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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.
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Autoimmune haemolytic anaemia (AIHA) is rare but described after the SARS-CoV- 2 Pfizer-BioNTech vaccine. We present a case of severe refractory warm AIHA after this vaccine, managed with emergency splenectomy and complement inhibition with eculizumab. A male in his teens with a history of liver transplant for biliary atresia (aged 2 years) and AIHA (aged 6 years) presented to his district general hospital with jaundice, dark urine, fatigue and chest discomfort 48 h after the first dose of SARS-CoV- 2 Pfizer-BioNTech vaccine (BNT162b2 mRNA). Investigations revealed haemoglobin (Hb) of 70 g/L and bilirubin of 98 mumol/L, which was treated as AIHA. The patient initially responded to prednisolone (1 mg/kg, 60 mg) but subsequently deteriorated and failed to respond to second-line rituximab (375 mg/m2) and two units of packed red blood cells (PRBC). By day 29 the patient had developed life-threatening anaemia culminating in a Hb of 35 g/L (after transfusion), lactate dehydrogenase (LD) of 1293 units/L and bilirubin of 228 mumol/L. This necessitated an immediate transfer to our tertiary centre for specialist support. Further investigations revealed a haptoglobin <0.1 g/L and direct antiglobulin test (DAT) strongly positive for IgG (4+) and negative for C3d. The peripheral blood film showed severe anaemia, nucleated red cells, anisocytosis and spherocytes with no autoagglutination, schistocytes or platelet clumps. Thrombocytopaenia (platelets 49 +/- 109/L) was present. Differentials were ruled out, such as paroxysmal nocturnal haemoglobinuria and heparin-induced thrombocytopaenia. HIV and hepatitis serology were negative, as were adenovirus, cytomegalovirus and Epstein-Barr virus PCR assays. A CT showed splenomegaly of 15.5 cm. Urinalysis found urobilinogen and bilirubin at high concentrations and negative urinary haemosiderin. Together, the investigations were consistent with warm AIHA. On day 29, four units of PRBC were transfused alongside 100 mg methylprednisolone and 1 g/kg IVIG. On day 30 the patient deteriorated despite the escalated treatment: Hb had only increased to 54 g/L, bilirubin was 200 mumol/L and LD was rising. Considering this life-threatening fulminant haemolysis, an emergency splenectomy was performed. This slowed haemolysis but did not completely ameliorate it: by day 33 the patient had received 15 units of PRBC. Thus, eculizumab, a terminal complement pathway inhibitor, was trialled to arrest intravascular haemolysis, alongside rituximab, repeat IVIG 1 g/kg, prednisolone 40 mg and tacrolimus 2 mg. This showed a favourable response, requiring less frequent transfusions and settling haemolysis. This case highlights the rare complication of warm AIHA with the SARS-CoV- 2 Pfizer-BioNTech vaccine, the use of emergency splenectomy for disease control, and the potential of eculizumab for refractory cases.
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Introduction: STAT1 gain-of-function (GOF) disease is associated with chronic mucocutaneous candidiasis (CMC) and a broad spectrum of infectious, inflammatory, and vascular manifestations. The Janus Kinase inhibitor ruxolitinib has been used successfully for CMC and autoimmune phenomena. We describe a case of warm autoimmune hemolytic anemia (WAIHA) in a patient with STAT1 GOF disease after initiating ruxolitinib. Case report: A 36-year-old man with STAT1 c.850G>A (p.Glu284Lys) mutation presented with CMC as well as recurrent viral and bacterial infections, lymphadenopathy, enteritis, nodular regenerative hyperplasia (NRH) and splenomegaly. Immune workup confirmed a combined immunodeficiency with hypogammaglobulinemia and T-cell lymphopenia. Ruxolitinib was initiated at 5 mg twice daily (due to pre-existing thrombocytopenia) with up titration over 3 months to 20 mg twice daily. He improved with weight gain, increased energy, resolution of chronic anemia, and improved lymphadenopathy and splenomegaly on imaging. Serum CXCL9 only minimally decreased from 4660 pg/ml to 3990 pg/ml. Soon after reaching ruxolitinib 20 mg twice daily, he developed JC viremia, prompting dose reduction to 15 mg BID. Within two weeks, he developed a non-COVID upper respiratory tract infection followed by fatigue, shortness of breath with ambulation, and dark urine. Emergency evaluation revealed warm antibody positive hemolytic anemia with a hemoglobin of 5 g/dL, and worsened thrombocytopenia. He was treated with blood transfusions, pulse steroids, and high-dose IVIG with stabilization but continued hemolysis. Due to the JC viremia, there was concern to give rituximab with increased PML risk. Bone marrow showed trilineage hematopoiesis, a mild increase in megakaryocytes and RBC precursors, and a loss of B-cell progenitors with retention of mature B cells. His B and T lymphocyte numbers had increased since prior to ruxolitinib, with a predominance of Tfh1-cells (58.7% of total Tfh-cells). He was started on sirolimus with a slow taper of prednisone with continued stable hemoglobin and platelets, and resolution of hemolysis after 3 months. Conclusion(s): To our knowledge, this is the first case of a STAT1 GOF patient developing WAIHA while receiving ruxolitinib therapy. Treatment choices were complicated by the risks of PML. Sirolimus combined with ruxolitinib allowed wean of corticosteroid and subsequent resolution of hemolysis.Copyright © 2023 Elsevier Inc.
