A Case of X-Linked Moesin-Associated Immune Deficiency in a Pediatric Patient

Background: X-Linked Moesin-Associated Immune Deficiency (X-MAID) is a rare severe combined immunodeficiency (SCID) subtype that can present at any age due to its variability. Depending on severity, patients demonstrate failure to thrive, recurrent bacterial and viral infections, and increased susceptibility to varicella zoster. It has been characterized by marked lymphopenia with hypogammaglobulinemia and impaired T-cell migration and proliferation. Case Presentation: This is a report of a Cuban 7-year-old male with poor weight gain and facial dysmorphia. He had a history of recurrent bacterial gastrointestinal infections and pneumonia beginning at 4 months of age. He additionally had 4-6 upper respiratory tract and ear infections annually. While still living in Cuba, he was admitted for a profound EBV infection in the setting of significant leukopenia. A bone marrow biopsy confirmed no malignancy. After he moved to the United States, his laboratory work-up revealed marked leukopenia with low absolute neutrophil and lymphocyte count with low T and B cells, very low immunoglobulin levels IgG, IgA, and IgM, and poor vaccination responses to streptococcus pneumonia, varicella zoster, and SARS-CoV-2. Genetic testing revealed a missense pathogenic variant c.511C>T (p.Arg171Trp) in the moesin (MSN) gene associated with X-MAID. He was managed with Bactrim and acyclovir prophylaxis, and immunoglobulin replacement therapy, and considered for hematopoietic stem cell transplantation. Discussion(s): Diagnosis of X-MAID should be considered in patients with recurrent infections and profound lymphopenia. As with SCID, early diagnosis and intervention is of utmost importance to prevent morbidity and mortality. This case demonstrates the importance of genetic testing in identifying this disease as it may prompt an immunologist to consider HSCT if conservative management is suboptimal. In the current literature, HSCT appears promising, but the long-term outcomes have yet to be described.Copyright © 2023 Elsevier Inc.

A Case of a Relapsing Remitting Macrophage Activating Syndrome After Covid-19 Vaccine In a Teenager with UNC13D Heterozygous Variant of Uncertain Significance

Introduction: Macrophage activation syndrome (MAS) is a severe hyper inflammatory condition caused by the over-activation and proliferation of T cells, NK cells and macrophages. It is often associated with complications of rheumatic/immune diseases. We present a case of a 15-year-old female who experiences recurrent episodes of MAS without any known definitive underlying etiology. Case Presentation: A 15-year-old previously healthy female developed fatigue, fevers, myalgia, chest pain, splenomegaly and lymphadenopathy 10 days after receiving her first Pfizer COVID-19 vaccine. Her symptoms recurred 10 days after receiving the second dose. Her myocarditis, MIS-C, and infectious work up was negative except for positive EBV IgG. Laboratory studies revealed anemia, hypertriglyceridemia, hypofibrinogenemia, and hyperferritinemia. She initially responded to decadron;however, her symptoms recurred with steroid taper. Bone marrow biopsy revealed hemophagocytosis. Whole exome sequencing (WES) revealed a heterozygous variant of uncertain significance in UNC13D c.962C>A (p.Thr321Asn). She had multiple re-admissions with significantly elevated inflammatory markers, including extremely high IL2-R, IL-18 and CXCL9. Each episode was complicated by an acute viral infection. She responds to high dose steroids, anti-IL-1, and JAK inhibitors. Nonetheless, it has been difficult to wean decadron without triggering a flare. She continues to require increasing doses of baricitinib. Discussion(s): MAS may be seen as a complication of rheumatic diseases, as well as inborn errors of immunity. However, none of these conditions have been diagnosed in this patient despite extensive testing, including WES. The degree of her immune dysregulation has been very severe making her disease process unpredictable and extremely difficult to control. She has frequent flares precipitated by viral infections or attempts at adjusting her immunomodulators. Weaning her medications has been challenging as she continues to require increasing doses of baricitinib and corticosteroids. The UNC13D gene is associated with autosomal recessive familial hemophagocytic lymphohistiocytosis type 3 (FHL3). Our patient is heterozygous for an UNC13D variant of uncertain significance. Additional genetic inquiries with whole genome sequencing to help elucidate the underlying etiology of her severe condition is being conducted. We hypothesize she developed MAS due to a combination of genetic predisposition, prior EBV infection, and immune stress associated with the COVID-19 vaccine. [Formula presented] [Formula presented] [Formula presented]Copyright © 2023 Elsevier Inc.

