Italian Association of Clinical Endocrinologists (AME) 20th National Congress

The proceedings contain 9 papers. The topics discussed include: dulaglutide and NAFLD risk reduction;correlation between plasmatic long pentraxin PTX3 and nodular thyroid disease: a preliminary report;the fructose-bisphosphate aldolase a act as autoantigen in primary autoimmune hypophysitis;cortisol deficiency in Lenvatinib treatment;side effects of mitotane treatment: a retrospective study in 35 patients with adrenocortical carcinoma in adjuvant therapy;non-functioning pituitary adenoma: do predictor factors exist?;incidence and features of adrenal crisis in a series of 133 patients with Addison's disease;serological evidence and self-reported outcomes in patients with adrenal insufficiency during the first waves of COVID-19 in the North-East Italy;and persistent effects of spironolactone after its withdrawal in patients with hyperandrogenic skin disorders.

Bibliometric approach to trehalulose research trends for its potential health benefits

Trehalulose (1-O-alpha-D-glucopyranosyl-D-fructose) is a naturally occurring disaccharide composed of fructose and glucose. It is a sucrose isomer with a unique alpha-1,1 glycosidic bond that is more stable than the 1,2 glycosidic bond found in sucrose, giving it a lower glycemic index (GI). Trehalulose sugar production is often complicated, and the literature on the production is scarce. However, trehalulose is gaining popularity after a recent study revealed the abundance of this sugar in stingless bee honey (13 to 44 g per 100 g). The current short review discusses the chemical and physiological properties of trehalulose and its potential health benefits based on a bibliometric approach. Furthermore, it evaluates the antidiabetic potential of trehalulose as an emerging alternative sweetener.

Rare Case of Immune-Mediated Necrotizing Myopathy With Isolated Dysphagia as Presenting Symptom

Introduction: Immune mediated necrotizing myopathy (IMNM) is a rare, but progressive disease that accounts for about 19% of all inflammatory myopathies. Dysphagia occurs in 20-30% of IMNM patients. It often follows proximal muscle weakness and ensues in the later stages of the disease. We report a rare case of IMNM, presenting with dysphagia as the initial symptom, followed by proximal muscle weakness. Case Description/Methods: A 74-year-old male with a past medical history of coronary artery disease, hypertension, and hyperlipidemia presented to the ED with 2-3 weeks of intractable nausea, vomiting, and dysphagia for solids and liquids. Vital signs were stable, and initial labs displayed an AST of 188 U/L and ALT of 64 U/L with a normal bilirubin. Computed tomogram of the chest, abdomen, and pelvis were negative. An esophagram showed moderate to severe tertiary contraction, no mass or stricture, and a 13 mm barium tablet passed without difficulty. Esophagogastroduodenoscopy exhibited a spastic lower esophageal sphincter. Botox injections provided no significant relief. He then developed symmetrical proximal motor weakness and repeat labs demonstrated an elevated creatine kinase (CK) level of 6,357 U/L and aldolase of 43.4 U/L. Serology revealed positive PL-7 autoxantibodies, but negative JO-1, PL-12, KU, MI-2, EJ, SRP, anti-smooth muscle, and anti-mitochondrial antibodies. Muscle biopsy did not unveil endomysial inflammation or MHC-1 sarcolemmal upregulation. The diagnosis of IMNM was suspected. A percutaneous endoscopic gastrostomy feeding tube was placed as a mean of an alternative route of nutrition. He was started on steroids and recommended to follow up with outpatient rheumatology. He expired a month later after complications from an unrelated COVID-19 infection. Discussion(s): The typical presentation of IMNM includes painful proximal muscle weakness, elevated CK, presence of myositis-associated autoantibodies, and necrotic muscle fibers without mononuclear cell infiltrates on histology. Dysphagia occurs due to immune-mediated inflammation occurring in the skeletal muscle of the esophagus, resulting in incoordination of swallowing. Immunotherapy and intravenous immunoglobulin are often the mainstay of treatment. Our patient was unique in presentation with dysphagia as an initial presenting symptom of IMNM, as well as elevated enzymes from muscle breakdown. It is critical as clinicians to have a high degree of suspicion for IMNM due to the aggressive nature of the disease and refractoriness to treatment.

Lactulose Works in the Large Bowel: But How Does It Improve Hepatic Encephalopathy in a Patient Without a Large Bowel?

