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Case Report: Although the coronavirus disease 2019 (COVID-19) affects the respiratory system, neurological complications in children have been reported. Neurological manifestations in children with acute COVID-19 infection are rare and range from headaches, transverse myelitis, strokes, and encephalitis which presents as a part of Multisystem Inflammatory Syndrome in Children (MIS-C). However, encephalitis presenting post-COVID-19 in the absence of MIS-C in children has not been described. Case presentation: A 9-year-old Hispanic female with no past medical history presented with altered mental status and seizures. Associated symptoms prior to seizures included worsening headaches and vomiting. Initial labs were significant for an elevated erythrocyte sedimentation rate of 32 mm/hr, C-reactive protein of 2 mg/dL, and white blood cell (WBC) count of 28 000 cells/mcl with neutrophilia. Comprehensive metabolic panel was normal. Computed tomography of the head and urine drug screen were normal. Magnetic resonance imaging of the brain demonstrated diffusion restriction in the left frontal lobe as well as mild leptomeningeal enhancement concerning for meningoencephalitis. Lumbar puncture (LP) showed pleocytosis (WBC 169 cells/mcl, 76% neutrophils), elevated glucose 77 mg/dl, normal protein 56 mg/dl, and elevated myelin basic protein indicative of a demyelinating disease. Infectious workup was significant for a positive COVID-19 immunoglobulin (Ig) G (19.66), positive Mycoplasma pneumoniae (M. pneumoniae) IgM (0.87 units/L), with an equivocal IgG (0.11 units/L). Autoimmune workup was negative. She received dexamethasone 0.15 mg/kg/dose for 1 day, followed by methylprednisolone (10 mg/kg/dose) for 3 days and oral prednisone for 5 days resulting in significant improvement. Although CSF cultures returned negative, she received a 7-day course of doxycycline for a possible coexisting M. pneumoniae infection. Repeat LP showed improving pleocytosis, and lymphocytic predominance. Discussion: In this case report, rapid neurological recovery after administration of corticosteroids in the presence of positive COVID-19 IgG and demyelinating disease was suggestive of encephalitis presenting post- COVID-19 infection. Although M. pneumoniae can present with neurological symptoms (e.g., encephalitis), repeat titers at follow-up after recovery did not show the expected 4-fold increase in IgG, making it less likely the cause of this presentation. The proposed pathophysiology of COVID-19-mediated encephalitis includes direct invasion of the nervous system, immune-mediated cytokine response, and molecular mimicry between coronaviruses and neuronal proteins causing demyelination. The mainstay treatment includes immunomodulators such as corticosteroids, Intravenous Immunoglobulin, monoclonal antibodies (eg., rituximab), or plasma exchange. Conclusion: COVID-19 infection should be considered when evaluating a patient with meningoencephalitis or post-infectious encephalitis.
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The development of COVID-globulin, a COVID-19-specific human immunoglobulin preparation, involved choosing a method to quantify antibodies to SARS-CoV-2. Antibody titre determination by virus neutralisation (VN) is labour-intensive and unsuitable for large-scale application. To enable routine testing, it was necessary to develop a less demanding method;the enzyme-linked immunosorbent assay (ELISA) was the most appropriate of solutions. The lack of international and industry reference standards (RS) prompted the preparation and certification of an RS for COVID-globulin potency control. The aim of the study was to examine the possibility of substituting ELISA for VN and to develop an RS for SARS-CoV-2 antibody quantification in immunoglobulin preparations. Materials and methods: the authors used commercial ELISA kits by several manufacturers, COVID-globulin by Microgen (48 batches), and human plasma samples from multiple sources (1499 samples). The tests were performed by VN, ELISA, and chemiluminescent microparticle immunoassay. Results: the authors validated an ELISA method for SARSCoV-2 antibody quantification with the selected reagent kits by the National Medical Research Center for Hematology (NMRC for Hematology) and Euroimmun AG. The authors demonstrated the possibility of using ELISA instead of VN (with a correlation coefficient of more than 0.9). They developed and characterised an in-house RS for SARS-CoV-2 antibody content in human immunoglobulin preparations. The RS was certified in newly introduced anti-COVID units (ACU) and in international binding antibody units (BAU) using the World Health Organisation (WHO) international reference panel (NIBSC code: 20/268). The RS's potency was measured in terms of its neutralising activity in ACU (320 ACU/mL) and BAU (2234.8 BAU/mL). The authors established the relationship between ACU and BAU units. For the selected ELISA reagent kits, the conversion factors were 6.4 (NMRC for Hematology) and 7.0 (Euroimmun AG). Conclusions: the ELISA method for SARS-CoV-2 antibody quantification and the RS for SARS-CoV-2 antibody content can be applied to determine the potency of human anti-COVID-19 immunoglobulins.
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Introduction and Objective: Idiopathic inflammatory myopathies(IIMs) is a group of autoimmune disease characterized by muscular and extra-muscular manifestation. IIMs with anti-MDA5 antibody positivity carries poor prognosis due to rapid progressive interstitial lung disease (RP-ILD). We report clinical course of patients cared in our centre. Method(s): Patients medical record were reviewed for data collection. Result(s): Four patients with MDA5 antibody positive IIMs following up in our clinic (Table 1). None has reported Covid infection. Two has respiratory disease responded to induction therapy. One still undergoing titration of immunosuppressant. One female patient presented unwell with pleural effusion and acute pneumonitis. Patient later developed rapid progression of interstitial lung inflammation with refractory supraventricular tachycardia. IVIG was initiated, however she succumbed to adult respiratory distress syndrome (ARDS) due to pneumonia. Plasma exchange was not carried out due to source limitation at that time of period. Conclusion(s): Prevalence of anti MDA-5 positive is 30%-50% in Asians patients with IIMs particularly the east. However, it is likely under-reported in Malaysia due to lack of understanding of the pattern of disease in our multiracial population as well as lack of myositis serology tests availability especially in government hospitals. Research and registry should be instituted to allow better study of this disease in our population, to better the treatment and reduce morbidity and mortality due to rapid progressing interstitial lung disease. (Table Presented).
