Recurrent Fever Research Articles

E34 Coexisting sickle cell disease and autoimmune diseases among Nigerian children

Abstract Introduction Patients with sickle cell disease (SCD) do have a defective activation of the alternate complement pathway which increases their risk of having infections. This is thought to predispose to autoimmune disease (AID) in them. However, there is paucity of data on coexisting AID and SCD in children which may be due to under diagnosis as a result of overlapping symptoms of the two disease conditions. Objectives To highlight the clinical features, diagnostic challenge and importance of early recognition and treatment of autoimmune diseases in children with sickle cell disease. Methods Retrospective review of records of four children with sickle cell disease who were diagnosed with autoimmune diseases at the paediatric Rheumatology Clinic of Lagos State University Teaching Hospital (LASUTH) between May 2018 to February 2023. Results Case 1 15 –year –old girl known haemoglobin SC patient of haematology unit who was referred to rheumatology unit with history of worsening jaundice, abdominal swelling, headache, constitutional symptoms, left knee pain, and two episodes of blood transfusion within two months. Initally being managed for hyperhaemolytic and vaso-occlusive crisis but later referred to rheumatology unit on suspicion of autoimmune disease due to recurrent anaemia, and five episodes of blood transfusion within two months. ESR was 65 mm/h, ANA of 1:2560, positive anti-smith antibodies, elevated urine protein creatinine ratio (UPCR), low C3 and C4 and positive direct coomb’s test. Diagnosis was juvenile systemic lupus erythematosus (JSLE). She had pulse methylprednisolone, oral prednisolone, hydroxychloroquine and mycophenolate mofetil. She has improved clinically and being followed up in clinic. Case 2 10-year-old girl, known sickle cell anaemia patient who had unproductive cough of one-month duration and chest radiograph findings of bronchiectatic and fibrotic changes in the right upper/middle lobes with reduction in lung volume. Gene xpert was negative for tuberculosis but chest CT showed honeycombing in the right upper lobe implying Interstitial lung disease. Further investigations showed ESR of 5, ANA of 1:1280, borderline anti-dsDNA, positive anti-SM/RNP, normal urinalysis, normal renal function and restrictive lung disease on spirometry. She is being managed as a case connective tissue disorder with associated Interstitial Lung Disease. She is presently on mycophenolate mofetil and being followed up in clinic. Case 3 11-year-old female living with sickle cell anaemia who presented with inflammatory arthritis of the small joints of the hands, elbows and knees of nine-month duration, sclerodactyly, contractures of the PIP of the fingers, narrowing of oral aperture, generalized hypopigmented macules and abnormal nailfold capillaroscopy. ANA was 1:640, positive anti-Scl 70, negative anti-centromere, ESR of 130 mm/h, thrombocytosis, severe restriction on spirometry and features of interstitial lung disease on HRCT of the chest. She commenced mycophenolate mofetil, prednisolone and nifedipine. She later had 2 doses of rituximab due to slow clinical improvement and is being followed up. Case 4 13-year-old female with sickle cell anaemia who presented with recurrent fever & severe haemolytic anaemia requiring frequent blood transfusions (13 pints of blood over 6 months!!!). Initial diagnosis was septicaemia, and autoimmune haemolytic anaemia. Following rheumatology review, ANA was 1:640, positive anti-DsDNA, negative anti-Smith antibodies, ESR of > 150mm/h, elevated UPCR and pancytopaenia. She was later diagnosed with Lupus nephritis. She had Mycophenolate mofetil, prednisolone and hydroxychloroquine. She died of acute lupus flare 4 weeks after discharge from the hospital. Conclusions Physicians should have high index of suspicion for possible association of sickle-cell disease and autoimmune diseases so as not to delay definitive diagnosis and initiation of appropriate treatment.