Introduction: Lactulose is a non-absorbable disaccharide which acts in the large bowel, and is commonly used in the treatment of hepatic encephalopathy. We present an interesting case of altered mental status due to hepatic encephalopathy successfully managed with lactulose in a patient with history of total colectomy. Case Description/Methods: A 67-year-old male with non-alcoholic cirrhosis and inflammatory bowel disease (IBD) post total proctocolectomy with a continent ileostomy known as a Kock-pouch (K-pouch) presented to the hospital with flu like symptoms and altered mental status. He was subsequently found to be positive for COVID-19. At the time of initial evaluation, the patient was obtunded with an elevated ammonia level of 91 umol/L. Colorectal surgery was consulted as the patient was not able to empty his K-pouch. Recently, he complained of inability to catheterize and with bleeding from the stoma. Initial catheterization with a Water's tube yielded 400 cc of effluent. Nasogastric tube was placed through which he was receiving lactulose 30 mg q8 hours. The patient's mental status improved within 24 hours. The patient ultimately underwent flexible pouchoscopy with endoscopic dilation and placement of a 22 French mushroom catheter for decompression of the K-pouch. Discussion(s): Lactulose is a non-absorbable disaccharide composed of galactose and fructose. The small intestine does not have the enzymes required to breakdown lactulose so it reaches the large bowel in its original form. In the large bowel, it is metabolized by colonic bacteria into monosaccharides and then to volatile fatty acids, hydrogen and methane. Lactulose decreases both the production and absorption of ammonia mainly through the presence of gut bacteria. The question arises as to how lactulose decreased ammonia levels in this patient without a large bowel. One proposed mechanism is the translocation of bacteria normally found in the large bowel to the small intestine. Small Intestinal Bacterial Overgrowth (SIBO), is a condition causing an increased number of bacteria in the small intestine. Patients with IBD and structural abnormalities are at increased risk of developing SIBO. Lactulose is commonly used in the diagnosis through the administration of lactulose and subsequent measurements of hydrogen and methane gas in expired air. This condition, in our patient with history of ulcerative colitis and colectomy, is a proposed mechanism of the efficacy of lactulose in the treatment of hepatic encephalopathy.

Semen Quality in Males Suffering From COVID-19

Background: It is well knowledge that various viral illnesses may interfere with a man's ability to father children. Through the angiotensin-converting enzyme-2 receptor, which is highly concentrated in testicular tissue, the corona virus illness known as COVID-19 may cause harm to several organs. On the other hand, there is a paucity of data about the transmission of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) in sperm, as well as the virus's influence on spermatogenesis and the capacity for fertility. We intended to look into whether or not COVID-19 guys' sperm contained SARS-CoV-2 as well as examine how COVID-19 affected the overall quality of the sperm and the degree to which it's DNA was fragmented. Material(s) and Method(s): The survey was conducted between May 2022 to October 2022, with the participation of 40 male COVID-19 patients who were between the ages of 19 and 45 and enrolled at the RSDKS, Government Medical College, Ambikapur, Chhattisgarh. We tested each sample of sperm with a real-time reverse transcriptase and found no abnormalities. At the time of the initial sample, which took place during COVID-19, a comprehensive examination of the sperm was carried out. This analysis included the calculation of the sperm DNA Fragmentation Index. After 74 days had passed since the first sample, we were able to get the second specimen and carried out the aforementioned tests once again. Result(s): All of the sperm samples that were examined using real-time reverse transcription-polymerase chain reaction (RT-PCR) came back negative for SARS-CoV-2. These samples were taken during the first and second sampling. The initial sample had considerably lower levels of fructose, semen volume, vitality, total motility, sperm concentration, total sperm count, percentage of normal morphology, and cytoplasmic droplet percentage than the subsequent samples. On the other hand, the agglutination of the semen, the percentage of head defects, the DNA Fragmentation Index, the liquefaction time, the viscosity of the semen, and the number of leukocytes all rose. At the second sample, these results were inverted, but not to the level that would be considered optimal. These results all had a p-value less than 0.05, meaning they were statistically significant. As a result, COVID-19 has a detrimental impact on the characteristics of the sperm, including the sperm DNA fragmentation index. Conclusion(s): The quality of the semen remained low up until the second time it was sampled, despite the fact that we were unable to discover SARS-CoV-2 in the sample. It is recommended that assisted reproductive technology (ART) clinics and sperm banking facilities evaluate the quality of the sperm produced by males infected with COVID-19 and exclude men who have a history of being infected with SARS-CoV-2 until the men's sperm quality recovers to normal.Copyright © 2023 Ubiquity Press. All rights reserved.

44th Annual Conference of the Association of Clinical Biochemists in Ireland, ACBI 2022

The proceedings contain 16 papers. The topics discussed include: false identification of icterus by eye in a complex patient with severe neutropenic sepsis;an unusual cause of Hypertriglyceridemia in an Infant;a confectionary cause of biochemical mimic for fructose-1,6-bisphosphatase (FBP1) deficiency;forward thinking for reverse PseudoHyperKalaemia;an unexpected follow-up of increased leucine on newborn blood spot screening;'that's gas!' - evaluation of the Abbott Alinity carbon dioxide assay;calcium verification with a difference?;changes in diagnosis of gestational diabetes mellitus during the Covid-19 pandemic at a large maternity hospital in Southwest Ireland;NT-proBNP in primary care. What's the indication and can it be interpreted? and elevated serum neurofilament light chain (NfL) as a potential biomarker in neuropsychiatric disorders.