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Background: Autoimmune Syndrome Induced by Adjuvants, or ASIA, suggests certain environmental exposures, including vaccination can cause hyperstimulation of the innate and adaptive immune system leading to production of autoantibodies in a genetically predisposed individual. A diagnosis of exclusion, proposed diagnostic criteria suggested ASIA if specified major and minor criteria are fulfilled. Suspicion for ASIA was raised in our patient due to identified exposure accompanied by typical manifestations not explained by another cause. Case: A 71-year- old Filipino female with controlled hypertension and diabetes, came in due to progressive right eye pain, supraorbital headache, ptosis and limitation of extra-ocular movements for 3 weeks. No blurring of vision, color vision changes, or visual field cuts. She didn't have other systemic features but received 2 doses of inactivated COVID-19 vaccine 1 month (1st) and 1 day (2nd) prior to the symptom onset. The left eye was unremarkable. ESR was elevated (109) with normal CRP. ANA was 1:80 with a speckled pattern. The complements were normal and lupus confirmatory panel was negative. CSF studies showed slightly elevated protein and glucose with no pleiocytosis, IgG level was normal with negative oligoclonal panel and cultures. EMG-NCV showed acute partial incomplete bilateral facial neuropathy. Cranial MRI/MRA showed chronic lacunar infarct in the right corona radiata. The MRI of the orbits showed right optic nerve enhancement with hyperintense nerve sheath compatible with optic neuritis. She underwent pulse IV steroid therapy (Methylprednisolone 1 g) for 3 days and was maintained on oral steroid 1 mg/kg/day. There was minimal improvement of symptoms for which she received intravenous immunoglobulin for 5 days. Her symptoms gradually improved upon discharge. Conclusion(s): Identification of the possible autoimmunity from adjuvants is not to discourage vaccination but rather raise awareness of the need for further studies to screen who might be at risk and to prepare or even develop alternatives, such as vaccines with a different type of adjuvant.
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Introduction: An unusual case presentation of MOG-positive Acute Disseminated Encephalomyelitis (ADEM) in a preschool child following meta-pneumo viral infection responded to the combination of immune modulatory treatment with a favourable outcome. Material: Three-year-old female child presented with acute encephalopathy, high fever, vomiting, starring episodes, floppiness, and left abducent nerve palsy with rapid deteriorating GCS necessitating intubation and ventilation. Two weeks earlier, she was treated for suspected CNS infection with 10 days of antibiotics in the PICU with a positive meta-pneumo-virus. On admission, she had a GCS score of 6 with left-sided increased tone, bilateral hyperreflexia, and bilateral extensor response and on Day 14 demonstrated hyperkinetic movements of the upper and lower limbs. Method(s): Serum MOG antibody positive, CSF MOG low positive, metabolic investigations, Mycoplasma, EBV, Influenza, corona PCR, SARS-COV-2 Antibody, viral CSF panel unremarkable. MRI brain demonstrated T2 hyperintense signal in bilateral medial thalami and brain stem with a normal spine. Progressive changes were shown on repeated MRI Brains on day 4 and day 14 suggestive of multifocal changes involving deep cortical and subcortical white matter bilaterally with a new short segment of the spinal lesion at the T8 level. Repeated EEG and ambulatory EEG showed a diffusely slow background with intermittent slow runs of slow waves suggestive of generalized cerebral dysfunction. Result(s): After receiving the combination of high pulse steroids with a taper over 10 weeks, IVIG and 10 cycles of plasmapheresis she demonstrated gradual and remarkable clinical improvement over 10-12 weeks with a minimal focal neurological deficit. Conclusion(s): Initial differentiating CNS infection, metabolic disease and ADEM may be clinically challenging. Her clinical presentation, investigations and imaging were in keeping with the diagnosis of MOG-positive ADEM. Previous CNS infection may be related. MOG-positive ADEM treated with the early combination of immunomodulation may lead to positive clinical outcomes.