E48 Thinking about auto inflammatory diseases in front of a periodicity of fever in children: a case report

Abstract Introduction Auto-inflammatory diseases (AIDs) are caused by mutations in genes involved in the regulation of innate immunity. The prototypical diseases are the hereditary recurrent fevers (HRFs), whose intermittent inflammatory manifestations are similar between the different diseases; they preferentially affect the serous membranes, skin, eyes, joints, muscles and sometimes the central nervous system. Their onset is often early in life. Objectives To think of an auto inflammatory disease in front of a periodic fever in children Method We report the case of a child with periodic fever. Results A 4-year-old boy with no particular family or personal history, who presented at the age of 1 year with episodes of high fever without evident cause lasting from 7 to 14 days, with a monthly recurrence. There was associated pharyngitis, bilateral cervical lymphadenopathy, oral aphthosis, abdominal pain, sometimes with arthralgia, vomiting, diarrhoea and skin rash. During the fever episode the inflammatory work-up is frankly positive with neutrophilic hyperleukocytosis and an elevated C-reactive protein. The duration and characteristics of the episodes are not modified by the usual antibiotic and antipyretic therapy. Viral serologies for CMV, EBV, parvovirus B19 and HIV are negative. Recurrent bacterial infections of the upper airways were ruled out in view of the periodic character, the negativity of the procalcitonin and throat swabs and the inefficiency of the antibiotic therapy during the attacks. The immune deficiency test came back normal. Autoinflammatory diseases in the absence of autoimmune signs were strongly suggested. Urinary mevalonate kinase/mevalonic acid during the episode was normal. Cyclic neutropenia was eliminated in the presence of PNN hyperleukocytosis at each episode. Genetic study of familial Mediterranean fever syndrome, cryopyrin-caps associated periodic syndrome and TRAPS syndrome came back normal. Our patient met al.l the Vanoni criteria for Marshall's syndrome. He received a single dose of prednisone 1 mg/kg which resulted in a spectacular defervescence in < 24 h and disappearance of other symptoms in a few days and their absence between attacks. This corticosteroid therapy was subsequently prescribed at each attack, which allowed rapid control and a reduction in the duration of the attacks. Discussion and conclusion The exact etiopathogenesis and diagnostic biomarkers of Marshall's disease are still unknown. It is rather a diagnosis of exclusion based mainly on clinical criteria. It is retained in our patient in view of the presence of all diagnostic criteria and the therapeutic test. There is no consensus on the treatment of Marshall's at present. Antipyretics can be used but are only partially effective. Single dose corticosteroids result in cessation of attacks; tonsillectomy is a secondary treatment option. Colchicine is promising for preventing or reducing the frequency of attacks. Marshall's syndrome is a self-limiting autoinflammatory disease of early childhood with spontaneous resolution without impact on the child's growth and development and without major sequelae in most cases within 3–5 years of onset.

Lichenoid dermatitis following PD-1 inhibitor-induced toxic epidermal necrolysis: a case report and literature review.

Immune checkpoint inhibitorssuch as anti-PD-1receptor antibodies have been shown to be effective in patients with advanced gastric cancer. However, there is a growing concern about immune-related adverse events. A case of a patient with gastric adenocarcinoma who developed toxic epidermal necrolysis (TEN) induced by sintilimab and subsequently developed lichenoid dermatitis is reported. TEN was diagnosed according to a history of sintilimab use, clinical symptomsand physical examination. During hospitalization, the patient developed recurrent fever caused by bacteremia and recovered from TEN after anti-infection and anti-inflammatory treatments. However, when TEN was controlled, the patient developed the lesional manifestations of lichenoid dermatitis. To date, no cases of lichenoid dermatitis after TEN have been reported following the use of PD-1 inhibitors.

Congenital Insensitivity to Pain with Anhidrosis (CIPA): The First Reported Case in Bangladesh

Congenital insensitivity to pain with anhidrosis (CIPA) is also known as hereditary sensory and autonomic neuropathy type IV. It is an exceedingly rare autosomal recessive disease which occurs due to lack of maturation of small myelinated and unmyelinated fibers of peripheral nerves. These fibers are required for transmission of pain and temperature sensation. This disorder is characterized by insensitivity to pain with intact tactile perception, anhidrosis, self mutilation, recurrent unexplained fever, auto amputation, mental retardation & autonomic nervous system abnormality from infancy. The clinical presentation of a 4-year-old boy with this rare disease is worth to describe, as the first case to be reported in Bangladesh. Rehabilitative treatments for prevention of disease complications and their progress should be given emphasis in every encounter Journal of Current and Advance Medical Research, July 2022;9(2):91-94

