skewing cytokines.Overall, our findings underline the potential of targeted CD11b ligation on human dendritic cells for the engineering of suppressive immunotherapy for Th17-related autoimmune disorders.

  View details for DOI 10.1016/j.jaut.2018.05.005

  View details for PubMedID 29908907

  View details for PubMedCentralID PMC6498856

• Myelodysplastic syndrome presenting as a Behçet's-like disease with aortitis. BMJ case reports Wang, S., Broder, N., Marchetta, P., Nowatzky, J. 2018; 2018

  Abstract

  A 46-year-old Hispanic man presented with fever, genital ulcers, left eye redness and chest pain. Physical examination was notable for a healed oral ulcer and scrotal ulcers, and bilateral superficial thrombophlebitis. He was found to have new-onset pancytopenia. CT of the chest showed pericardial and pleural effusions and rapidly progressing inflammation of the aortic arch and ascending vessels. Although the patient had Behcet's disease (BD)-like symptoms, pancytopenia could not be explained by the diagnosis, prompting a bone marrow biopsy which showed myelodysplastic syndrome. This report highlights the importance of excluding alternate disorders before making a diagnosis of Behcet's disease if atypical, BD-incompatible or incomplete constellations of symptoms and findings are present.

  View details for DOI 10.1136/bcr-2017-220649

  View details for PubMedID 29545422

  View details for PubMedCentralID PMC5878384

• Headaches related to rheumatologic disease. Current pain and headache reports Schwartz, N., Mitnick, H. J., Nowatzky, J. 2013; 17 (12): 381

  Abstract

  Headaches are a common, but under-recognized and understudied symptom in the context of the rheumatic diseases. They can result from intracranial pathology, such as parenchymal and meningeal inflammation, thrombosis, space-occupying lesions, and more. Inflammation, irritation, or degeneration of anatomically related structures such as the eyes, neck, and sinuses can equally cause headaches. In addition, patients with rheumatologic disorders have the same tendencies as the general population to develop primary headaches. While the latter are benign in nature, and generally require only symptomatic relief, the former type of headaches may signal disease manifestation, progression, or complication. Thus, familiarity with common and uncommon headache syndromes related to rheumatologic disorders as well as with their possible underlying disease processes and mechanisms is important. This will help to successfully develop an effective approach toward the evaluation of patients presenting with headaches in a rheumatologic context, and, ultimately, diagnose and treat potentially severe underlying disease.

  View details for DOI 10.1007/s11916-013-0381-4

  View details for PubMedID 24163052

• Behcet's disease with major vascular involvement. BMJ case reports Geng, L. N., Conway, D., Barnhart, S., Nowatzky, J. 2013; 2013

  Abstract

  A 40-year-old Chinese man was admitted for haemoptysis and progressive deep vein thrombosis involving the inferior vena cava (IVC) despite anticoagulation. An IVC filter had been placed earlier at an outside hospital. CT angiography revealed two pulmonary artery aneurysms. The patient was found to have a history of oral and genital ulcers, uveitis and erythema nodosum, thus meeting criteria for Behçet's disease. Other causes of the haemoptysis and thrombophilia were excluded. He underwent successful coil embolisation of the pulmonary artery aneurysms and responded well to immunosuppressive therapy with cyclophosphamide and steroids. Anticoagulation was cautiously continued to limit the long-term risk of secondary thrombosis from his IVC filter. The patient remains well 5 months after initiation of immunosuppressive therapy. Making a diagnosis of Behçet's disease in the setting of thrombosis is crucial, as treatment must include immunosuppression, and, thus, fundamentally differs from the management of most other thrombotic disorders.

  View details for DOI 10.1136/bcr-2013-200893

  View details for PubMedID 24214153

  View details for PubMedCentralID PMC3830209

• Active systemic lupus erythematosus is associated with decreased blood conventional dendritic cells. Experimental and molecular pathology Khan, S. A., Nowatzky, J., Jiménez-Branda, S., Greenberg, J. D., Clancy, R., Buyon, J., Bhardwaj, N. 2013; 95 (2): 121-123

  Abstract

  The aim of the study is to determine the frequency and functionality of blood conventional dendritic cells (cDCs) in relation to disease activity in systemic lupus erythematosus.Blood cDCs were enumerated for 34 SLE patients, defined as "active" (SLEDAI ≥ 4) or "inactive" (SLEDAI < 4), 26 RA subjects and 8 healthy subjects by FACS. cDC activation was measured by IL-12p40/70 staining following resiquimod stimulation.The frequency of blood cDCs was significantly lower in active compared to inactive patients, however, with comparable cDC functionality.cDC frequency in active SLE is decreased with no perturbation in cDC function, possibly due to enhanced turnover and/or tissue-specific migration.