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Background: Disseminated infections such as tuberculosis are known to result in a systemic inflammatory response leading to thrombosis, with increasing reported cases of thrombotic event being observed in patients infected with covid-19. This is the first reported case on co-infection with COVID-19 pneumonia and disseminated tuberculosis causing catastrophic antiphospholipid syndrome (CAPS). Method(s): The report highlighted the challenges in the diagnosis and management which include the use of corticosteroid in setting of systemic infections. Another diagnostic dilemma was to explain the cause of myositis by tuberculous or autoimmune. Case Presentation: We report a 26-year- old man with HbE trait thalassemia who reported unintentional weight loss, night sweats for 1 month prior to the diagnosis of covid-19 infection on 10th March 2022. Seven days later, he was hospitalized for suspected perforated appendix. Computed tomography (CT) abdomen revealed hepatosplenomegaly, prostatitis, seminal vesiculitis. Multiple matted abdominal lymph nodes were not amenable for biopsy. Soon, he appeared toxic, dyspneic required non-invasive ventilation with bilateral parotitis. He had raised erythrocyte sedimentation (ESR) 52 mm/hour, C-reactive protein (CRP) 221 mg/dl, lactate dehydrogenase (LDH) 730U/L. Direct Coomb's antibody was positive but did not have any form of haemolysis. Complement 3 (0.45 g/L) and complement 4 (0.1 g/L) levels were low. Serum IgG4, procalcitonin, anti-nuclear antibody, cultures and virology were negative. Sputum for acid fast bacilli (AFB) was positive on Auramine O stain but the Ziehl-Nelson (ZN) stain and tuberculous PCR (GeneXpert) were negative. Diagnosis of disseminated tuberculosis was made but his abdominal pain persisted despite being on anti-tuberculous therapy (ATT), and he had new evidence of splenic infarct. CT angiogram also revealed celiac trunk and superior mesenteric artery thrombosis. Antiphospholipid (aPL) test was positive for lupus anticoagulant, beta 2 glycoprotein 1 and anti-cardiolipin antibodies. Therapeutic anticoagulation and plasma exchange were initiated for probable CAPS followed by intravenous immunoglobulin and corticosteroid. Thereafter, the patient developed severe bilateral pelvic girdle pain with evidence of myositis on the MRI (Figure 2). Serum creatine kinase was never elevated. Anti-PL- 7 and anti Ro-52 were borderline elevated. He recovered well and ambulant before discharged home. Conclusion(s): Our case highlight the complexicity of presentation of CAPS who manifested as multiple arterial thrombosis. The diagnosis of disseminated tuberculosis relied strongly on microbiological, imaging and clinical presentation as histopathological evidence was not feasible. Management challenges were deciding on corticosteroid in disseminated infection and the need for confirmation of persistent positive aPL test and to monitor myositis symptom to help guide decision making. (Figure Presented).
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Case Report:We present a 5-year-old male with two days of fever, cough, vomiting, and loose stools. His history is significant for premature birth (35 weeks gestational age) and shunted hydrocephalus. A ventriculoperitoneal (VP) shunt was placed 6 days prior to presentation. Parental report included episodes of post-tussive, nonbloody, non-bilious emesis, poor oral intake, tachypnea, and increased work of breathing. Physical examination demonstrated a dehydrated infant with sunken fontanelles. He had no notable rash, no lymphadenopathy, and clear conjunctiva. His VP shunt site appeared normal without swelling or erythema. Initial evaluation showed elevated inflammatory markers -ESR 51 and CRP 12.32 mg/dL. A viral respiratory PCR panel returned positive for coronavirus (not SARS-CoV-2). A head CT scan and shunt radiography series showed no abnormalities with his shunt. The following morning, Radiology reported an incidental retropharyngeal fluid collection on a re-read of the patient's initial CT scan. A neck CT was obtained and demonstrated a fluid pocket with secondary mass effect in addition to bilateral cervical lymphadenopathy. Screening blood cultures were negative. The patient remained febrile (tmax 103.6F) and developed a transaminitis (ALT 264.9, AST 654), elevated fibrinogen 476, elevated INR 1.4, and low albumin 2.1. Abdominal ultrasound showed a normal the liver and biliary tract. His transaminitis resolved without treatment. The next day, the patient developed lip erythema and conjunctival injection. An echocardiogram showed a dilated right coronary artery (z-score of 3.59) and his inflammatory markers (ESR 26, CRP 9.63) remained elevated. Treatment was initiated with IVIG and moderate-dose aspirin. The patient defervesced, and he remained afebrile for over 48 hours prior to discharge. A repeat echocardiogram 2 days later showed a slight reduction in coronary artery dilatation (z-score 3.39). Hewas discharged on lowdose aspirin, and followed up with cardiology as an outpatient. Kawasaki's Disease (KD) is most common in children from ages 1 to 4 years and is classically characterized by persistent fever with a constellation of symptoms including limbal sparing conjunctivitis, cervical lymphadenopathy, polymorphous rash, strawberry tongue, oral changes, and extremity changes. Our patient presented at a younger age with a concurrent diagnosis of coronavirus upper respiratory tract infection. His atypical hospital course and incidental finding of retropharyngeal edema and transaminitis increased the clinical suspicion for KD. His symptoms rapidly improved after administration of IVIG. Younger patients are at an increased risk for severe complications of KD including coronary aneurysm. KD has been shown in the literature to have an association with coronavirus infection as well as presentation with retropharyngeal edema. Clinicians should consider KD in their differential even if patients do not meet all criteria for diagnosis on initial presentation. Copyright © 2023 Southern Society for Clinical Investigation.