Systemic-onset Juvenile Idiopathic Arthritis in a young child

We present a 31-month-old female child who was referred by the pediatricians with 1-year history of recurrent high-grade fever associated with polyarthritis and recurrent skin rash, which disappears within 24 hours of resolution of fever. She had lost the ability to walk unsupported because of persistent arthritis. Her Full Blood Count (FBC) was remarkable for marked leucocytosis, thrombocytosis, and a mild normocytic normochromic anemia; Erythrocyte Sedimentation Rate (ESR) and C-reactive Protein (CRP) were both elevated at 110mm/hour and 200mg/L (<7) respectively while serial blood cultures were negative for septicemia and blood films were negative for acute leukemia; HIV, hepatitis B and C virus, tuberculosis, rheumatic fever, rheumatoid arthritis, and connective tissue disease screenings were all negative. Her hemoglobin genotype is AA. She had repeatedly received treatments for malaria and ‘sepsis’ with parenteral and oral antimalarials and antibiotics with no permanent relief, hence the reason for referral to the rheumatologist. An assessment of Systemic-onset Juvenile Idiopathic Arthritis (SoJIA) was made when her serum ferritin came back elevated at 670ng/mL (4.63 – 204) and she was commenced on oral ibuprofen with remarkable improvement evidenced by resolution of fever, joint pain and rash and normalization of ESR, CRP and serum ferritin within 8 weeks of treatment. Although SoJIA is rare, it would be worthwhile to include this disease in the differential diagnoses and subsequent evaluation in any child presenting with unexplained recurrent fever associated with body rash and polyarthritis.

Increase in pediatric recurrent fever evaluations during the first year of the COVID-19 pandemic in North America.

The impact of the COVID-19 pandemic on new diagnoses of recurrent fevers and autoinflammatory diseases is largely unknown. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) PFAPA/AID Working Group aimed to investigate the impact of the COVID-19 pandemic on the number of pediatric patients evaluated for recurrent fevers and autoinflammatory diseases in North America. The absolute number of new outpatient visits and the proportion of these visits attributed to recurrent fever diagnoses during the pre-pandemic period (1 March 2019-29 February 2020) and the first year of the COVID-19 pandemic (1 March 2020-28 February 2021) were examined. Data were collected from 27 sites in the United States and Canada. Our results showed an increase in the absolute number of new visits for recurrent fever evaluations in 21 of 27 sites during the COVID-19 pandemic compared to the pre-pandemic period. The increase was observed across different geographic regions in North America. Additionally, the proportion of new visits to these centers for recurrent fever in relation to all new patient evaluations was significantly higher during the first year of the pandemic, increasing from 7.8% before the pandemic to 10.9% during the pandemic year (p < 0.001). Our findings showed that the first year of the COVID-19 pandemic was associated with a higher number of evaluations by pediatric subspecialists for recurrent fevers. Further research is needed to understand the reasons behind these findings and to explore non-infectious triggers for recurrent fevers in children.

A 66-year-old Woman of Leukemia with Extramedullary Pulmonary Infiltration Manifesting as Lung Mass

&lt;p&gt;白血病髓外肺浸潤是一種罕見的臨床疾病，因其胸部X光和臨床表徵不具特異性，診斷困難往往延誤適當的治療。本案例為66歲女性，因發燒、咳嗽、活動後呼吸急促就醫，胸部電腦斷層顯示疑似肺膿瘍。因初步診斷為肺膿瘍故行豬尾巴導管置放術併切片檢查，病理報告僅顯示慢性發炎，且以多線抗生素藥物治療。爾後因周邊血液出現芽細胞，經骨髓切片診斷為急性骨髓性白血病，隨著病人發燒未改善，醫療團隊針對肺膿瘍，安排胸腔鏡行右上葉切除、右下葉楔狀切除及肺剝離術，最終肺組織病理報告確診為急性骨髓性白血病併髓外肺浸潤。經此案例予臨床重要省思是當病人反覆發燒且電腦斷層影像疑似肺膿瘍生成，抗生素藥物治療效果不彰，必須將白血病併髓外肺浸潤列入鑑別診斷，且一經確診為白血病髓外肺浸潤，應及早針對白血病疾病治療， 以免誤判病人肺部有感染情形，而延後癌症治療，增加病人死亡風險。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;Acute myeloid leukemia with extramedullary pulmonary infiltration is a rare clinical case. Without specific clinical manifestations and imaging features, the diagnosis is often challenging, leading to a delay in treatment. The case is of a 66-year-old female patient, who visited the emergency department due to cough, fever and exertional dyspnea. Due to recurrent fever, a chest CT scan was performed and revealed lung abscess. Based on the initial diagnosis of lung abscess, pigtail catheter placement and bronchial biopsy were performed. The pathological report showed only chronic inflammation. Thus, the patient was treated with multiple antibiotics and antifungals. Due to the detection of blast cells in the peripheral blood via the complete blood count, bone marrow biopsy was performed and then acute myeloid leukemia was confirmed. However, the recurrent fever continued for one month. The medical team arranged thoracoscopy for right upper lobe resection, right lower lobe wedge resection, and lung pneumonolysis for the lung abscess. Pulmonary histopathological report eventually confirmed acute myeloid leukemia with extramedullary pulmonary infiltration. This case suggested that when a patient has recurrent fever and the CT image shows suspected lung abscess formation, antibiotic treatment may not be effective. Extramedullary infiltration of leukemia should be suspected in the differential diagnosis. Once confirmed as extramedullary pulmonary infiltration of leukemia, leukemia related treatment should be provided as soon as possible. The delay of cancer treatment, which may increase the risk of mortality.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