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Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.
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Purpose of study A 32-years old male with known multi-system sarcoidosis in remission for 5 years off treatment presented to the emergency room with complaints of generalized weakness, hematemesis, epistaxis, and bruises. Physical examination was notable for petechiae, ecchymosis along with papules and plaques suggestive of active sarcoid skin lesions on his extremities. Laboratory workup was significant for thrombocytopenia 3000/uL, acute kidney injury with sub-nephrotic proteinuria. Peripheral blood smear did not show evidence of hemolysis and direct Coombs test was negative. Infectious workup including COVID-19, HIV, and hepatitis serologies were negative. Computed Tomography (CT) of chest, abdomen, and pelvis showed mild splenomegaly and an increased number of sub-centimeter hilar and mediastinal lymph nodes. The patient was treated with dexamethasone 40 mg daily for 4 days and intravenousimmunoglobulins (IVIG-2 gm/kg) for possible Immune Thrombocytopenic Purpura (ITP) with improvement in platelet count to 42000/uL by day 3. His workup for AKI and sub-nephrotic proteinuria was negative apart from a positive ANA (1: 160) with low complements. The anti-phospholipid antibody panel was negative. The ACE level was markedly elevated (>80U/L). The patient could not get a renal biopsy due to severe thrombocytopenia. He was discharged but was re-admitted in 15 days for severe thrombocytopenia of 1000/uL, epistaxis, and bruising. We continued high dose steroids along with IVIG 1 gm/kg for refractory ITP with minimal response and started anti-CD20 agent (Rituximab) 375 mg/m2 weekly with thrombopoietin-receptor agonist (Eltrombopag). His platelets count improved in response to treatment and subsequent renal biopsy showed focal and segmental glomerulosclerosis along with mild interstitial fibrosis, tubular atrophy thought to be from long standing sarcoidosis. There was also evidence of focal arteriosclerosis with no evidence of granulomas, immune complex, complement, or IgG4 deposition. Given skin lesions, thrombocytopenia, extensive lymphadenopathy, and renal involvement with markedly elevated ACE levels the overall picture was consistent with active multi-system sarcoidosis. His platelet count increased to 177,000/uL at the time of discharge. Currently, the patient is on slow steroid taper along with Eltrombopag 25 mg every other day without any recurrence of his symptoms so far. Methods used We described one case of sarcoidosis with hematologic and renal involvement. Summary of results Our patient developed hematologic and renal complications approximately 6 years after being diagnosed with sarcoidosis. Initially, he did not demonstrate sufficient clinical response to IVIG and high dose steroids. However, after a course of anti-CD20 agent (Rituximab) and with the addition of thrombopoietin-receptor agonist (Eltrombopag) he showed improvement of platelet count and stabilization of the renal function. Currently, the patient is receiving maintenance therapy with Prednisone 7.5 mg daily along with Eltrombopag 25 mg twice weekly with no recurrence of ITP and stable renal function. A further decision on whether the patient needs another cycle of Rituximab will be determined by the patient's clinical course. Conclusions Highly variable manifestations of Sarcoidosis can pose a significant diagnostic and therapeutic challenge as can be seen from our case. ITP is a rare hematological manifestation of sarcoidosis and addition of anti-CD20 agents should be considered in refractory cases.