Changes in Juvenile Dermatomyositis after the Covid-19 Pandemic

Background. Prior research has shown that viruses may trigger JDM, although the degree to which COVID-19 may serve as a trigger for JDM remains unknown. We present two case reports of JDM occurring after COVID-19 infection. We also provide case numbers of new JDM diagnoses pre-and post-COVID-19 as well as an analysis of JDM population characteristics pre-and post-COVID-19. A 5year-old female developed upper respiratory infection (URI) symptoms and was diagnosed with COVID-19 in December of 2020. She developed Gottron's sign, heliotrope rash, and weakness resulting in admission in February of 2021. She had elevated CK, AST, ALT, LDH, and aldolase. Her CMAS (childhood myositis assessment scale) was 24. An MRI showed diffuse myositis. Myositis specific antibody (MSA) testing revealed a positive MJ antibody. She was diagnosed with JDM and started on steroids, methotrexate, hydroxychloroquine, and IVIG with improvement. The second patient was a 4year-old female who was diagnosed with COVID-19 in October 2020. In January 2021, she developed heliotrope rash and Gottron's papules. She developed decreased exercise tolerance in May 2021 found to have elevated Aldolase and LDH. Her CMAS was 34. An MRI showed diffuse myositis. MSA testing was significant for a positive P155/140 antibody. She was started on hydroxychloroquine, steroids, IVIG and methotrexate with improvement. Due to the aforementioned cases a retrospective analysis was performed assessing the characteristics of JDM pre-and post-COVID-19 at Lurie Children's Hospital. Methods. The Cure JM biorepository houses clinical data, laboratory data, and patient samples obtained at the onset of JDM. The following information was obtained from newly diagnosed JDM patients: MSA, DAS (disease activity score), flow cytometry results, vWF antigen, neopterin, CMAS, capillary end row loop(ERL), LDH, Aldolase, ESR, CRP, IgG, complements, ANA, and age at diagnosis. We identified 10 patients with a diagnosis of JDM from January 1st 2020 -July 1st 2021 who were designated as the post-COVID-19 group. This population was compared to a total of 51 patients diagnosed with JDM between Jan 1st 2010 and December 31st 2019 who were designated as the pre-COVID-19 group. Data analysis was performed using Welch T-testing. Research enrollment was impacted due to the COVID-19 pandemic. To better assess JDM rates, chart review and EMR reports were obtained to determine the total number of JDM diagnoses. Results. T-testing showed no significant change in DAS, ERL count, T or B cell flow cytometry, vWF antigen, CK, CMAS, CRP, Aldolase, LDH, IgG, complements or ANA titer between the pre-and post-COVID-19 JDM groups. The analysis showed a significant change in NK cell population with a decrease in the absolute NK cell number (pre 163, post 90.75. P value 0.03), and NK cell percentage (pre 6.6%, post 3.625%, P value 0.008). Both of the patients presented in this case report showed a low NK cell number (1% and 3% respectively). The total number of new JDM cases rose from an average of 6.3 cases per year to an average 9 cases per year from January 1st 2020 to December 31st 2021. Conclusion. This study provides two case reports of COVID-19 likely triggering JDM. This study also shows a modest increase in the number of new JDM cases since the onset of the pandemic. Interestingly, the NK cell population in the post-COVID-19 JDM patients were significantly decreased. NK cells have multiple roles in not only immune regulation, but also the immune response to viruses. This study suggests that NK cells play a role in the development of in virally mediated JDM, specifically in cases triggered by COVID-19. Future studies will be important to further delineate the function of NK cells in these patients. Markers of JDM disease severity, including DAS, Neopterin, CK, and CMAS, did not significantly change in our institution's JDM population after the onset of the COVID-19 pandemic.

Myositis Associated with the Anti-COVID-19 Covishield Vaccine

Introduction: The SARS-CoV-2 made the world stop its activities, and the only chance of returning to normal life is the vaccine. But like any vaccination, some complications have been reported. We report the case of a patient who presented a myositis following the administration of the Covishield* (AZD1222, ChAdOx1 nCoV-19, AstraZeneca) COVID-19 vaccine. Case Report: 12 hours after his first dose, an 84-year-old patient presented to us reporting a decrea-sed muscle strength: the patient can move against gravity but not against resistance. The biological assessment showed that CK was at 4,250 IU/L, myoglobin was at 144 microgram/L and aldolases at 16.9 U/L. The patient received high doses of corticosteroids. Discussion(s): The development of vaccines and immunization programs reduced the morbidity and mortality of several diseases. Other case reports suggested the possible association between myopathies and the administration of the hepatitis B vaccine and H1N1 plus the seasonal trivalent influenza and other vaccines. The exact mechanism is still unknown, but a presumable autoimmune phe-nomenon is incriminated. Conclusion(s): The main purpose of this case report is to raise awareness about the possible link between the COVID-19 vaccination and polymyositis and the urge to take charge to avoid further complications.Copyright © 2023 Bentham Science Publishers.