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Background: A 54-year- old male presented to our centre with a chronic non-productive cough and breathlessness. Recent history of COVID treated and resolved few months back. He had a history of brain surgery performed five years back but details not known. Physical examination revealed no oedema and bilateral coarse creps with bronchiolar breathing. Laboratory findings indicated neutrophilic leucocytosis, elevated inflammatory markers, with elevated troponin I and D dimers. Urine analysis suggested microscopic haematuria with sediments. While 24 hour quantification revealed sub nephrotic proteinuria. As auto immune workup and vasculitis profile was negative and patient has not improved in spite of standard of therapy hence we went ahead with CT-Chest indicating ground-glass opacities in bilateral lung parenchyma and prominent interlobular/intralobular septal thickening. Then Bronchoscopy done which revealed the blood-stained secretions in the main stem bronchi and diffuse alveolar haemorrhage in bilateral bronchial segments indicating an inflammatory study, while tuberculosis diagnostic panel and infective bio fire panel in BAL was negative. Meanwhile, his repeat BAL culture suggested Carbapenem resistant Acinetobacter baumannii complex infection. As the patient did not respond to the standard of care for vasculitis. Probability considered was a small vessel vasculitis (namely Granulomatous polyangiitis) was considered due to lung manifestation involving upper respiratory tract with epistaxis, neutrophilic leucocytosis, elevated acute reactive protein, and renal manifestation including microscopic haematuria and proteinuria. However he responded poorly to conventional standard of treatment including pulse steroids and IVIG. Hence after MDT discussion we proceeded with lung biopsy which showed linear cores of lung tissue infiltrated by a malignant neoplasm and acinar pattern suggesting Invasive mucinous adenocarcinoma. Hence we went ahead with the biopsy diagnosis for the treatment plan. As he was to be started on chemotherapy, but he suddenly collapsed and went into hypotension, bradycardia, and cardiac arrest. In spite of high supports and post 4 cycles of CPR, was unable to revive and sadly succumbed to his illness. Discussion(s): In this rare case, the original diagnosis pointed to the pulmonary-renal syndrome, an autoimmune disease characterized by diffuse pulmonary haemorrhage and glomerulonephritis. However, negative autoimmune antibodies and vasculitis profile along with lung biopsy results indicated an unusual case of malignant lung adenocarcinoma presented with pulmonary renal syndrome. Conclusion(s): In cases suggesting pulmonary-renal syndromes, if autoimmune work up is negative and response is suboptimal relook the diagnosis.
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Background: Multisystem inflammatory syndrome in children (MIS-C), causing high morbidity and mortality, is the hyperinflammatory response following COVID-19 infection (CI). According to the MISC management guideline, Anakinra (anti-IL1) is the preferable agent among other biologic agents: Infliximab, Tocilizumab (TCZ), and baricitinib if the patient is refractory to intravenous immunoglobulin (IVIG) and systemic corticosteroid (CS). However, these are not available in a number of countries, including Thailand. Our case represents refractory MIS-C in a systemic juvenile idiopathic arthritis (SJIA) patient responding well to TCZ. Method(s): Diagnostic investigations, including basic and immunological blood tests, and echocardiography assessment, were conducted. Result(s): A 12-year- old boy has been diagnosed with SJIA since he was 2 years old, according to the presentation of prolonged fever, hepatomegaly, and evanescent rash. CS, cyclosporin-a, and TCZ have been prescribed, and he has been in clinical remission off medication for two years. He experienced acute fever, rash, shortness of breath, nausea and vomiting for few days. Physical examination revealed a febrile boy with respiratory failure, compensated shock, and a generalized persistent maculopapular rash. The other was unremarkable. MIS-C was one of the possible diagnoses according to fever accompanied by more than two systems involved and his previous CI four weeks prior. Laboratory investigation revealed an elevated inflammatory response (Figure 1). The echocardiography was done by an experienced cardiologist with concern for myocardial dysfunction in MIS-C and showed a significant poor ejection fraction of the left ventricle of 42% under dobutamine, milrinone, and norepinephrine. Broad spectrum antibiotics and IVIG (1 g/kg/dose for two days) were initiated. After hemoculture did not report bacteria growth, pulse intravenous methylprednisolone (IVMP) 1000 mg for 3 days was given for the MIS-C treatment. After initial aggressive treatment with IVIG and pulse IVMP, the patient still has a high grade fever with laboratory revealed ongoing elevated inflammatory markers. The other possible causes of fever, such as infection and active SJIA were suspected. Immunological profiles returned with positive SAR-COV2 IgG, negative SAR-COV2 IgM, which confirmed the diagnosis of MIS-C with refractory to IVIG and CS. After multidisciplinary team discussion, TCZ was given. He had neither fever, dyspnea, nor heart failure. His clinical condition gradually improves together with laboratory parameters (Figure 1). Conclusion(s): In conclusion, our case demonstrated TCZ as a potential therapeutic agent in refractory MIS-C patients living in countries with limited access to anti-IL1 agents. The multidisciplinary care team together with prompt management is advisable to the best benefit of the patient. (Figure Presented).