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Hairy cell leukemia (HCL) is a rare, chronic, mature B-cell lymphoproliferative disorder accounting for 2% of all leukemias. In this paper, we would like to present our experience in the management of HCL in a financially limited setting where other diagnostic tests and chemotherapy are unavailable. The case report aims to emphasize the recognition of the distinctive morphology of hairy cells in the peripheral blood in the consideration of the initial diagnosis. A 60-year-old Filipino male was incidentally found to have anemia, thrombocytopenia and an absolute neutrophilic count below 1,000 in a pre-operative clearance for elective herniorrhaphy. Blood smear revealed atypical lymphocytes with hair like cytoplasmic projections. CT-scan of the abdomen showed splenomegaly and prominent paraaortic nodes. Flow cytometry of the bone marrow aspirate was consistent with an involvement of a Mature B cell neoplasm markers CD19, CD20, CD22 and surface immunoglobulin lambda and hairy cell leukemia markers CD11c, CD103 and CD25. He responded to six-weekly sessions of Cladribine with remission of the bone marrow and hematologic parameters. HCL is a rare type of a mature B cell neoplasm characterized by pancytopenia, splenomegaly, bone marrow fibrosis and the presence of atypical lymphoid cells with hairy projections in blood, bone marrow and spleen. Immunophenotyping express CD11c, CD103, CD123, and CD25. BRAF V600E mutation is the disease defining genetic event. Cladribine and Pentostatin are the first line of treatment. Cases of leukemia can be easily overlooked because of the mild derangement in the complete blood count. A meticulous differential review of the atypical lymphocyte, is the first step in the diagnosis of this rare disease.Copyright © 2022, Philippine College of Physicians. All rights reserved.
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Case report Cytomegalovirus (CMV) causes latent asymptomatic infection in most adults worldwide. Immunodeficiency or immune activation can disrupt viral suppression and lead to viral reactivation, occasionally causing a mononucleosis-like illness in otherwise healthy immunocompetent people. A 37-year- old female presented with a 10-day history of fevers, chills, right-sided neck tenderness, rapidly expanding rash, as well as myalgia, arthralgia, and weakness. She had received her first dose of tozinameran (Pfizer-BioNTech COVID-19 mRNA vaccine) 11 days prior to symptom onset. She was admitted to hospital for further investigations, and was seen by an allergy/clinical immunology specialist, with the diagnosis initially felt to be a delayed serum sickness-like reaction to the vaccine. On admission to hospital, the patient was febrile (37.8C) and tachycardic (122 beats/min). Her physical examination was remarkable for right-sided submandibular tenderness, diffuse blanchable, nonpruritic, erythematous, maculopapular rash, and mild facial swelling. There were no effused joints, lymphadenopathy, nor splenomegaly. Bloodwork showed pancytopenia and mild liver transaminase elevation. Blood cultures were negative. Multiple PCR tests for COVID-19 were negative. Monospot and serology for HBV, HIV, and B. burgdorferi were negative. CMV serology was positive, but unavailable until after discharge. ANA and rheumatoid factor were negative. CT head demonstrated nonspecific edema in the right submandibular area without abscess. On outpatient follow-up, the patient reported symptom resolution over two months. Repeat CMV titres two months post hospitalisation showed strongly elevated IgG, which upon consultation with infectious diseases was felt to represent CMV reactivation (Table 1). CMV viral load was negative. Pancytopenia resolved and transaminases normalized. She received her second dose of tozinameran 4 months post first dose with prophylactic valacyclovir 1g once daily for 1 week prior to and 1 week post vaccination as recommended by infectious diseases and remained asymptomatic. This case is the first known description of CMV reactivation secondary to COVID-19 vaccination. It may be underdiagnosed due to nonspecific symptomatology, as CMV seropositivity ranges from 60-100% of all adults. While causality has yet to be established, recognition of this condition may allow appropriate treatment and prophylaxis in order to facilitate safe COVID-19 vaccination in affected individuals. The patient has provided verbal consent through the telephone for the publication of this case report due to the current COVID-19 pandemic, with written consent to follow.