Acute motor and sensory axonal neuropathy in a patient with undiagnosed mixed connective tissue disease

Case Report: Acute motor and sensory axonal neuropathy (AMSAN) syndrome is a rare subtype of Guillain-Barre syndrome (GBS) with poor recovery [1]. While respiratory and gastrointestinal infections may precipitate AMSAN, an underlying autoimmune disorder is seldom reported in literature. We herein report the complex case of a patient with undiagnosed, asymptomatic mixed connective tissue disease (MCTD) who developed AMSAN syndrome. Case: A 44-year-old Asian male without medical history presented with progressively worsening weakness of both upper and lower extremities and inability to perform daily activities. His symptoms started 12 weeks prior with difficulty standing from a seated position. He felt subjectively better for some time until a week prior, when he became bedbound. He had diarrhea 6 months ago, with 5-6 loose bowel movements a day for a few weeks. Vital signs on admission was normal. On neurological examination, he was alert and oriented, with bilateral upper and lower extremity flaccid paralysis, diffuse muscle atrophy, bilateral hand and foot drop, negative Hoover sign, diffuse areflexia, and intact sensation. Cerebrospinal fluid (CSF) analysis showed WBC 0 and protein level 136. MRI cervical, thoracic, and lumbar spine were normal. EMG revealed sensory involvement with positive sharp waves in proximal muscles along with fibrillations. Intravenous immunoglobulin (IVIG) was initiated at 0.4 mg/kg for 5 days. Infectious workup for COVID-19, stool culture, HIV, TB, RPR and campylobacter jejuni antibody (Ab), was negative. ANA was positive in a speckled pattern with titres 1:1280, with a positive RNP Ab, SS-A, and RF IgM, IgG and IgA. Rest of the autoimmune workup (anti-dsDNA, anti-CCP, SS-B, aldolase, anti-Jo-1, anti-Scl-70, p-ANCA, c-ANCA, anti-GM1, anti-GQ1b, and anti-GD1a ganglioside Ab) was negative. The myositis specific 11 Ab panel was negative. Despite IVIG therapy, he developed dysphagia, respiratory distress, with a negative inspiratory force of -0, requiring intubation. He had a tracheostomy and PEG tube placed and remains quadraplegic nearly 120 days later. Discussion(s): The authors report a unique case of a patient who became progressively weak over 3 months, leading to complete quadriplegia. Interestingly, this is more consistent with chronic inflammatory demyelinating poly-neuropathy (CIDP), as AMSAN typically develops over a short period of 2 to 4 weeks [2]. Despite having negative anti-GM1 and anti-GD1a Ab (in which positive Ab are pathognomonic but not always present in AMSAN syndrome), the patient had weakness that began in the lower extremities, progressing to paralysis, along with albuminocytological dissociation on CSF analysis, pointing to a GBS diagnosis [3]. He had sensory involvement in the EMG, thus making the diagnosis as AMSAN. He had an undiagnosed, asymptomatic autoimmune process most consistent with MCTD. Whether the two disease processes are related to each other is a concept that has not yet been investigated. Pediatric Clinical Case Reports Concurrent Session Saturday February 4, 2023 1:00 PM Copyright © 2023 Southern Society for Clinical Investigation.

A paralysis poser: a growing COVID concern

Purpose of Study: Report a rare case of onset of seronegative, juvenile dermatomyositis likely potentiated by Covid-19 infection Methods Used: Case analysis and literature research Summary of Results: A 7 year-old previously healthy male presented with 3 weeks of progressive, bilateral upper and lower extremity weakness, difficulty swallowing, voice changes, periorbital edema, and rash. Recent history was notable for diagnoses of COVID-19 one month prior to presentation and streptococcal pharyngitis 2 months prior to presentation. Notably, there is a family history of systemic lupus erythematosus. On examination, the patient demonstrated bilateral periorbital swelling with purple discoloration of the upper eyelids, a violaceous, pruritic, macular rash on his upper extremities and on his abdomen. Musculoskeletal exam was significant for severe axial (strength 2/5) and proximal (strength 3/5) muscleweakness with notable inability to sit unsupported or maintain head control. His neurologic exam was nonfocal;however, diffuse hyporeflexia in both upper and lower extremities were elicited. Initial screening labs were notable for mild transaminitis;positive ANA (1:80 in speckled pattern), negative ANCA, negative dsDNA/Anti- Sm, elevated aldolase of 10.3, CK 464, and LDH 665;normal thyroid studies and normal inflammatory markers. MRI with and without contrast of the spine indicated diffuse myositis of all muscle groups. Due to concern for autoimmune mediated myositis, Rheumatology was involved early in the patient's course. Empiric treatment was initiated early in the patient's presentation with IVIG, steroids, methotrexate, and plaquenil leading to gradual improvement in symptoms. Subsequent muscle biopsy was consistent with juvenile dermatomyositis (JDM). Conclusion(s): JDM is rare, occurring in 1 to 15 per million children. It classically presents with proximal myopathy and dermatologic findings of Gattron's papules, a heliotrope and malar rash. Its pathophysiology is not yet well defined but is thought to be a humoral mediated autoimmune disease. Muscle biopsies characteristically show perifascicular and perivascular infiltration. Early diagnosis and treatment with steroids, immune modulators, and physical therapy is critical to limit muscle atrophy. Viral infections are known triggers of rheumatologic diseases broadly;however, the more pronounced type 1 interferon response associated with COVID-19, which is known to be a driving pathway of JDM, may be a risk factor for severe, recalcitrant disease. Future research is needed to better identify involved pathophysiology and target future treatment efforts. Additionally, more education and case reports could focus on dermatologic presentations of individuals with pigmented skin. Copyright © 2023 Southern Society for Clinical Investigation.