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Case report - Introduction: Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening disease occurring in up to 1% of antiphospholipid syndrome (APS) cases. It was first defined in 1992 and remains a difficult to treat entity with a mortality rate of 37%. We describe a patient with systemic lupus erythematosus (SLE) and CAPS presenting with simultaneous multi-organ injuries who was successfully managed with 'triple' therapy including cyclophosphamide. Case report - Case description: A 42-year-old female presented to her local hospital with chest pain and worsening vision. She had a background of SLE, triple antibody-positive APS (previous DVT, pregnancy loss and strokes), hypertension, a metallic mitral valve, a previous myocardial infarction and pre-existing visual impairment due to a prior intra-cerebral bleed related to anticoagulation. Examination revealed a faint malar rash, cortical blindness and long tract neurological signs. Her ECG showed ischaemic changes and the admission troponin was significantly raised (3773ng/L). An echocardiogram showed new left ventricular dysfunction and a subsequent cardiac MRI was in keeping with coronary artery disease. Investigations showed an acute kidney injury, newly deranged liver function tests and a raised INR (>11, with no bleeding). Complement was normal with a low dsDNA titre. Urinalysis revealed proteinuria and a protein creatinine ratio measured 176mg/mmol. MRI diffusion weighted brain imaging showed acute bilateral occipital and left fronto-parietal infarcts. She had symptoms of a lupus flare with arthralgia and a butterfly facial rash. COVID-19 PCR tests were negative and she had not been recently vaccinated. She was diagnosed with CAPS and transferred to St Thomas' hospital intensive care. On arrival, she received 1mg intravenous vitamin K followed by triple therapy for CAPS: an unfractionated heparin infusion, oral prednisolone 40mg daily, 5 days of plasma exchange and, given her background of SLE, she was treated with intravenous cyclophosphamide (according to the EUROLUPUS regimen). Intravenous methylprednisolone was avoided due to a previous hypertensive encephalopathy reaction. She responded rapidly. Her troponin fell from a peak of 5054 to 294ng/ L, her creatinine settled at a new baseline (232umol/L) and her liver function normalised. She was switched back to warfarin due to her metallic valve and started on aspirin for cardiovascular secondary prevention. She required physical and occupational therapy due to her strokes but recovered well. Case report - Discussion: According to the 2003 criteria, CAPS can be classified as definite when there is evidence of: -3 organs involved, development of manifestations simultaneously or within a week, confirmation by imaging and/or histopathology of small vessel occlusion and positive antiphospholipid antibodies. Probable CAPS is when 3 out of the 4 criteria are present. In this case, three organs were confirmed to be involved with imaging showing cerebral and cardiac ischaemia. Her creatinine rose from a base of 190 to 289umol/L coupled with a high protein creatinine ratio confirming renal involvement. A Budd-Chiari syndrome was also suspected due to deranged liver function tests and INR, though imaging performed after therapy did not confirm this. A biopsy of any of these four organs was not feasible given the severity of her presentation and coagulopathy. There are no randomised controlled trials but data from the CAPS registry guides treatment and management follows a logical approach: anticoagulation to treat thrombosis, glucocorticoids for inflammation and plasma exchange (or IVIG) to remove the circulating autoantibodies. Triple therapy was associated with a reduced mortality compared to no treatment (28.6% versus 75%, respectively). Following analyses from the CAPS registry we also chose to treat with cyclophosphamide, which is associated with improved survival in patients with SLE. This decision was based on the clinical features of an SLE flare as opposed to serological grounds. There have b en reports of rituximab and eculizumab being used successfully in CAPS, though generally as a last resort. As complement activation is seen in animal models of antiphospholipid syndrome thrombosis and rituximab is often used in refractory SLE, they may prove to be promising agents for refractory CAPS. Case report - Key learning points: 1. Prompt recognition and early treatment is vital in managing CAPS 2. Triple therapy with anticoagulation, glucocorticoids and plasma exchange / IVIG is associated with better survival in CAPS 3. Cyclophosphamide is associated with better survival in patients with CAPS and concomitant SLE.
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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.
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Background/Purpose: MIS-C is uncommon and yet potentially life threatening disorder associated with COVID-19 infection. MIS-C Malaysia Study Group had reported 174 cases, mostly affecting children < 12 years old (93.7%). The fatality rate was 4%. Hereby, we report a case of MIS-C at our adult rheumatology centre. Method(s): Patient's admission note and electrical medical information were reviewed. Result(s): This is a 17 year-old adolescent with underlying obesity (BMI 42 kg/m2). He completed COVID-19 vaccination (Pfizer-BioNTech x 2 doses) in October 2021. In end-February 2022, he presented acutely with recurrent seizures associated with fever (40.3degreeC) and headache. The COVID-19 RTK antigen and PCR tests were positive, and COVID-19 IgM & IgG were negative. At emergency room, he developed haemodynamic instability, needing ventilatory support for respiratory failure and inotropic therapy on Day 1 of illness. The initial diagnosis was severe COVID-19 infection with encephalitis and secondary bacterial infection. Subsequent investigations showed evidence of systemic inflammation with organ dysfunction involving neurological (seizures, CNS vasculitis), cardiac (myocarditis), renal (acute kidney injury) and gastrointestinal (acute livery injury) systems. MIS-C was then diagnosed with early initiation of immunomodulatory treatment (IVIg 2 g/kg and IV methylprednisolone 1-2 mg/kg/day) according to ACR recommendation. Low dose aspirin and high intensity prophylactic SC enoxaparin were prescribed but were discontinued soon due to bleeding tendency. Antimicrobial therapy was continued until microbiological study was proven sterile. With the immunomodulatory treatment, he had rapid clinical and laboratory improvement within first week and was transferred out from ICU on Day 10 of illness. The organ dysfunction was mostly resolved with no sequelae except for high blood pressure requiring antihypertensive. Inflammatory markers were markedly reduced;Serum ferritin reduced from 22,339 to 565.8 mug/L, procalcitonin decreased from 26.7 ng/ml to 1.5 ng/ml and CRP normalised (<5 mg/L). Home discharge was made on Day 16 of illness with oral prednisolone 60 mg daily without antiplatelet. During clinic visit after D30 of illness, he remained asymptomatic with good effort tolerance and normal blood pressure readings. He subsequently completed the high school examination in April 2022 and even enrolled at college later. Oral prednisolone was eventually tapered off at 3rd month of illness with appointments for MRI cardiac and brain scheduled for further assessment. Conclusion(s): MIS-C is a hyperinflammatory syndrome which requires high clinical suspicion as many patients response well to early immunodulatory treatment without sequelae. Long term follow up maybe needed for those with cardiac involvement. (Table Presented).