A 78-year-old Man Presented with Knee Pain and Recurrent Fever

&lt;p&gt;發燒為常見臨床症狀，本案例是一位78歲末期腎臟疾病接受長期血液透析治療男性，近一個月曾發生永久性透析導管感染合併金黃色葡萄球菌菌血症，此次因左膝關節疼痛就醫，理學檢查發現關節發熱腫脹，診斷感染性關節炎入院治療， 關節液及血液培養顯示金黃色葡萄球菌，在抗生素治療及行左膝切除關節成形術後仍反覆發燒， 經由專科護理師完整病史收集、全身理學檢查、實驗室檢驗結果，排除導管感染及心內膜炎等相關鑑別診斷，電腦斷層血管攝影顯示囊狀主動脈合併周圍積液確診為感染性動脈瘤。因年紀大合併多種慢性共病（塵肺症、慢性阻塞性肺病及末期腎臟疾病等），在家屬考量動脈瘤切除、結紮及血管重建手術利弊後決定採保守治療（6週Piperacillin-Tazobactam和Vancomycin抗生素靜脈注射療程），發燒及低血壓狀況改善，且血液培養亦未發現新的感染。臨床上，當病人主訴反覆發燒合併金黃色葡萄球菌菌血症時，根據我們的案例及文獻回顧，應強調以焦點式理學檢查積極探查可能的轉移性感染（包括：導管感染、軟組織感染、感染性關節炎、心內膜炎及感染性動脈瘤等），輔以影像學檢查。以此案例提升專科護理師於類似複雜案例時的照顧能力，利於醫療團隊即早確定診斷及介入治療，以降低延遲治療對於脆弱老年病人帶來負面影響。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;Fever is a common symptom in clinical practice. A 78-year-old male with end-stage kidney disease (ESKD) who underwent hemodialysis was admitted due to left knee pain. Upon physical examination, there were signs of joint heat, swelling, and tenderness in addition to febrile state, suggesting a diag&amp;shy;nosis of septic arthritis. Staphylococcus aureus (SA) was later identified in both the synovial fluid and blood culture. However, the patient experienced recurrent fever despite receiving appropriate antimi&amp;shy;crobial treatment and undergoing left knee resectional arthroplasty. To rule out other potential diagno&amp;shy;ses related to SA bacteremia, a thorough evaluation involving medical history, physical examination, and laboratory tests was conducted. The computed tomography angiography revealed the presence of a saccular aortic aneurysm with perianeurysmal fluid collection, confirming a diagnosis of mycotic an&amp;shy;eurysm. The patient and his family carefully considered the advantages and disadvantages of surgical options, such as aneurysm excision, ligation, or vessel reconstruction. Under the considerations of the age and underlying comorbidities such as pneumoconiosis, chronic obstructive pulmonary disease, and ESKD, conservative treatment was performed (a 6-week course of intravenous piperacillin-tazobactam and vancomycin). The fever and hypotension gradually subsided, and there was no evidence of blood&amp;shy;stream infection. Based on our case and extensive literature reviews, it is crucial to actively evaluate metastatic complications, including infective endocarditis, catheter infection, septic arthritis, and my&amp;shy;cotic aneurysm, among patients who present with persistent fever and concurrent SA bacteremia. This case aims to enhance the abilities of nurse practitioners in conducting comprehensive assessments, providing vital information to the medical team, facilitating accurate diagnoses, timely interventions, and ultimately reducing the adverse impact of delayed treatment in vulnerable older adults.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