  View details for DOI 10.1016/j.yexmp.2013.06.003

  View details for PubMedID 23773850

  View details for PubMedCentralID PMC3963522

• Major vessel thrombosis in Behçet's disease: the dilemma of anticoagulant therapy - the approach of rheumatologists from different countries. Clinical and experimental rheumatology Tayer-Shifman, O. E., Seyahi, E., Nowatzky, J., Ben-Chetrit, E. 2012; 30 (5): 735-40

  Abstract

  The best treatment for patients with Behçet's disease (BD) with major vessel thrombosis has not been fully determined. Our objective was to raise this therapeutic dilemma and to call for controlled studies to help establish guidelines to address this problem.Three patients with BD and major vessel thrombosis whom we recently encountered are described. Their cases were presented to rheumatologists from Turkey, Israel and the USA. The physicians were asked about the kind of treatment they would give each patient at diagnosis of thrombosis and if they chose to give anticoagulation and for long.Fifty-five Turkish, 33 Israeli and 25 American rheumatologists responded to the questionnaire. More than 87% of the Israeli and American rheumatologists would give anticoagulation at the time of diagnosis for the cases of venous thrombosis compared with only 40-44% of the Turkish physicians. In these cases 56% of the American and 45% of the Israeli rheumatologists would give warfarin for life compared with only 5-18% of the Turkish physicians. Regarding a case with intra-cardiac thrombus, 96% of American, 94% of Israeli, and 60% of Turkish rheumatologists would start anticoagulation at diagnosis while 70%, 39% and 33%, respectively would give this treatment for life.The therapeutic approach towards thrombosis in Behçet's disease differs significantly among rheumatologists from different countries. The different prevalence of the disease in these countries may explain this difference. A randomised controlled prospective trial is needed in order to determine the exact role of anticoagulant treatment in BD.

  View details for PubMedID 22703971

• The role of uric acid and other crystals in osteoarthritis. Current rheumatology reports Nowatzky, J., Howard, R., Pillinger, M. H., Krasnokutsky, S. 2010; 12 (2): 142-8

  Abstract

  Clinicians have long assumed that an association exists between crystal arthropathies and the presence of osteoarthritis (OA). However, studies establishing an independent association between calcium pyrophosphate or uric acid crystal disease and OA are sparse. Even less is known about a possible pathogenic relationship. Whereas some studies suggest that the relationships between crystals and OA may not be incidental and that crystal deposition may contribute to the onset and/or acceleration of OA joint damage, other authors have challenged this assertion. In this review, we provide an overview of past and current research elucidating the role of crystal deposition, including monosodium urate, calcium pyrophosphate, and other crystals, in OA. Given the clinical frequency of gout and that agents exist to modulate serum UA levels, special attention is given to the role of monosodium urate crystals.

  View details for DOI 10.1007/s11926-010-0091-4

  View details for PubMedID 20425024

• ST deviation pattern and infarct related artery in acute myocardial infarction. Clinical cardiology Rott, D., Nowatzky, J., Teddy Weiss, A., Chajek-Shaul, T., Leibowitz, D. 2009; 32 (11): E29-32

  Abstract

  Myocardial infarction (MI) may be classified as ST-elevation MI (STEMI) or non-ST-elevation MI (NSTEMI). There is little data regarding the relationship between the infarct related artery (IRA), clinical characteristics of the patients, and the ST deviation pattern (ie, STEMI or NSTEMI).There is a predilection of any coronary artery to a particular ST deviation pattern of acute MI.We reviewed our institutional database and selected patients who presented with an acute MI and underwent coronary angiography within 7 days of admission. The analysis included 830 patients of whom 563 had STEMI and 267 had NSTEMI. The culprit lesion was defined by reviewing each patient's angiographic report, electrocardiogram, and echocardiogram. TIMI flow rate was determined.The IRA in STEMI was most frequently the left anterior descending coronary artery (LAD) followed by the right coronary artery (RCA) and then the left circumflex coronary artery (LCX), a statistically significant difference. In patients with NSTEMI there were no significant differences in IRA. Patients with STEMI and LCX as the IRA were significantly younger and had a higher percentage of TIMI grade 3 flow then patients with STEMI and LAD or RCA as IRAs. These differences were not noted in patients with NSTEMI regardless of IRA.In STEMI there were significant differences in age and TIMI flow depending on the IRA. These findings were not demonstrated in patients with NSTEMI.