Newly diagnosed extranodal NK/T-cell lymphoma, nasal type, at the injected left arm after BNT162b2 mRNA COVID-19 vaccination.

Anti-SARS-CoV-2 vaccines were developed in response to the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the BNT162b2 mRNA vaccine is effective, adverse effects have been reported. Here, we report a case of extranodal NK/T-cell lymphoma, nasal type (ENKL), of the left arm following BNT162b2 mRNA vaccination. A 73-year-old male presented with a lump in the left arm, which was the site where he received the BNT162b2 mRNA vaccine 3 months prior. He was treated with topical corticosteroids and debridement, but the tumor progressed. Additionally, fever, night sweats, and general fatigue were observed. Laboratory findings included thrombocytopenia, elevated lactate dehydrogenase, and soluble interleukin-2 receptor levels. Skin biopsy led to a diagnosis of ENKL. The patient was treated with a 50% dose of SMILE therapy and radiotherapy, resulting in regression of the tumor. It seems that latent Epstein-Barr virus (EBV)-infected NK/T cells were reactivated by vaccination and contributed to the onset of ENKL. This is the first report of ENKL after BNT162b2 mRNA vaccination. The present case highlights the possible risk of development of malignant lymphoma, including ENKL at the injection site, after BNT162b2 COVID-19 vaccination.

An Unusual case of epstein-barr virus hepatitis mistaken for multisystem inflammatory syndrome in children

Case Report: As COVID-19 infections became more common, children began presenting with multisystem inflammatory syndrome (MIS-C). It can be difficult to distinguish rare presentations of common diseases from MIS-C, especially when there has been a close contact with COVID-19. Epstein-Barr virus (EBV) is a universally common infection with 90% of individuals showing serological signs of past infection. Both MIS-C and EBV can present with similar signs and symptoms. Our case aims to remind the reader to keep in mind uncommon presentations of common viral infections which may mimic MIS-C. Case Presentation: A previously healthy 5-year-old girl presented with persistent fevers for 12 days, associated with stomatitis, vomiting, and diarrhea. Physical exam was significant for a moderately ill-appearance, small (<1 cm) left posterior cervical lymphadenopathy, and soft palate and buccal oral ulcers. Initial labs (see Table) revealed leukocytosis with reactive lymphocytes and cholestatic hepatitis with mild coagulopathy. Although she had no respiratory symptoms, CT chest revealed left upper lobe pneumonia. Abdominal ultrasound showed diffuse hepatosplenomegaly, gallbladder wall thickening, and enlarged epigastric lymph nodes. Echocardiogram showed normal systolic function and coronary arteries without dilation. Extensive viral and bacterial nasal swab and serologic testing, including for SARS-CoV-2 antibodies, was negative. On Day 2, her Monospot was positive, along with EBV viral capsid antigen IgM and IgG with the absence of EBV nuclear antigen IgG. In addition, serum PCR was positive for EBV. Management and Outcome: Due to persistent fevers on Day 3 of broad-spectrum antibiotics, coupled with a close contact with active COVID infection, she was treated with the MIS-C protocol of intravenous immunoglobulin G (IVIG), prednisone, and aspirin. Within a day of IVIG, she improved clinically and fever resolved. By discharge on Day 8, her lab values had begun to normalize. Discussion(s): EBV is known to present in children with typical infective mononucleosis symptoms such as fever, sore throat, and lymphadenopathy. However, these can be lacking which makes the diagnosis challenging. Although hepatitis is a common sequalae of EBV, EBV induced pneumonitis and stomatitis are rare, especially in immunocompetent individuals. While our patient improved after treatment with IVIG, suggesting MIS-C, we still attribute her illness to EBV, as IVIG has been shown to provide antiviral and anti-inflammatory benefit in EBV infections. This case highlights the challenge of recognizing and overtreating rare presentations of common viral infections in the face of an emerging disease such as MIS-C. Significant Laboratory Values [Table presented] Copyright © 2023 Southern Society for Clinical Investigation.