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Case Report: Prolonged fever in children is a symptom that is seen in many different diseases, infections, malignancies, and autoimmune conditions. This can, at times, make the correct diagnosis challenging. A previously healthy 10-year-old male was transferred to our institution with one week history of fever, fatigue, abdominal pain, and vomiting. Laboratory studies demonstrated pancytopenia, transaminitis, electrolyte abnormalities, elevated pro-inflammatory markers & D-Dimer, and hypoalbuminemia. COVID-19 IgG was reactive. Due to the severity in presentation the patient was transferred to the ICU with a presumptive diagnosis of MIS-C. Hewas started on IVIG as well as a five-day course of high-dose methylprednisolone per protocol. Aspirin was added, but later discontinued, due to worsening thrombocytopenia. CT imaging with contrast showed small bilateral pleural effusions & periportal edema, mild splenomegaly, and echocardiogram showed diffuse dilation of the left main and left anterior descending arteries. Given the laboratory findings the differential diagnosis was expanded, Ehrlichia caffeensis serology was sent and empiric Doxycycline started. EBV Nuclear Antigen IgG antibody and EBV Viral Capsid Antigen IgM Antibody resulted as positive suggesting recent or reactivated infection. Respiratory viral PCR with COVID-19, Cytomegalovirus and Parvovirus PCR were negative. Despite initial treatment, the patient continued to have persistent fever, severe pancytopenia, and high ferritin up to 24 426 ng/mL, raising suspicion for Haemophagocytic Lymphohistiocytosis (HLH). Soluble interleukin-2 level was elevated & his presentation was then considered to be more consistent with HLH given that he met 6/8 criteria. Screening for primary HLH including CD107a, perforin and granzyme B, SAP, and XIAP resulted in the latter three being normal but CD107a was abnormal. Next generation sequencing for primary criteria was negative. E. Chaffeensis resulted positive: IgM 1:80, IgG 1:256. MIS-C and HLH have overlapping features but differ in some clinical manifestations. Timely recognition and management is paramount as the management differs. This case illustrates the importance of performing a broad search for potential causes, allowing for appropriate and timely treatment. COVID-19 serology alone should not be the basis for diagnosis of MIS-C in a patient with fever and inflammation. This is important as SARS-CoV2 becomes endemic. Infections such as EBV and Ehrlichiosis should be on the differential particularly in endemic areas and during seasons of higher prevalence for the latter, as these have been well documented to cause HLH. Copyright © 2023 Southern Society for Clinical Investigation.
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Objectives: Several case series have been identified describing adult patients with a secondary Multisystem Inflammatory Syndrome (MIS) after a recent COVID-19 infection, presenting with features similar to Kawasaki Disease (KD). This paper aims to describe the first case of Kawasaki-like presentation in an adult Filipino with COVID-19 infection. Method(s): A case of Kawasaki-like presentation in an adult Filipino with COVID-19 infection was reviewed in a tertiary hospital. Result(s): This is a case of a 38-year- old Filipino woman who presented with fever, malaise, dry cough, sore throat, diarrhea and rashes. On examination, she had classic features of KD: non-exudative conjunctivitis, cracked lips, edema of the hands and feet, palmar erythema, diffuse rash, and cervical lymphadenopathy. Laboratory results showed anemia, leukocytosis with neutrophilia, hyponatremia, hypokalemia, transaminitis, hypoalbuminemia, and elevated inflammatory markers. COVID-19 PCR test was negative but serologic studies showed positivity for IgM and IgG, suggesting a recent infection. Treatment included methylprednisolone pulse therapy, intravenous immunoglobulin (IVIG) and anticoagulation, which resulted in rapid clinical improvement. Conclusion(s): As the knowledge of COVID-19 and its associated clinical features continually evolves, it is imperative to be aware of the possibility of KD as a delayed post-viral multisystem inflammatory response in adults that may warrant prompt treatment.
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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.