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The management of primary immune thrombocytopenia (ITP) is becoming a subject of interest as there appears to be treatment failure and resistance to modern conventional treatment, necessitating a more universal and goal-directed approach to management. Our patient is a 74-year-old male who was diagnosed with ITP six years ago and recently presented to the emergency department (ED) with complaints of melena stools and severe fatigue lasting for two days. Prior to the ED presentation, he had received multiple lines of treatment including splenectomy. On admission, the pathology after splenectomy showed a benign enlarged spleen with a focal area of intraparenchymal hemorrhage/rupture and changes compatible with ITP. He was managed with multiple platelet transfusions, IV methyl prednisone succinate, rituximab, and romiplostim. His platelet counts improved to 47,000, and he was discharged home on oral steroids with outpatient hematology follow-up. However, in a few weeks, his condition deteriorated, and he presented with an increased platelet count and further multiple complaints. Romiplostim was discontinued, and he was continued on prednisone 20 mg daily, after which he improved, and his platelet count reduced to 273,000 on 20 mg prednisone. This case calls attention to the need to review the role of combination therapy in treating refractory ITP and the prevention of complications of thrombocytosis secondary to advanced therapy. Treatment needs to be more streamlined, focused, and goal-directed. Escalation and de-escalation of treatment should be synchronized to prevent adverse complications from overtreating or undertreating.
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Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by a pathologic immune response in the setting of infection, malignancy, acute illness, or any immunological stimulus. Infection is the most common etiology of HLH. HLH involves aberrant activation of lymphocytes and macrophages with resultant hypercytokinemia due to an inappropriately stimulated and ineffective immune response. Here, we present the case of a previously healthy 19-year-old male presenting with hiccups and scleral icterus, who was found to have HLH due to a severe Epstein-Barr virus infection. Despite a morphologically normal bone marrow biopsy, the patient met the diagnostic criteria for HLH, including a low natural killer cell count and elevated soluble interleukin-2 receptor. Notably, ferritin was severely elevated at 85,810 ng/mL. The patient was treated with an induction course of dexamethasone intravenously for eight weeks. Since HLH can progress into multi-organ failure, timely diagnosis and prompt initiation of treatment are critical. Novel disease-modifying therapies and further clinical trials are warranted to treat this potentially fatal immunological disease with multisystem ramifications.
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Background Information on infective endocarditis (IE) caused by the Streptococcus anginosus (S. anginosus) group is scarce. We present a case of IE with multiple splenic septic infarcts that was further complicated by renal involvement and osteomyelitis, caused by S. anginosus in a patient with diabetes. Case 58-year-old male with diabetes presented with fever and bilateral flank pain. His CT showed splenomegaly with multiple splenic infarctions and symmetric bilateral perinephric stranding indicative of nephritis. His Labs showed leukocytosis and two blood culture sets grew S.anginosus. Transesophageal echocardiogram confirmed vegetations on aortic valve (1.3 x 1.0 cm)(Image A, red arrow) and mitral valve (1.4 x 1.0 cm)(Image B, blue arrow). Lumbar spine MRI showed L2-3 vertebral osteomyelitis. [Formula presented] Decision-making Due to patient's normal oxygen saturation and clear lung auscultation and imaging, COVID-19 was ruled out. The etiology of his fever was diagnosed as S. anginosus IE, as evidenced by his vegetations and positive cultures. The patient started on IV antibiotics and IV fluids and was transferred to another facility to receive aortic and mitral bioprostheses. Conclusion This, to the best of our knowledge, is the first documented case of S. anginosus with splenic and renal involvement. The presence of multiple splenic infarcts in immunocompromised patients, in this case in someone with diabetes, should raise suspicion for the presence of vegetations and the diagnosis of S. anginosus IE.Copyright © 2023 American College of Cardiology Foundation