An Adult Woman Diagnosed with Recurrent Rheumatic Fever and Infective Endocarditis with Manifestations of Prolonged Fever and Heart Murmur

An Adult Woman Diagnosed with Recurrent Rheumatic Fever and Infective Endocarditis with Manifestations of Prolonged Fever and Heart Murmur

Traditional Chinese Medicine external treatment and nursing for a patient with recurrent fever in the sequelae of stroke with phlegm-heat stasis syndrome

Traditional Chinese Medicine external treatment and nursing for a patient with recurrent fever in the sequelae of stroke with phlegm-heat stasis syndrome

NLRP12-associated autoinflammatory disease: much more than the FCAS phenotype.

NLRP12-associated autoinflammatory disease (NLRP12-AID) is a rarely seen periodic fever syndrome also known as familial cold autoinflammatory syndrome-2 (FCAS2), caused by autosomal dominant inherited mutations in the NLRP12 gene. We aimed to present our clinical experience constituting one of the largest paediatric NLRP12-AID cohort. The patients with preliminary diagnosis of systemic autoinflammatory disease (SAID) other than familial Mediterranean fever (FMF) and PFAPA syndrome were evaluated with the next-generation-sequence (NGS) genetic-panel analysis between January-2016 and January-2022. Among children carrying NLRP12-variant, patients with recurrent episodes of autoinflammatory disease manifestations were diagnosed with NLRP12-AID. Demographic, clinical and laboratory data, treatments and outcomes of patients were presented. Seventeen patients were diagnosed with NLRP12-AID. The mean age at diagnosis was 114.7±69.5 months. The most frequently seen clinical manifestations were respectively; fever (100%), arthritis/arthralgia (58.8%), rash (52.9%), abdominal pain (52.9%), diarrhoea (41.2%), myalgia/fatigue (53.2%) and, conjunctivitis (11.7%). Clinical manifestations were triggered by cold exposure in three patients (17.6%). Seven patients had pathogenic, one had likely pathogenic, seven had VUS, and two had novel heterozygous variants. The most common defined variant in the NLRP12 gene was R352C. Complete response was achieved in 5 patients and partial response was in 6 with colchicine treatment. Attacks were prevented with anti-IL-1 treatments in 6 patients unresponsive to colchicine. In conclusion, the disease can cause effects on various tissues, especially the musculoskeletal and gastrointestinal systems, apart from FCAS symptoms. We think that a patient who can be defined as syndrome of undifferentiated recurrent fever should also be evaluated genetically in terms of NLRP12 previously.

A case of familial mediterranean fever in an elderly patient experiencing recurrent fever and weigh loss

Familial Mediterranean Fever (FMF) is a rare hereditary autoinflammatory disease. In particular, the onset is rare in the elderly, and the symptoms are atypical, making diagnosis difficult.

Therapy resistant urticaria as a long-term symptom of an incomplete Schnitzler syndrome

BackgroundRecurring therapy resistant hives, accompanied by IgM-gammopathy, fever and joint pain can indicate Schnitzler syndrome, a rare autoimmune disorder. There is currently no approved treatment, but complete remission of symptoms can be induced with IL-1 antagonists.Case presentationA patient with a history of chronic urticaria presented frequently at the outpatient clinic with severe hives and was treated unsuccessfully with antihistamines and omalizumab. After several years, additional symptoms such as joint pain, recurrent fever, and IgM-gammopathy developed. After the diagnostic criteria for Schnitzler syndrome were met, treatment with anakinra was initiated and resulted in an improvement of the symptoms. Shortly after the first injection, the patient developed large and painful erythematous lesions at the injection sites, leading to discontinuation of treatment and a rapid recurrence of symptoms. Subsequently, treatment with a longer-acting IL-1 antagonist (canakinumab) was initiated, resulting in a complete remission of symptoms.ConclusionThis case report demonstrates that patients with urticarial symptoms that are not relieved by typical treatments should prompt repeated reassessments of the diagnosis, even years later, because gammopathy and other diagnostic criteria for Schnitzler syndrome can occur with a delay.