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Background/Purpose: Multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C) is a rare but severe disease associated with coronavirus infection, in which various systems and organs are affected, including the heart, lungs, kidneys, brain, skin, eyes and gastrointestinal tract. One of the most severe features of this disease can be hemophagocytosis. The aim of this study is to assess the features of hemophagocytosis in MIS-C. Method(s): The retrospective study included 166 children (99 male, 67 female), aged from 4 months to 17 years (median 8.2 years), who met the WHO criteria for MIS-C. The analysis of the obtained data was performed using the STATISTICA software package, version 10.0 (StatSoft Inc., USA). Result(s): To study the signs of hemophagocytosis in patients with MIS-C they were divided into 2 equal groups: with HScore<=91 (n = 79) and with a HScore value >91 (n = 79). This division was done, since this value was associated with the severe life-threatening course of MIS-C and need in ICU admission (70.9% vs. 32.3%, P = 0.000002). Patients with HScore > 91 were more likely to have symptoms such as cervical lymphadenopathy (80.6% vs 54.1%, P = 0.0007), red dry cracked lips (63% vs 34.3%, P = 0.0007), face swelling (66.7% vs 34.7%, P = 0.001), hepatomegaly (84.2% vs 43.1%, P = 0.000000), splenomegaly (54.7% vs 43.1%, P = 0.0003), hypotension/shock (63.3% vs 25.3%, P = 0.000002), had higher levels of ESR (47 mm/h vs 34 mm/h, P = 0.0001), CRP (175.5 mg/L vs 125.8 mg/L, P = 0.01), D-dimer (2135 ng/mL vs. 1079 ng/mL, P = 0.0003), but lower levels of fibrinogen (3.1 g/L vs 5.6 g/L, P = 0.000002) erythrocytes (3.6 x 1012/L vs 4.0 x 1012/L, P = 0.000005), hemoglobin (98 g/L vs 112 g/L, P = 0.000000), and a tendency to thrombocytopenia (110 x 109/l vs 192 x 109/L, P = 0.0002) in 63.3% of patients. According to EchoCG data, signs of myocardial (45.5% vs 15.6%, P = 0.00006) and pericardial (45.5% vs 14.3%, P = 0.00002) lesions were more common in patients with HScore > 91. Patients with HScore > 91 more often needed treatment with IVIG (66.2% vs 24%, P = 0.000000), acetylsalicylic acid (65.7% vs. 47.1%, P = 0.027) and biological drugs (9.1% vs. 1.6%, P = 0.061). The average duration of hospitalization was also much longer in patients with HScore > 91 (23 days vs 14 days, P = 0.000000). Also, the identification of clinical and laboratory signs that were more common in the group of patients with HScore > 91 was performed using sensitivity and specificity analysis, and calculation of odds ratio. Results are presented in Table 1. Conclusion(s): Hemophagocytic syndrome is one of the most severe manifestations of MIS-C occuring in 35.4% of patients. It was found that HScore > 91 is associated with such a severe signs of MIS-C as myocarditis, pericarditis, hypotension/shock, and ICU admission. HScore is a simple tool that can also be used to assess the severity of MIS-C and dynamic monitoring.
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Case Report: Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) can commonly present with gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea. These symptoms along with high fever and elevated inflammatory markers can often mask underlying gastrointestinal inflammation and lead to a diagnostic dilemma. Case Presentation: We report a case of a 16-month-old with a history of exposure to SARS-Cov-2 virus, who presented with fever, cough, vomiting, and decreased activity. Her initial workup showed neutrophil-predominant leukocytosis with elevated CRP, ferritin, NTProBNP, and fibrinogen. Serology was positive for COVID-19 IgG antibodies, strongly favoring a diagnosis of MIS-C. Initial CT of the abdomen showed findings consistent with mild enteritis. Intravenous immunoglobulin was not administered as leukocytosis and all inflammatory markers except CRP improved during the course of her hospital stay with parenteral antibiotics, but she remained febrile with worsening abdominal symptoms. She then developed classic symptoms of peritonitis with tenderness and rigidity. Ultrasound of abdomen was inconclusive due to overlying bowel gas. Repeat CT of the abdomen showed multiple intra-abdominal abscesses with the largest rim enhancing lesion in the right lower quadrant. Her presentation was consistent with acute appendiceal abscess due to perforated appendix that improved with CT guided drainage and three weeks of intravenous antibiotics. She was then discharged and planned for an interval appendectomy after two weeks. [Figure presented] Conclusion(s): Symptoms of appendiceal abscess can mimic MIS-C. This case underscores the importance of considering appendicitis in the differential diagnosis in patients with MIS-C. Appendicitis can be missed in toddlers. Hence, clinical suspicion and repeat imaging is key for early diagnosis in this age group. CT Abdomen and Pelvis with intravenous and oral contrast showing findings of perforated, complicated acute appendicitis, with multiple abscesses. Copyright © 2023 Southern Society for Clinical Investigation.
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Case Report: A 4-year-old African American male presented to an outside emergency department (ED) following sudden inability to move left upper extremity. Past medical history was unremarkable and routine vaccinations were up to date. Radiograph of affected extremity ruled out fractures and patient was discharged to follow up with primary care physician. Two days later mother brought him to our ED due to persistent left upper extremity paralysis, poor appetite, and subjective fever. On exam his left arm was warm and tender to dull and sharp touch;he had definite loss of active movement, hypotonia and absence of deep tendon reflexes. The patient had winging of left scapula and could not shrug left shoulder. MRI of cervical and thoracic spine showed enlargement of spinal cord from C2-C6 level with gray matter hyperintensity, slightly asymmetric to the left. Laboratory studies showed leukocytosis (14 000/mcL) and CSF studies showed pleocytosis of 89 WBC/mcL (93.3% mononuclear cells and 6.7% polymorphonuclear cells), 0 RBCs, normal glucose and protein, and a negative CSF meningoencephalitis multiplex PCR panel. Due to high suspicion of demyelinating or autoimmune condition he was treated with high dose steroids and IVIG. Subsequently neuromyelitis optica was ruled out as aquaporin-4 receptor antibodies (AB) and myelin oligodendrocyte glycoprotein AB were normal. CSF myelin basic protein and oligoclonal bands were absent ruling out demyelinating disorders. CSF arboviruses IgM and West Nile IgM were negative. He showed minimal improvement in left upper extremity movement but repeat spinal cord MRI one week later showed improved cord thickness with less hyperintensity. Respiratory multiplex PCR was negative including enteroviruses. Repeat CSF studies after IVIG showed increased IgG index and IgG synthesis suggestive of recent spinal cord infection, consistent with acute flaccid myelitis (AFM). Pre-IVIG blood PCR was invalid for enteroviruses due to PCR inhibitors found in the sample. Blood post-IVIG was negative for mycoplasma IgM, West Nile IgM, and arboviruses IgM. Enterovirus panel titers (post-IVIG) were positive for coxsackie A (1:32), coxsackie B type 4 (1:80) and 5 (1:320), echovirus type 11 (1:160) and 30 (1:80) as well as positive for poliovirus type 1 and 3. These titers could not distinguish acute infection from patient's immunity or false-positives as a result of IVIG. He was discharged with outpatient follow-up visits with neurology, infectious disease, occupational and physical therapy, showing only mild improvement after discharge. Discussion(s):With the anticipated resurgence of AFM after the peak of COVID-19 pandemic, our case illustrates the need to consider this diagnostic possibility in patients with flaccid paralysis. It is important to remember CSF IgG synthesis is not affected by IVIG. In addition when treatment plans include IVIG, appropriate samples should be collected before IVIG to facilitate accurate work-up for infectious diseases. Copyright © 2023 Southern Society for Clinical Investigation.