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Introduction: Sarcoidosis is a rare granulomatosis. The absence of well-defined criteria for definition and the existence of differential diagnosis makes the positive diagnosis difficult. Method(s): We report a case of sarcoidosis that illustrates the difficulty of this diagnosis in the presence of atypical clinical manifestations and a strong suspicion of tuberculosis. Ultimately, renal histology allowed the positive diagnosis and the response to corticosteroids confirmed it retrospectively. Result(s): Our patient was a 66 years-old female with a history of hypertension who presented with a sensory and motor polyneuropathy a couple of months after a mild COVID-19 pneumonia, hospitalized for exploration of a worsening renal function due to a tubulointerstitial neuropathy (creatinine upon admission at 250 micromol/l, eGFR = 16 ml/min/1,73m2 -MDRD). Kidney biopsy revealed an interstitial infiltrate of monocytes and fibrosis alongside non-necrotic and giant-cell epithelioid interstitial granulomas. Extra-renal signs consisted of the above-mentioned neuropathy, bilateral mediastinal adenopathies with no signs of a pulmonary disease at the bodyscan, a hepatomegaly, splenomegaly, a pleural and pericardial effusion of low abundance, and a peritoneal thickening. Bronchoscopy and bronchoalveolar washing found no evidence for malignancies and screening for mycobacterial infections by polymerase chain reaction was negative. No granulomas were found at the hepatic biopsy. Digestive tract endoscopy and biopsies showed no abnormalities. During hospitalization, the patient presented an episode of acute polyradiculonevritis confirmed by cerebral-spine fluid study and nerve conduction study results. Our patient received intraveinous immunoglobulins (IgIV) with a favorable outcome but relapsed one month later, showing signs of respiratory failure. Upon the second relapse of the chronic polyradiculonevritis and based on the absence of bacteriological and histological evidence for a mycobacterial infection and the results or the renal biopsy, the patient received high-dose corticosteroids alongside a second course of IgIV. The neuropathy regressed totally within a month with a decrease of creatinine level to 140 micromol/l (eGFR = 35ml/min/1,73m2) alongside the polyserositis and organomegaly. The final diagnosis was that of a sarcoidosis with pulmonary and renal involvement. Although the neuropathy could be considered a manifestation of sarcoidosis, its origin was intricated as post-viral original could not be formally excluded. Conclusion(s): The etiological diagnosis for granulomatous interstitial nephropathies can be challenging due to similar clinical presentations and the need to start specific treatments especially in the presence of life-threatening situations and the absence of clear criteria defining sarcoidosis further enhances the level of difficulty. No conflict of interestCopyright © 2023
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Gastrointestinal tract damage is a part of the course of multisystem inflammatory syndrome in children (MVS-D) associated with the new COVID-19 coronavirus infection. According to the results of a retrospective study, gastrointestinal tract damage was detected in 77% of patients with MVS-D and is represented by signs such as abdominal pain, vomiting, diarrhea and peritoneal symptoms. In children with gastrointestinal tract lesions, significant differences were noted in the frequency of occurrence of the following signs: hepatomegaly, splenomegaly, hypotension/shock, as well as conjunctivitis and facial swelling. Among laboratory abnormalities, hypoalbuminemia is more characteristic, but the level of CRP and troponin is higher. The article shows that gastrointestinal tract damage is an important early predictor of the severity of MVS-D.
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Background/Purpose: Multisystem inflammatory syndrome in children (MIS-C), associated with COVID-19 infection is a life-threatening condition, required intensive care. The aim of this study was to determine risk factors for severe/life-threatening course of 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 criterion of severity was the fact of the ICU admission. The analysis of the obtained data was performed using the STATISTICA software package, version 10.0 (StatSoft Inc., USA). Result(s): To assess the factors associated with the severe course of MIS-C, patients were divided into two groups: those who were hospitalized in the ICU (n = 84;50.6%), and those who did not (n = 82;49.4%). Patients with a more severe course of MIS-C were significantly older. They had a high frequency of signs such as rash, edema, hepatomegaly, splenomegaly, neurological and respiratory symptoms. Hypotension/shock and myocardial damage were much more common in patients hospitalized in the ICU. Among the laboratory changes there were significant differences in the levels of hemoglobin, leukocytes and platelets, CRP, creatinine, troponin and D-dimer. The presence of macrophage activation syndrome was higher in patients, admitted in the ICU. Children, required intensive care required high dose corticosteroids and IVIG more often (table 1). FIGURE: 1) The first symptoms of progeria in infancy: scleroderma-like changes in the skin of the lower extremities and stiffness of knee joints at the age of 2 months. 2) Girl at the age of 3 years 5 months. Almost total alopecia with the absence of eyebrows and eyelashes. Pronounced venous pattern in the forehead, nasal bridge and nasolabial triangle. Conclusion(s): MIS-C is potentially a severe life-threatening condition, in which more than half (50.6%) of patients needed the ICU admission. The main factors determining the severity of MIS-C were: cardiovascular, resiratory and central nervous system disorders. It has been found that factors such as hepatomegaly, splenomegaly, D-dimer >2568 ng/ml, troponin >10 pg/ml, make it possible to identify a group of patients with high risk of severe MIS-C who may potentially need hospitalization in the ICU.