SARS-CoV-2 INFECTION DID NOT TRIGGER HLH RELAPSE IN A PATIENT WITH CTLA-4 INSUFFICIENCY WHO PREVIOUSLY PRESENTED WITH LEISHMANIA AND EBV INFECTION-INDUCED HLH

Purpose: Cytotoxic T-lymphocyte antigen-4 (CTLA-4) checkpoint pathway may related to hemophagocytic lymphohistiocytosis (HLH);the association between COVID-19 and HLH is still debated. Our aim is to describe a CTLA-4 deficient patient presenting with leishmania and EBV triggered-HLH, and the clinical and immune responses to SARS-CoV-2 generated during her follow-up Methods: NK-cytotoxic function assessed by 51Cr-K562 lytic assay;lymphocyte subsets, perforin expression, NK-cell degranulation and coexpression of CD25 and CD134 on memory T-cells by flow cytometry Whole exome sequencing with Sanger confirmation Results: A 16-year-old female was first admitted in March 2020 with severe thrombopenia and readmitted 3 months later to study polyadenopathy. In October 2020, she suffered a mild COVID-19 mild (ageusia, anosmia) showing positive IgG anti-SARS-CoV-2-Spike (694.0 UA/mL) 6 months after the infection. In March 2021 -during her third hospital admission- she fullfilled HLH criteria along with leishmaniasis infection and EBV reactivation. Later on we have found granulomatous-lymphocytic interstitial lung disease (GLILD). Normal serum immunoglobulins, weakly positive ASMA and anti-thyroglobulin autoantibodies were detected. Circulating lymphocytes and HLHoriented studies were all normal. A new, 'de novo' heterozygous missense mutation c.425G>A (p.Gly142Asp) in CTLA-4 was identified affecting a conserved domain of the protein and probably pathogenic according to our in silico results (PolyPhen). Following both the second (June 2021) and third SARS-CoV-2 BNT162b2 vaccine immunization specific IgG>40.000 UA/mL and positive anti-SARS-CoV-2-Spike memory CD4+ T-cell responses were detected Conclusion(s): We report a young patient with a new heterozygous germline mutation in CTLA-4 associating HLH induced by common triggers (leishmania, EBV) but no by SARS-CoV-2 infection. This case does not support a relevant role of SARS-Cov-2 as potential etiological trigger of HLH. Our patient has been able to generate robust specific responses against SARS-CoV-2, while other reported insufficient CTLA-4 patients show suboptimal antibody responses to SARS-CoV-2 probably due to their stronger immunosuppressor therapies.

Mononucleosis: Peculiarity of Blood Count Scattergram Performed on Abbott Alinity Hq

Introduction: Mononucleosis is an infectious disease caused by Epstein-Barr virus (EBV, human herpes virus type 4, HHV-4) and is characterized by asthenia, fever pharyngitis, and lymphadenopathy. In our laboratory diagnosis is made by rapid test and Epstein-Barr virus antibody assay. The presence of Epstein-Barr virus (VCA) specific IgM antibodies indicates primary infection. A marked lymphocytosis with inversion of the formula can be seen on the blood count. The smear shows numerous activated lymphocytic elements By examining the complete scattergram of patients with confirmed primary infection we noticed a peculiar arch arrangement of the lymphocytes in the FL1 x ALL specific leukocyte scatters. Method(s): In this study Vircell's Virapid mono M&G is used, an immunotest for the qualitative determination of 4 serological markers of EBV: two IgM, VCA and heterophile, and two IgG, VCA and EBNA. The presence of anti-VCA IgM antibodies and the absence of anti-EBNA antibodies are indicative of primary infection. CBC was performed on Abbott Alinity hq, which uses a combination of photometry optical counting and fluorescence analysis in order to enumerate cells and cellular constituens. The instrument utilizes eight light scatter detectors which include ALL (axial light loss), IAS (intermediate angles of light scatter), PSS (polarized side scatter), DSS (depolarized side scatter) and FL1 ( fluorescent channel). Result(s): The sixteen cases examined, all of which resulted positive for primary infection on the rapid test, showed a peculiar FL1 x ALL scattergram (see Fig.1). In the lymphocytes' scattergram cloud, we observed an archshaped trend going upwards and rightwards, thus highlighting cells with greater fluorescence and size Often these lymphocytes are identified as monocytes In cases of lymphocytosis from other causes (CLL lymphomas) we can see how the lymphocytes' scattergram cloud is totally different. In such a case the cloud seems like a short bar due to lymphocytes with increased fluorescence signal though with small size (see Fig.2). Conclusion(s): In the 16 cases of primary EBV infection examined, the blood count shows a peculiar FL1 x ALL scattergram, which compared with the scattergram of other causes of lymphocytosis highlights a substantial difference that could support the laboratory technician in the diagnostic differentiation of a lymphocytosis: lymphocytic response to viral infection (EBV, SARS-Cov19, ecc) or monoclonal lymphocyte proliferation.