Diagnosis and management of acute rheumatic fever

Acute rheumatic fever is a nonsuppurative, immune-mediated consequence of group A streptococcal pharyngitis. Recurrent or severe acute rheumatic fever can cause permanent cardiac valve damage and rheumatic heart disease. Universally, the most common major manifestations during the first episode of ARF remain carditis and arthritis. Subclinical carditis now can fulfils a major criterion for ARF in all populations as in revised Jones criteria – AHA 2015. Many of the clinical features of ARF are non-specific, so a wide range of differential diagnoses should be considered. Primary prevention requires accurate recognition and proper antibiotic treatment of GAS pharyngitis. Prevention of recurrent attacks of rheumatic fever (secondary prevention) is the most cost-effective way of preventing further rheumatic heart disease (RHD). Penicillin remains the antibiotic of choice. Intramuscular penicillin is preferred as it is more effective than oral penicillin and results in better compliance.

Haploinsufficiency of A20 caused by a novel pathogenic missense variant of TNFAIP3 and successfully treated with anti-TNF and immunosuppressive therapies

Loss-of-function of protein A20, encoded by TNFAIP3, leads to an early-onset haploinsufficiency of A20 (HA20). This study reports one Chinese child with HA20 and explores the genetic etiology of TNFAIP3 variant. The patient exhibited transient recurrent episodes of fever, intermittent signs of arthritis, gastrointestinal symptoms and multiple colonic ulcers. Laboratory tests revealed elevated inflammatory indicators and mild to moderate anemia. Genetic analysis identified a heterozygous de novo variant in his TNFAIP3 gene (c.740C＞T, p. P247L), which had never been reported before. The novel missense variation was validated to be pathogenic through causing insufficient expression of A20, over-activation of NF-κB signaling pathway and elevated levels of proinflammatory cytokines in response to stimulation by lipopolysaccharide. A combination of oral corticosteroids, TNF-α inhibitors and thalidomide freed him from symptoms and abnormal inflammatory indicators. Furthermore, continual improvement of the patient's condition was observed during a follow-up period of five months. We demonstrate a case with a de novo missense variant resulting in a loss-of-function of TNFAIP3, which expands the clinical spectrum of HA20. Cytokine antagonists and immunosuppressants may be effective drugs.

Immunodeficiency due to a novel variant in PIK3CD: a case report

BackgroundPrimary immunodeficiencies are immunological disorders caused by gene mutations involved in immune system development and activation. Recently, activated phosphoinositide 3-kinase delta syndrome (APDS) due to mutations in the phosphoinositide 3-kinase (PI3K), phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit delta gene (PIK3CD), and phosphoinositide 3-kinase regulatory subunit 1 (PIK3R1) genes have been reported to induce a combined immunodeficiency syndrome leading to senescent T cells, lymphadenopathy, and immunodeficiency. The exact diagnosis of these deficiencies is essential for treatment and prognosis. In recent years, targeted treatment with selective PI3Kd inhibitors has had a significant effect on controlling the symptoms of these patients.Case presentationIn this case report, we represent a 27-month-old girl with recurrent fever, an increased level of inflammatory markers, and erythema nodosum, who was referred to the rheumatology clinic. In the course of evaluations, because of the lack of clinical improvement with usual treatments, and a history of frequent respiratory infections, combined immunodeficiency was diagnosed in the immunological investigations. Moreover, whole-exome sequencing was performed for her.ConclusionThe genetic analysis found a novel variant of PIK3CD (c.1429 G > A) in the patient. Following daily antibiotic prophylaxis and monthly IV therapy, the patient’s frequent infections and fevers were controlled.

Susceptibility of nucleotide-binding oligomerization domain 2 mutations to Whipple's disease.

Whipple's disease (WD) results from infection of the bacteria Tropheryma whipplei (TW). This disease is characterized by macrophage infiltration of intestinal mucosa and primarily affects Caucasian males. Genetic studies of host susceptibility are scarce. Nucleotide-binding oligomerization domain containing protein 2 (NOD2) is an innate immune sensor, resides mainly in monocytes/macrophages and contributes to defence against infection and inflammatory regulation. NOD2 mutations are associated with autoinflammatory diseases. We report the association of NOD2 mutations with TW and WD for the first time. A multicentre, retrospective study of three patients with WD was conducted. Patients received extensive multidisciplinary evaluations and were cared for by the authors. NOD2 and its association with infection and inflammation were schematically represented. All patients were Caucasian men and presented with years of autoinflammatory phenotypes, including recurrent fever, rash, inflammatory arthritis, gastrointestinal symptoms and elevated inflammatory markers. All patients underwent molecular testing using a gene panel for periodic fever syndromes and were identified to carry NOD2 mutations associated with NOD2-associated autoinflammatory disease. Despite initially negative gastrointestinal evaluations, repeat endoscopy with duodenal tissue biopsy ultimately confirmed WD. After initial ceftriaxone and maintenance with doxycycline and/or HCQ, symptoms were largely controlled, though mild relapses occurred in follow-up. Both NOD2 and TW/WD are intensively involved in monocytes/macrophages. WD is regarded as a macrophage disease. NOD2 leucin-rich repeat-associated mutations in monocytes/macrophages cause functional impairment of these cells and consequently may make the host susceptible for TW infection and WD, especially in the setting of immunosuppression.