Maternal fructose boosts the effects of a Western-type diet increasing SARS-COV-2 cell entry factors in male offspring.

Fructose-rich beverages and foods consumption correlates with the epidemic rise in cardiovascular disease, diabetes and obesity. Severity of COVID-19 has been related to these metabolic diseases. Fructose-rich foods could place people at an increased risk for severe COVID-19. We investigated whether maternal fructose intake in offspring affects hepatic and ileal gene expression of proteins that permit SARS-CoV2 entry to the cell. Carbohydrates were supplied to pregnant rats in drinking water. Adult and young male descendants subjected to water, liquid fructose alone or as a part of a Western diet, were studied. Maternal fructose reduced hepatic SARS-CoV2 entry factors expression in older offspring. On the contrary, maternal fructose boosted the Western diet-induced increase in viral entry factors expression in ileum of young descendants. Maternal fructose intake produced a fetal programming that increases hepatic viral protection and, in contrast, exacerbates fructose plus cholesterol-induced diminution in SARS-CoV2 protection in small intestine of progeny.

Negative Effects of Chronic High Intake of Fructose on Lung Diseases.

In the modern diet, excessive fructose intake (>50 g/day) had been driven by the increase, in recent decades, of the consumption of sugar-sweetened beverages. This phenomenon has dramatically increased within the Caribbean and Latin American regions. Epidemiological studies show that chronic high intake of fructose related to sugar-sweetened beverages increases the risk of developing several non-communicable diseases, such as chronic obstructive pulmonary disease and asthma, and may also contribute to the exacerbation of lung diseases, such as COVID-19. Evidence supports several mechanisms-such as dysregulation of the renin-angiotensin system, increased uric acid production, induction of aldose reductase activity, production of advanced glycation end-products, and activation of the mTORC1 pathway-that can be implicated in lung damage. This review addresses how these pathophysiologic and molecular mechanisms may explain the lung damage resulting from high intake of fructose.

A Case of Rapidly Progressive Interstitial Lung Disease Due to Antisynthetase Syndrome

Introduction: Antisynthetase syndrome is a rare autoimmune disease. Clinical characteristics include interstitial lung disease (ILD), myositis, Raynaud's phenomenon, mechanic's hands, and arthritis. The condition is characterized by antibodies targeting an aminoacyl transfer RNA synthetase. Compared to other inflammatory myopathies, there is a higher prevalence and increased severity of ILD. Case Report: A 34-year-old female with a history of polycystic ovarian syndrome presented with progressive dyspnea during her third trimester of pregnancy. Initial computed tomography angiography (CTA) chest showed widespread multifocal and multilobar ground-glass opacities and nodular areas of consolidation. COVID-19 testing was negative. She went into preterm labor and delivered her baby at 30 weeks. About 10 days after delivery, her respiratory symptoms worsened. Transbronchoscopic lung biopsy was nondiagnostic. She subsequently underwent surgical lung biopsy which revealed organizing pneumonia and interstitial fibrosis. Laboratory studies revealed a high Jo-1 antibody of 1033U (normal less than 20U), positive ANA, creatine kinase 186 U/L, as well as aldolase 22.3 U/L leading to a diagnosis of antisynthetase syndrome. The patient continued to be dyspneic and developed increased oxygen requirements. Treatment was initiated with 1 dose of 125 mg of methylprednisolone followed by 1 g of methylprednisolone for 3 days, after which she was continued on oral prednisone. She was additionally started on 250 mg of mycophenolate mofetil. Despite these therapies she continued to have increased oxygen requirements, eventually requiring noninvasive positive pressure ventilation and ultimately intubation with mechanical ventilation. Chest x-ray demonstrated worsening bilateral patchy infiltrates. Given her clinical deterioration, she underwent 5 treatments of plasma exchange after which she received 1000 mg of rituximab. The patient improved on this therapy and was able to be extubated after 3 days. Her oxygen requirements subsequently decreased and she was discharged on a prednisone taper;mycophenolate with a goal dose of 1000 mg twice daily;and plan for continued rituximab infusions. At 2 months follow-up, the patient was doing well without the need for supplemental oxygen. Discussion: This case demonstrates a rare disease in a peripartum patient. A high suspicion for antisynthetase syndrome is required to initiate autoimmune testing, particularly since there can be ILD predominant phenotypes without significant evidence of a myositis. Treatment is not standardized but typically consists of corticosteroids and other immunosuppressive agents. In severe cases of antisynthetase syndrome that are refractory to initial corticosteroid therapy, therapeutic plasma exchange can be performed.