Broader Epstein-Barr virus-specific T-cell receptor repertoire in patients with multiple sclerosis

Introduction: Epstein-Barr virus (EBV) infection precedes signs of multiple sclerosis (MS) pathology and cross-reactive antibodies might link EBV infection mechanistically to CNS autoimmunity. Objective(s): As an altered immune reaction against EBV antigens in T cells of MS patients has been suggested, we queried deep, peripheral blood T-cell receptor beta chain (TCRbeta) repertoires of 1395 MS patients, 887 controls, and 35 monozygotic, MS-discordant twin pairs for multimerconfirmed, viral antigen-specific TCRbeta sequences. Aim(s): Quantification of HLA-matched EBV-specific, CMV-specific, Influenza A virus-specific, and SARS-CoV-2-specific TCRbeta sequences in MS patients, controls, and COVID-19 patients. Result(s): We detected higher numbers of MHC-I restricted EBVspecific TCRbeta sequences in MS patients, and validated this with independent cohorts and sequencing methods. Genetic as well as early environmental factors could be excluded by validation in diseased siblings of monozygotic twin pairs discordant for MS. Therapeutic blockade of VLA-4-mediated T-cell extravasation amplified this observation, while interferon beta treatment and B-cell depletion did not modulate occurrence of EBV-specific T cells. EBV-specific CD8+ T cells were characterized as effectormemory cells in peripheral blood and cerebrospinal fluid of healthy controls. In MS patients, the cerebrospinal fluid also contained EBV-specific central-memory CD8+ T cells, suggesting recent priming. Conclusion(s): MS is not only preceded by EBV infection, but also associated with a broader EBV-specific TCR repertoire, which would be consistent with an ongoing anti-EBV immune reaction in MS patients.

REACTIVATION OF EPSTEIN-BARR VIRUS AND CYTOMEGALOVIRUS INFECTION IN PATIENTS WITH COVID-19

SESSION TITLE: Studies on COVID-19 Infections Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: Latent Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are commonly reactivated in critically ill patients with severe infections. This study aimed to evaluate the proportion of reactivation of EBV and CMV and its impact on length of stay, need for ventilation, and Ichikado CT scores in patients with coronavirus disease 2019 (COVID-19). METHODS: A retrospective study was conducted comprising adult patients admitted to our hospital with COVID-19 infection from June 2021 to September 2021. Patients were divided into groups: virus-free, EBV-only, CMV-only, and EBV and CMV detected. Primary outcomes were length of stay, need for ventilation, and Ichikado CT score. Descriptive statistics, one-way ANOVA, Games-Howell, and Kruskal-Wallis tests were used. RESULTS: 189 patients were included with a median age of 51 years [41 – 66], 80 (42.3%) were female and 109 (57.7%) were male. CD4(+) counts were lower in all viral reactivation groups. EBV-only (157 cell/µl [93 – 279.2] ), CMV-only (82.5 cell/µl [65.5 – 323.7] ), both viruses (62.5 cell/µl [47.5 – 135.5]) and virus-free (221 cell/µl [117 – 318]), (H(3) = 12.029, p = < 0.01). A significant increase in the Ichikado CT score was seen in the viral reactivation groups. EBV 186.5 [43.6], CMV 177.5 [41.6], both-viruses group 204 [50.3] vs. virus-free 161 [45.8],( H(3) = 15.770, p = < 0.01). There was an increase in days of hospitalization when comparing the virus-free and the viral reactivation groups. EBV (9 days [5.5-15.5]), CMV (17 days [3-33]), both viruses (23 days [8-31]) vs. virus-free (5 days [3.5-9]), (H(3) = 15.487, p = < 0.01). Regarding the need for assisted ventilation, there was no difference between groups. 7 (9.1%) patients in the virus-free group, 29 (29.9%) patients in the EBV group, 2 (33.3%) patients in the CMV group, and 2 (22.2%) patients in the both-viruses group needed mechanical ventilation (X2 (3, N=189) = 11.699, p= 0.08). Additionally, a statistically significant decrease in albumin levels on admission was found in the EBV-only patients compared to the virus-free group, (3.4 g/dL [0.44] vs 3.75 g/dL [0.46], F(3,185) = 5.483, p = < 0.01). CONCLUSIONS: Viral reactivation is associated with lower CD4(+) count, an increase in length of stay, and higher Ichikado CT scores. CLINICAL IMPLICATIONS: EVB and CMV reactivation is associated with low CD4(+) counts and longer hospital stay. DISCLOSURES: No relevant relationships by David Akinwale No relevant relationships by Angelica Almaguer No relevant relationships by Sushen Bhalla No relevant relationships by Ailine Canete Cruz No relevant relationships by Ndiya Emeaba Speaker/Speaker's relationship with johnson and johnson Please note: approx year 2000 Added 03/31/2022 by Joseph Gathe, value=Honoraria clinical research relationship with gilead Please note: since 1990 Added 03/31/2022 by Joseph Gathe, value=Grant/Research clinical research relationship with ansun Please note: 2020 Added 03/31/2022 by Joseph Gathe, value=Grant/Research Support clinical research relationship with regeneron Please note: 2020 Added 03/31/2022 by Joseph Gathe, value=Grant/Research Support No relevant relationships by Jesus Salvador Gonzalez Lopez No relevant relationships by Najia Hussaini No relevant relationships by Claudia Ramirez No relevant relationships by Salim Surani No relevant relationships by Daryelle Varon No relevant relationships by Joseph Varon No relevant relationships by Mohamed Ziad