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Case Report: Our patient is an 8-year-old Caucasian female with a history of choanal atresia, first degree heart block, recurrent urinary tract infections, and recent COVID-19 infection, who initially presented with an episode of syncope and vomiting. By history, she had two weeks of daily fever and an intermittent nonspecific rash. She was diagnosed with a UTI 5 days prior to presentation but had not defervesced despite treatment. Shewas initially found to be in shock with tachycardia and poor perfusion and was treated with fluid resuscitation, antipyretics, and empiric antibiotics. Labs were significant for leukopenia, elevated inflammatory markers, lactic acidosis, coagulopathy, and mildly elevated troponin. Chest x-ray showed abnormal but non-specific widespread infiltrates. She was initially treated with IVIG and pulse steroids for a working diagnosis of MIS-C, however she did not improve and a more extensive infectious, oncologic, and rheumatologic work-up was performed. Her workup revealed a disseminated Mycobacterium abscessus infection. Bone marrow biopsy revealed myelodysplasia with monosomy 7. Her buccal swab testing revealed a heterozygous germline mutation in the GATA2 gene, a variant that is predicted to cause loss of normal protein function. She is presently on multidrug regimen for her mycobacterial infection. Her myelodysplasia evolved into an acute leukemia, and she is undergoing chemotherapy for that at this time. Discussion(s): GATA2 deficiency, first identified in 2011, is a rare immune disorder resulting in a wide variety of clinical presentations. It is caused by a germline mutation of the GATA2 gene that disrupts blood cell differentiation, resulting in decreased or absent monocytes, B cells, NK cells, and dendritic cells1. This case presented multiple challenges due to the broad range of differential diagnoses. This patient was ultimately diagnosed with myelodysplastic syndrome associated with monosomy 7 and GATA2 deficiency, confirmed by FISH testing. Due to the presentation and lab derangements this patient had, there was a delay in targeted treatment while managing her cytopenias and presumed pulmonary infection. GATA2 deficiency carries a high risk of progression from myelodysplastic syndrome to acute myelogenous leukemia. The best long-term treatment for GATA2 deficiency is hematopoietic stem cell transplant, which is the ultimate goal for our patient. Copyright © 2023 Southern Society for Clinical Investigation.
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Background/Purpose: The coronavirus disease 2019 (COVID-19) pandemic has led to the emergence of a severe associated condition, multisystem inflammatory syndrome in adults (MIS-A). Initially identified in children as MIS-C, literature regarding the clinical manifestations, illness progression, and treatment of MIS-A are limited. Method(s): This study describes a case of MIS-A presenting as fever and seizures. She was initially given steroids and IVIG, and due to recurrence of fever, she was later treated with tocilizumab. Result(s): The patient was a 55-year- old Filipino female presenting to the emergency department with five days of fever, headache, and disorientation. Lumbar tap was done, which showed elevated opening pressure, normal leukocyte count, normal glucose, slightly elevated protein, and no microorganisms. She was admitted and managed as a case of viral encephalitis. On hospital day 6, she had sudden onset of head-jerking and further decrease in sensorium, hence she was transferred to the intensive care unit. Brain MRI was unremarkable, and subsequent immune-mediated encephalitis was considered. The patient underwent methylprednisolone pulse therapy and IVIG infusion, which provided immediate improvement of sensorium and resolution of fever episodes. Her condition stabilized, and she was transferred out of intensive care. She underwent physical and occupational rehabilitation as preparation for discharge. Two weeks after infusion therapy, on hospital day 26, patient had recurrence of fever episodes and persistence of elevated inflammatory markers. The patient had reported a previous COVID-19 infection 10 weeks prior to admission and received a booster dose of Moderna (Spikevax) COVID-19 vaccine three weeks prior. She tested positive for ANA (1:640, nuclear speckled), while the rest of the autoimmune antibody tests were negative. She was diagnosed as MIS-A based on the following: documented fever (>=38 degrees centigrade) for >=24 hours prior to hospitalization;new-onset neurologic signs and symptoms including seizures and encephalopathy in a patient without prior cognitive impairment;elevated CRP, ferritin, IL-6, and ESR;and a positive SARS-CoV- 2 test for recent infection by RT-PCR. Patient was treated with a locally available monoclonal antibody, tocilizumab, which was given on hospital day 43. Following infusion, she had lysis of fever and marked decrease in CRP, ferritin, IL-6, and ESR. Patient was discharged improved and without end-stage organ damage. Conclusion(s): Immunomodulators target hyperinflammation seen in MIS-A. There may be a role for the use of tocilizumab via blockage of IL-6. MIS-A remains a topic for research, particularly its disease characteristics, management, and relation to a dysregulated immune system.