A Case of Anti-Ro52 Antibody Myositis-Associated Interstitial Lung Disease

Introduction: Recognition of myositis-associated interstitial lung disease (ILD) has been increasing due to the recent identification of specific antibodies that are linked to a particular phenotype of myositis-ILD such as antisynthetase syndrome. The anti-Ro52 antibody has been found in multiple connective tissue diseases but its association with ILD is unclear. In fact, the literature on the phenotype of patients with an isolated anti-Ro52 antibody is very scarce. Case Presentation: A 57-year-old retired firefighter with history of gastroesophageal reflux presented to the hospital with a 4-week history of cough and progressive dyspnea with no other symptoms. He had presented to an urgent care facility where he tested negative for SARs-CoV-2 and was given antibiotics and inhalers without a clinical response. Patient required 2L/min of oxygen on admission. He had no other signs of autoimmune disease or other organ involvement. Chest CT showed peripheral ground glass opacities with basilar reticulations and bronchiectasis (Figure 1). WBC and CPK were normal and aldolase was mildly elevated. Initial serologies revealed an ANA 1:320 and a weakly positive p-ANCA with negative PR3/MPO antibodies. Patient was started on prednisone 60 mg and discharged five days later on mycophenolate mofetil (MMF) and 2L/min of oxygen. At 2-week follow-up, his extensive autoimmune panel showed a high titer of Anti-Ro52 antibody. An in depth ILD questionnaire revealed a family history of lupus and the remote use of a short course of steroids 20 years ago after a biceps biopsy showed polymyositis. On chart review, 10 years ago the patient had elevated CPK levels of 255 to 404, in the context of a nonspecific flank pain that resolved without intervention. At his 3-month follow-up, the patient still required 40mg of prednisone, reported dyspnea on exertion and required oxygen with ambulation. Rituximab was added to his regimen and his symptoms significantly improved;at 6-month follow-up, his FVC% improved from 53% to 70% and the patient was no longer on oxygen. Prednisone was titrated down to 10mg and he was continued on MMF 3g/day and Rituximab every 6 months. Discussion: We present a patient with Anti-Ro52 antibody myositisassociated ILD who required 3 immunosuppressive agents to control his disease. This case adds to the very scarce literature on ILD secondary to Anti-Ro52 antibody and highlights the importance of an extensive antibody testing for patients with ILD of unclear etiology, for diagnostic and therapeutic purposes. Further studies describing the phenotype of these patients are warranted. (Figure Presented).

Rapidly Progressive Cellular NSIP in a Young Female Found to Have Antisynthetase Syndrome

Introduction: Antisynthetase syndrome(ASS) is a rare autoimmune disease characterized by myositis, arthritis, cutaneous findings and interstitial lung disease (ILD). In 15-30% cases of ASS, ILD can be the presenting feature making this a very challenging diagnosis to make, especially during the COVID 19 pandemic. We present a unique case of ILD as presenting feature of ASS. Case: A 31 yr old female, never smoker, with asthma and obesity was referred to the pulmonary clinic for dyspnea of 2 months. Dyspnea was on exertion, associated with cough and pleuritic chest pain. Oxygen saturation on exam was 91% at rest and 86% on exertion. PCR and antibodies for COVID was negative. CXR showed bilateral infiltrates. She was treated with several courses of antibiotics and steroids. Her symptoms improved with steroids yet returned when course completed. Chest CT revealed bilateral parenchyma opacities with sparing of the lung apices. This was repeated 3 months after her course of antibiotics and steroids which revealed worsening of ground glass opacities, now diffuse with areas of organizing pneumonia. Bronchoalveolar lavage showed alveolar macrophages with a mixture of acute and chronic inflammatory cells. PFTs revealed severe restrictive lung disease. Infectious work up including bacterial, viral and fungal causes was negative. Complete blood count with differential was normal. B-type natriuretic peptide, creatine kinase, liver function test, basic metabolic panel, HIV and fungal serologies were unrevealing. A rheumatologic work up revealed elevated ESR (48), CRP (6.9), aldolase (48) with positive anti OJ antibodies. She underwent VATs with wedge lung biopsy which revealed cellular non specific interstitial pneumonia (NSIP). She was diagnosed with ASS and started on a gradual taper of high dose steroids and steroid sparing agent Mycophenolate Mofetil. With time her respiratory symptoms improved and she no longer required supplemental oxygen. She was enrolled in pulmonary rehabilitation and encouraged to loose weight as her BMI of 55 could preclude lung transplantation if needed. Discussion: ASS is a rare autoimmune connective tissue disorder characterized by myositis, polyarthritis, cutaneous findings and ILD. It occurs more commonly in women with average age of onset in 50s. ILD has been reported in 69-100% with NSIP being most common followed by cryptogenic organizing pneumonia and UIP. Treatment consists of steroids, with or without a steroid-sparing agent. Timely diagnosis of ASS is imperative for patients presenting with ILD as delay can lead to progression of ILD which serves as a predictor for morbidity and mortality. (Figure Presented).