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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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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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Background: Due to the paucity of scientific evidence, it is unclear among pulmonologists and physicians in critical care units if and when splenomegaly in novel coronavirus disease (2019) (COVID-19) patients is worrisome. This study aims to evaluate the significance of splenic volume during COVID-19 infection with or without cytokine storm and correlates splenic volume to the volume of pathological lung changes through linear regression analysis. Result(s): A retrospective study collected 509 polymerase chain reaction proved COVID-19 patients (399 males, 110 females;mean age 48 years, age range 24-78 years) between June and November 2021, without a history of splenic pathology. A control group of age and sex-matched 509 healthy subjects was used and analyzed according to the splenic volume. Five consulting radiologists evaluated initial and follow-up computed tomography (CT) examinations using lung CT volumetry and splenic volume calculation in consensus. Three consulting pulmonologists correlated the severity of clinical and laboratory findings, including oxygen requirements and interleukin-6 (IL-6) levels. The T test results for comparison between the COVID-19 patients and the healthy subjects control group regarding the splenic volume were significant (T value was - 4.731452 and p value was 0.00002). There was no significant correlation between the severity of the disease and normal-sized spleen (26% of patients, p = 0.916) or splenomegaly (24% of patients, p = 0.579). On the other hand, all patients with a small spleen or progressive splenomegaly during serial follow-up imaging had clinically severe disease with a statistically significant correlation (p = 0.017 and 0.003, respectively). Ninety-seven percent of patients with clinically mild disease and splenomegaly had 0-20% lung involvement (CT-severity score 1) while all patients with clinically severe disease and splenomegaly had 27-73% lung involvement (CT-severity score 2 and 3) (r = 0.305, p = 0.030). Conclusion(s): Splenomegaly is a non-specific sign that may be found during mild and severe COVID-19 infection, it was not statistically correlated with the clinical severity and a weak positive relationship was found between the splenic size and the CT-severity score of the pathological lung volume. On the other hand, the presence of splenic atrophy or progressive splenomegaly was correlated with severe COVID-19 presentation and "cytokine storm". Therefore, the splenic volume changes should not be overlooked in COVID-19 serial CT examinations, particularly in severe or critically ill patients with cytokine storms. Copyright © 2022, The Author(s).
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Rationale: The impact of COVID-19 in patients with autoimmune liver disease treated with immunosuppressive therapy has not been described so far. This case report describes the clinical course of a patient with autoimmune hepatitis (AIH) who developed COVID-19 and the features of cytokine syndrome leading to its deterioration in our intensive care unit. Patient's Concern: A 28-year-old male presented with generalized anasarca for two weeks and chronic liver disease for 8 months. Diagnosis: AIH and Covid-19 with features of cytokine storm syndrome. Interventions: Intravenous furosemide, mannitol, syrup lactulose, steroids (prednisolone 40 mg), azathioprine 1 mg/kg body weight, rifaximin, vitamin K, and blood products. Outcomes: The patient had hepatic encephalopathy and AIH and died on the 10th day after admission despite ventilatory support, sustained low-efficiency hemodialysis, and resuscition. Lessons: The dramatic release of cytokines and the inflammatory-immune responses not only alter the pathophysiology but also affects the onset and severity of disease progression in patients with AIH.
