PATIENTS WITH PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS AND ADENITIS (PFAPA) SYNDROME HAVE ALTERED METHYLATION PATTERNS IN PIK3AP1 (BCAP) AND SPON2 (SPONDIN-2) GENES
- Ema Lovsin, Slovenia
Abstract
Background and Aims
Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome is the most common autoinflammatory disease in children, often grouped together with hereditary periodic fever syndromes, although its cause and hereditary nature remain unexplained. We investigated whether a differential DNA methylation was present in DNA from peripheral blood mononuclear cells (PBMC) in patients with PFAPA versus healthy controls.
Methods
A whole epigenome analysis (MeDIP and MBD) was performed using pooled DNA libraries enriched for methylated genomic regions and identified candidate genes, of which two were further evaluated with methylation specific restriction enzymes coupled with qPCR (MSRE-qPCR).
Results
The analysis showed that PIK3AP1 and SPON2 intronic gene regions are differentially methylated in patients with PFAPA. MSRE-qPCR proved to be a quick, reliable and cost-effective method to confirm results from MeDIP and MBD.
Conclusions
Our findings indicate that B cell adapter protein (BCAP) as PI3K binding inhibitor of inflammation and spondin-2 (SPON2) as a pattern recognition molecule and integrin ligand could play a role in etiology of PFAPA. Their role and impact of changed DNA methylation in PFAPA etiology and autoinflammation need further investigation.
AN IDIOPATHIC CASE OF COMBINED WARM AND COLD AIHA
- Nuno V. Vieira e Brito, Portugal
Abstract
Background and Aims
Autoimmune hemolytic anemia (AIHA) is usually either warm or cold. In some rare cases patients present with both autohemagglutinins. In this text authors report a case of a male presenting with idiopathic combined warm and cold AIHA which had complete resolution of the anemia following treatment with corticosteroids
Methods
An 81-year-old male was referred to the emergency department (ED) by his primary care physician for asthenia, vomiting, upper abdominal pain and darkened urine in the past 2 months
Results
He presented hemoglobin of 7,1g/dL, leukocytosis, hyponatremia increased total bilirubin. Urine elevated urobilinogen. Worsening anemia with hemoglobin 5,4 g/dL, thrombocytosis, increased LDH and total bilirubin and unmeasurable haptoglobin. Peripheral blood smear showed anisocytosis. Positive DAT test (IgG1/IgG3 and C3d positive) without specificity and cold antibody, anti-I specific with 16 titer. Secondary causes wielded positive serologies for Chlamydia Pneumoniae. Serum protein electrophoresis demonstrated slight polyclonal hypergammablobulinemia, immunofixation demonstrated slight oligoclonal profile with increased lambda chains, urine immunofixation without Bence-Jones protein. No other test results were altered including normal bone marrow biopsy and autoimmune screening. Prednisolone was administered with resolution of hemolysis. At 4 weeks no increase in titer was noted on C. Pneumoniae serologies and presents resolution of hemolysis under no treatment.
Conclusions
An increasing number of mixed or combined warm and cold AIHA cases have been reported in the last few decades. Patients presenting with this disease have been described as severely anemic and having very good response to corticosteroid therapy. In accordance we report another case in which an idiopathic form of this rare disease presented itself in our practice.
FROM INFLUENZA TO STROKE: A MOSAIC OF MECHANISMS LINKING THE VIRUS, THE VACCINE AND THE DISEASE.
- Vânia Borba, Portugal
Abstract
Background and Aims
A 62-year-old female presented with low-grade fever, malaise and pronounced fatigue few days after she received the influenza vaccine for the first time. The symptoms persisted for five weeks until she was hospitalized with severe headaches associated with nausea, vomiting and left-side hemiparesis. The computed tomography (CT) revealed an extensive intracranial hemorrhage. Curiously, no cause of intracranial hemorrhage was identified, and the patient did not have previous history of illness or medication intake predisposing to hemorrhagic stroke.
Methods
Case report and literature review.
Results
Although confirming the relationship between the stroke and the vaccine might be challenging, some aspects raise great suspicion, including the absence of risk factors on her past history, no causes for intracranial bleeding identified on the CT scan, and finally the occurrence of the event five weeks after vaccination, preceded by an illness status suggestive of an exaggerated systemic inflammatory response.