A Case of MyastheniaGravis and Myositis after Immunotherapy and COVID Vaccine

Objective: To explore triple overlap syndrome and immune effects of COVID-19 vaccination. Background: Neurologic immune related adverse events (nIRAE) are potential complications of Immune Checkpoint Inhibitors (ICI). nIRAE of the Peripheral Nervous System (PNS) can present fulminantly, especially myositis, myasthenia gravis (MG), and overlap syndrome of myositis, MG, and myocarditis. Design/Methods: NA Results: 77-year old male with metastatic melanoma presented to hospital with leg weakness, hoarseness, dyspnea, and ptosis 1 week after first cycle of ipilimumab and nivolumab and 3 days after COVID-19 vaccine. He had bradycardia with heart block, and hepatorenal failure. Exam was remarkable for dysarthria, right eye ptosis, hip flexion weakness 4+/5, without fatigability. Labs showed CK 21,325, Troponin-T 4,888, Aldolase 307, AChR antibody positive, and AntiStriated Muscle Antibody 1:3840. Vital Capacity (VC) was 1.9L and Negative Inspiratory Force (NIF) -20cmH2O. Patient received BiPAP, plasmapheresis, and methylprednisolone 1000mg. After this, he developed fatigability of ocular muscles, voice, and proximal arms;VC dropped to 1.3L. He was diagnosed with triple overlap syndrome, but MG manifested after receiving first dose of high-dose steroids. Heart biopsy showed lymphohystiocytic inflammation. Muscle biopsy showed focal and dispersed lymphomononuclear cell endomysial infiltration. Electromyography demonstrated patchy myositis in lower extremities. Patient completed 3 days of high-dose steroids, 5 days of plasmapheresis, abatacept, and rituximab, followed by slow steroid taper. He did not require intubation despite tenuous respiratory status. Conclusions: nIRAE of the PNS are rare potential complications of immunotherapy, usually presenting by 6 weeks, although overlap syndrome can present hyper-acutely after 1 dose. Our patient presented 1 week after first treatment, perhaps influenced by COVID vaccine. Management of nIRAE is consensus-based, as no standard evidence-based treatment exists. Our patient was successfully treated with plasmapheresis prior to high-dose steroids (obviating steroid-induced myasthenic crisis), abatacept and rituximab. The myasthenic crisis was successfully managed with BiPAP, avoiding intubation, and he ultimately improved.

Juvenile dermatomyositis: Five new cases during the SARS-Cov2 pandemic

Objectives: To describe the clinical and laboratory characteristics of pediatric patients diagnosed with dermatomyosis during the COVID pandemic. Method: Description of the clinical and laboratory findings in patients under 15 years of age, who were admitted at our hospital with signs and symptoms suggestive of dermatomyositis, from March 2020 until November 2021. Results: Five patients, three boys and two girls, aged between 8 and 13 years, were diagnosed with juvenile dermatomyositis (JDM). The most frequent symptom was asthenia. Heliotrope erythema, malar rash, periungual erythema, and papules on elbows and knees were present in all cases. Three of our patients had perniosis on their toes. Four patients presented lesions in the oral mucosa, such as geographic tongue or gingivitis. The time between the onset of symptoms and the first visit with the pediatrician ranged from 1 to 6 months. In all cases, GOT/GPT enzymes, and aldolase were elevated at diagnosis, and the SARS-CoV-2 PCR was negative. Two patients had anti-TIF1 antibodies, and two had anti-MDA5 antibodies. In one girl, no specific autoantibodies for JDM were detected. Magnetic resonance imaging showed muscle oedema in all patients. All cases are in remission after systemic treatment with steroids, methotrexate or immunoglobulins. Discussion: JDM is a severe disease of childhood. Our cases did not present symptoms suggestive of COVID and the PCR for SARS-CoV-2 was negative on admission in all of them, but the presence of perniosis on the toes of three patients could correspond to “COVID toes,” and be a late manifestation of an asymptomatic or oligosymptomatic infection of SARS-CoV-2. It has been suggested that SARS-CoV-2 infection could trigger the development of JDM, possibly through the induction of IFNα. Long-term follow-up is necessary to establish a relationship between the prognosis of specific autoantibodies, the involvement of acral and mucosal areas, and the possible relation with COVID.