SEVERE COVID-19 COMPLICATED WITH HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS: A CASE REPORT

SESSION TITLE: Challenging Cases of Hemophagocytic Lymphohistiocytosis SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Worsening respiratory disease is the most common complication of severe COVID-19. However, when patients develop multi-organ dysfunction, clinicians must have a high index of suspicion for rare syndromes such as hemophagocytic lymphohistiocytosis (HLH). CASE PRESENTATION: A 39-year-old male smoker presented with 1 week of shortness of breath and malaise. Initial physical examination revealed T 37.3 C, pulse 85 min-1, respiratory rate 18 breaths min-1, SPO2 96% and clear breath sounds without labored respirations. Chest X-ray showed bilateral patchy airspace opacities in the mid and lower lung fields. A SARS-COV2 PCR test was positive. The patient was prescribed antibiotics and discharged home. Subsequently, the patient's symptoms worsened and he presented 1 week later with SPO2 90% (O2 10 L/min via nasal cannula). He was admitted to the hospital with COVID-19 pneumonia and began remdesivir, barcitinib, systemic steroids, albuterol and IV antibiotics. On admission his complete blood count and complete metabolic panel were unremarkable. After 3 weeks of hospitalization, he developed multi-organ failure with acute liver injury, acute kidney injury, shock, pancytopenia and worsening hypoxemia leading to endotracheal intubation and mechanical ventilation. CT chest imaging showed bilateral ground glass opacities in the lungs with superimposed consolidation (figure 1). Blood cultures remained sterile, HIV, hepatitis B and C viral serologies were negative. Serum viral polymerase chain reaction detected Herpes Simplex Virus-1 (HSV-1) and Epstein Barr Virus (EBV) infections. Trans-jugular liver biopsy confirmed HSV-1 hepatitis and showed sub-massive hemorrhagic necrosis of the liver (figure 2). Bone marrow biopsy demonstrated phagocytic histiocytes engulfing red blood cells and platelets consistent with HLH (figure 3). The patient began HLH targeted therapy with anakinra and high dose steroids. Despite this, the patient continued to deteriorate, developed refractory shock and subsequently expired. DISCUSSION: HLH is a rare disease of the immune system in which a genetic or infectious trigger causes uncontrolled T cell activation. T cell activation triggers macrophage activation, cytokine storm and macrophage phagocytosis of erythrocytes, leukocytes, platelets and precursors in the bone marrow and other tissues. If the syndrome is unrecognized, it can quickly lead to multi-organ failure and death. EBV is the most common infectious trigger of HLH;however, infection with HSV-1 and SARS-COV-2 viruses have been identified as rare and independent causes. CONCLUSIONS: This case illustrates the high index of suspicion providers should have for HLH in patients with severe COVID-19 who develop multi-organ injuries. Once HLH is suspected, prompt initiation of HLH-94 protocol with etoposide and dexamethasone may be lifesaving. For those patients with liver failure, other agents (e.g. anakinra) may be provided. Reference #1: Ramos-Casals M, Brito-Zerón P, López-Guillermo A, et al.: Adult haemophagocytic syndrome. Lancet 2014;383:1503–1516 Reference #2: Risma K, Jordan MB: Hemophagocytic lymphohistiocytosis: updates and evolving concepts. Curr Opin Pediatr 2012;24:9–15 Reference #3: Trottestam H, Horne A, Aricò M, et al.: Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol. Blood 2011;118:4577–4584 DISCLOSURES: No relevant relationships by Erin Biringen No relevant relationships by Christine Brennan No relevant relationships by Joann Hutto No relevant relationships by Daniel Puebla Neira