Conclusions
A considerable number of autoimmune diseases such as Guillain-Barré syndrome, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, pemphigus vulgaris and more commonly, vasculitis may occur as adverse events following influenza infection and vaccination by mechanisms that remain undetermined. In this structured review, we describe a case report and summarize the current evidence on the association between influenza and cerebral vasculitis, focusing on molecular mimicry as the underlying ties which link the virus, the vaccine and the disease.
NEUROMYELITIS OPTICA SPECTRUM DISORDERS (NMOSD) AND SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): DOUBLE DISEASE BURDEN AND DILEMMA
- Anna Abou-Raya, Egypt
Abstract
Background and Aims
Neuromyelitis optica (NMO), neuromyelitis optica spectrum disorders (NMOSD) and transverse myelitis are auto-antibody mediated chronic inflammatory demyelinating CNS diseases that can occur idiopathic or in conjunction or may overlap with autoimmune rheumatic diseases. Although rare, these immune-mediated CNS diseases pose a diagnostic and therapeutic challenge to the treating physician posing a dilemma in clinical practice.
Methods
To illustrate the difficulty and dilemma in distinguishing NPSLE from NMOSD we present a case report of a 42-year-old female with a six-year history of SLE that presented with a 2-day complaint of progressive numbness and flaccid paralysis in both legs, fatigue and a malar rash. She then developed urinary and rectal incontinence and was unable to walk or stand unassisted. Flaccid leg paralysis, lower extremity paresthesia, and a positive Babinski response on the right side were noted on physical exam.The workup included serology for antinuclear, anti-double-stranded, antiphospholipid antibodies, blood count, ESR and CRP, lumbar puncture and MRI of her spine and brain.
Results
Workup revealed strong ANA positivity, NMO-IgG antibody (antibody to aquaporin 4 IgG (AQP4-IgG)) was positive and MRI of the spine demonstrated extensive hyperintense T2 signal abnormality throughout the spinal cord.
Conclusions
This case is further evidence that they can be co-existing conditions and although demyelination can be related to SLE activity it can sometimes be difficult to distinguish NPSLE from NMOSD. Early recognition of NMOSD in patients with autoimmune rheumatic diseases presenting with a CNS event is key.The therapeutic implications of these relationships are important because they can influence the timing and selection of immunosuppressive therapy.
THE RISK OF INFECTION IN PATIENTS WITH POLYMYOSITIS AND DERMATOMYOSITIS TREATED WITH DIVERSE IMMUNOSOPRESSIVE THERAPY: A LARGE CROSS-SECTIONAL STUDY
- Naim Mahroum, Israel
Abstract
Background and Aims
Polymyositis and dermatomyositis (PM/DM) are chronic inflammatory diseases affecting the muscle, often require immunosuppressive therapy that may increase the risk for infections.
Methods
We utilized the CLALIT database (2,085 cases – 1,475 with DM and 610 with PM) and conducted a cross-sectional study to assess which drug conferred a higher risk of infection.
Results
At the multivariate regression analysis, adjusting for confounding factors such as age and gender, azathioprine was associated with a higher risk of developing parvovirus (OR 4.16 [95%CI 2.39-7.23]), EBV (OR 2.35 [95%CI 1.74-3.16]) and tuberculosis (OR 4.14 [95%CI 1.12-15.25]). The administration of methotrexate was associated with a higher risk of developing EBV (OR 2.09 [95%CI 1.64 to 2.66]) and VZV (OR 2.07 [95%CI 1.34 to 3.20]). The use of cyclophosphamide did not significantly impact on the risk of infections, whereas plasmapheresis conferred a higher risk of developing HCV (OR 19.83 [95%CI 2.18 to 180.71], parvovirus (OR 49.31 [95%CI 8.55 to 284.27]) and EBV (OR 5.89 [95%CI 1.27 to 27.31]). The use of rituximab resulted in a higher risk of developing HBV (OR 5.10 [95%CI 1.77 to 14.71]), parvovirus (OR 4.69 [95%CI 2.13 to 10.31]), and EBV (OR 3.84 [95%CI 2.46 to 5.98]). Finally, the use of steroids conferred a higher risk of EBV.
Conclusions
Patients with PM/ DM and mainly those treated with immunosuppressive therapy ar at higher risk of viral infections and clinicians could use these findings to properly plan the management and treatment of PM/DM patients.