DATA MINING AND BIOINFORMATIC ANALYSIS REVEAL DYSREGULATION OF ANDROGEN BIOSYNTHESIS AND SIGNALING PATHWAYS IN TESTIS OF SARS-COV-2 INFECTED MEN

INTRODUCTION AND OBJECTIVE: COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) impacts male reproductive health. Nearly 50% of men who recovered from COVID-19 (without vaccination) had low levels of testosterone/ androgen and thus, are at greater risk of developing hypogonadism. Although a recent transcriptomic report showed molecular alterations in the testis of SARS-CoV-2 infected men, their impact on androgen biosynthesis and associated signaling pathways is unknown. The main objective of this study is to analyze androgen biosynthesis and signaling pathways in testis of COVID-19 patients using a bioinformatic approach. METHODS: Transcriptomic data (PRJNA661970) of testis from men infected with SARS-CoV-2 were retrieved from European Nucleotide Archive (ENA). The FASTQ files were processed using the BioJupies web tool (http://biojupies.cloud) to identify the differentially expressed genes (DEGs) in the SARS CoV-2 infected group compared to the control group (non-infected). Furthermore, DEGs were subjected to downstream analysis using Ingenuity Pathway Analysis (IPA) software (Qiagen, USA) to investigate both androgen biosynthesis and associated signaling pathways. RESULTS: Data mining and analysis resulted in the identification of 8,906 DEGs, among which 101 genes (40 downregulated and 61 upregulated) were found to be associated with hypogonadism. IPA analysis revealed that the function of enzymes involved in the androgen biosynthesis such as steroid 17a-monooxygenase, 17a-hydroxyprogesterone aldolase, steroid D-isomerase, testosterone 17b-dehydrogenase (NADP) and 3-oxo-5a-steroid 4-dehydrogenase were differentially regulated by the DEGs. Furthermore, expression of molecules regulating the androgen signaling pathways were altered in the testes of men infected with SARS-CoV-2 (Figure 1). CONCLUSIONS: Our findings demonstrate that androgen biosynthesis and associated signaling pathways important for testosterone production are dysregulated in testis of men infected with COVID-19. This may result in prolonged testosterone deficiency leading to hypogonadism in COVID-19 patients. Future studies are warranted to assess the impact of SARS-CoV-2 on accessory sex glands (especially prostrate) which are under the regulation of androgen signaling pathway.

EARLY DIAGNOSIS OF EOSINOPHILIC FASCIITIS IN A 16 YEAR-OLD FEMALE

Introduction: Eosinophilic fasciitis (EF) is an uncommon scleroderma-like disorder resulting from infiltration of eosinophils and other white blood cells into the fascia. The etiology of EF is frequently idiopathic, but triggers have included trauma, medications, infection, and autoimmune conditions. Case Description: We present a case of EF in a 16-year old female with a history of Hashimoto’s thyroiditis, food allergies, and allergic rhinitis. Two weeks following her 1st dose of the Pfizer mRNA SARS-CoV-2 vaccine, she presented with generalized edema, weight gain (for 2-3 months prior), and polyarthritis. She did not have any scleroderma-like skin changes. Laboratory analysis was remarkable for eosinophilia (2130 cells/uL), elevated aldolase (15.6 U/L), and normal creatinine kinase. Lupus testing was unremarkable. MRI of bilateral thighs showed fasciitis and muscle/fascial biopsy demonstrated inflammatory myofasciitis consistent with EF. Given pending parasite studies, she received ivermectin prior to IV methylprednisolone therapy. Our patient has demonstrated significant improvement on prednisone, methotrexate, intravenous immunoglobulin, and hydroxychloroquine. Infectious work-up revealed positive Toxocara IgG levels, which prompted albendazole treatment. Discussion: Our case demonstrates an interesting perspective on the rare diagnosis of eosinophilic fasciitis. The etiology of her EF is unclear with confounding factors including her history of Hashimoto’s thyroiditis, positive Toxocara serology (IgG positive, IgM testing not available), and temporal relationship to Pfizer SARS-CoV-2 vaccine. This vaccine could have triggered an inflammatory process in the patient’s already hyper-reactive immune system. It is important to promptly recognize EF, as prolonged symptoms prior to diagnosis is associated with a poor treatment response.

Reply letter to "safety of SARS-Cov-2 vaccines administration for adult patients with hereditary fructose intolerance".

In the letter, Urro et al. performed a search on the sucrose, fructose and sorbitol content in the approved Sars-Cov-2 vaccines and they concluded that these vaccines can be safely administered in adults affected by Hereditary fructose intolerance.The Pfizer-BioNTech COVID-19 Vaccine is currently approved for use in adolescents ≥ 12 years and the Moderna COVID-19 vaccine is close to approval for use in children over 12 years of age. Furthermore, both vaccines have initiated clinical trials that will include infant as young as 6 months. Therefore, we considerate important to analyze the safely administration of this two vaccines in children with Hereditary fructose intolerance.