The Yield, Safety, and Cost-effectiveness of Decreasing Repeat Blood Cultures Beyond 48 Hours in a Pediatric Hematology-Oncology Unit.

Clear recommendations are needed on when repeat blood cultures (BCxs) in hospitalized children with cancer should be obtained. We reviewed all BCx obtained on the Hematology-Oncology Unit at Riley Hospital for Children, regardless of reason for patient admission or neutropenia status, between January 2015 and February 2021. Patients with positive BCx within 48 hours of initial cultures, history of stem cell transplant, or admitted to the intensive care unit were excluded. Medical records of patients with new positive BCx drawn >48 hours after initial BCx were reviewed. Seven (1.2%) hospitalization episodes grew new pathogens, or commensals treated as pathogens, on cultures beyond 48 hours. All patients with new, true pathogens were hemodynamically unstable or had recurrent fever when the new positive BCx was obtained. Twenty-three (4.0%) hospitalization episodes had contaminant cultures beyond 48 hours, with 74 (5.4%) of 1362 BCx collected beyond 48 hours being contaminated, resulting in an additional cost of $210,519 from increased length of stay. In conclusion, repeat BCx beyond 48 hours in pediatric hematology-oncology patients with negative initial cultures are low yield and costly. Repeat BCx can be safely and cost-effectively ceased after 48 hours of negative cultures in hemodynamically and clinically stable patients.

Bladder stone in a 1-year infant with recurrent urinary tract infections: a rare case report

Background: Bladder stone is a rare disease accounting for 5% of all urinary calculi. It is more common in middle- and low-income countries due to nutritional obstacles, water sanitation, and warm climates. Primary bladder calculi are most common in children younger than 10 years old, with a peak incidence at 2 to 4 years. There have been no reports of bladder stones in children under 2 years of age. This case study aims to evaluate the bladder stone in a 1-year infant with recurrent urinary tract infections. Case Presentation: An infant boy 1 year and 2 months presented with a 6-month history of complaints of pain on micturition presented with pulling the penis, cloudy urine, and recurrent fever in our clinic. During the 6 months before admission, he visited several pediatric clinics and was diagnosed with and treated for UTI. On ultrasonography, we found a bladder stone 1,9 x 1,3 cm in size. Then we performed open cystolithotomy under general anesthesia. One day after surgery, the patient was discharged from the hospital. Conclusion: Children who live in endemic areas are more likely to develop bladder stones due to dietary issues. Preventing dehydration, treating urinary tract infections effectively, and securing metabolic abnormalities are the methods for reducing the prevalence of pediatric bladder stones. Pediatric bladder stones must be diagnosed and treated to avoid the stones' recurrence and improve quality of life.

Successful transabdominal treatment of a chronic splenic abscess caused byClostridium perfringensafter penetrating external trauma in a horse

SummaryThis report describes the successful treatment of a traumatic splenic abscess by transabdominal drainage under ultrasonographic guidance. The gelding presented for investigation of recurrent pyrexia, mild abdominal pain and weight loss after a penetrating trauma to the caudolateral abdomen 5 weeks previously. At this stage, the abdominal wall had healed and a splenic abscess was diagnosed. Before treatment, mature adhesions between the abdominal wall and the spleen were confirmed by diagnostic laparoscopy in the standing horse. Transabdominal ultrasound‐guided drainage was performed, followed by intralesional placement of a balloon catheter for 2 weeks and a silicone drain for an additional week. Postoperatively, the horse was treated with intralesional and systemic antibiotics. The healing process was unremarkable and the horse was discharged 4 weeks postoperatively. At 10 months post‐surgery, after the body condition score had normalised, the horse returned to its previous level of performance.