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SESSION TITLE: Critical Gastrointestinal Case Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Histoplasma capsulatum is a dimorphic fungus most commonly encountered as an opportunistic infection in immunosuppressed patients, particularly those with HIV/AIDS. However, patients immunosuppressed from other causes can also be at risk. Here is presented the case of a patient on multi-immunosuppressant therapy as treatment for Crohn's disease, who developed disseminated histoplasmosis. CASE PRESENTATION: A 44-year-old male with a past medical history of Crohn's disease (previously been on azathioprine, adalimumab and currently on Prednisone therapy), recently started on infliximab infusion for uncontrolled symptoms of IBD, diabetes mellitus, hypothyroidism, and COVID-19 infection (not requiring oxygen therapy) one month prior to the current admission initially presented to the hospital with chief complaints of exacerbated weakness, myalgias, fevers and diarrhea for 5 days;Symptoms of weakness, myalgias began after first infusion of infliximab and it got progressively worse after the 2nd infusion 2 weeks prior to the admission. White Blood Cell count was 1.1 K/uL, platelet count was 7 K/uL, hemoglobin was 7.9 g/dL. CRP was elevated to 142 mg/L, and ferritin was elevated to 39,000 ug/L. CT abdomen and pelvis demonstrated probable rectosigmoid colitis and splenomegaly. Subsequent chest x-ray demonstrated bilateral opacities with haziness over bilateral lung fields. Respiratory viral panel, stool panel, blastomyces antigen, cryptococcal antigen, toxoplasma antibodies, HIV antibody, CMV PCR, and blood cultures were unrevealing. Urinary histoplasma antigen was positive, and BD-glucan was elevated to over 500 ng/L. EBV panel was positive for reactivation, with EBV DNA 2.02 IU/mL. He was subsequently started on amphotericin B lipid complex, with itraconazole destination therapy. He was treated empirically for pneumocystis jiroveci pneumonia (PJP) with sulfamethoxazole-trimethoprim due to him being on chronic Prednisone therapy. Echocardiogram demonstrated left ventricular ejection fraction (LVEF) of 40%, with diffuse hypokinesis and wall motion abnormalities, posing some question of myocarditis. He was later discharged home in an improved state. DISCUSSION: Disseminated histoplasmosis in the setting of Crohn's disease on chronic immunosuppressive therapy has been very rarely reported,(1) with similar reports in patients on immunosuppressive therapy in the setting of rheumatologic disease being slightly more common.(2) The most commonly involved areas in gastrointestinal histoplasmosis are the terminal ileum and colon,(3) with this patient's rectosigmoid colitis and symptomatology being consistent with this pattern. The patient's myocarditis is also consistent with disseminated histoplasmosis infection. CONCLUSIONS: Clinicians should maintain suspicion for opportunistic infections in patients on immunosuppressive therapy in the setting of critical illness. Reference #1: Bhut, B., Kulkarni, A., Rai, V. et al. A rare case of disseminated histoplasmosis in a patient with Crohn's disease on immunosuppressive treatment. Indian J Gastroenterol 37, 472–474 (2018). https://doi.org/10.1007/s12664-018-0886-1 Reference #2: Wood KL, Hage CA, Knox KS, et al. Histoplasmosis after treatment with anti-tumor necrosis factor-alpha therapy. Am J Respir Crit Care Med. 2003;167(9):1279-1282. doi:10.1164/rccm.200206-563OC Reference #3: Galandiuk S, Davis BR. Infliximab-induced disseminated histoplasmosis in a patient with Crohn's disease. Nat Clin Pract Gastroenterol Hepatol. 2008;5(5):283-287. doi:10.1038/ncpgasthep1119 DISCLOSURES: no disclosure on file for Donald Dumford;No relevant relationships by Abhilash Bhat Marakini No relevant relationships by Palak Rath No relevant relationships by Sterling Shriber
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SESSION TITLE: Unique Inflammatory and Autoimmune Complications of COVID-19 Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Hemophagocytic Lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome caused by severe, dysregulated hypercytokinemia. This can be associated with genetic defects or immunologic triggers such as infection, malignancy or autoimmune disorder. The clinical picture consists of multi-organ failure including fever, hepatosplenomegaly, cytopenia,hypertriglyceridemia, hemophagocytosis, high ferritin and IL-2 levels, neurological and liver dysfunction. We present a case of a patient with HLH in the setting of Herpes Simplex Virus (HSV) and SARS-CoV-2 co-infection. CASE PRESENTATION: A 39-year-old male presented to the ER with dyspnea and was found to have COVID-19 pneumonia. He had worsening hypoxemia and was admitted to ICU. He rapidly developed multi-system