A case of reactivation of chronic Epstein-Barr viral infection, complicated by hepatitis, in a teenager with COVID-19

The article presents a clinical case of reactivation of chronic Epstein-Barr viral (EBV) infection complicated by the development of hepatitis in a 15-year-old teenager with COVID-19, which is of interest to infectious disease practitioners, pediatricians and other specialists in terms of the clinical course and differential diagnosis of these two viral diseases. It is shown that the reactivation of EBV against the background of the current new coronavirus infection COVID-19, accompanied by an increase in the level of aminotransferases in the blood, leads to a more severe course and prolonged stay of the patient in the hospital, as well as the appointment of additional drug therapy with subsequent rehabilitation measures.

Challenges in diagnostic research of multisystem inflammatory syndrome in children associated with COVID-19 in combination with the early stage of Epstein-Barr virus infection

Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 is a rare life-threatening immunopathological complication of COVID-19 that develops 1-6 weeks after the acute coronavirus infection. MIS-C is characterized by fever and multiorgan inflammation. We present a clinical case of a 10-year-old boy with skin lesions at the onset of MIS-C (erythematous malar rash, lacelike rash on the trunk and extremities and petechiae) with macrophage activation syndrome development and the early stage of primary Epstein-Barr virus infection (EBV infection) which required the exclusion of X-linked lymphoproliferative disease. This clinical case demonstrates the complexity of diagnosis in MIS-C with skin manifestations at the onset of the disease, especially with concurrent activation of other infections, particularly EBV infection.

Acute cerebellitis in an Adolescent after SARS-Cov-19 Infection: A case report

We report a 15-year-old boy presenting at our emergency department with acute onset of dysarthria and prior headache, rotary vertigo, nausea, vomiting and gait disturbance for 2 days. 18 days earlier he was tested positive for SARS CoV-19. Physical examination showed pronounced dys-arthria, nystagmus, absent reflexes, dysmetria and ataxia. Laboratory findings showed relative lymphocytosis with a negative C-reactive pro-tein, normal coagulation and elevated liver enzymes (AST, ALT, GGT). Drug screening was negative. First suspicion was postinfectious cerebellitis and he was admitted to IMC for observation. Subsequently, vomiting fre-quency rose, hence cMRI was performed, but showed no abnormalities. Miller-Fisher syndrome was suspected, however CSF examination showed no cytoalbumin dissociation, but discrete mononuclear cell count eleva-tion. Ceftriaxone and acyclovir were administered empirically. In addition, intravenous immunoglobulin and corticosteroids were given to treat viral cerebellitis/encephalitis. Due to suggestive atypical lymphocytes in the blood count, EBV testing was performed and serologies were positive. Multiple CSF viral/bacterial testings (Borrelia burgdorferi, Enterovirus, VZV, HSV 1/2) showed slightly positive EBV (PCR), congruent with blood results. Additionally, SARS-CoV-19 IgG were positive. The patient's condi-tion barely improved, a follow up cMRI showed no changes. Mobilization was fostered with a wheel chair and physical therapy. After two and a half weeks, he was discharged to pediatric neurorehabilitation in order to im-prove dysarthria, ataxia and address neuropsychological abnormalities. Two months after the diagnosis he is walking without aids but still shows trunk ataxia and dysarthria. He is still making constant progress and will hopefully recover completely. Neurological manifestation of EBV infection is extremely rare with the ma-jority of cases described in children. Nevertheless, some neurological manifestations have already been described including encephalitis, cere-bellitis, meningitis, transverse myelitis, and Guillain-Barré syndrome. These manifestations can occur alone or in the setting of infectious mon-onucleosis. In our case a co-infection of SARS-Cov-19 and EBV or a reactivation of EBV due to SARS-Cov-19 is possible as cause of the cerebellitis. Treatment op-tions were fully employed, but the recovery presented a slow course.