  View details for DOI 10.1002/clc.20484

  View details for PubMedID 19816991

  View details for PubMedCentralID PMC6653728

• Acute hyperglycemia and spontaneous reperfusion in acute myocardial infarction. Acute cardiac care Leibowitz, D., Nowatzky, J., Weiss, A. T., Rott, D. 2009; 11 (3): 151-4

  Abstract

  Spontaneous reperfusion (SR) may occur in patients with ST elevation myocardial infarction (STEMI) prior to reperfusion therapy. Hyperglycemia is common on admission in patients with STEMI and is associated with a worse prognosis. Mechanisms remain unclear but may include impairment of coronary flow. The objective of this study was to examine whether acute hyperglycemia influenced the occurrence of SR in patients with STEMI.All patients presenting to our institution with acute STEMI with measurement of glucose levels on presentation were eligible. SR was defined as a combination of significant relief of chest pain associated with an at least 70% resolution of ST segment elevation on follow-up ECG.465 patients were studied of whom 77 patients met criteria for SR. Average glucose levels were not significantly different between the SR and non-SR groups (10.0+/-5.6 mmol/l versus 10.1+/-5.3; P=NS). When patients were divided into normoglycemic and hyperglycemic groups, there was no significant difference in the percentages of such patients in the SR and non-SR groups. (52% versus 54%; P=NS).Acute hyperglycemia on admission does not predict the occurrence of SR in a general population of patients with acute MI.

  View details for DOI 10.1080/17482940903039939

  View details for PubMedID 19548129

• Herpes zoster duplex bilateralis. BMJ case reports Peretz, A., Nowatzky, J., Steiner, I. 2009; 2009: bcr2006114116

  View details for DOI 10.1136/bcr.2006.114116

  View details for PubMedID 21687240

  View details for PubMedCentralID PMC3106081

• ST deviation pattern in acute myocardial infarction is not related to lesion location. Journal of thrombosis and thrombolysis Rott, D., Greganski, P., Nowatzky, J., Weiss, A. T., Chajek-Shaul, T., Leibowitz, D. 2009; 27 (2): 163-7

  Abstract

  In ST-elevation MI (STEMI) the culprit artery is usually occluded, whereas non-STEMI (NSTEMI) it is usually patent. The location of the ruptured plaque may influence MI type. We examine whether the distance from the coronary ostium to the culprit lesion is different in STEMI as compared to NSTEMI.We selected patients who presented with an acute MI and underwent coronary angiography during hospitalization. The analysis included 754 patients of whom 514 had STEMI and 240 had NSTEMI. The distance from the coronary ostium to the site of thrombosis was measured.For both STEMI and NSTEMI patients the first 60 mm of the coronary artery contained 75% of the culprit lesions. There were no significant differences in median distances from the vessel ostium to the site of thrombosis as well.The distance from coronary ostium to culprit lesion is similar in STEMI and NSTEMI. Culprit lesion location does not appear to influence the development of STEMI as opposed to NSTEMI.

  View details for DOI 10.1007/s11239-008-0193-2

  View details for PubMedID 18188509

• Relation of spontaneous reperfusion in ST-elevation myocardial infarction to more distal coronary culprit narrowings. The American journal of cardiology Leibowitz, D., Gerganski, P., Nowatzky, J., Weiss, A. T., Rott, D. 2008; 101 (3): 308-10

  Abstract

  Spontaneous reperfusion (SR) of the infarct-related artery may occur in patients with ST-segment-elevation myocardial infarctions (STEMIs). Limited data are available on the angiographic characteristics of these patients. The objective of this study was to determine if there are differences in the distance of the culprit lesion from the coronary ostium in patients with STEMIs with and without SR. Patients who presented with acute STEMIs<12 hours after pain onset and who underwent coronary angiography were entered into the study. Measurement of the distance from the coronary ostium to the culprit lesion was performed. A total of 469 patients with STEMIs were included in the study, of whom 77 met criteria for SR (significant relief of chest pain associated with >or=50% resolution of ST-segment elevation on follow-up electrocardiography) and 392 did not. A highly significant difference was seen in ostial to culprit lesion distance, with the culprit lesions in the SR group being more distal than those in the non-SR group (45+/-22 vs 39+/-20 mm, p<0.009). In conclusion, the findings of this study demonstrate that the location of the culprit lesion in patients with STEMIs who undergo SR is more distal in the involved artery than in patients with STEMIs who do not undergo SR.

  View details for DOI 10.1016/j.amjcard.2007.08.036

  View details for PubMedID 18237590

• Neurological picture. Herpes zoster duplex bilateralis. Journal of neurology, neurosurgery, and psychiatry Peretz, A., Nowatzky, J., Steiner, I. 2007; 78 (8): 818

  View details for DOI 10.1136/jnnp.2006.114116

  View details for PubMedID 17635977

  View details for PubMedCentralID PMC2117756