organ failure (MSOF)including severe hepatitis with AST 13,950 U/L and ALT 10,000 U/L, pancytopenia (Hb 12.9 g/dL, WBC 1.7 K/uL, platelet 15,000 K/uL), acute kidney injury (Cr 6.61 mg/dL), and severe ARDS requiring mechanical ventilation. Abdominal ultrasonography showed splenomegaly. Blood HSV1 DNA PCR was positive with liver biopsy revealing viral inclusions consistent with HSV hepatitis. He had elevated ferritin > 100,000 ug/L and LDH > 2500 U/L. Bone marrow biopsy demonstrated hemophagocytosis and trilineage hematopoiesis. He met 6 of 8 diagnostic criteria for HLH per the HLH-2004 protocol. He received dexamethasone. Risks and benefits of HLH-specific therapy were considered in the setting of liver dysfunction and the decision was made to withhold etoposide and administer anakinra. He died of refractory septic shock and disseminated intravascular coagulopathy. DISCUSSION: Diagnosis of HLH can be challenging due to its rarity and the clinical picture may be initially attributed to sepsis in the presence of infection, as in our patient who had COVID-19 infection and HSV hepatitis. However, a ferritin level >10,000 ng/mL is 90% sensitive and 96 % specific for HLH, with very minimal overlap with sepsis, infections, and liver failure. Additionally, infection is a known trigger of HLH. Despite high mortality without therapy, survival can be significantly increased with HLH-specific therapy, such as etoposide. Treatment with etoposide in the setting of severe liver disease can raise concern because it is metabolized by the liver but it is an essential component of optimal therapy and can be considered in patients with hepatic dysfunction with dose reduction. CONCLUSIONS: Our case highlights the importance of maintaining a high index of suspicion for HLH in critically ill patients with MSOF and liver failure, despite an apparent infectious etiology. This may allow timely diagnosis, early referral to a specialist center and consideration of HLH-specific therapy such as etoposide despite liver dysfunction, to prevent high morbidity and mortality in this potentially fatal disease. Reference #1: Filipovich AH. Hemophagocytic lymphohistiocytosis (HLH) and related disorders. Hematology Am Soc Hematol Educ Program 2009;:127. DISCLOSURES: No relevant relationships by Abdul Khan No relevant relationships by Nehan Sher No relevant relationships by yuttiwat vorakunthada
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Background: Castleman disease (CD), classified as unicentric CD (UCD) or multicentric CD (MCD), is a rare non-neoplastic lymphoproliferative disorder of unknown origin. Owing to its rarity, the clinical characteristics, therapeutic modalities, treatment outcomes, and prognostic factors related to UCD or MCD are not well defined. Method: We retrospectively analyzed 88 patients with CD, including those with hyaline-vascular, plasma-cell, mixed type, hypervascular, and plasmablastic subtypes, for presenting symptoms, physical, laboratory, and radiologic findings, and treatment response in the Korean population. Results: The median patient age was 44 years (range: 18-84 years) with slight predominance of women (53.4%). UCD and MCD accounted for 38.6% (n=34) and 61.4% (n=54) of cases, respectively. Histopathologically, UCD patients were classified as 88.2% (n=30) hyaline-vascular and 11.8% (n=4) plasma cell types, whereas MCD patients were classified as 27.8% (n=15) hypervascular, 61.1% (n=33) plasma cell, 7.4% (n=4) mixed, and 3.7% (n=2) plasmablastic types. Twelve (13.6%) patients exhibited a poor performance status with an Eastern Cooperative Oncology Group score of 2. The most common presenting symptom was sustained fever, followed by fatigue, anorexia, peripheral edema, and weight loss. Furthermore, splenomegaly, pleural effusion, and ascites were observed to be associated with CD. Surgical resection and siltuximab were the preferred treatment modalities for UCD and MCD, respectively, with favorable symptomatic, laboratory, and radiologic outcomes and safety profiles. The overall survival was 90.2%, with no significant difference between the UCD and MCD groups (p=0.073), but progression-free survival was significantly poorer in the MCD group (p=0.001). Age ≥60 years and splenomegaly significantly affected the overall and progression-free survival rates. Conclusion: Patients with UCD had favorable outcomes with surgical resection of a solitary mass, whereas in patients with MCD, old age and splenomegaly were identified as independent prognostic factors. Further well-designed prospective studies under advancing knowledge of the pathophysiology of MCD are warranted to establish suitable guidelines for the discontinuation or prolonging infusion intervals of siltuximab and treatment modalities for HHV-8 positive MCD patients or patients with siltuximab failure.