Lipshutz's acute vulvar ulceration and SARS-CoV-2: possible correlation?

Background Vulvar ulcers are mostly caused by sexually transmitted microorganisms, like T. pallidum, HSV and, occasionally, HIV. When genital ulcers occur in not sexually active women and girls, Lipschutz's acute vulvar ulceration is the leading cause. This benign and self-remitting condition is a non-sex-ually acquired condition, generally related to flu-like infections or mono-nucleosis syndrome. A concurrent EBV infection occurs in nearly 50% of cases. Local hygiene, ulcers care and pain control are the mainstay of man-agement of this condition. Case study A 14-year-old-girl, not sexually active, arrives to the emergency referring since four days severe pain in the genital area, enhanced during voiding and associated with vulvar ulcers. No other symptoms are referred. A two days therapy with acyclovir has shown to be ineffective. Local inspection of external genitalia shows 4 ulcerated lesions <5 mm, with no active bleeding and a slight oedema of the right labium minus. Hymen shows to be intact. A diagnosis of Lipschutz ulcers is hypothesize. Some tests are thus performed: microbiological cultures of the lesions are negative for HSV and VZV. Blood panel shows mild isolated lymphopenia and CRP is 2 mg/L. Serologies for CMV, HBV, HCV, HIV, Toxoplasmosis and T. pallidum are negative. Serologies for EBV turn out positive for past infection. PCR for SARS-Cov-2 is otherwise positive. We set home symptomatic therapy with ibuprofen alternating with co-paracetamol, and cold-water vulvar ir-rigation for voiding. A spontaneous resolution takes place in ten days. Due to her moving to Italy and to problems related to non-recognition of swiss immunity documents, the girl had to take the third dose of vaccine (BioN-Tech/Pfizer) one month after healing. Four days later the ulcers recur in the same place, although with eased symptoms. Conclusion According with other literature cases, Covid-19 infection could represent a likely explanation for this clinical situation. The recurrence after vaccine represents a strong evidence for this hypothesis. We therefore suggest to always include Covid-19 infection in the lab tests from now on, while screening for Lipschutz ulcers. Although benign, this clinical picture is con-firmed to be highly invalidating and do not respond to any specific ther-apy. The treatment of pain is critical. It is always important to consider whether pain management can be carried out at home, if hospitalization and eventual catheterization can be avoided.

Hemophagocytic lymphohistiocytosis: What's new in old diagnostic and clinical criteria?

Hemophagocytic lymphohistiocytosis (HLH) is a condition of overexpressed inflammatory response resulting in hypercytokinemia, macrophages infiltration and subsequent multiple organ failure. Without treatment, it leads to death. The main etiological factors include: viral, bacterial and parasitic infections, malignancies and autoinflammatory diseases. The main clinical manifestations are: high fever ≥38°C, lymphadenopathy, splenomegaly, and hepatomegaly. Central nervous system involvement occurs in 30-70% of cases. Less common symptoms include: dyspnea, cough, arrhythmias, jaundice, peripheral edema, rashes, albinism and diarrhea. The picture of the disease seen in laboratory tests consists of: duopenia, hypofibrinogenemia (<150 mg/dL) high D-dimers level, and hyperferritinemia. Other abnormalities include hypertriglyceridemia, elevated liver enzymes, hyperbilirubinemia, hypoalbuminemia and hyponatremia. Diagnostics include: laboratory tests, histopathological examination, lumbar puncture, radiological imaging, functional test and genetic checking. It is important to rule out factors mimicking HLH. Some of the old, well-known criteria are of less relevance nowadays. The aim of the therapy is immunosuppressive, immunomodulatory and anti-cytokine treatment, using the HLH-2004 protocol. In secondary HLH, elimination of the causative agent is critical. In primary HLH, or relapse of secondary forms, allogeneic transplantation is the only curative treatment. The prognosis is uncertain.